Clinical trial NCT03090100
Conditions: Psoriasis
Sponsor: Janssen Research & Development, LLC
Start date: 2017-04-27; Completion date: 2018-09-20
Enrollment: 1048 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the efficacy of guselkumab compared with secukinumab for the treatment of participants with moderate to severe plaque-type psoriasis.

Detailed description:
The study consists of Screening Phase(4 weeks before administration of study drug),Active Treatment Phase(Week 0-Week 44),Follow Up Phase(Week 44-Week 56).During various study periods,safety assessments(example\[e.g\] recording of adverse events,Vital signs,Tuberculosis evaluation,Chest radiograph,Urine pregnancy Test);Efficacy assessments(e.g IGA,PASI);Clinical Laboratory Assessments(e.g haematology,chemistry);Biomarkers/Genetic evaluations,will be performed per the study procedures.The primary hypotheses are that guselkumab treatment is non-inferior to secukinumab as assessed by proportion of participants achieving PASI 90 response at Week 48 with noninferiority margin of 10% and,once non-inferiority is established,that guselkumab is superior to secukinumab as assessed by proportion of participants achieving PASI 90 response at Week 48.

Arms: arm 1: Participants will receive 1 injection of active guselkumab and 1 injection of placebo when guselkumab is scheduled to be administered (Weeks 0, 4, 12, 20, 28, 36, and 44) or 2 injections of placebo when no guselkumab is scheduled to be administered (Weeks 1, 2, 3, 8, 16, 24, 32, and 40). Placebo injections will be administered to maintain the blind. arm 2: Participants will receive 2 injections of active secukinumab subcutaneously (SC) at Weeks 0, 1, 2, 3, 4 and every 4 weeks (q4w) thereafter through Week 44.
Interventions: intervention 1: Guselkumab intervention 2: Placebo intervention 3: Secukinumab
Intervention descriptions: intervention 1: Participants will receive 1 injection of active guselkumab at Weeks 0, 4, 12, 20, 28, 36, and 44. intervention 2: Participants will receive 1 injection of placebo at Weeks 0, 4, 12, 20, 28, 36, and 44 and 2 injections of placebo at Weeks 1, 2, 3, 8, 16, 24, 32, and 40. intervention 3: Participants will receive 2 injections of active secukinumab at Weeks 0, 1, 2, 3, 4 and every 4 weeks (q4w) thereafter through Week 44.

Protocol documents:
Prot_000.pdf: 
1
Status: Approved,  Date: 5 October 2017
Janssen Research & Development*
Clinical Protocol
A Phase 3, Multicenter, Randomized, Double-blind Study Evaluating the Comparative 
Efficacy of CNTO 1959 (Guselkumab) and Secukinumab for the Treatment of Moderate to 
Severe Plaque-type Psoriasis
ECLIPSE
Protocol CNTO1959PSO3009; Phase 3
AMENDMENT 1
CNTO 1959 (guselkumab)
*Janssen Research & Development is a global organization that operates through different legal entities in 
various countries. Therefore, the legal entity acting as the sponsor for Janssen Research & Development 
studies may vary, such as, but not limited to Janssen Biotech, Inc.; Janssen Products, LP; Janssen 
Biologics, BV; Janssen-Cilag International NV; Janssen, Inc; Janssen Sciences Ireland UC; or Janssen 
Research & Development, LLC. The term “sponsor” is used throughout the protocol to represent these 
various legal entities; the sponsor is identified on the Contact Information page that accompanies the 
protocol.
This study will be conducted under US Food & Drug Administration IND regulations 
(21 CFR Part 312).
EudraCT NUMBER: 2016-002995-29
Status:
Approved
Date:
5 October 2017
Prepared by:
Janssen Research & Development, LLC
EDMS number:
EDMS-ERI-128153718
GCP Compliance: This study will be conducted in compliance with Good Clinical Practice, and applicable regulatory 
requirements.
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and may 
not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed by 
them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as privileged or 
confidential.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
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Approved, Date: 5 October 2017
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF ATTACHMENTS............................................................................................................................ 4
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 4
PROTOCOL AMENDMENTS....................................................................................................................... 5
SYNOPSIS.................................................................................................................................................... 7
TIME AND EVENTS SCHEDULE .............................................................................................................. 13
ABBREVIATIONS ...................................................................................................................................... 16
1.
INTRODUCTION................................................................................................................................ 17
1.1.
Background .................................................................................................................................... 17
1.2.
Comparator .................................................................................................................................... 19
1.3.
Overall Rationale for the Study...................................................................................................... 19
1.3.1.
Role of IL-23 in the Treatment of Psoriasis ................................................................................ 19
1.3.2.
Dose Rationale ........................................................................................................................... 20
1.3.3.
Rationale for Trial Design and Efficacy Analyses....................................................................... 20
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESES.......................................................................... 20
2.1.
Objectives and Endpoints .............................................................................................................. 20
2.1.1.
Objectives ................................................................................................................................... 20
2.1.2.
Endpoints.................................................................................................................................... 21
2.2.
Hypotheses .................................................................................................................................... 22
3.
STUDY DESIGN AND RATIONALE ................................................................................................. 23
3.1.
Overview of Study Design.............................................................................................................. 23
3.2.
Study Design Rationale.................................................................................................................. 24
4.
SUBJECT POPULATION.................................................................................................................. 26
4.1.
Inclusion Criteria ............................................................................................................................ 26
4.2.
Exclusion Criteria ........................................................................................................................... 29
4.3.
Prohibitions and Restrictions ......................................................................................................... 33
5.
TREATMENT ALLOCATION AND BLINDING................................................................................. 34
6.
DOSAGE AND ADMINISTRATION .................................................................................................. 35
7.
TREATMENT COMPLIANCE............................................................................................................ 36
8.
CONCOMITANT THERAPY.............................................................................................................. 36
8.1.1.
Concomitant Medications for Treatment of Psoriasis................................................................. 36
8.1.1.1.
Topical Therapy....................................................................................................................... 36
8.1.1.2.
Phototherapy or Systemic Therapy for Psoriasis .................................................................... 37
8.1.2.
Concomitant Medications for Conditions Other than Psoriasis .................................................. 37
9.
STUDY EVALUATIONS .................................................................................................................... 37
9.1.
Study Procedures........................................................................................................................... 37
9.1.1.
Overview..................................................................................................................................... 37
9.1.2.
Screening Phase ........................................................................................................................ 38
9.1.3.
Screen Failure/Rescreening ....................................................................................................... 39
9.1.4.
Double-Blind Treatment Phase .................................................................................................. 39
9.1.5.
Posttreatment Phase (Follow-Up) .............................................................................................. 40
9.2.
Efficacy Evaluations....................................................................................................................... 40
9.2.1.
Evaluations ................................................................................................................................. 40
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Approved, Date: 5 October 2017
9.2.1.1.
Investigator’s Global Assessment ........................................................................................... 40
9.2.1.2.
Psoriasis Area and Severity Index .......................................................................................... 40
9.3.
Pharmacokinetics and Immunogenicity ......................................................................................... 41
9.4.
Biomarkers ..................................................................................................................................... 41
9.5.
Genetic (DNA) Analysis ................................................................................................................. 42
9.6.
Safety Evaluations ......................................................................................................................... 42
9.6.1.
Electronic Columbia-Suicide Severity Rating Scale ................................................................... 46
9.7.
Sample Collection and Handling.................................................................................................... 48
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL 
FROM THE STUDY ........................................................................................................................... 48
10.1.
Completion ..................................................................................................................................... 48
10.2.
Discontinuation of Study Treatment/Withdrawal from the Study ................................................... 48
10.3.
Withdrawal From the Use of Research Samples........................................................................... 50
11.
STATISTICAL METHODS................................................................................................................. 51
11.1.
Subject Information ........................................................................................................................ 52
11.2.
Sample Size Determination ........................................................................................................... 52
11.3.
Efficacy Analyses ........................................................................................................................... 53
11.3.1.
Analysis Data Set ....................................................................................................................... 53
11.3.2.
Primary Analysis ......................................................................................................................... 53
11.3.3.
Major Secondary Analyses......................................................................................................... 54
11.3.3.1.
Multiplicity Control ................................................................................................................... 54
11.3.4.
Other Efficacy Analyses.............................................................................................................. 54
11.4.
Criteria for Endpoints ..................................................................................................................... 55
11.5.
Pharmacokinetic Analyses............................................................................................................. 55
11.6.
Immunogenicity Analyses .............................................................................................................. 56
11.7.
Biomarker Analyses ....................................................................................................................... 56
11.8.
Safety Analyses ............................................................................................................................. 56
11.9.
Interim Analysis.............................................................................................................................. 58
12.
ADVERSE EVENT REPORTING ...................................................................................................... 58
12.1.
Definitions ...................................................................................................................................... 58
12.1.1.
Adverse Event Definitions and Classifications ........................................................................... 58
12.1.2.
Attribution Definitions.................................................................................................................. 59
12.1.3.
Severity Criteria .......................................................................................................................... 60
12.2.
Special Reporting Situations.......................................................................................................... 60
12.3.
Procedures..................................................................................................................................... 61
12.3.1.
All Adverse Events...................................................................................................................... 61
12.3.2.
Serious Adverse Events ............................................................................................................. 62
12.3.3.
Pregnancy................................................................................................................................... 63
12.3.4.
Events of Special Interest........................................................................................................... 64
12.4.
Contacting Sponsor Regarding Safety........................................................................................... 64
13.
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 64
13.1.
Procedures..................................................................................................................................... 64
13.2.
Contacting Sponsor Regarding Product Quality ............................................................................ 64
14.
STUDY DRUG INFORMATION......................................................................................................... 64
14.1.
Physical Description of Study Drug(s) ........................................................................................... 64
14.1.1.
Guselkumab................................................................................................................................ 64
14.1.2.
Cosentyx (Secukinumab)............................................................................................................ 65
14.2.
Packaging ...................................................................................................................................... 65
14.3.
Labeling.......................................................................................................................................... 65
14.4.
Preparation, Handling, and Storage............................................................................................... 65
14.4.1.
Guselkumab................................................................................................................................ 65
14.4.2.
Cosentyx (Secukinumab)............................................................................................................ 65
14.5.
Drug Accountability ........................................................................................................................ 66
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Approved, Date: 5 October 2017
15.
STUDY-SPECIFIC MATERIALS....................................................................................................... 66
16.
ETHICAL ASPECTS ......................................................................................................................... 67
16.1.
Study-Specific Design Considerations........................................................................................... 67
16.2.
Regulatory Ethics Compliance....................................................................................................... 67
16.2.1.
Investigator Responsibilities ....................................................................................................... 67
16.2.2.
Independent Ethics Committee or Institutional Review Board ................................................... 67
16.2.3.
Informed Consent ....................................................................................................................... 69
16.2.4.
Privacy of Personal Data ............................................................................................................ 70
16.2.5.
Long-Term Retention of Samples for Additional Future Research ............................................ 70
16.2.6.
Country Selection ....................................................................................................................... 71
17.
ADMINISTRATIVE REQUIREMENTS .............................................................................................. 71
17.1.
Protocol Amendments.................................................................................................................... 71
17.2.
Regulatory Documentation ............................................................................................................ 71
17.2.1.
Regulatory Approval/Notification ................................................................................................ 71
17.2.2.
Required Prestudy Documentation............................................................................................. 71
17.3.
Subject Identification, Enrollment, and Screening Logs ................................................................ 72
17.4.
Source Documentation................................................................................................................... 73
17.5.
Case Report Form Completion ...................................................................................................... 73
17.6.
Data Quality Assurance/Quality Control ........................................................................................ 74
17.7.
Record Retention ........................................................................................................................... 74
17.8.
Monitoring ...................................................................................................................................... 75
17.9.
Study Completion/Termination....................................................................................................... 75
17.9.1.
Study Completion/End of Study.................................................................................................. 75
17.9.2.
Study Termination....................................................................................................................... 76
17.10.
On-Site Audits ................................................................................................................................ 76
17.11.
Use of Information and Publication................................................................................................ 76
REFERENCES............................................................................................................................................ 78
INVESTIGATOR AGREEMENT ................................................................................................................. 86
LIST OF ATTACHMENTS
Attachment 1:
Investigator’s Global Assessment .............................................................................. 79
Attachment 2:
Psoriasis Area and Severity Index ............................................................................. 80
Attachment 3:
QuantiFERON®-TB Gold Testing ............................................................................... 81
Attachment 4:
Tuberculin Skin Testing.............................................................................................. 83
Attachment 5:
Hepatitis B Virus (HBV) Screening With HBV DNA Testing....................................... 84
Attachment 6:
Anticipated Events...................................................................................................... 85
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 1:
Power to Detect a Treatment Effect Based on Different Proportions of Subjects 
Achieving the Primary Endpoint PASI 90 at Week 48 and the Major Secondary 
Endpoint PASI 100 at Week 48 ................................................................................................ 53
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................. 24
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
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Approved, Date: 5 October 2017
PROTOCOL AMENDMENTS
Protocol Version
Issue Date
Original Protocol
6 December 2016
Amendment 1
5 October 2017
Amendments below are listed beginning with the most recent amendment.
Amendment 1 (5 October 2017)
This amendment is considered to be nonsubstantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union, in that it does not significantly 
impact the safety or physical/mental integrity of subjects, nor the scientific value of the study.
The overall reason for the amendment: The overall reason for the amendment is to delete the reference to the 
Week 48 database lock (DBL) as detailed in the original study design.  The study will have a singular database lock
(DBL) at Week 56.
Applicable Section(s)
Description of Change(s)
Rationale: To delete the reference to the database lock (DBL) at Week 48 from the Study Design, and clarify that 
only one database lock (DBL) will occur at Week 56.
Synopsis, Overview 
of Study Design;
3.1. Overview of 
Study Design, After 
Week 44 through 
Week 56 (Follow-up 
Period)
There are 2is 1 DBL in this study , 1 at Week 48, and 1 at Week 56. The sponsor will be 
unblinded after the last subject has completed the Week 48 visit and the Week 48 DBL 
has occurred. The sponsor, the investigators and subjects will be unblinded after the 
Week 56 DBL has occurred.
Figure 1: Schematic 
Overview of the Study
The reference to the DBL at Week 48 has been deleted from the study schematic 
timeline.
Rationale: To clarify that subjects who complete their final study visit prior to Week 48 are not to have blood 
samples drawn for analysis of serum biomarkers.
Time and Events 
Schedule
Footnote b and j.
b:  All Week 48 study procedures should be performed on any subject who terminates 
the study prior to Week 48, except for collection of serum for biomarkers.
j: Serum biomarker measurements will include but are not limited to: serum IL-17A, 
IL-17F, and IL-22. For subjects who discontinue from the study prior to 
Week 48, serum is not to be collected for measurement of biomarkers.
10.2 Discontinuation 
of Study 
Treatment/Withdrawal 
from the Study
Discontinuation of Study Treatment [last paragraph]
If the subject discontinues study treatment before his or her last scheduled injection, he 
or she should return for the remaining regularly scheduled study visits for at least 12 
weeks after receiving the last administration of study drug. For subjects who complete 
their final study visit prior to Week 48, every effort should be made to conduct the 
Week 48 assessments as indicated in the Time and Events Schedule. For subjects who 
discontinue from the study prior to Week 48, serum is not to be collected for 
measurement of biomarkers.
Rationale: To correct Exclusion Criterion #23 to specify that Exclusion Criterion #24 and not #28 applies to 
BCG vaccination.
4.2. Exclusion Criteria
Criterion #23
23. 
Has received, or is expected to receive, any live virus or bacterial vaccination 
within 3 months before the first administration of study drug. For BCG vaccine, 
see Exclusion Criterion 2824.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
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Approved, Date: 5 October 2017
Applicable Section(s)
Description of Change(s)
Rationale: To clarify the subject study visits at which each version of the Electronic Columbia-Suicide Severity 
Rating Scale (eC-SSRS) is to be conducted.
9.6.1. Electronic 
Columbia-Suicide 
Severity Rating Scale
The ‘Baseline/Screening’ version of the eC-SSRS will be conducted during the 
screening visit followed by the ‘Since Last Visit’ version of the eC-SSRS at Week 0, 
and all visits from baseline/Week 0starting at Week 4 through Week 56.
Rationale: To replace X-ray with ECG Manual since an x-ray manual was not provided to the sites.
15. Study-Specific 
Materials

X-rayECG Manual.
Rationale: Minor errors were noted.
Throughout the 
protocol.
Minor grammatical, formatting, or spelling changes were made.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
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Approved, Date: 5 October 2017
SYNOPSIS
A Phase 3, Multicenter, Randomized, Double-blind Study Evaluating the Comparative Efficacy of 
CNTO 1959 (Guselkumab) and Secukinumab for the Treatment of Moderate to Severe Plaque-type 
Psoriasis
Protocol Number: CNTO1959PSO3009
OBJECTIVES, ENDPOINTS, AND HYPOTHESES
Primary Objective
The primary objective is to evaluate the efficacy of guselkumab compared with secukinumab for the 
treatment of subjects with moderate to severe plaque-type psoriasis.
Secondary Objective
The secondary objectives are to assess:

The safety and tolerability of guselkumab in subjects with moderate to severe plaque-type psoriasis.

The PK and immunogenicity of guselkumab after subcutaneous (SC) administrations in subjects with 
moderate to severe plaque-type psoriasis.
Primary Endpoint
The primary endpoint in this study is the proportion of subjects who achieve a Psoriasis Area and Severity 
Index (PASI) 90 response at Week 48, comparing the guselkumab group and the secukinumab group.
Major Secondary Endpoints
The major secondary endpoints to compare the guselkumab group and the secukinumab group are listed 
below and are the proportion of subjects who achieve:

A PASI 75 response at both Week 12 and Week 48.

A PASI 90 response at Week 12.

A PASI 75 response at Week 12.

A PASI 100 response at Week 48.

An Investigator’s Global Assessment (IGA) score of cleared (0) at Week 48.
Other Secondary Endpoints

The other secondary endpoints to compare the guselkumab group and the secukinumab group are 
listed below and are the proportion of subjects who achieve:

A PASI 90 response at both Week 16 and Week 48.

A PASI 75 response at Week 16.

A PASI 90 response at Week 16.

A PASI 90 response at all 7 visits from Week 24 through Week 48.

An IGA score of cleared (0) or minimal (1) at Week 16.

An IGA score of cleared (0) or minimal (1) at Week 12.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
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Approved, Date: 5 October 2017

The proportions of subjects who achieve a PASI 75 response at Week 48 among PASI 75 responders 
at Week 12.

The proportions of subjects who achieve a PASI 90 response at Week 48 among PASI 90 responders 
at Week 16.

The proportions of subjects who achieve a PASI 50/75/90/100 response over time through Week 48.

The proportions of subjects who achieve an IGA score of cleared (0) response, IGA score of cleared 
(0) or minimal (1) response, and IGA of cleared (0), minimal (1), or mild (2) response over time 
through Week 48.

Percentages of improvement from baseline in PASI over time through Week 48.
Hypotheses
The proposed randomized, blinded, two-active-arm trial will evaluate the relative performance of 
guselkumab and secukinumab utilizing a comprehensive battery of endpoints (eg, PASI 75, 90, and 100) 
at various timepoints (eg, Week 12 and Week 48) using rigorous statistical methodology to control for 
multiplicity.
While the ultimate goal of the trial is to demonstrate that the efficacy of guselkumab is superior to 
secukinumab for PASI 90 at Week 48, an initial test for non-inferiority is included for this endpoint 
because the overall profile of guselkumab will likely be favorable compared with secukinumab (in terms 
of potential for increased compliance and lesser patient burden), even if final results only indicate the 
relative efficacy is no worse for this endpoint.
The primary hypotheses are that guselkumab treatment is non-inferior to secukinumab as assessed by the 
proportion of subjects achieving a PASI 90 response at Week 48 with a non-inferiority margin of 10%
and, once non-inferiority is established, that guselkumab is superior to secukinumab as assessed by the 
proportion of subjects achieving a PASI 90 response at Week 48.
The major secondary hypotheses are that guselkumab treatment is:

Non-inferior to secukinumab for the maintenance of a PASI 75 response as assessed by the 
proportion of subjects who achieve a PASI 75 response at both Week 12 and Week 48 with a non-
inferiority margin of 10% and, once non-inferiority is established, that guselkumab is superior to 
secukinumab as assessed by the proportion of subjects who achieve a PASI 75 response at both 
Week 12 and Week 48.

Non-inferior to secukinumab at Week 12 as assessed by the proportion of subjects who achieve 
PASI 90 at Week 12 with a non-inferiority margin of 10%.

Non-inferior to secukinumab at Week 12 as assessed by the proportion of subjects who achieve 
PASI 75 at Week 12 with a non-inferiority margin of 10%.

Non-inferior to secukinumab at Week 48 as assessed by the proportion of subjects who achieve 
PASI 100 at Week 48 with a non-inferiority margin of 10% and, once non-inferiority is established, 
that guselkumab is superior to secukinumab as assessed by the proportion of subjects who achieve a 
PASI 100 response at Week 48.

Non-inferior to secukinumab at Week 48 as assessed by the proportion of subjects who achieve an 
IGA score of cleared (0) at Week 48 with a non-inferiority margin of 10% and, once non-inferiority 
is established, that guselkumab is superior to secukinumab as assessed by the proportion of subjects 
who achieve an IGA score of cleared (0) at Week 48.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
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Approved, Date: 5 October 2017
OVERVIEW OF STUDY DESIGN
This is a Phase 3, randomized, double-blind, multicenter, active-controlled study evaluating the 
comparative efficacy of CNTO 1959 (guselkumab) and secukinumab in subjects with moderate to severe 
plaque-type psoriasis.
There is 1 database lock (DBL) in this study at Week 56. The sponsor, the investigators and subjects will 
be unblinded after the Week 56 DBL has occurred. The end of the study is defined as the timepoint when 
the last subject completes the Week 56 visit.
SUBJECT POPULATION
The target population is adult men or women with a diagnosis of plaque-type psoriasis (with or without 
psoriatic arthritis) for at least 6 months before the first administration of study drug. Subjects must have 
moderate to severe plaque-type psoriasis defined by PASI ≥12, IGA ≥3, and involved body surface 
area ≥10%. Subjects must be candidates for either systemic therapy or phototherapy for psoriasis, may 
have previously received some systemic therapies or phototherapy for psoriasis, and be considered, in the 
opinion of the investigator, suitable candidates for secukinumab (Cosentyx®) therapy according to their 
country's approved secukinumab product labeling.
DOSAGE AND ADMINISTRATION
For those subjects randomized to guselkumab, a 100 mg/mL solution of guselkumab in a single-use 
prefilled syringe (PFS) assembled with the UltraSafe PLUS™ Passive Needle Guard (PFS-U) device will 
be used. Subjects who are randomized to the guselkumab treatment arm will receive 2 injections: 
1 injection of active guselkumab and 1 injection of placebo when guselkumab is scheduled to be 
administered (Weeks 0, 4, 12, 20, 28, 36, and 44) or 2 injections of placebo when no guselkumab is 
scheduled to be administered (Weeks 1, 2, 3, 8, 16, 24, 32, and 40), to mimic the secukinumab 300 mg 
dosing schedule consisting of 2 injections and to maintain the blind. For those subjects randomized to 
Cosentyx, commercially available secukinumab (Cosentyx) will be supplied as a single-use PFS and 
administered according to the manufacturer’s directions. Each 300 mg dose is given as 2 subcutaneous
injections of 150 mg each. An appropriately qualified, unblinded member of the study staff will 
administer the drug and will have no other role in the conduct of the study.
All study drug injections will be administered at the investigational site. With the exception of the 
unblinded site personnel who dispense and/or administer the investigational product, all other site 
personnel and subjects will remain blinded to the treatment assignments until the last subject completes 
Week 56 evaluations and the database has been locked. Sites must ensure that they have the ability to 
physically blind and/or separate the blinded subject from the unblinded administrator. A physical barrier 
must be used such that the study drug can be administered by the unblinded site personnel, and the subject 
and other site personnel remain blinded.
EFFICACY EVALUATIONS
Efficacy evaluations chosen for this study are consistent with those utilized to evaluate other therapies for 
psoriasis. Efficacy evaluations include:

IGA

PASI
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
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Approved, Date: 5 October 2017
BIOMARKER EVALUATIONS
Biomarker sample collections will be conducted to measure serum markers, gene expression and cellular 
profiles in skin biopsies, 
 and genetic 
associations with psoriasis or response to treatment. Data collected from these samples will be used for 
exploratory research that will include the following objectives:
1.
To understand the molecular effects of guselkumab and secukinumab.
2.
To understand psoriasis pathogenesis.
3.
To understand why individuals differ in their responses to guselkumab or secukinumab.
4.
 
GENETIC (DNA) EVALUATIONS
Genetic (DNA) research may consist of the analysis of one or more candidate genes or analysis of the 
entire genome (as appropriate) in relation to guselkumab, secukinumab or psoriasis clinical endpoints. 
Whole blood samples will be collected for genetic analyses. Epigenetic evaluation may be conducted on 
skin samples obtained in the biopsy substudy. Only subjects who sign the consent form to participate in 
the genetic (DNA) assessment will have whole blood DNA or skin samples collected.
SAFETY EVALUATIONS
Safety evaluations include assessments of the following: adverse events (AEs; including injection-site and 
allergic reactions), clinical laboratory tests (hematology, chemistry, and pregnancy testing), physical 
examinations, vital sign measurements, electrocardiograms, concomitant medication review, electronic 
Columbia-Suicide Severity Rating Scale (eC-SSRS) questionnaires, and early detection of tuberculosis
(TB).
STATISTICAL METHODS
Approximately 1,040 subjects will be randomized in a 1:1 ratio to guselkumab 100 mg (n=520) or 
secukinumab 300 mg (n=520). With a non-inferiority margin of 10% and assumed treatment difference of 
10 percentage point difference favoring guselkumab for the proportion of subjects achieving a PASI 90 
response at Week 48, this study will have > 99% power to demonstrate the non-inferiority for the primary 
endpoint of PASI 90 at Week 48 and at least 90% power to detect a treatment difference (ie, superiority of 
guselkumab over secukinumab) for the primary endpoint of PASI 90 at Week 48.
In order to compare the proportion of subjects responding to the two treatments, the 
Cochran-Mantel-Haenszel chi-square test stratified by investigator site will be used. To test the non-
inferiority of guselkumab to secukinumab, a 1-sided (α=0.025) Z-test with Mantel-Haenszel weights 
adjusted by investigator site will be used. A longitudinal modeling approach will also be used as a 
sensitivity analysis to compare the proportion of subjects responding to treatment. All statistical testing 
will be performed 2-sided at a significance level of 0.05 for superiority and 1-sided at a significance level 
of 0.025 for non-inferiority.
Subjects who discontinue study agent due to lack of efficacy or an AE of worsening of psoriasis, or who 
started a protocol-prohibited medication/therapy during the study that could improve psoriasis are 
considered treatment failures. The baseline values will be assigned regardless of the observed data for 
continuous endpoints, zero will be assigned to improvement and percent improvement, and nonresponder 
status will be assigned to binary response variables. After applying the treatment failure rules, the 
remaining missing data will be assigned nonresponder status for binary variables. For the longitudinal 
analyses, treatment failure rules or missing data handling rules will not be applied.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
11
Approved, Date: 5 October 2017
Primary Analysis
The primary endpoint in this study is the proportion of subjects who achieve a PASI 90 response at 
Week 48. To address the primary efficacy objective, the proportion of subjects achieving a PASI 90 
response at Week 48 will be evaluated with a non-inferiority test followed by a superiority test. The 
following stepwise comparisons will be made to compare the efficacy of guselkumab to that of 
secukinumab at Week 48:
a.
A non-inferiority margin of 10% was chosen based on a minimal clinically meaningful 
difference. This margin was also used as the non-inferiority margin for the ustekinumab psoriasis 
study C0743T12 and the guselkumab psoriasis CNTO1959PSO3001 and CNTO1959PSO3002 
studies. To claim the non-inferiority of guselkumab to secukinumab, the lower bound of the 
2-sided 95% confidence interval of P1 – P2 must be ≥ –10%, where P1 and P2 are the proportions 
of subjects achieving a PASI 90 response at Week 48 in the guselkumab and the secukinumab 
groups, respectively. If non-inferiority is not established, no further test will be conducted and 
Step b will be skipped.
b.
If non-inferiority is established in Step a, the superiority test of guselkumab to secukinumab will 
be performed at 2-sided (α=0.05).
If both the non-inferiority test and the superiority test are positive, the major secondary hypotheses
comparing the guselkumab group and the secukinumab group will be tested sequentially. Otherwise, all 
remaining p-values will be considered nominal.
Major Secondary Analyses
For the major secondary analysis, all non-inferiority tests will be performed at 1-sided (α=0.025) with a 
non-inferiority margin of 10%. The major secondary analyses are:

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving a PASI 75 response at both Week 12 and Week 48 will be performed. If non-inferiority is 
established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving a PASI 90 response at Week 12 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving a PASI 75 response at Week 12 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving a PASI 100 response at Week 48 will be performed. If non-inferiority is established, the 
superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving an IGA score of cleared (0) at Week 48 will be performed. If non-inferiority is established, 
the superiority test on this endpoint will be performed.
In order to control the overall Type 1 error rate, the primary analysis and major secondary analyses will 
be tested in a fixed sequence as ordered above. That is, the first major secondary analysis will be 
performed only if the primary endpoint is positive for both non-inferiority and superiority, and the 
subsequent analysis will be performed only if the preceding analysis in the sequence is positive.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
12
Approved, Date: 5 October 2017
Other Efficacy Analyses
In addition to the primary and major secondary analyses, the analyses for other efficacy endpoints will be 
performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving a PASI 90 response at both Week 16 and Week 48 will be performed. If non-inferiority is 
established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving a PASI 75 response at Week 16 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving a PASI 90 response at Week 16 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving a PASI 90 response at all 7 visits from Week 24 through Week 48 will be performed. If 
non-inferiority is established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving an IGA score of cleared (0) or minimal (1) at Week 16 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of subjects 
achieving an IGA score of cleared (0) or minimal (1) at Week 12 will be performed.

The proportions of subjects who achieve a PASI 75 response at Week 48 among PASI 75 responders 
at Week 12 will be summarized by treatment group.

The proportions of subjects who achieve a PASI 90 response at Week 48 among PASI 90 responders 
at Week 16 will be summarized by treatment group.

The proportions of subjects who achieve a PASI 50/75/90/100 response over time through Week 48 
will be summarized by treatment group.

The proportions of subjects who achieve an IGA score of cleared (0) response, IGA score of cleared 
(0) or minimal (1) response, and IGA of cleared (0), minimal (1), or mild (2) response over time 
through Week 48 will be summarized by treatment group.

The percentages of improvement from baseline in PASI over time through Week 48 will be 
summarized by treatment group.
Safety such as AEs, vital signs, eC-SSRS, laboratory values and ECG parameters will be summarized 
statistics.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
13
Approved, Date: 5 October 2017
TIME AND EVENTS SCHEDULE
Phase
Screeninga
Active Treatment
Follow-up
Week
0
1
2
3
4
8
12
16
20
24
28
32
36
40
44
48b
56
Study Procedures
Screening/Administrative
Informed consent
X
Medical history 
and demographics
X
Inclusion/
exclusion criteria
X
X
Study Drug Administration
Randomization
X
Administrationc
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety Assessments
Physical 
examination 
(including skin 
exam)
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
12-lead ECG
X
X
X
Tuberculosis 
evaluation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chest radiograph
X
Urine pregnancy 
testd
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X
Weight
X
Concomitant therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
eC-SSRSe
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
14
Approved, Date: 5 October 2017
TIME AND EVENTS SCHEDULE
Phase
Screeninga
Active Treatment
Follow-up
Week
0
1
2
3
4
8
12
16
20
24
28
32
36
40
44
48b
56
Study Procedures
Efficacy Assessments
IGA
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PASI
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Body Surface Area 
(BSA)%
X
X
Clinical Laboratory Assessment
QuantiFERON-TB 
testf
X
Hepatitis B and C 
serology
X
HIV antibody test
X
Hematology
X
X
X
X
X
X
X
X
Chemistryg
X
X
X
X
X
X
X
X
Lipid panelh
X
Hs-CRP
X
Pharmacokinetics and Immunogenicity i
Serum guselkumab 
concentration
X
X
X
X
X
X
X
Antibodies to 
guselkumab
X
X
X
X
X
X
X
Biomarkers
Serum biomarkers j
X
X
X
X
Skin biopsy (RNA)k
X
X
X
 
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
15
Approved, Date: 5 October 2017
TIME AND EVENTS SCHEDULE
Phase
Screeninga
Active Treatment
Follow-up
Week
0
1
2
3
4
8
12
16
20
24
28
32
36
40
44
48b
56
Study Procedures
Genetic (DNA) evaluations
Genetic (DNA) 
analysesm
X
FOOTNOTES:
a: The screening visit should occur within approximately 4 weeks before the Week 0 visit.
b: All Week 48 study procedures should be performed on any subject who terminates the study prior to Week 48, except for collection of serum for biomarkers. If a subject terminates 
post-Week 48, sites should make every effort to conduct the Week 56 assessments.
c: All study procedures and evaluations should be completed before administration of study drug. Assessments for subjects who discontinue study agent administration or withdraw from 
the study are discussed in Section 10.2.
d: Women of childbearing potential must have a negative urine pregnancy test before randomization, before study drug administration, and at all study visits.
e: The eC-SSRS should be completed by the subject before any tests, procedures, or other consultations to prevent influencing subject perceptions,
f: A tuberculin skin test is additionally required if the QuantiFERON-TB Gold test is not approved/registered in the country in which this study is being conducted.
g: Laboratory tests are listed in Section 9.6.
h: Subjects must fast (ie, no food or beverages [except water]) for at least 8 hours before blood is drawn for lipid panel. All other visits can be nonfasting.
i: All blood samples must be collected before study agent administration at visits when a study agent administration is scheduled. Details will be provided in the Laboratory Manual.
j Serum biomarker measurements will include but are not limited to: serum IL-17A, IL-17F, and IL-22. For subjects who discontinue from the study prior to Week 48, serum is not to be 
collected for measurement of biomarkers.
k Biopsy samples for RNA and tissue histology will be collected only from subjects who consent to participate in the optional biopsy substudy. Biopsy samples will be used to assess the 
cellular and molecular profiles of psoriatic skin lesions at baseline and during treatment.
 
m: Blood samples for genetic (DNA) analyses will be collected only from subjects who sign a separate consent form to participate in the genetic (DNA) evaluations.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
16
Approved, Date: 5 October 2017
ABBREVIATIONS
BCG
Bacille Calmette-Guérin
BSA
body surface area
CSR
clinical study report
DBL
database lock
ECG
electrocardiogram
eCRF
electronic case report form
eC-SSRS
electronic Columbia-Suicide Severity Rating Scale
eDC
electronic data capture
GCP
Good Clinical Practice
HBV
hepatitis B virus
HCV
hepatitis C virus
HIV
human immunodeficiency virus
ICF
informed consent form
ICH
International Conference on Harmonisation
IEC
Independent Ethics Committee
IGA
Investigator’s Global Assessment
IL
interleukin 
IL-23R
interleukin-23 receptor
IM
intramuscular
IRB
Institutional Review Board
IWRS
interactive web response system
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
MTX
methotrexate
NAb
neutralizing antibodies
NCI-CTCAE
National Cancer Institute-Common Terminology Criteria for Adverse Events
PASI
Psoriasis Area and Severity Index
PD
pharmacodynamic(s)
PFS
prefilled syringe 
PFS-U
prefilled syringe assembled with the UltraSafe PLUS™Passive Needle Guard
PK
pharmacokinetic
PQC
Product Quality Complaint
PsA
psoriatic arthritis
SAP
Statistical Analysis Plan
SC
subcutaneous
SUSAR
suspected unexpected serious adverse reaction
TB
tuberculosis
Tc17
CD8+ T cells
Th17
T helper 17
ULN
upper limit of normal
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
17
Approved, Date: 5 October 2017
1.
INTRODUCTION
Guselkumab (CNTO 1959) is a fully human immunoglobulin G1 lambda monoclonal antibody 
(mAb) that binds to human interleukin (IL)-23 with high specificity and affinity. The binding of 
guselkumab to IL- blocks the binding of extracellular IL-23 to the cell surface IL-23 receptor
(IL-23R), inhibiting IL-23-specific intracellular signaling and subsequent activation and cytokine 
production. In this manner, guselkumab inhibits the biological activity of IL-23 in all in vitro 
assays examined.
For the most comprehensive nonclinical and clinical information regarding guselkumab, refer to
the latest version of the Investigator's Brochure and Addenda for guselkumab.
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.
1.1.
Background
The clinical development program to support use of guselkumab in the treatment of moderate to 
severe plaque-type psoriasis includes two Phase 1 studies, one Phase 2 study, and three Phase 3 
global studies. The two Phase 1 studies and the Phase 2 study have been completed, and formed 
the basis to proceed to Phase 3. Details about these 3 individual studies are provided in the 
Investigator’s Brochure. Results from two of the Phase 3 studies (CNTO1959PSO3001 and 
CNTO1959PSO3002) are presented below. Specifically, these two Phase 3 studies were both 
conducted using placebo and an active comparator, adalimumab (HUMIRA®). In these studies, 
guselkumab demonstrated superior efficacy to both placebo and adalimumab. The results of 
these 2 studies provide valuable benchmark data to assess the comparative efficacy of 
guselkumab and secukinumab.
Phase 3 Study (CNTO1959PSO3001, VOYAGE 1)
Study CNTO1959PSO3001 (VOYAGE 1) was a multicenter, Phase 3, randomized, double-blind, 
placebo- and active-comparator-controlled study in subjects with moderate to severe plaque-type 
psoriasis with 3 parallel treatment groups: placebo, guselkumab 100 mg, and adalimumab. 
Subjects in the placebo group crossed over to guselkumab 100 mg beginning at Week 16. In that
study, 837 adult subjects were randomized to receive guselkumab (n=329) or adalimumab 
(n=334) or placebo (n=174).
At Week 16, a significantly greater proportion of subjects randomized to guselkumab achieved 
the co-primary endpoints of an Investigator’s Global Assessment (IGA) score of cleared (0) or 
minimal (1) and Psoriasis Area and Severity Index (PASI) 90 response (85.1% and 73.3%,
respectively; p<0.001 for both endpoints) compared with placebo (6.9% and 2.9%, respectively).
At Week 24, a significantly higher proportion of subjects achieved IGA score of cleared (0), IGA 
score of cleared (0) or minimal (1), and PASI 90 response in the guselkumab group than in the 
adalimumab group. Similar to the observations at Week 24, a significantly higher proportion of 
subjects achieved an IGA score of cleared (0), an IGA score of cleared (0) or minimal (1), and a 
PASI 90 response in the guselkumab group than in the adalimumab group at Week 48.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
18
Approved, Date: 5 October 2017
Treatment with guselkumab was well-tolerated through Week 48. The frequency of AEs was 
comparable between the guselkumab, placebo, and adalimumab groups through Week 16 and 
between the guselkumab and adalimumab groups through Week 48. The most common AEs 
were nasopharyngitis and upper respiratory tract infection. Through Week 16, the percentage of 
subjects with 1 or more serious adverse events (SAEs) was 1.7% (n=3) in the placebo group, 
2.4% (n=8) in the guselkumab group and 1.8% (n=6) in the adalimumab group, and was 
comparable between the guselkumab (4.9% [n=16]) and adalimumab (4.5% [n=15]) groups 
through Week 48. The incidence of infections was comparable between placebo, guselkumab 
and adalimumab groups through Week 16, and between the guselkumab group (52.3%) and the 
adalimumab group (50.2%) through Week 48. No opportunistic infections or active tuberculosis
(TB) were reported. No anaphylactic or serum-sickness reactions were reported in the 
guselkumab group, and the incidence of injection site reactions was lower in the guselkumab 
group than the adalimumab group.
Phase 3 Study (CNTO1959PSO3002, VOYAGE 2)
Study CNTO1959PSO3002 (VOYAGE 2) was a multicenter, Phase 3, randomized, double-blind, 
placebo- and active-comparator-controlled study in subjects with moderate to severe plaque-type 
psoriasis with 3 treatment groups: placebo, guselkumab 100 mg, and adalimumab. In that study, 
992 adult subjects were randomized to either the placebo (n=248), guselkumab (n=496), or 
adalimumab (n=248) treatment groups at Week 0. Subjects in the placebo group crossed over to 
guselkumab 100 mg beginning at Week 16. This study evaluated the benefit of maintenance 
therapy using a randomized withdrawal design starting at Week 28.
At Week 16, a significantly greater proportion of subjects randomized to guselkumab achieved 
the co-primary endpoints of an IGA score of cleared (0) or minimal (1) and a PASI 90 response 
(84.1% and 70.0%, respectively; p<0.001 for both endpoints) compared with placebo (8.5% and 
2.4%, respectively). In addition, a significantly greater proportion of subjects achieved IGA 
score of cleared (0), IGA score of cleared (0) or minimal (1), and PASI 90 response in the 
guselkumab group than in the adalimumab group at Week 24.
Treatment with guselkumab was well tolerated. Through Week 16, the proportion of subjects 
experiencing 1 or more AEs was comparable between treatment groups. Nasopharyngitis and 
upper respiratory tract infection were the most common AEs. The percentage of subjects with 1
or more SAEs was comparable between the placebo and guselkumab groups, and slightly higher 
in the adalimumab group. The incidence of infections was comparable between placebo, 
guselkumab, and adalimumab groups through Week 16. Through Week 28, the proportion of 
subjects experiencing 1 or more AEs was comparable between the guselkumab and adalimumab
groups. Two adalimumab-treated subjects reported active TB. No opportunistic infections were 
reported. No anaphylactic or serum-sickness reactions were reported.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
19
Approved, Date: 5 October 2017
1.2.
Comparator
Cosentyx® (secukinumab)
Secukinumab (Cosentyx, Novartis Pharmaceuticals Corporation), a recombinant, high affinity, 
fully human mAb that selectively targets IL17A, is the first approved anti-IL-17 mAb for the 
treatment of moderate to severe plaque psoriasis. Secukinumab was selected as the active 
comparator because it is one of the newer, subcutaneously (SC) self-administered agents shown 
to achieve very high levels of efficacy in moderate to severe plaque psoriasis, and therefore 
provides a valuable and relevant benchmark for comparison with guselkumab. Subjects 
randomized to secukinumab must be dosed according to the labeled dose regimen for plaque 
psoriasis: 300 mg at Weeks 0, 1, 2, 3, and 4 followed by 300 mg q4w (through Week 44 in this 
study).
For further information regarding secukinumab, refer to the current prescribing information.
1.3.
Overall Rationale for the Study
1.3.1.
Role of IL-23 in the Treatment of Psoriasis
Psoriasis pathogenesis involves the dysregulation of IL-23- and IL-17-mediated immune 
responses. IL-23 is a key regulatory cytokine produced by activated antigen presenting cells that 
affects the differentiation, expansion and maintenance of CD4+ IL-17 producing T helper 17 
(Th17) cells, IL-22 producing T helper 22 cells, and CD8+ T cells (Tc17).9 Th17 cells secrete 
several inflammatory mediators including IL-17A, IL-17F, and IL-22. In addition to being 
produced by Th17 cells, IL-17A is also produced by γδ-T cells and Tc17 cells, which are also 
regulated to some extent by IL-23.12 Th17 and Tc17 cells have been shown to be elevated in 
psoriatic plaques and antagonism of either IL-23 or IL-17 has demonstrated clinical benefit in 
psoriasis.1 Inhibition of IL-23 may impact the differentiation, expansion, and maintenance of 
Th17 and Tc17 cells providing sustained disruption of Th17 and Tc17 cell involvement in 
psoriasis lesions. Antagonism of soluble IL-17 inhibits local IL-17-mediated pathology in 
psoriasis lesions in addition to soluble IL-17 produced by non-Th17 cells. Selective inhibition of 
IL-23R-expressing Th17 and Tc17 cells, the source of IL-17 in psoriasis lesions, by blocking 
IL-23, may yield sustained clinical benefit in psoriasis.
Guselkumab, a human mAb specifically targets IL-23. A rapidly growing body of literature 
suggests that the IL-23/IL-17 pathway contributes to the chronic inflammation underlying the 
pathophysiology of many immune-mediated diseases,14,19 including psoriasis.8 In addition, 
susceptibility to psoriasis, psoriatic arthritis (PsA), and inflammatory bowel disease has been 
shown to be associated with genetic polymorphisms in IL-23/IL-23R components.2,4,7,11,13
Finally, the clinical response to guselkumab observed in Phase 1, 2, and 3 psoriasis studies 
demonstrates the specific importance of IL-23 in the pathogenesis of plaque-type psoriasis and 
supports further investigation of the clinical benefit of guselkumab compared to secukinumab.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
20
Approved, Date: 5 October 2017
1.3.2.
Dose Rationale
A dose regimen of guselkumab 100 mg at Weeks 0 and 4 and q8w thereafter was selected for the 
global Phase 3 studies of guselkumab for the treatment of moderate to severe plaque-type
psoriasis. This dose regimen was chosen based on results of the guselkumab dose-ranging study 
(CNTO1959PSO2001) in subjects with moderate to severe plaque-type psoriasis and 
pharmacokinetic (PK)/pharmacodynamic (PD) modeling based on the data from that study. The
same dose regimen studied in the global phase 3 program will be used in this study.
1.3.3.
Rationale for Trial Design and Efficacy Analyses
The proposed randomized, blinded, two-active-arm trial will evaluate the relative performance of 
guselkumab and secukinumab utilizing a comprehensive battery of endpoints (eg, PASI 75, 90, 
and 100) at various timepoints (eg, Week 12 and Week 48) using rigorous statistical 
methodology to control for multiplicity.
The statistical analyses will employ a sequential testing approach to control for multiplicity that 
includes both superiority and non-inferiority testing for specified endpoints.
While the ultimate goal of the trial is to demonstrate that the efficacy of guselkumab is superior 
to secukinumab for PASI 90 at Week 48, initial testing for non-inferiority is included for this 
endpoint because the overall profile of guselkumab will likely be favorable compared with 
secukinumab (in terms of potential for increased compliance and lesser patient burden), even if 
relative efficacy is no worse for this endpoint.
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESES
2.1.
Objectives and Endpoints
2.1.1.
Objectives
Primary Objective
The primary objective is to evaluate the efficacy of guselkumab compared with secukinumab for 
the treatment of subjects with moderate to severe plaque-type psoriasis.
Secondary Objectives
The secondary objectives are to assess:

The safety and tolerability of guselkumab in subjects with moderate to severe plaque-type 
psoriasis.

The PK and immunogenicity of guselkumab after subcutaneous (SC) administrations in 
subjects with moderate to severe plaque-type psoriasis.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
21
Approved, Date: 5 October 2017
Exploratory Objectives
The exploratory objectives are to explore:

The PD effects (biomarkers) of treatment with guselkumab or secukinumab in subjects with 
moderate to severe plaque-type psoriasis.

The impact of treatment with guselkumab or secukinumab on psoriasis skin lesion gene 
expression profiles and cellular content in subjects with moderate to severe plaque-type 
psoriasis.

 

The association between genetic factors and 1) the efficacy of guselkumab or secukinumab 
and 2) psoriasis.
2.1.2.
Endpoints
Primary Endpoint
The primary endpoint in this study is the proportion of subjects who achieve a PASI 90 response 
at Week 48, comparing the guselkumab group and the secukinumab group.
Major Secondary Endpoints
The major secondary endpoints to compare the guselkumab group and the secukinumab group
are listed below and are the proportion of subjects who achieve:

A PASI 75 response at both Week 12 and Week 48.

A PASI 90 response at Week 12.

A PASI 75 response at Week 12.

A PASI 100 response at Week 48.

An IGA score of cleared (0) at Week 48.
Other Secondary Endpoints

The other secondary endpoints to compare the guselkumab group and the secukinumab 
group are listed below and are the proportion of subjects who achieve:

A PASI 90 response at both Week 16 and Week 48.

A PASI 75 response at Week 16.

A PASI 90 response at Week 16.

A PASI 90 response at all 7 visits from Week 24 through Week 48.

An IGA score of cleared (0) or minimal (1) at Week 16.

An IGA score of cleared (0) or minimal (1) at Week 12.
NCT03090100


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3009 Amendment 1
22
Approved, Date: 5 October 2017

The proportions of subjects who achieve a PASI 75 response at Week 48 among PASI 75 
responders at Week 12.

The proportions of subjects who achieve a PASI 90 response at Week 48 among PASI 90 
responders at Week 16.

The proportions of subjects who achieve a PASI 50/75/90/100 response over time through 
Week 48.

The proportions of subjects who achieve an IGA score of cleared (0) response, IGA score of
cleared (0) or minimal (1) response, and IGA of cleared (0), minimal (1), or mild (2)
response over time through Week 48.

Percentages of improvement in PASI over time through Week 48.
2.2.
Hypotheses
The proposed randomized, blinded, two-active-arm trial will evaluate the relative performance of 
guselkumab and secukinumab utilizing a comprehensive battery of endpoints (eg, PASI 75, 90, 
and 100) at various timepoints (eg, Week 12 and Week 48) using rigorous statistical 
methodology to control for multiplicity.
While the ultimate goal of the trial is to demonstrate that the efficacy of guselkumab is superior 
to secukinumab for PASI 90 at Week 48, initial testing for non-inferiority is included for this 
endpoint because the overall profile of guselkumab will likely be favorable compared with 
secukinumab (in terms of potential for increased compliance and lesser patient burden), even if 
final results only indicate the relative efficacy is no worse for this endpoint.
The primary hypotheses are that guselkumab treatment is non-inferior to secukinumab as 
assessed by the proportion of subjects achieving a PASI 90 response at Week 48 with a non-
inferiority margin of 10% and, once non-inferiority is established, that guselkumab is superior to 
secukinumab as assessed by the proportion of subjects achieving a PASI 90 response at 
Week 48.
The major secondary hypotheses are that guselkumab treatment is:

Non-inferior to secukinumab for the maintenance of a PASI 75 response as assessed by the 
proportion of subjects who achieve a PASI 75 response at both Week 12 and Week 48 with 
a non-inferiority margin of 10% and, once non-inferiority is established, that guselkumab is 
superior to secukinumab as assessed by the proportion of subjects who achieve a PASI 75 
response at both Week 12 and Week 48.

Non-inferior to secukinumab at Week 12 as assessed by the proportion of subjects who 
achieve PASI 90 at Week 12 with a non-inferiority margin of 10%.

Non-inferior to secukinumab at Week 12 as assessed by the proportion of subjects who 
achieve PASI 75 at Week 12 with a non-inferiority margin of 10%.
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
Non-inferior to secukinumab at Week 48 as assessed by the proportion of subjects who 
achieve PASI 100 at Week 48 with a non-inferiority margin of 10% and, once non-
inferiority is established, that guselkumab is superior to secukinumab as assessed by the 
proportion of subjects who achieve a PASI 100 response at Week 48.

Non-inferior to secukinumab at Week 48 as assessed by the proportion of subjects who 
achieve an IGA score of cleared (0) at Week 48 with a non-inferiority margin of 10% and, 
once non-inferiority if established, that guselkumab is superior to secukinumab as assessed 
by the proportion of subjects who achieve an IGA score of cleared (0) at Week 48.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
This is a Phase 3, randomized, double-blind, multicenter, active-comparator-controlled study in 
subjects with moderate to severe plaque-type psoriasis. The target population is adult men or 
women, with a diagnosis of plaque-type psoriasis (with or without PsA) for at least 6 months 
before the first administration of study drug. Subjects must have moderate to severe plaque-type 
psoriasis defined by IGA ≥3, PASI ≥12, and involved body surface area (BSA) ≥10%. Subjects 
must be candidates for either systemic therapy or phototherapy for psoriasis, and may have 
previously received some systemic therapies or phototherapy for psoriasis. Subjects with 
nonplaque forms of psoriasis (eg, erythrodermic, guttate, or pustular) or with drug-induced 
psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium 
channel blockers, or lithium) are excluded. Subjects who have ever received guselkumab or 
secukinumab are also excluded.
Key features of study drug administration for each treatment group are outlined below; for 
details regarding concomitant placebo administrations to maintain the blind, see Section 6.
Week 0 through Week 44 (Blinded Treatment Period)
As depicted in Figure 1, approximately 1,040 subjects who satisfy all inclusion and exclusion 
criteria will be randomized in a 1:1 ratio to 1 of 2 treatment arms:

Group I (n=520): guselkumab 100 mg SC at Weeks 0, 4, 12, and q8w thereafter through 
Week 44.

Group II (n=520): secukinumab 300 mg SC at Weeks 0, 1, 2, 3, 4 and q4w thereafter 
through Week 44.
After Week 44 through Week 56 (Follow-up Period)
The follow-up period will begin after Week 44 and extend through Week 56.
There is 1 database lock (DBL) in this study at Week 56. The sponsor, the investigators, subjects, 
and site monitors will be unblinded after the Week 56 DBL has occurred. The end of the study is 
defined as the timepoint when the last subject completes the Week 56 visit.
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A pharmacogenomic blood sample will be collected from subjects who consent separately to this 
component of the study (where local regulations permit). Subject participation in 
pharmacogenomic research is optional.
A diagram of the study design is provided in Figure 1.
Figure 1:
Schematic Overview of the Study
3.2.
Study Design Rationale
This Phase 3, randomized, double-blind, multicenter study will evaluate the comparative efficacy 
and assess the safety of guselkumab, compared with secukinumab for the treatment of subjects 
with moderate to severe plaque-type psoriasis.
Multiple therapeutic options exist for the treatment of moderate to severe psoriasis; however, 
none of the currently approved agents, including several highly effective biologic agents, can 
provide complete clearance of disease in all patients. Several studies suggest that complete 
clearance is associated with quantifiable improvements in quality of life,21,18,16 and is 
increasingly sought by patients and physicians in this era of highly effective therapies for plaque 
psoriasis. A recent publication reported that patients who were considered to be responders, but 
lacked complete clearance, may still experience negative impact on their health-related quality of 
life as compared to those patients who achieved complete clearance. The patients who were 
considered cleared had a substantial improvement in their quality of life. 17 While available 
clinical studies have demonstrated that secukinumab treatment leads to rapid, clinically 
significant improvement in subjects with psoriasis,20,6 it is anticipated that guselkumab treatment 
will result in higher proportions of patients achieving a nearly clear (PASI 90) or clear 
(PASI 100) response compared with treatment with secukinumab over 1 year of treatment.
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A placebo arm was not included in this study for two main reasons. First, the primary endpoint is 
at Week 48 and it is not feasible to keep patients with moderate to severe psoriasis on placebo for 
that period of time. Second, given the historically low placebo rates observed in large Phase 3 
moderate to severe psoriasis studies, and the proven efficacy of these two highly effective drugs, 
the value of the placebo arm for the purpose of demonstrating assay sensitivity is minimal. The 
efficacy of secukinumab was established (in individual studies vs placebo) using primary 
endpoints at Week 12.6 However, it is known that neither agent reaches their maximal effect 
until after Week 12. In addition, psoriasis is a chronic disease that often requires chronic 
treatment, such that longer-term outcomes are clinically important. Therefore, endpoints at 
Weeks 12, 16, and 48 (with the primary endpoint of PASI 90 at Week 48) were selected to 
provide the most clinically meaningful evaluations of the relative performance of the 
2 treatments. Ultimately, this study is designed to show superiority of efficacy of guselkumab
after 1 year of treatment.
Biomarker and DNA Collection
Biomarker samples will be collected to evaluate the cellular and molecular mechanism of action 
of guselkumab and secukinumab, and to assess inter-individual variability in clinical outcomes to 
identify population subgroups that may respond differently to either drug. The goal of the 
biomarker analyses is to evaluate the PD effects of guselkumab and secukinumab, to further 
define the mechanism of action of blocking IL-23 compared to blocking IL-17A in psoriasis, and 
to aid in evaluating the drug’s clinical response relationship. Serum biomarkers will be collected 
in all subjects to assess PD markers associated with the response to guselkumab and 
secukinumab.
Additionally, 3 optional substudies are planned: skin biopsy, 
 and genetic 
analysis. Skin biopsies will be collected in a subset of subjects at selected sites who consent to 
participate in the optional skin biopsy substudy to determine gene expression profiles and 
cellular content associated with response to guselkumab or secukinumab. Epigenetic evaluation 
may be conducted on skin samples obtained in the biopsy substudy. These exploratory analyses 
of psoriatic skin lesions may help to further define the cellular and molecular mechanism of 
action associated with blockade of IL-23 compared to blockade of IL-17A in psoriasis. 
 
 
 
 
 
 
It is recognized that genetic variation can be an important contributory factor to inter-individual 
differences in drug distribution and response and can also serve as a marker for disease 
susceptibility and prognosis. Genetic (DNA) analysis may help to explain inter-individual 
variability in clinical outcomes and may help to identify population subgroups that respond 
differently to a drug. The goal of the genetic (DNA) analysis is to collect a single DNA sample 
(from whole blood) to allow the identification of genetic factors, including single nucleotide 
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polymorphisms, that may influence the PD effects, efficacy, or tolerability of guselkumab and 
secukinumab, and to identify genetic factors associated with psoriasis. Epigenetic evaluation 
may be conducted on skin samples obtained in the biopsy substudy to assess potential epigenetic 
modifications associated with different immune cell infiltrates in psoriatic skin lesions. Only 
subjects who sign the consent form to participate in the genetic assessment will have whole 
blood DNA or skin samples collected.
4.
SUBJECT POPULATION
Screening for eligible subjects will be performed within approximately 4 weeks before 
administration of the study drug.
The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following 2 subsections. If there is a question about the inclusion or exclusion criteria below, the 
investigator must consult with the appropriate sponsor representative and resolve any issues 
before enrolling a subject in the study. Waivers are not allowed.
For a discussion of the statistical considerations of subject selection, refer to Section 11.2, 
Sample Size Determination.
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
Subject population-related inclusion criteria
1.
Be a man or a woman at least 18 years of age (or the legal age of consent in the 
jurisdiction in which the study is taking place).
2.
Have a diagnosis of plaque-type psoriasis (with or without PsA) for at least 6 months 
before the first administration of study drug.
3.
Have a PASI ≥12 at screening and at baseline.
4.
Have an IGA ≥3 at screening and at baseline.
5.
Have an involved BSA ≥10% at screening and at baseline.
6.
Be a candidate for phototherapy or systemic treatment for psoriasis (either naïve or 
history of previous treatment).
7.
Be considered, in the opinion of the investigator, suitable candidates for secukinumab
(Cosentyx) therapy according to their country's approved secukinumab product labeling.
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Reproduction-related inclusion criteria
8.
Before the first administration of study drug, a woman must be either:

Not of childbearing potential: premenarchal; postmenopausal (>45 years of age 
with amenorrhea for at least 12 months or any age with amenorrhea for at least 
6 months and a serum follicle-stimulating hormone level >40 IU/L); permanently 
sterilized (eg, tubal occlusion, hysterectomy, bilateral salpingectomy); or otherwise 
be incapable of pregnancy.

Of childbearing potential and practicing a highly effective method of birth control, 
consistent with local regulations regarding the use of birth control methods for 
subjects participating in clinical studies: eg, established use of oral, injected or 
implanted hormonal methods of contraception; placement of an intrauterine device 
or intrauterine system; barrier methods: condom or occlusive cap (diaphragm or 
cervical/vault caps) plus spermicidal foam/gel/film/cream/suppository (if available 
in their locale); male partner sterilization (the vasectomized partner should be the 
sole partner for that subject); true abstinence (when this is in line with the preferred 
and usual lifestyle of the subject).
Note: If a female subject’s childbearing potential changes after start of the study (eg, a 
woman who is not heterosexually active becomes active, a premenarchal woman 
experiences menarche), she must begin practicing a highly effective method of birth 
control, as described above.
9.
A woman of childbearing potential must have a negative urine pregnancy test at 
screening and at Week 0 and agree to urine pregnancy testing before receiving 
injections.
10.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for at least 16 weeks after receiving the last 
administration of secukinumab or at least 12 weeks after receiving the last 
administration of guselkumab.
11.
A man who is sexually active with a woman of childbearing potential and who has not 
had a vasectomy must agree to use a barrier method of birth control (eg, either a 
condom [with spermicidal foam/gel/film/cream/suppository if available in their locale] 
or a partner with an occlusive cap [diaphragm or cervical/vault caps] plus spermicidal 
foam/gel/film/cream/suppository if available in their locale), during the study and for at 
least 16 weeks after receiving the last administration of secukinumab or at least
12 weeks after receiving the last administration of guselkumab. All men must also agree 
to not donate sperm during the study and for at least 16 weeks after receiving the last 
administration of secukinumab or at least 12 weeks after receiving the last 
administration of guselkumab.
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Infectious disease-related inclusion criteria
12.
Are considered eligible according to the following TB screening criteria:

Have no history of latent or active TB before screening.
o
An exception is made for subjects 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 
study drug,

or have documentation of having completed appropriate treatment for 
latent TB within 5 years before the first administration of study drug.
o
It is the responsibility of the investigator to verify the adequacy of previous 
anti-TB treatment and provide appropriate documentation.

Have no signs or symptoms suggestive of active TB upon medical history and/or 
physical examination.

Have had no recent close contact with a person with active TB or, if there has 
been such contact, will be referred to a physician specializing in TB to undergo 
additional evaluation and, if warranted, receive appropriate treatment for latent 
TB before the first administration of study drug.

Within 2 months before the first administration of study drug, have a negative 
QuantiFERON®-TB Gold test result, or have a newly identified positive 
QuantiFERON-TB Gold test result (Attachment 3) in which active TB has been 
ruled out and for which appropriate treatment for latent TB has been initiated 
before the first administration of study drug. Within 2 months before the first 
administration of study drug, a negative tuberculin skin test, or a newly 
identified positive tuberculin skin test in which active TB has been ruled out and 
for which appropriate treatment for latent TB has been initiated before the first 
administration of study drug, is additionally required if the QuantiFERON-TB 
Gold test is not approved/registered in that country or the tuberculin skin test is 
mandated by local health authorities.
NOTE: The QuantiFERON-TB Gold test and the tuberculin skin test are not 
required at screening for subjects with a history of latent TB and ongoing 
treatment for latent TB or documentation of having completed adequate 
treatment as described above; subjects with documentation of having completed 
adequate treatment as described above are not required to initiate additional 
treatment for latent TB.

Have a chest radiograph (posterior-anterior and lateral views, or per country 
regulations where applicable), taken within 3 months before the first 
administration of study drug and read by a qualified radiologist, with no 
evidence of current, active TB or old, inactive TB.
13.
Agree not to receive a live virus or live bacterial vaccination during the study, or within 
3 months after the last administration of study drug. For information on Bacille 
Calmette-Guérin (BCG) vaccination, see Inclusion Criterion 14.
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14.
Agree not to receive a BCG vaccination during the study, or within 12 months after the 
last administration of study drug.
Clinical laboratory-related inclusion criteria
15.
Have screening laboratory test results within the following parameters, if one or more of 
the laboratory parameters is out of range, a single retest of laboratory values is 
permitted:

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: ≤137 μmol/L)

Aspartate aminotransferase ≤2 × upper limit of normal (ULN)

Alanine aminotransferase
≤2 × ULN

Alkaline phosphatase
≤2 × ULN
Other inclusion criteria
16.
Agree to avoid prolonged sun exposure and avoid use of tanning booths or other 
ultraviolet light sources during study.
17.
Be willing and able to adhere to the prohibitions and restrictions specified in this 
protocol.
18.
Must sign an informed consent form (ICF) [(or their legally acceptable representative 
must sign)] indicating that he or she understands the purpose of, and procedures 
required for, the study and is willing to participate in the study. 
19.
Must sign a separate ICF if he or she agrees to provide an optional DNA sample for 
research (where local regulations permit). Refusal to give consent for the optional DNA 
research sample does not exclude a subject from participation in the study.
4.2.
Exclusion Criteria
Any potential subject who meets any of the following criteria will be excluded from participating 
in the study:
Medical history-related exclusion criteria
1.
Has a history or current signs or symptoms of severe, progressive, or uncontrolled renal, 
cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, hematologic, 
rheumatologic, psychiatric, or metabolic disturbances.
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2.
Has unstable cardiovascular disease, defined as a recent clinical deterioration (eg, 
unstable angina, rapid atrial fibrillation) in the last 3 months or a cardiac hospitalization 
within the last 3 months.
3.
Has unstable suicidal ideation or suicidal behavior, that may be defined as an electronic 
Columbia-Suicide Severity Rating Scale (eC-SSRS) rating at screening of: Suicidal 
ideation with intention to act (“4”), Suicidal ideation with specific plan and intent (“5”), 
or a suicide attempt (interrupted suicide attempt, aborted suicide attempt, or preparatory 
behaviors for making a suicide attempt) in the last 6 months and is confirmed to be at 
risk by the investigator based on an evaluation by a mental health professional. The final 
decision on excluding a subject will be made at the judgment of the investigator.
4.
Has a transplanted organ (with exception of a corneal transplant >3 months before the 
first administration of study drug).
5.
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.
6.
Is pregnant, nursing, or planning a pregnancy (both men and women) while enrolled in 
this study and within 12 weeks following the last administration of study drug.
7.
Has a nonplaque form of psoriasis (eg, erythrodermic, guttate, or pustular).
8.
Has current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of 
psoriasis from beta blockers, calcium channel blockers, or lithium).
9.
Has had major surgery (eg, requiring general anesthesia and hospitalization) within 
8 weeks before screening, or will not have fully recovered from such surgery, or has 
such surgery planned during the time the subject is expected to participate in the study 
(56 weeks).
Note: Subjects with planned surgical procedures to be conducted under local anesthesia 
may participate.
10.
Is known to have had a substance abuse (drug or alcohol) problem within the previous 
12 months.
11.
Had a known allergy or sensitivity to products containing latex.
Concomitant or previous medical therapies-related exclusion criteria
12.
Has previously received guselkumab or secukinumab.
13.
Has any contraindications to the use of secukinumab per local prescribing information.
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14.
Is not a suitable candidate for secukinumab therapy due to a history of inflammatory 
bowel disease.
15.
Has received any anti-tumor necrosis factor α biologic therapy within 3 months before 
the first administration of study drug.
16.
Has received any therapeutic agent directly targeted to IL-12, IL-17A, IL-17R, or IL-23 
within 6 months of the first administration of study drug (including but not limited to 
ustekinumab, tildrakizumab [MK3222], risankizumab [BI-655066], ixekizumab 
[LY2439821], or brodalumab [AMG 827]) with the exception of secukinumab (which is 
completely excluded).
17.
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 study drug.
18.
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 study drug.
19.
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 and analogues, psoralens, 
sulfasalazine, hydroxyurea, apremilast, fumaric acid derivatives, herbal treatments, or 
traditional Taiwanese, Korean, or Chinese medicines) within 4 weeks of the first 
administration of study drug.
20.
Has used topical medications/treatments that could affect psoriasis or IGA evaluations 
(including, but not limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D 
derivatives, retinoids, tazarotene, methoxsalen, trimethylpsoralens, pimecrolimus, 
tacrolimus, or topical traditional Taiwanese, Korean, or Chinese medicines) within 
2 weeks of the first administration of study drug.
21.
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 
study drug.
22.
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 study drug administration or 
is currently enrolled in another study using an investigational agent or procedure.
23.
Has received, or is expected to receive, any live virus or bacterial vaccination within 3 
months before the first administration of study drug. For BCG vaccine, see Exclusion 
Criterion 24.
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24.
Has had a BCG vaccination within 12 months of screening.
25.
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.
26.
Subject has known allergies, hypersensitivity, or intolerance to guselkumab or its 
excipients (refer to Investigator's Brochure) or secukinumab or its excipients.
Infections or predisposition to infections
27.
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.
28.
Has a history of active granulomatous infection, including histoplasmosis or 
coccidioidomycosis, before screening. Refer to Inclusion Criterion 12 for information 
regarding eligibility with a history of latent TB.
29.
Has a chest radiograph within 3 months before the first administration of study drug that 
shows an abnormality suggestive of a malignancy or current active infection, including 
TB.
30.
Has had a nontuberculous mycobacterial infection or opportunistic infection (eg, 
cytomegalovirus, pneumocystosis, aspergillosis). Subjects with a history of esophageal 
candidiasis or thrush would also be exceptions to this criterion.
31.
Has persistently indeterminate (indeterminate on repeat sampling) QuantiFERON-TB 
Gold test results. Indeterminate results should be handled as described in Section 9.1.2.
32.
Is infected with human immunodeficiency virus (HIV, positive serology for HIV 
antibody).
33.
Tests positive for hepatitis B virus (HBV) infection (Attachment 5) or who are 
seropositive for antibodies to hepatitis C virus (HCV), unless they have 2 negative HCV 
RNA test results 6 months apart after completing antiviral treatment and prior to 
screening, and have a third negative HCV RNA test result at screening
34.
Has or has had a serious infection (eg, sepsis, pneumonia or pyelonephritis), or has been 
hospitalized or received intravenous antibiotics for an infection during the 2 months 
before screening.
35.
Has or has had herpes zoster within the 2 months before screening.
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Malignancy or increased potential for malignancy
36.
Currently has a known malignancy or has a history of malignancy within 5 years before 
screening (with the exception of a nonmelanoma skin cancer that has been adequately 
treated with no evidence of recurrence for at least 3 months before the first study drug 
administration or cervical carcinoma in situ that has been treated with no evidence of 
recurrence for at least 3 months before the first study drug administration).
37.
Has a history of lymphoproliferative disease, including lymphoma; a history of 
monoclonal gammopathy of undetermined significance; or signs and symptoms 
suggestive of possible lymphoproliferative disease, such as lymphadenopathy or 
splenomegaly.
Other exclusion criteria
38.
Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or 
lack of easy access to veins.
39.
Lives in an institution on court or authority order.
40.
Has any condition that, in the opinion of the investigator, would make participation not 
be in the best interest (eg, compromise the well-being) of the subject or that could 
prevent, limit, or confound the protocol-specified assessments.
41.
Is an employee of the investigator or study site, with direct involvement in the proposed 
study or other studies under the direction of that investigator or study site, as well as 
family members of the employees or the investigator.
NOTE: Investigators should ensure that all study enrollment criteria have been met at screening. 
If the subject's clinical status changes (including any available laboratory results or receipt of 
additional medical records) after screening but before the first dose of study drug is given such 
that he or she no longer meets all eligibility criteria, then the subject should be excluded from 
participation in the study. Section 9.1.3, Screen Failure/Rescreening, describes options for 
retesting. Section 17.4, Source Documentation, describes the required documentation to support 
meeting the enrollment criteria.
4.3.
Prohibitions and Restrictions
Potential subjects must be willing and able to adhere to the following prohibitions and 
restrictions during the course of the study to be eligible for participation:
1.
A woman of childbearing potential who is heterosexually active must remain on a 
highly effective method of birth control (Inclusion Criterion 8) during the study and for 
at least 16 weeks after the last administration of secukinumab or at least 12 weeks after 
receiving the last administration of guselkumab.
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2.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for at least 16 weeks after the last administration of 
secukinumab or at least 12 weeks after receiving the last administration of guselkumab.
3.
A man who is sexually active with a woman of childbearing potential and has not had a 
vasectomy must agree to use a barrier method of birth control (ie, male condom, female 
diaphragm or cervical cap, or condom, Inclusion Criterion 11) during the study and for 
at least 16 weeks after the last administration of secukinumab or at least 12 weeks after 
receiving the last administration of guselkumab.
4.
All men must agree to not donate sperm during the study and for at least 16 weeks after 
the last administration of secukinumab or at least 12 weeks after receiving the last 
administration of guselkumab.
5.
Subjects must not receive a live virus or bacterial vaccination during the study and for 
3 months after the last administration of any study drug. See Prohibition 6 for 
information regarding BCG vaccination.
6.
Subjects must not receive a BCG vaccination during the study and for 12 months after 
the last administration of study drug.
7.
Subjects must comply with restrictions on concomitant medications and therapies 
during the study (Section 8).
8.
Subjects must avoid prolonged sun exposure and avoid use of tanning booths or other 
ultraviolet light sources during the study.
5.
TREATMENT ALLOCATION AND BLINDING
Treatment Allocation
Central randomization will be implemented in this study. Subjects will be randomly assigned to 
1 of 2 treatment groups based on a computer-generated randomization schedule prepared before 
the study by or under the supervision of the sponsor. The randomization will be balanced by 
using randomly permuted blocks and will be stratified by study site. The interactive web 
response system (IWRS) will assign a unique treatment code, which will dictate the treatment 
assignment and matching study drug kit for the subject. The requestor must use his or her own 
user identification and personal identification number when contacting the IWRS, and will then 
give the relevant subject details to uniquely identify the subject.
Blinding
The investigator will not be provided with randomization codes. The codes will be maintained 
within the IWRS, which has the functionality to allow the investigator to break the blind for an 
individual subject.
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Data that may potentially unblind the treatment assignment (eg, treatment allocation, study drug
preparation/accountability data [including unblinded personnel], and administration of study 
drug (see details in Section 6) will be handled with special care to ensure that the integrity of the 
blind is maintained and the potential for bias is minimized. This can include making special 
provisions, such as segregating the data in question from view by the investigators, clinical team, 
or others as appropriate until the time of DBL and unblinding.
Under normal circumstances, the blind should not be broken for subjects, investigators, or site 
monitors until the Week 56 database is locked and finalized. Otherwise, the blind should be 
broken only if specific emergency treatment/course of action would be dictated by knowing the 
treatment status of the subject. In such cases, the investigator may in an emergency determine the 
identity of the treatment by contacting the IWRS. It is recommended that the investigator contact 
the sponsor or its designee if possible to discuss the particular situation, before breaking the 
blind. Telephone contact with the sponsor or its designee will be available 24 hours per day, 
7 days per week. In the event the blind is broken, the sponsor must be informed as soon as 
possible. The date and reason for the unblinding must be documented by the IWRS, in the 
appropriate section of the electronic case report form (eCRF), and in the source document. The
documentation received from the IWRS indicating the code break must be retained with the 
subject's source documents in a secure manner.
Subjects who have had their treatment assignment unblinded should continue to return for 
scheduled evaluations. The decision to continue or discontinue study treatment for these subjects 
will be based upon consultation of the investigator with the medical monitor.
6.
DOSAGE AND ADMINISTRATION
A 100 mg/mL solution of guselkumab in a single-use prefilled syringe (PFS) assembled with the 
UltraSafe PLUS™Passive Needle Guard (PFS-U) device will be used. Subjects who are 
randomized to the guselkumab treatment arm will receive 2 injections: 1 injection of active 
guselkumab and 1 injection of placebo when guselkumab is scheduled to be administered
(Weeks 0, 4, 12, 20, 28, 36, 44) or 2 injections of placebo when no guselkumab is scheduled to 
be administered (Weeks 1, 2, 3, 8, 16, 24, 32, and 40). The purpose of administering 2 injections 
is to mimic the 2 injections required for each secukinumab dose, and to thus maintain the blind. 
Commercially available secukinumab (Cosentyx) will be supplied as a single-use PFS and 
administered according to the manufacturer’s directions. Each 300 mg dose is given as 2 SC 
injections of 150 mg each. An appropriately qualified, unblinded member of the study staff will 
administer the drug and will have no other role in the conduct of the study.
All study drug injections will be administered at the investigational site. With the exception of 
the unblinded site personnel who dispense and/or administer the investigational product, all other 
site personnel and subjects will remain blinded to the treatment assignments until the last subject 
completes Week 56 evaluations and the database has been locked. Sites must ensure that they 
have the ability to physically blind and/or separate the blinded subject from the unblinded 
administrator. A physical barrier must be used such that the study drug can be administered by 
the unblinded site personnel, and the subject and other site personnel remain blinded.
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7.
TREATMENT COMPLIANCE
Because study drug will be administered at the investigational site for all randomized subjects, 
treatment compliance will be controlled by site personnel.
From Weeks 0 to 4 it is expected that all subjects will attend visits within a range of ± 3 days. 
After Week 4 and through Week 44, it is expected that all visits will occur within a range of 
± 7 days. Any visits outside of these ranges should be discussed with the sponsor. If a study visit 
occurs outside the specified visit window, the subject should then resume his or her normal dose 
schedule relative to the baseline visit (Week 0) as soon as possible. All other follow-up study 
visits should occur within ± 14 days of the scheduled study visit. Any out-of-range visit should 
be documented in the subject’s source notes.
Study-site personnel will maintain a log of all study drug administered. Drug supplies for each 
subject will be inventoried and accounted for. Information regarding study drug administrations
that are administered outside of the scheduled windows or missed will be recorded. Subject 
charts and worksheets may be reviewed and compared with the data entries on the eCRFs to 
ensure accuracy. Although it is understood that treatment may be interrupted for many reasons, 
compliance with the treatment schedule is strongly encouraged.
8.
CONCOMITANT THERAPY
Concomitant therapies must be recorded throughout the study from screening and continuing 
until 12 weeks after the last dose of study drug for randomized subjects. Concomitant therapies 
should also be recorded beyond Week 56 only in conjunction with SAEs that meet the criteria 
outlined in Section 12.3.2. Serious Adverse Events.
All therapies (prescription or over-the-counter medications, including vaccines, vitamins, herbal 
supplements) different from the study drug, as well as all shampoos used to treat psoriasis, 
moisturizers, or emollients, must be recorded in the eCRF. Modification of an effective 
preexisting therapy should not be made for the explicit purpose of entering a subject into the 
study.
If a prohibited therapy is administered during the blinded active treatment phase (ie, Week 0 to 
Week 44 - unless agreed to by the medical monitor), the subject should be discontinued from 
study treatment. If a prohibited therapy is initiated during the safety follow-up period (Week 48 
to Week 56), the subject should still complete his or her final study visit at Week 56, and the 
medication should be recorded as a concomitant medication.
The sponsor must be notified in advance (or as soon as possible thereafter) of any instances in 
which prohibited therapies are administered.
8.1.1.
Concomitant Medications for Treatment of Psoriasis
8.1.1.1.
Topical Therapy
Topical therapies that could affect psoriasis or the IGA evaluation (eg, corticosteroids, tar, 
anthralin, calcipotriene, tazarotene, methoxsalen, pimecrolimus, tacrolimus, and traditional 
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Taiwanese, Korean, or Chinese medicines) are not permitted at any time during the study. The 
only allowable concomitant treatments for psoriasis throughout the study are shampoos 
(containing tar or salicylic acid only) and topical moisturizers. Subjects 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.
8.1.1.2.
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 tumor necrosis factor α
(including but not limited to infliximab, adalimumab, or etanercept), drugs targeted for reducing 
IL-12, IL-17A, IL-17R, or IL-23 (including but not limited to ustekinumab, tildrakizumab 
[MK3222], risankizumab [BI-655066], ixekizumab [LY2439821], or brodalumab [AMG827]), 
alpha-4 integrin antagonists (including but not limited to natalizumab), apremilast, 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.
8.1.2.
Concomitant Medications for Conditions Other than Psoriasis
Every effort should be made to keep subjects 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 subject’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. Lithium and antimalarial agents may not be used.
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.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The Time and Events Schedule summarizes the frequency and timing of efficacy, biomarker, and
safety measurements applicable to this study.
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Investigator-reported efficacy assessments (ie, IGA and PASI) should be completed before any 
study drug administrations, will be performed by an assessor trained by the sponsor, and 
captured electronically on a tablet device at the appropriate visits, as outlined in the Time and 
Events Schedule.
A urine pregnancy test will be performed to confirm the absence of pregnancy at every study 
drug administration visit. Additional 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 subject's participation in the study.
The total blood volume to be collected from each subject will be approximately 189.5 mL. In 
addition, repeat or unscheduled samples may be collected for safety reasons or for technical 
issues with the samples.
9.1.2.
Screening Phase
All subjects will have a screening visit that will occur approximately 4 weeks before their 
Week 0 visit. The screening phase is designed to assess inclusion/exclusion criteria and establish 
baseline characteristics for a subject's psoriasis.
The recording of AEs and concomitant medications will start after the signing of the informed 
consent and will continue until the last study-related procedure has been completed. The eC-
SSRS (‘Baseline/Screening’ version) should be completed after the subject signs consent but as 
the first assessment by the subject before any tests, procedures, or other consultations to prevent 
influencing subject perceptions.
Each subject will be asked to sign the consent form at the screening visit before any study-related 
procedures are conducted.
The recording of AEs and concomitant medications will start after the signing of the informed 
consent and will continue until the last study-related procedure has been completed.
As outlined in the eligibility criteria, all subjects must be questioned about a history of TB or 
other personal exposure to individuals with active TB. Potential subjects should be asked about 
past testing for TB, including chest radiograph results and responses to tuberculin skin or other 
TB testing. With the exception of subjects with a history of appropriately treated latent TB 
within 5 years before the first administration of study drug (Inclusion Criterion 12), subjects 
must undergo testing for TB (see Attachment 3 or Attachment 4) and their medical history 
assessment must include specific questions about a history of TB or known occupational or other 
personal exposure to individuals with active TB. The subject should be asked about past testing 
for TB, including chest radiograph results and responses to tuberculin skin or other TB testing.
Investigators have the option to use both the QuantiFERON-TB Gold test and the tuberculin skin 
test to screen for latent TB if they believe, based on their judgment, that the use of both tests is 
clinically indicated in order to evaluate a subject who has high risk of having latent TB. If either 
the QuantiFERON-TB Gold test or the tuberculin skin test is positive, the subject is considered 
to have latent TB infection for the purposes of eligibility for this study.
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Subjects with a negative QuantiFERON-TB Gold test result (and a negative tuberculin skin test 
result in countries in which the QuantiFERON-TB Gold test is not approved/registered or the 
tuberculin skin test is mandated by local health authorities) are eligible to continue with 
prerandomization procedures. Subjects with a newly identified positive QuantiFERON-TB Gold 
or tuberculin skin test result must undergo an evaluation to rule out active TB and initiate 
appropriate treatment for latent TB. Appropriate treatment for latent TB is defined according to 
local country guidelines for immunocompromised patients. If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed, or the subject will be 
excluded from the study.
A subject 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 subject should be excluded from the study.
Subjects will undergo screening for HBV (see Attachment 5) and antibodies to HCV and HIV.
9.1.3.
Screen Failure/Rescreening
If, during the screening phase, the subject has not met all inclusion criteria or met any exclusion 
criteria, or is unable or unwilling to adhere to the prohibitions and restrictions of the study, the 
subject is considered to be a screen failure and is not eligible to be randomized at that time.
In general, if the subject is a screen failure, but at some timepoint in the future meets all the 
subject eligibility criteria, the subject may be rescreened after a new informed consent has been 
obtained. Subjects who are rescreened will be assigned a new subject number and will restart a 
new screening phase. Rescreening will be permitted once.
9.1.4.
Double-Blind Treatment Phase
Week 0/Randomization
At Week 0, subjects who meet all inclusion criteria and do not demonstrate any exclusion criteria 
will be randomized.
Randomization visit procedures will be performed as specified on the Time and Events Schedule. 
The ‘Since Last Visit’ version of the eC-SSRS questionnaire should be completed by the subject 
first before any tests, procedures, or other consultations to prevent influencing subject 
perceptions (Section 9.6.1) and to confirm eligibility. After completion of required study 
procedures, subjects will be administered study drug according to their randomization 
assignment (guselkumab and placebo or secukinumab).
At Week 0, if a mental health evaluation is required based on the Week 0 eC-SSRS score, either 
this evaluation must be conducted prior to randomization or, if not feasible, the subject should be 
screen-failed and then re-screened after a completed mental health evaluation, if appropriate (see 
Section 9.6.1).
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Week 1 through Week 44
All visit procedures will be performed as specified in the Time and Events Schedule. The ‘Since 
Last Visit’ version of the eC-SSRS should be completed by the subject first before any tests, 
procedures, or other consultations at postbaseline study visits to prevent influencing subject 
perceptions (Section 9.6.1) and to assess for potential discontinuation requirements. All other 
study procedures and evaluations should be completed before the subject is administered study 
drug.
9.1.5.
Posttreatment Phase (Follow-Up)
Subjects will be followed for efficacy, safety, and biomarker information through Week 56 as 
shown in the Time and Events Schedule. The ‘Since Last Visit’ version of the eC-SSRS should 
be completed by the subject first before any tests, procedures, or other consultations at the 
follow-up visit to prevent influencing subject perceptions (Section 9.6.1). Subjects will be 
instructed that study drug will not be made available to them after they have 
completed/discontinued study drug and that they should return to their primary physician to 
determine subsequent treatment of their psoriasis.
9.2.
Efficacy Evaluations
9.2.1.
Evaluations
Efficacy evaluations chosen for this study are consistent with those utilized to evaluate other 
therapies for psoriasis. Efficacy evaluations include:

IGA

PASI
Efficacy assessments (IGA, PASI) will be performed at the site by an efficacy assessor trained 
by the sponsor and captured electronically in a tablet device at the appropriate visits as outlined 
by the Time and Events Schedule. The sponsor will provide IGA and PASI training. 
Documentation of this training will be maintained in the site’s training files and by the sponsor.
9.2.1.1.
Investigator’s Global Assessment
The IGA documents the investigator’s assessment of the subject’s psoriasis at a given timepoint
(Attachment 1). Overall lesions are graded for induration, erythema, and scaling. The patient’s 
psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). A higher 
score indicates more severe disease.
9.2.1.2.
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 (Attachment 2).5 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 
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scaling, which are each rated on a scale of 0 to 4. The PASI produces a numeric score that could 
range from 0 (no psoriasis) to 72. A higher score indicates more severe disease.
9.3.
Pharmacokinetics and Immunogenicity
Serum samples will be analyzed to determine guselkumab concentrations and antibodies to 
guselkumab according to the Time and Events Schedule. Additionally, serum samples should be 
collected at the final visit from subjects who are withdrawn from the study.
Serum samples that test positive for antibodies to guselkumab will be further characterized to 
determine if antibodies to guselkumab could neutralize the biological effects of guselkumab in 
vitro (ie, neutralizing antibodies to guselkumab).
All sample analyses will be conducted by the sponsor or sponsor's designee.
9.4.
Biomarkers
Biomarker sample collections will be conducted at the timepoints presented in the Time and 
Events Schedule to measure serum markers, gene expression and cellular profiles in skin 
biopsies, 
 and genetic associations 
with psoriasis or response to treatment (each explained in detail below). Data collected from 
these samples will be used for exploratory research that will include the following objectives:
1.
To understand the molecular effects of guselkumab and secukinumab.
2.
To understand psoriasis pathogenesis.
3.
To understand why individuals differ in their responses to guselkumab or secukinumab.
4.
 
Instructions for the collection and shipment of these samples can be found in the appropriate 
Laboratory Manual.
Serum Biomarkers
Serum samples will be collected from all subjects according to the Time and Events Schedule. 
These samples will be analyzed for the presence of serum biomarkers related to psoriasis, 
inflammation, and/or any observable PD relationship with either guselkumab or secukinumab 
response to treatment. Measurements will include but are not limited to serum IL-17A, IL-17F 
and IL-22 levels.
Skin Biopsy (RNA and Histology)
Skin biopsy samples will be collected according to the Time and Events Schedule from a subset 
of subjects who consent to participate in the biopsy substudy (target n = 45 per group, at 
predefined study sites capable of performing the skin biopsy procedure). Enrollment will be 
optional at selected predefined sites. Consenting subjects will undergo collection of skin biopsies 
which will be used for assessment of RNA expression, T cell receptor repertoire assessment, 
histology, epigenetic evaluation, and immunohistochemistry. Psoriasis pathogenesis involves the 
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dysregulation of IL-23- and IL-17A-mediated immune responses, and antagonism of either IL-23 
or IL-17A has demonstrated clinical benefit in psoriasis.1 The goal of the exploratory skin biopsy 
substudy is to further define the cellular and molecular mechanism of action of blocking IL-23 
compared to blocking IL-17A in psoriasis. Skin samples will be processed to assess histologic 
changes pre-and post-treatment, including potential evaluation of specific immune cell subsets 
such as Th17 and regulatory T (Treg) cells. Skin samples will also be processed for RNA 
transcriptional profiling to determine gene expression profile changes associated with response 
to guselkumab or secukinumab. Evaluation may also be conducted on skin samples to assess 
epigenetic modifications associated with different immune cell infiltrates in psoriatic skin 
lesions.
 
 
 
 
 
 
 
9.5.
Genetic (DNA) Analysis
Genetic (DNA) research may consist of the analysis of one or more candidate genes, single 
nucleotide polymorphisms, or analysis of the entire genome (as appropriate) in relation to 
guselkumab, secukinumab or psoriasis clinical endpoints. Whole blood samples of 
approximately 12 mL will be collected for genetic analyses at a single timepoint as specified in 
the Time and Events Schedule. Epigenetic evaluation may be conducted on skin samples 
obtained in the biopsy substudy to assess potential epigenetic modifications associated with 
different immune cell infiltrates in psoriatic skin lesions. Only subjects who sign the consent 
form to participate in the genetic (DNA) assessment will have whole blood DNA or skin samples 
collected.
9.6.
Safety Evaluations
The safety and tolerability of study drugs (guselkumab, secukinumab, or placebo, where 
appropriate) will be monitored by collecting information on AEs, including injection site and 
allergic reactions, clinical laboratory tests, physical examinations, vital signs, eC-SSRS
questionnaires, electrocardiograms (ECGs), concomitant medication review, and early detection 
of TB, as specified in the Time and Events Schedule. Serum and/or plasma samples collected for 
biomarker analyses may also be used to evaluate safety concerns that may arise during or after 
the study period.
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Safety will be monitored through Week 56 or for 12 weeks after the last study drug 
administration for subjects who discontinue early. Any clinically relevant changes occurring 
during the study must be recorded on the AE section of the eCRF.
Clinically important abnormalities persisting at the end of the study/early withdrawal may be 
followed by the investigator until resolution or until a clinically stable endpoint is reached.
The study will include the following evaluations of safety and tolerability according to the 
timepoints provided in the Time and Events Schedule:
Adverse Events
Adverse events will be reported by the subject for the duration of the study. Adverse events will 
be followed by the investigator as specified in Section 12, Adverse Event Reporting.
Early Detection of Active Tuberculosis
To aid in the early detection of TB reactivation or new TB infection during study participation, 
subjects must be evaluated for signs and symptoms of active TB at scheduled visits (refer to 
Time and Events Schedule) 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 subject 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 subjects may present 
as disseminated disease or with extrapulmonary features. Subjects with evidence of active TB 
should be referred for appropriate treatment.
Subjects 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, a repeat 
tuberculin skin test in countries in which the QuantiFERON-TB Gold test is not 
approved/registered or the tuberculin skin test is mandated by local health authorities, and, if 
possible, referral to a physician specializing in TB to determine the subject’s risk of developing 
active TB and whether treatment for latent TB is warranted.
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Study drug administration should be interrupted during the investigation. A positive 
QuantiFERON-TB Gold test or tuberculin skin test result should be considered detection of 
latent TB. If the QuantiFERON-TB Gold test result is indeterminate, the test should be repeated. 
Subjects who discontinue treatment for latent TB prematurely or who are noncompliant with 
therapy must immediately discontinue further administration of study drug and be encouraged to 
return for all subsequent scheduled study visits according to the Time and Events Schedule.
Allergic Reactions
The sponsor will proactively monitor reported AEs and query the site, if necessary, to capture 
anaphylactic reaction/serum sickness events in eCRFs.
Injection Site Reactions
An injection site reaction is any unfavorable or unintended sign that occurs at the study drug 
injection site. After administration of study drug at Week 0, all subjects will be carefully 
observed at the study site for at least 30 minutes after the SC injection of study drug for 
symptoms of an injection site reaction. If an injection site reaction is observed, the subject should 
be treated at the investigator’s discretion. Any adverse reaction (eg, pain, erythema, and/or 
induration) should be noted on the AE page of the eCRF.
Clinical Laboratory Tests
Blood samples for serum chemistry and hematology will be collected. The investigator must 
review the laboratory results, document this review, and record any clinically relevant changes 
occurring during the study in the AE section of the eCRF. The laboratory reports must be filed 
with the source documents.
All abnormal laboratory values will be evaluated for clinical significance by the investigator. If 
clinically significant abnormal laboratory values (in the opinion of the investigator) are detected, 
then the test(s) should be repeated until they return to normal or are otherwise explained by the 
Investigator.
Instructions for the collection, handling, and shipping of blood samples are provided in the 
Laboratory Manual.
The following tests will be performed by the central laboratory:

Hematology Panel
-hemoglobin
-neutrophils
-hematocrit
-bands
-red blood cell count
-eosinophils
-white blood cell count
-basophils
-lymphocytes
-platelets
-monocytes
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
Serum Chemistry Panel
-sodium
-calcium
-potassium
-albumin
-chloride
-total protein
-alkaline phosphatase
-alanine aminotransferase
-urea
-total carbon dioxide
-creatinine
-total bilirubin
-glucose
- high-sensitivity C-reactive protein
-aspartate aminotransferase
-follicle-stimulating hormonea
aTesting required for selected subjects as defined in Inclusion Criterion 8.

Lipid Panela
-total cholesterol
-total cholesterol to high density lipoprotein 
cholesterol ratio
-low density lipoprotein cholesterol
-triglycerides
-high density lipoprotein cholesterol
a(Week 0 only; subjects must fast (ie, no food or beverages [except water]) for at least 8 hours before blood is 
drawn for lipid panel)

Serology: HBV, including HBV serology and HBV DNA (when indicated, see 
Attachment 5), and antibodies to HCV and HIV.
Pregnancy Testing
Urine pregnancy testing is required for all women of childbearing potential at all study visits
with study agent administration and at other visits as specified in the Time and Events Schedule.
Pregnancy tests must be completed and negative at the study visit prior to administration of study 
drug. All pregnancy test results must be recorded in study source documents.
Physical Examination
Physical examinations will be performed by the investigator or designated physician, nurse 
practitioner or physician assistant as specified in the Time and Events Schedules. Any new, 
clinically significant finding (in the opinion of the investigator) must be captured as an AE. In 
addition, resolution of any abnormal findings during the study will be noted in the source 
document and in the eCRF.
Height and Weight
Height and weight will be measured as specified in the Time and Events Schedule. Subjects will 
be instructed to remove shoes and outdoor apparel and gear prior to these measurements.
Vital Signs
Blood pressure and heart rate measurements will be assessed at the timepoints specified in the 
Time and Events Schedule. If any clinically significant changes in vital signs are noted, they 
must be reported as AEs and followed to resolution, or until reaching a clinically stable endpoint.
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Electrocardiogram
During the collection of ECGs, subjects should be in a quiet setting without distractions (eg, 
television, cell phones). Subjects 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 timepoint as ECG recording, the procedures 
should be performed in the following order: ECG(s), vital signs, blood draw.
9.6.1.
Electronic Columbia-Suicide Severity Rating Scale
In light of the recent reports concerning suicidal ideation and behavior in patients with plaque 
psoriasis treated with an IL-17R antagonist (brodalumab),3 the eC-SSRS will be used as a 
screening tool to prospectively evaluate the potential of guselkumab to induce suicidal ideation 
and behavior. The eC-SSRS defines 5 subtypes of suicidal ideation and behavior in addition to 
self-injurious behavior with no suicidal intent, and is a fully-structured, subject self-report 
C-SSRS questionnaire, including standardized questions, follow-up prompts, error handling 
routines, and scoring conventions.10,15 Two versions of the eC-SSRS will be used in this study, 
the ‘Baseline/Screening’ version and the ‘Since Last Visit’ version. The ‘Baseline/Screening’ 
version of the eC-SSRS will be conducted during the screening visit followed by the ‘Since Last 
Visit’ version of the eC-SSRS at Week 0, and all visits starting at Week 4 through Week 56.
Subjects will complete the eC-SSRS questionnaire using the sponsor-provided electronic tablets. 
Study site personnel will train the subjects on how to use the electronic device. The eC-SSRS 
will be provided in the local languages in accordance with local guidelines.
The eC-SSRS will be performed during each evaluation visit according to the assessment 
schedule. During a visit, subjects will be directed to a private, quiet place with the electronic 
device to complete the assessment. Subjects who do not have suicidal behavior or ideation will 
answer a limited number of questions and will usually complete the assessment in about 
3 minutes. Subjects with significant suicidal ideation and behavior may require up to 10 minutes 
to answer all relevant questions. The eC-SSRS will be performed first at the screening visit (after 
signing informed consent) and before study agent administration. At all postbaseline visits, the 
eC-SSRS will be the first assessment/questionnaire that the subject must complete.
At the conclusion of each assessment, the site will receive an eC-SSRS Findings Report. At 
screening and Week 0, subjects with an eC-SSRS score greater than 0 or a response to the 
question of “Self-injurious behavior without suicidal intent” other than ‘NO’ must be determined 
to be not at risk by the investigator based on an evaluation by a mental health professional in 
order to be randomized. Subjects with a score on the eC-SSRS that is greater than 0 or a response 
to the question of “Self-injurious behavior without suicidal intent” other than ‘NO’ at any post-
baseline visit will also be referred to an appropriate mental health professional for evaluation. If 
the subject’s psychiatric disorder can be adequately treated with psychotherapy and/or 
pharmacotherapy then the subject, at the discretion of the investigator, should be continued with 
treatment. Ultimately, the determination of suicidality and risk is up to the investigator’s clinical 
judgment following evaluation by a mental health professional (eg, psychiatrist, psychologist, or 
appropriately trained social worker or nurse).
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Positive reports are generated from the eC-SSRS vendor for ANY of the following findings:

Suicidal ideation with intention to act (“4”)

Suicidal ideation with specific plan and intent (“5”)

Made suicide attempt

Interrupted suicide attempt

Aborted suicide attempt

Preparatory behaviors for making a suicide attempt.
Negative suicidality indication reports are generated from the eC-SSRS vendor when there are 
NO indications of the above.
The subject should not be released from the site until the eC-SSRS Findings Report (both for 
negative and positive reports) is reviewed by the investigator and the subject’s risk has been 
assessed and follow-up determined, as appropriate.
For each score, the following actions and associated alerts will be generated, if applicable:

Score of 0: No further action is needed.

Score > 0: Subject risk assessed and referral to a mental health professional.

Score of 1, 2, or 3: Negative findings report will be generated.

Score of 4 or higher: Positive findings report will be generated. When the system 
reports that the subject has a positive suicidal indication (including for an incomplete 
assessment), the site will be immediately notified by fax/email and a telephone call 
from the eC-SSRS vendor.

Self-injurious behavior without suicidal intent = YES or ‘Question Mark (ambiguous 
response)’: Subject risk assessed and referral to a mental health professional. Negative 
findings report will be generated.
Interruption or the discontinuation of study treatment should be considered for any subject who 
reports suicidal ideation with intention to act (“4”), suicidal ideation with specific plan and intent 
(“5”), or a suicide attempt (interrupted suicide attempt, aborted suicide attempt, or preparatory 
behaviors for making a suicide attempt) on a post-baseline eC-SSRS assessment and who is 
deemed to be at risk by the investigator based upon evaluation by a mental health professional. 
Discussion of such subjects with the medical monitor or designee is required (See Section 10.2). 
The final decision on suitability for continuing in the study will be made by the investigator.
Any eC-SSRS finding, which in the opinion of the investigator is new or considered to be a 
worsening and clinically significant, should be reported on the AE eCRF (see Section 12).
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9.7.
Sample Collection and Handling
The actual dates and times of sample collection must be recorded in the eCRF or laboratory 
requisition form.
Refer to the Time and Events Schedule 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.
10.
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ 
WITHDRAWAL FROM THE STUDY
10.1.
Completion
A subject will be considered to have completed the study if he or she has completed assessments 
at Week 56 of the double-blind phase. Subjects who prematurely discontinue study treatment for 
any reason before completion of the double-blind phase will not be considered to have completed 
the study.
10.2.
Discontinuation of Study Treatment/Withdrawal from the Study
Discontinuation of Study Treatment
A subject will not be automatically withdrawn from the study if he or she has to discontinue 
treatment before the end of the treatment regimen.
A subject's study treatment must be discontinued if:

The investigator believes that for safety reasons or tolerability reasons (eg, AE) it is in the 
best interest of the subject to discontinue study treatment

The subject becomes pregnant

The subject is diagnosed with a malignancy, with the exception of no more than 2 localized 
basal cell skin cancers that are treated with no evidence of recurrence or residual disease.

The subject is deemed ineligible according to the following TB screening criteria:

A diagnosis of active TB is made.

A subject has symptoms suggestive of active TB based on follow-up assessment 
questions and/or physical examination, or has had recent close contact with a person 
with active TB, and cannot or will not continue to undergo additional evaluation.
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
A subject undergoing evaluation has a chest radiograph with evidence of current active 
TB and/or a positive QuantiFERON-TB Gold test result and/or an indeterminate 
QuantiFERON-TB Gold test result on repeat testing (refer to Section 9.6) (and/or a 
positive tuberculin skin test result in countries in which the QuantiFERON-TB Gold test 
is not approved/registered or the tuberculin skin test is mandated by local health 
authorities). Indeterminate QuantiFERON-TB Gold test results should be handled as 
described in Section 9.6.

A subject receiving treatment for latent TB discontinues this treatment prematurely or is 
noncompliant with the therapy.

The subject initiates a protocol-prohibited medication, eg, for a worsening of his or her 
psoriasis (unless agreed to by the medical monitor).

The subject withdraws consent for administration of study drug.

The subject is unable to adhere to the study visit schedule or comply with protocol 
requirements.

The subject develops an allergic reaction such as bronchospasm with wheezing and/or 
dyspnea requiring ventilatory support, or symptomatic hypotension that occurs following a 
study drug administration.

The subject has a reaction resulting in myalgia and/or arthralgia with fever and/or rash 
(suggestive of serum sickness and not representative of signs and symptoms of other 
recognized clinical syndromes) occurring 1 to 14 days after an injection of study drug. These 
may be accompanied by other events including pruritus, facial, hand, or lip edema, 
dysphagia, urticaria, sore throat, and/or headache.

Discontinuation of study treatment should be considered for subjects who report suicidal 
ideation with intention to act (“4”), suicidal ideation with specific plan and intent (“5”), or a 
suicide attempt (interrupted suicide attempt, aborted suicide attempt, or preparatory 
behaviors for making a suicide attempt) on a postbaseline eC SSRS assessment. Discussion 
of such subjects with the medical monitor or designee is required.

Discontinuation of study treatment should be considered for subjects who develop a serious 
or opportunistic infection. Discussion of such subjects with the medical monitor or designee 
should also be considered.
Subjects who decide to discontinue study drug administration must be interviewed by the 
investigator to determine if a specific reason for discontinuing study drug can be identified. 
Subjects should be explicitly asked about the possible contribution of AEs to their decision to 
discontinue study drug; investigators should confirm that any AE information elicited has been 
documented. If the subject elects to discontinue study drug due to an AE, the event should be 
recorded as the reason for study drug discontinuation, even if the investigator’s assessment is 
that the AE would not require study drug discontinuation. The reason for study drug 
discontinuation must be documented in the eCRF and in source documents. Study drug assigned 
to a subject who discontinues may not be assigned to another subject.
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If the subject discontinues study treatment before his or her last scheduled injection, he or she 
should return for the remaining regularly scheduled study visits for at least 12 weeks after 
receiving the last administration of study drug. For subjects who complete their final study visit 
prior to Week 48, every effort should be made to conduct the Week 48 assessments as indicated 
in the Time and Events Schedule. For subjects who discontinue from the study prior to Week 48, 
serum is not to be collected for measurement of biomarkers.
Withdrawal From the Study
A subject will be withdrawn from the study for any of the following reasons:

Lost to follow-up

Withdrawal of consent

Death
To ensure access for subject follow-up, study sites should try to obtain both primary and 
secondary telephone contact numbers from subjects (eg, home, work, and mobile phones), as 
well as other contact information such as email addresses, and emphasize the importance of 
follow-up information to the subject, before randomization. For subjects who withdraw from 
study participation, every effort should be made to conduct the Week 48 assessments, as 
indicated in the Time and Events Schedule.
If the subject fails to return for study visits (and thus is considered lost to follow-up), study site 
personnel must make all reasonable efforts to contact the subject to determine the subject’s 
reason for discontinuation/withdrawal before considering the subject to be lost to follow-up. 
Such efforts should include repeated telephone calls, certified letters, email requests, etc. 
Measures taken to obtain follow-up information must be documented.
Withdrawal of consent should be a very unusual occurrence in a clinical trial; the investigator 
should make every effort to maintain good subject relationships to avoid withdrawals of consent. 
For subjects who truly request withdrawal of consent, it is recommended that the subject 
withdraw consent in writing; if the subject or the subject’s representative refuses to do so or is 
physically unavailable, the study site should document the reason for the subject’s failure to 
withdraw consent in writing, sign the documentation, and maintain it with the subject’s source 
records. When a subject withdraws before completing the study, the reason for withdrawal is to 
be documented in the eCRF and in the source document. Study drug assigned to the withdrawn 
subject may not be assigned to another subject. Subjects who withdraw will not be replaced.
10.3.
Withdrawal From the Use of Research Samples
A subject who withdraws from the study will have the following options regarding the optional
research samples:

The collected samples will be retained and used in accordance with the subject's original 
separate informed consent for optional research samples.
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
The subject may withdraw consent for optional research samples, in which case the samples
will be destroyed and no further testing will take place. To initiate the sample destruction 
process, the investigator must notify the sponsor study site contact of withdrawal of consent 
for the optional research samples and to request sample destruction. The sponsor study site 
contact will, in turn, contact the biomarker representative to execute sample destruction. If 
requested, the investigator will receive written confirmation from the sponsor that the 
samples have been destroyed.
Withdrawal From the Optional Research Samples While Remaining in the Main Study
The subject may withdraw consent for optional research samples while remaining in the study. In 
such a case, the optional research samples will be destroyed. The sample destruction process will 
proceed as described above.
Withdrawal From the Use of Samples in Future Research
The subject may withdraw consent for use of samples for research (refer to Section 16.2.5, Long-
Term Retention of Samples for Additional Future Research). In such a case, samples will be 
destroyed after they are no longer needed for the clinical study. Details of the sample retention
for research are presented in the main ICF and in the separate ICF for optional research samples.
11.
STATISTICAL METHODS
Statistical analysis will be done by the sponsor or under the authority of the sponsor. A general 
description of the statistical methods to be used to analyze the efficacy and safety data is outlined 
below. Specific details will be provided in the Statistical Analysis Plan (SAP).
Descriptive statistics will include counts and proportions for categorical data, and median, mean, 
interquartile range, and range for continuous data. Graphical data displays may also be used to
summarize the data.
In order to compare the proportion of subjects responding to the two treatments, the Cochran-
Mantel-Haenszel chi-square test stratified by investigator site will be used. To test the non-
inferiority of guselkumab to secukinumab, a 1-sided (α=0.025) Z-test with Mantel-Haenszel 
weights adjusted by investigator site will be used. A longitudinal modeling approach will also be 
used as a sensitivity analysis to compare the proportion of subjects responding to treatment. All 
statistical testing will be performed 2-sided at a significance level of 0.05 for superiority and 
1-sided at a significance level of 0.025 for non-inferiority.
Subjects who discontinue study agent due to lack of efficacy or an AE of worsening of psoriasis, 
or who started a protocol-prohibited medication/therapy during the study that could improve 
psoriasis are considered treatment failures. The baseline values will be assigned regardless of the 
observed data for continuous endpoints, zero will be assigned to improvement and percent 
improvement, and nonresponder status will be assigned to binary response variables. After 
applying the treatment failure rules, the remaining missing data will be assigned nonresponder 
status for binary variables. For the longitudinal analyses, treatment failure rules or missing data 
handling rules will not be applied.
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11.1.
Subject Information
Subjects will be included in the efficacy analyses according to their assigned treatment group 
regardless of whether or not they received the assignment treatment. For the primary efficacy 
analysis, data from all randomized and treated subjects will be analyzed. The treated population, 
which includes all randomized subjects who received at least 1 dose (complete or partial) of 
study medication, will also be used for PK, immunogenicity, and safety analyses by the actual 
treatment received.
Descriptive statistics by the randomized treatment group based on all randomized and treated 
subjects will be provided for subject dispositions, demographics, baseline disease characteristics, 
and prior and concomitant medications. Details will be provided in the SAP.
11.2.
Sample Size Determination
This study is designed to evaluate the efficacy of guselkumab 100 mg vs secukinumab 300 mg. 
The assumptions for the sample size and power calculations were based on the data from the 
guselkumab CNTO1959PSO3001 and CNTO1959PSO3002 and the secukinumab Phase 3 
studies (ERASURE and FIXTURE). The assumptions used are as follows:

The proportion of subjects who achieve a PASI 90 response at Week 48 is 70% to 80% in 
subjects receiving guselkumab and 60% to 70% for subjects receiving secukimumab.

The proportion of subjects who achieve a PASI 100 response at Week 48 is 44% to 51% in 
subjects receiving guselkumab and 35% to 40% for subjects receiving secukimumab.
Approximately 1,040 subjects are planned to be randomized in a 1:1 ratio to either guselkumab 
100 mg (n=520) (administered at Weeks 0, 4, 12 and q8w thereafter until Week 44) or 
secukinumab 300 mg (n=520) (administered at Weeks 0, 1, 2, 3, and 4 and q4w thereafter until 
Week 44).
Based on the above assumptions, the planned sample size, and a noninferiority margin of 10%, 
the power to demonstrate the non-inferiority for the primary endpoint of PASI 90 at Week 48 
and the major secondary endpoint of PASI 100 at Week 48 will be > 99%.
Table 1 provides the power for detecting a treatment difference (superiority of guselkumab over 
secukinumab) under varying assumptions at a significance level of 0.05 for the primary endpoint 
PASI 90 at Week 48 and the select major secondary endpoint of PASI 100 at Week 48 specified 
in Section 2.1.2.
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Table 1:
Power to Detect a Treatment Effect Based on Different Proportions of Subjects Achieving the 
Primary Endpoint PASI 90 at Week 48 and the Major Secondary Endpoint PASI 100 at 
Week 48
Primary Endpoint
PASI 90 at Week 48
Secukinumab 300 mg (n=520)
Guselkumab 100 mg (n=520)
60%
70%
92%
75%
>99%
65%
75%
94%
80%
>99%
70%
80%
96%
Selected Major Secondary Endpoint
PASI 100 at Week 48
35%
44%
84%
45%
91%
46%
95%
40%
49%
83%
50%
90%
51%
95%
PASI = Psoriasis Area and Severity Index.
11.3.
Efficacy Analyses
11.3.1.
Analysis Data Set
For the primary analysis and major secondary analyses, all randomized and treated subjects will 
be included. For all the efficacy analyses, subjects will be analyzed according to the treatment 
group to which they are randomized, regardless of the treatment they actually receive.
11.3.2.
Primary Analysis
The primary endpoint in this study is the proportion of subjects who achieve a PASI 90 response 
at Week 48. In the primary efficacy analysis, data from all randomized and treated subjects will 
be analyzed according to their assigned group.
To address the primary efficacy objective, the proportion of subjects achieving a PASI 90 
response at Week 48 will be evaluated with a non-inferiority test followed by a superiority test. 
The following stepwise comparisons will be made to compare the efficacy of guselkumab to that 
of secukinumab at Week 48:
a.
A non-inferiority margin of 10% was chosen based on a minimally clinically meaningful 
difference. This margin was also used as the non-inferiority margin for the ustekinumab
psoriasis study C0743T12 and the guselkumab psoriasis CNTO1959PSO3001 and 
CNTO1959PSO3002 studies. To claim the non-inferiority of guselkumab over 
secukinumab, the lower bound of the 2-sided 95% confidence interval of P1 – P2 must be 
≥–10%, where P1 and P2 are the proportions of subjects achieving a PASI 90 response at 
Week 48 in the guselkumab and the secukinumab groups, respectively. If non-inferiority 
is not established, no further test will be conducted and Step b will be skipped.
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b. If non-inferiority is established in Step a, the superiority test of guselkumab to 
secukinumab will be performed at 2-sided (α=0.05).
If both the non-inferiority test and the superiority test are positive, the major secondary 
hypotheses comparing the guselkumab group and the secukinumab group will be tested
sequentially. Otherwise, all remaining p-values will be considered nominal.
11.3.3.
Major Secondary Analyses
For the major secondary analysis, all non-inferiority tests will be performed 1-sided (α=0.025) 
with a non-inferiority margin of 10%. The major secondary analyses are:

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 75 response at both Week 12 and Week 48 will be performed. If 
non-inferiority is established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 90 response at Week 12 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 75 response at Week 12 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 100 response at Week 48 will be performed. If non-inferiority is 
established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving an IGA score of cleared (0) at Week 48 will be performed. If non-
inferiority is established, the superiority test on this endpoint will be performed.
11.3.3.1.
Multiplicity Control
In order to control the overall Type 1 error rate, the primary analysis and major secondary 
analyses will be tested in a fixed sequence as ordered above. That is, the first major secondary 
analysis will be performed only if the primary endpoint is positive for both non-inferiority and 
superiority, and the subsequent analysis will be performed only if the preceding analysis in the 
sequence is positive.
11.3.4.
Other Efficacy Analyses
In addition to the primary and major secondary analyses, the analyses for other efficacy 
endpoints will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 90 response at both Week 16 and Week 48 will be performed. If 
non-inferiority is established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 75 response at Week 16 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 90 response at Week 16 will be performed.
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
The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 90 response at all 7 visits from Week 24 through Week 48 will be 
performed. If non-inferiority is established, the superiority test on this endpoint will be 
performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving an IGA score of cleared (0) or minimal (1) at Week 16 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving an IGA score of cleared (0) or minimal (1) at Week 12 will be performed.

The proportions of subjects who achieve a PASI 75 response at Week 48 among PASI 75 
responders at Week 12 will be summarized by treatment group.

The proportions of subjects who achieve a PASI 90 response at Week 48 among PASI 90 
responders at Week 16 will be summarized by treatment group.

The proportions of subjects who achieve a PASI 50/75/90/100 response over time through 
Week 48 will be summarized by treatment group.

The proportions of subjects who achieve an IGA score of cleared (0) response, IGA score of 
cleared (0) or minimal (1) response, and IGA of cleared (0), minimal (1), or mild (2)
response over time through Week 48 will be summarized by treatment group.

The percentages of improvement in PASI over time through Week 48 will be summarized 
by treatment group.
Furthermore, subgroup analyses will be performed to evaluate consistency of the primary 
endpoint and select major secondary endpoints over demographics (including baseline weight),
baseline disease characteristics and prior medications. Additional efficacy analyses may be 
performed and will be documented in the SAP.
11.4.
Criteria for Endpoints
PASI 50 Responders: Subjects with ≥50% improvement in PASI from baseline.
PASI 75 Responders: Subjects with ≥75% improvement in PASI from baseline.
PASI 90 Responders: Subjects with ≥90% improvement in PASI from baseline.
PASI 100 Responders: Subjects with 100% improvement in PASI from baseline.
11.5.
Pharmacokinetic Analyses
Serum guselkumab concentrations over time will be summarized for the guselkumab group. 
Descriptive statistics, including arithmetic mean, SD, median, interquartile range, minimum, and 
maximum will be calculated at each sampling timepoint. All concentrations below the lowest 
quantifiable sample concentration of the assay (BQL) or missing data will be labeled as such in 
the concentration data listing or statistical analysis system (SAS) dataset. The BQL 
concentrations will be treated as zero in the summary statistics.
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11.6.
Immunogenicity Analyses
The incidence and titers of antibodies to guselkumab will be summarized for all subjects who 
receive at least 1 dose of guselkumab and have appropriate samples for detection of antibodies to 
guselkumab (ie, subjects with at least 1 sample obtained after their first dose of guselkumab). A 
listing of subjects who are positive for antibodies to guselkumab will be provided in the clinical 
study report.
The incidence of neutralizing antibodies (NAbs) to guselkumab will be summarized for subjects 
who are positive for antibodies to guselkumab and have samples evaluable for NAbs.
11.7.
Biomarker Analyses
Biomarker samples outlined in Section 9.4 will be used to assess serum markers, skin gene 
expression and cellular profiles, 
 and genetic (DNA) data for 
biomarker analyses. Biomarker analyses will address the following objectives:
1.
To understand the molecular effects of guselkumab and secukinumab.
2.
To understand psoriasis.
3.
To understand why people may respond differently to guselkumab and secukinumab.
4.
 
These analyses are considered exploratory and will be summarized in a separate technical report.
Planned biomarker analyses may be deferred if emerging study data show no likelihood of 
providing useful scientific information.
Changes in serum/RNA or other biomarkers over time will be summarized by treatment group. 
Associations between baseline levels and changes from baseline in select biomarkers and clinical 
response will be explored. RNA analyses will be summarized in separate technical reports.
Results will be presented in a separate report.
11.8.
Safety Analyses
Safety data, including but not limited to, AEs, SAEs, infections, serious infections, changes in 
laboratory assessments, changes in vital signs, changes in electrocardiograms (ECGs), and 
suicidal ideation and behavior based on eC-SSRS will be summarized. Treatment-emergent AEs 
will be summarized by treatment group and Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class and preferred terms.
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Safety Definitions
Injection Site Reactions
An injection site reaction is any unfavorable or unintended sign that occurs at an injection site 
and will be recorded as an AE. Detailed instructions for the evaluation of injection site reactions 
are in the Trial Center File.
Adverse Events
The verbatim terms used in the eCRF by investigators to identify AEs will be coded using 
MedDRA. All reported AEs with onset during the treatment phase (ie, treatment-emergent AEs, 
and AEs that have worsened since baseline) will be included in the analysis.
Summaries, listings, or subject narratives may be provided, as appropriate, for those subjects 
who die, who discontinue treatment due to an AE, or who experience a severe AE or an SAE.
The following analyses will be used to assess the safety of subjects in the study:

The incidence and type of AEs.

The incidence and type of SAEs.

The incidence and type of infections.

The incidence and type of reasonably related AEs.

The incidence and type of injection site reactions.

The laboratory parameters and change from baseline in laboratory parameters (hematology 
and chemistry).
In addition, National Cancer Institute-Common Terminology Criteria for Adverse Events (NCI-
CTCAE) grades will be used in the summary of laboratory data. A listing of subjects with post-
baseline abnormal laboratory results based on NCI-CTCAE grades will also be provided.
Vital Signs
Descriptive statistics of heart rate and blood pressure (systolic and diastolic) values and changes 
from baseline will be summarized by treatment group.
Electrocardiogram
Electrocardiogram data will be collected at baseline and Weeks 16 and 48. Electrocardiogram 
data at each visit and change from baseline will be summarized by ECG parameters and by 
treatment group.
Electronic Columbia-Suicide Severity Rating Scale
Suicide-related thoughts and behaviors based on the eC-SSRS will be summarized descriptively 
by treatment group.
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Anticipated Events
An anticipated event is an AE (serious or non-serious) that commonly occurs as a consequence 
of the underlying disease or condition under investigation (disease related) or background 
regimen. For the purposes of this study the event of psoriasis will be considered an anticipated 
event. Serious adverse events relating to lack of efficacy (eg, events attributed to “psoriasis”) or 
progression of the disease under study will not be individually unblinded for expedited reporting. 
These anticipated events will be recorded and reported as outlined in Attachment 6.
11.9.
Interim Analysis
No formal interim analysis is planned for this study.
12.
ADVERSE EVENT REPORTING
Timely, accurate, and complete reporting and analysis of safety information from clinical studies 
are crucial for the protection of subjects, 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.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An AE is any untoward medical occurrence in a clinical study subject administered a medicinal 
(investigational or non-investigational) product. An AE does not necessarily have a causal 
relationship with the treatment. An AE 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 Section 12.3.1, All 
Adverse Events, for time of last AE recording).
Serious Adverse Event
An SAE, based on ICH and European Union Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use, is any untoward medical occurrence that at any dose:
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
Results in death

Is life-threatening
(The subject 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 subject 
or may require intervention to prevent one of the other outcomes listed in the definition above. 
These should usually be considered serious.
If a serious and unexpected AE occurs for which there is evidence suggesting a causal 
relationship between the study drug and the event (eg, death from anaphylaxis), the event must 
be reported as a serious and unexpected suspected adverse reaction.
Unlisted (Unexpected) Adverse Event/Reference Safety Information
An AE is considered unlisted if the nature or severity is not consistent with the applicable 
product reference safety information. For guselkumab, the expectedness of an AE will be 
determined by whether or not it is listed in the Investigator's Brochure. For secukinumab the 
expectedness of an AE will be determined by whether or not it is listed in the package 
insert/summary of product characteristics.
Adverse Event Associated With the Use of the Drug
An AE is considered associated with the use of the drug if the attribution is possible, probable, or 
very likely by the definitions listed in Section 12.1.2, Attribution Definitions.
12.1.2.
Attribution Definitions
Not Related
An AE that is not related to the use of the drug.
Doubtful
An AE for which an alternative explanation is more likely, eg, concomitant drug(s), concomitant 
disease(s), or the relationship in time suggests that a causal relationship is unlikely.
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Possible
An AE that might be due to the use of the drug. An alternative explanation, eg, concomitant 
drug(s), concomitant disease(s), is inconclusive. The relationship in time is reasonable; therefore, 
the causal relationship cannot be excluded.
Probable
An AE that might be due to the use of the drug. The relationship in time is suggestive 
(eg, confirmed by dechallenge). An alternative explanation is less likely, eg, concomitant 
drug(s), concomitant disease(s).
Very Likely
An AE that is listed as a possible adverse reaction and cannot be reasonably explained by an 
alternative explanation, eg, concomitant drug(s), concomitant disease(s). The relationship in time 
is very suggestive (eg, it is confirmed by dechallenge and rechallenge).
12.1.3.
Severity Criteria
An assessment of severity grade will be made using the following general categorical 
descriptors:
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not 
interfering with everyday activities.
Moderate: Sufficient discomfort is present to cause interference with normal activity.
Severe: Extreme distress, causing significant impairment of functioning or incapacitation. 
Prevents normal everyday activities.
The investigator should use clinical judgment in assessing the severity of events not directly 
experienced by the subject (eg, laboratory abnormalities).
12.2.
Special Reporting Situations
Safety events of interest on a sponsor study drug that may require expedited reporting or safety 
evaluation include, but are not limited to:

Overdose of a sponsor study drug

Suspected abuse/misuse of a sponsor study drug

Accidental or occupational exposure to a sponsor study drug

Medication error involving a sponsor product (with or without subject/patient exposure to 
the sponsor study drug, eg, name confusion)
Special reporting situations should be recorded in the eCRF. Any special reporting situation that
meets the criteria of an SAE should be recorded on the SAE page of the eCRF.
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12.3.
Procedures
12.3.1.
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 subject's last study-related 
procedure, which may include contact for follow-up of safety. Serious adverse events, including 
those spontaneously reported to the investigator within 12 weeks after the last dose of study 
drug, must be reported using the SAE Form. The sponsor will evaluate any safety information 
that is spontaneously reported by an investigator beyond the time frame specified in the protocol.
All events that meet the definition of an SAE will be reported as SAEs, regardless of whether 
they are protocol-specific assessments. Anticipated events will be recorded and reported as 
described in Attachment 6.
All AEs, regardless of seriousness, severity, or presumed relationship to study drug, must be 
recorded using medical terminology in the source document and the eCRF. Whenever possible, 
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough, 
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory 
infection"). Investigators must record in the eCRF their opinion concerning the relationship of 
the AE to study therapy. All measures required for AE management must be recorded in the 
source document and reported according to sponsor instructions.
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). For anticipated 
events reported as individual SAEs the sponsor will make a determination of relatedness in 
addition to and independent of the investigator’s assessment. The sponsor will periodically 
evaluate the accumulating data and, when there is sufficient evidence and the sponsor has 
determined there is a reasonable possibility that the drug caused a serious anticipated event, they 
will submit a safety report in narrative format to the investigators (and the head of the
investigational institute where required). The investigator (or sponsor where required) must 
report SUSARs to the appropriate Independent Ethics Committee/Institutional Review Board 
(IEC/IRB) that approved the protocol unless otherwise required and documented by the 
IEC/IRB. A SUSAR will be reported to regulatory authorities unblinded. Participating 
investigators and IEC/IRB will receive a blinded SUSAR summary, unless otherwise specified.
Serious adverse events relating to lack of efficacy (eg, events attributed to “psoriasis”) or 
progression of the disease under study will not be individually unblinded for expedited reporting. 
These anticipated events will be recorded and reported as described in Attachment 6. All SAEs 
and nonserious AEs that represent any of the following diagnoses or any symptoms associated 
with the following diagnoses (eg, chest pain, dizziness) must be reported to the sponsor and will 
require efforts to obtain additional medical records:
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
Myocardial infarction.

Stroke.

Cardiovascular death.

Unstable angina.

Coronary revascularization (percutaneous coronary intervention or coronary artery bypass 
graft surgery).

Transient ischemic attack.

Venous and peripheral arterial vascular thrombotic events (ie, deep vein thrombosis and 
pulmonary embolism).

Congestive heart failure.

Cardiac arrhythmia.

Syncope of a cardiovascular origin.

Severe/accelerated hypertension leading to hospitalization.
If the event is an SAE, the procedures outlined in Section 12.3.2, Serious Adverse Events, should 
be followed. If the event is a nonserious AE, procedures outlined in the Trial Center File for 
nonserious AEs (as described above) should be followed.
For all studies with an outpatient phase, including open-label studies, the subject 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 subject is participating in a clinical study

Investigator's name and 24-hour contact telephone number

Local sponsor's name and 24-hour contact telephone number (for medical staff only)

Site number

Subject number

Any other information that is required to do an emergency breaking of the blind
12.3.2.
Serious Adverse Events
All SAEs occurring during the study must be reported to the appropriate sponsor contact person 
by study-site personnel within 24 hours of their knowledge of the event.
Information regarding SAEs will be transmitted to the sponsor using the SAE Form, 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 an SAE should be made by facsimile (fax).
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All SAEs that have not resolved by the end of the study, or that have not resolved upon 
discontinuation of the subject'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 drug or to factors unrelated to 
study conduct

It becomes unlikely that any additional information can be obtained (subject 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 an SAE. 
Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the 
course of a subject's participation in a study must be reported as an SAE, except hospitalizations 
for the following:

Hospitalizations not intended to treat an acute illness or AE (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 
subject’s source documentation). 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 AE that results in a 
prolongation of the originally planned hospitalization is to be reported as a new SAE.

For convenience, the investigator may choose to hospitalize the subject for the duration of 
the treatment period.
The cause of death of a subject in a study within 12 weeks, whether or not the event is expected 
or associated with the study drug, is considered an SAE.
12.3.3.
Pregnancy
All initial reports of pregnancy in female subjects or partners of male subjects 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 SAE Form. Any subject who becomes pregnant during the study 
must be promptly withdrawn from the study and discontinue further study treatment.
Because the effect of the study drug on sperm is unknown, pregnancies in partners of male subjects 
included in the study will be reported as noted above.
Follow-up information regarding the outcome of the pregnancy and any postnatal sequelae in the 
infant will be required.
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12.3.4.
Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first administration of 
study agent(s) in subjects participating in this clinical study must be reported by the investigator 
according to the procedures in Section 9.6. Investigators are also advised that active TB is 
considered a reportable disease in most countries. These events are to be considered serious only 
if they meet the definition of an SAE.
12.4.
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.
13.
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 subjects, 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.
13.1.
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 an SAE, the study-site personnel must report the PQC to the 
sponsor according to the SAE reporting timelines (refer to Section 12.3.2, Serious Adverse 
Events). A sample of the suspected product should be maintained for further investigation if 
requested by the sponsor.
13.2.
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.
14.
STUDY DRUG INFORMATION
14.1.
Physical Description of Study Drug(s)
14.1.1.
Guselkumab
The guselkumab supplied for this study is a sterile liquid for SC injection in a single-use PFS
assembled with the PFS-U. Each single-use PFS-U contains 100 mg (1 mL fill of liquid) 
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guselkumab in a 1 mL glass syringe with a 27 gauge, ½-inch fixed needle and a latex-free rigid 
needle shield. No preservatives are present. The guselkumab solution should be essentially free 
of visible particulate matter. Guselkumab will be manufactured and provided under the 
responsibility of the sponsor. Refer to the Investigator's Brochure for a list of excipients.
Placebo is supplied as a sterile liquid for SC injection at a fill volume of 1.0 mL in a single-use 
PFS assembled with the PFS-U. Each PFS-U contains 10 mM L-histidine, 8.5% (w/v) sucrose, 
and 0.055% (w/v) polysorbate 80 at pH 5.8.
14.1.2.
Cosentyx (Secukinumab)
Commercial secukinumab (Cosentyx) will be supplied as an active comparator to the study sites. 
Details on secukinumab are available in the secukinumab (Cosentyx) package insert, and details 
regarding the secukinumab drug product for individual countries are available in the Site 
Investigational Product Procedures Manual.
14.2.
Packaging
The investigational supplies will be uniquely packaged to assure that they are appropriately 
managed throughout the supply chain process.
14.3.
Labeling
Study drug labels will contain information to meet the applicable regulatory requirements.
14.4.
Preparation, Handling, and Storage
14.4.1.
Guselkumab
Guselkumab and placebo for guselkumab will be supplied to the study sites. All guselkumab and 
placebo for guselkumab must be stored at controlled temperatures ranging from 36°F to 46°F
(2°C to 8°C) and protected from exposure to light. The sterile product does not contain 
preservatives and is designed for single use only. Protection from light is not required during 
dose preparation or administration of guselkumab.
Further details regarding the preparation and storage of guselkumab and placebo will be 
provided in the Site Investigational Product Procedures Manual.
14.4.2.
Cosentyx (Secukinumab)
Cosentyx will be supplied to the sites. All Cosentyx must be stored in a refrigerator at 2ºC to 8ºC 
(36ºF to 46ºF). Keep the product in the original carton to protect from light until the time of use. 
Do not freeze. To avoid foaming do not shake. The sterile product does not contain preservatives 
and is designed for single use only. Before injection, remove Cosentyx prefilled syringe from the 
refrigerator and allow Cosentyx to reach room temperature (15 to 30 minutes) without removing 
the needle cap.
The removable cap of the Cosentyx PFS contains natural rubber latex and should not be handled 
by latex-sensitive individuals.
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Visually inspect Cosentyx for particulate matter and discoloration prior to administration. 
Cosentyx injection is a clear to slightly opalescent, colorless to slightly yellow solution. Do not 
use if the liquid contains visible particles, is discolored or cloudy. Cosentyx does not contain 
preservatives; therefore, administer the PFS within 1 hour after removal from the refrigerator. 
Discard any unused product remaining in the PFS.
14.5.
Drug Accountability
The investigator is responsible for ensuring that all study drug received at the site is inventoried 
and accounted for throughout the study. The study drug administered to the subject must be 
documented on the drug accountability form. All study drug will be stored and disposed of 
according to the sponsor's instructions. Study-site personnel must not combine contents of the 
study drug containers.
Study drug must be handled in strict accordance with the protocol and the container label, and 
must be stored at the study site in a limited-access area or in a locked cabinet under appropriate 
environmental conditions. Unused study drug must be available for verification by the sponsor's 
study site monitor during on-site monitoring visits. The return to the sponsor of unused study 
drug will be documented on the drug return form. When the study site is an authorized 
destruction unit and study drug supplies are destroyed on-site, this must also be documented on 
the drug return form.
Potentially hazardous materials such as used ampules, needles, syringes and vials containing 
hazardous liquids, should be disposed of immediately in a safe manner and therefore will not be 
retained for drug accountability purposes.
Study drug should be dispensed under the supervision of the investigator or a qualified member 
of the study-site personnel, or by a hospital/clinic pharmacist. Study drug will be supplied only 
to subjects participating in the study. Study drug may not be relabeled or reassigned for use by 
other subjects. The investigator agrees neither to dispense the study drug from, nor store it at, 
any site other than the study sites agreed upon with the sponsor.
15.
STUDY-SPECIFIC MATERIALS
The investigator will be provided with the following supplies:

Investigator's Brochure for guselkumab.

Package Insert/Summary of Product Characteristics for secukinumab.

Site Investigational Product Procedures Manual.

Laboratory Manual.

IWRS Manual.

Electronic Data Capture (eDC) Manual.

Electronic Device and User Manual.

Electronic Columbia-Suicide Severity Rating Scale.
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
Sample ICF.

Sample genetic research for ICF, as applicable.

ECG Manual.

Recruitment materials, as needed.

Biopsy Manual (for biopsy substudy sites only).
16.
ETHICAL ASPECTS
16.1.
Study-Specific Design Considerations
Potential subjects will be fully informed of the risks and requirements of the study and, during the 
study, subjects 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 subjects 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 is considered to be an acceptable amount of blood to be 
collected over this time period from the population in this study based upon the standard of the 
American Red Cross (1 pint/473 mL of blood for donation).
16.2.
Regulatory Ethics Compliance
16.2.1.
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 subjects. 
Compliance with this standard provides public assurance that the rights, safety, and well-being of 
study subjects are protected, consistent with the principles that originated in the Declaration of 
Helsinki, and that the study data are credible.
16.2.2.
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 subjects)

Investigator's Brochure (or equivalent information) and amendments/addenda

Sponsor-approved subject recruiting materials
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
Information on compensation for study-related injuries or payment to subjects 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 subjects

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 subjects, data or study conduct, unless required locally), the ICF, applicable 
recruiting materials, and subject 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 subjects, data or study conduct)

Revision(s) to ICF and any other written materials to be provided to subjects

If applicable, new or revised subject recruiting materials approved by the sponsor

Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable

New edition(s) of the Investigator's Brochure and amendments/addenda

Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)

Reports of AEs that are serious, unlisted/unexpected, and associated with the study drug

New information that may adversely affect the safety of the subjects or the conduct of the 
study

Deviations from or changes to the protocol to eliminate immediate hazards to the subjects

Report of deaths of subjects under the investigator's care

Notification if a new investigator is responsible for the study at the site

Development Safety Update Report and Line Listings, where applicable

Any other requirements of the IEC/IRB
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For all protocol amendments (excluding the ones that are purely administrative, with no
consequences for subjects, 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).
16.2.3.
Informed Consent
Each subject 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 subject 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 subjects the aims, methods, reasonably anticipated benefits, 
and potential hazards of the study, and any discomfort participation in the study may entail. 
Subjects 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 subject will receive for the treatment of his or her disease. Subjects 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 subject 
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 subject, to the extent permitted by the applicable law(s) or regulations. By 
signing the ICF the subject is authorizing such access. It also denotes that the subject agrees to 
allow his or her study physician to recontact the subject for the purpose of obtaining consent for 
additional safety evaluations, and subsequent disease-related treatments, if needed. The 
physician may also recontact the subject for the purpose of obtaining consent to collect
information about his or her survival status.
The subject 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 subject's personally dated signature. After having obtained the consent, a copy of 
the ICF must be given to the subject.
Subjects 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 subject 
will be asked to sign and personally date a separate ICF indicating agreement to participate in the 
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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 subject.
16.2.4.
Privacy of Personal Data
The collection and processing of personal data from subjects 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 subjects confidential.
The informed consent obtained from the subject 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 subject has the right to request through the investigator access to his or her personal data and 
the right to request rectification of any data that are not correct or complete. Reasonable steps 
will be taken to respond to such a request, taking into consideration the nature of the request, the 
conditions of the study, and the applicable laws and regulations.
Exploratory DNA and biomarker research is not conducted under standards appropriate for the 
return of data to subjects. In addition, the sponsor cannot make decisions as to the significance of 
any findings resulting from exploratory research. Therefore, exploratory research data will not be 
returned to subjects 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.
16.2.5.
Long-Term Retention of Samples for Additional Future Research
Samples collected in this study may be stored for up to 15 years (or according to local 
regulations) for additional research. Samples will only be used to understand guselkumab and 
co-medications in the protocol, if applicable, to understand plaque-type psoriasis, to understand 
differential drug responders, and to develop tests/assays related to guselkumab
and 
co-medications in the protocol, if applicable and plaque-type 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. Subjects may withdraw their consent for their samples to be 
stored for research (refer to Section 10.3, Withdrawal From the Use of Samples in Future 
Research).
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16.2.6.
Country Selection
This study will only be conducted in those countries where the intent is to launch or otherwise 
help ensure access to the developed product if the need for the product persists, unless explicitly 
addressed as a specific ethical consideration in Section 16.1, Study-Specific Design 
Considerations. Only countries where secukinumab is approved for use in psoriasis will be 
involved in this study.
17.
ADMINISTRATIVE REQUIREMENTS
17.1.
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 subjects, in which case the 
amendment must be promptly submitted to the IEC/IRB and relevant competent authority. 
Documentation of amendment approval by the investigator and IEC/IRB must be provided to the 
sponsor. When the change(s) involves only logistic or administrative aspects of the study, the 
IEC/IRB (where required) only needs to be notified.
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 eCRF and source documents will reflect any departure from the protocol, and the source 
documents will describe this departure and the circumstances requiring it.
17.2.
Regulatory Documentation
17.2.1.
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.
17.2.2.
Required Prestudy Documentation
The following documents must be provided to the sponsor before shipment of study drug 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, subject compensation programs. This approval must clearly identify the specific 
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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 subject:

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
17.3.
Subject Identification, Enrollment, and Screening Logs
The investigator agrees to complete a subject identification and enrollment log to permit easy 
identification of each subject during and after the study. This document will be reviewed by the 
sponsor study-site contact for completeness.
The subject identification and enrollment log will be treated as confidential and will be filed by 
the investigator in the study file. To ensure subject confidentiality, no copy will be made. All 
reports and communications relating to the study will identify subjects by subject identification
and date of birth. In cases where the subject is not randomized into the study, the date seen and 
date of birth will be used.
The investigator must also complete a subject screening log, which reports on all subjects who 
were seen to determine eligibility for inclusion in the study.
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17.4.
Source Documentation
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: 
subject 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; drug 
receipt/dispensing/return records; study drug administration information; and date of study 
completion and reason for early discontinuation of study drug 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 equivalent document).
Investigator-completed efficacy evaluations (IGA, PASI) and the subject-completed eC-SSRS 
will be recorded directly into an electronic tablet device during the visit at the study site. These 
data will be considered electronic source documentation.
The minimum source documentation requirements for Section 4.1, Inclusion Criteria and 
Section 4.2, 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 subject interview or other protocol required assessment (eg, physical examination, 
laboratory assessment) and documented in the source documents.
17.5.
Case Report Form Completion
Case report forms are prepared and provided by the sponsor for each subject in electronic format.
All eCRF entries, corrections, and alterations must be made by the investigator or authorized 
study-site personnel. The investigator must verify that all data entries in the eCRF are accurate 
and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
electronic eCRF, if applicable. Study-specific data will be transmitted in a secure manner to the 
sponsor.
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Worksheets may be used for the capture of some data to facilitate completion of the eCRF. Any 
such worksheets will become part of the subject's source documents. Data must be entered into 
eCRF in English. The eCRF must be completed as soon as possible after a subject visit and the 
forms should be available for review at the next scheduled monitoring visit.
All subjective measurements (eg, pain scale information or other questionnaires) will be 
completed by the same individual who made the initial baseline determinations whenever 
possible.
If necessary, queries will be generated in the eDC tool. If corrections to an eCRF are needed 
after the initial entry into the eCRF, this can be done in either of the following ways:

Investigator and study-site personnel can make corrections in the eDC tool at their own 
initiative or as a response to an auto query (generated by the eDC tool).

Sponsor or sponsor delegate can generate a query for resolution by the investigator and 
study-site personnel.
17.6.
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 and direct transmission of 
efficacy and eC-SSRS data into the sponsor's data base. Written instructions will be provided for 
collection, handling, storage, and shipment of samples.
Guidelines for eCRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The sponsor will review eCRF for accuracy and completeness during on-
site monitoring visits and after transmission to the sponsor; any discrepancies will be resolved 
with the investigator or designee, as appropriate. After upload of the data into the study database 
they will be verified for accuracy and consistency with the data sources.
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all eCRF
and all source documents that support the data collected from each subject, 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 
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agreement with the sponsor. It is the responsibility of the sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will 
accept the responsibility. The sponsor must be notified in writing of the name and address of the 
new custodian. Under no circumstance shall the investigator relocate or dispose of any study 
documents before having obtained written approval from the sponsor.
If it becomes necessary for the sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such 
reports.
17.8.
Monitoring
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 eCRF
with the source documents
(eg, hospital/clinic/physician’s office medical records). At these visits, the monitor will compare 
data entered into the eCRF 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 eCRF are 
known to the sponsor and study-site personnel and are accessible for verification by the sponsor 
study-site contact. If electronic records are maintained at the study site, the method of 
verification must be discussed with the study-site personnel.
Direct access to source documents (medical records) must be allowed for the purpose of 
verifying that the recorded data are consistent with the original source data. Findings from this 
review will be discussed with the study-site personnel. The sponsor expects that, during 
monitoring visits, the relevant study-site personnel will be available, the source documents will 
be accessible, and a suitable environment will be provided for review of study-related 
documents. The monitor will meet with the investigator on a regular basis during the study to 
provide feedback on the study conduct.
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during 
these remote contacts, study-site personnel will be available to provide an update on the progress 
of the study at the site.
Central monitoring will take place for data identified by the sponsor as requiring central review.
17.9.
Study Completion/Termination
17.9.1.
Study Completion/End of Study
The study is considered completed with the last scheduled study assessment shown in the Time 
and Events Schedule for the last subject participating in the study. The final data from the study
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site will be sent to the sponsor (or designee) after completion of the final subject assessment at 
that study site, in the time frame specified in the Clinical Trial Agreement.
17.9.2.
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 subjects by the investigator

Discontinuation of further study drug development
17.10. 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. Subject 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.
17.11. Use of Information and Publication
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 genetic or exploratory biomarker research data, 
generated as a result of this study, are considered confidential and remain the sole property of the 
sponsor. The investigator agrees to maintain this information in confidence and use this 
information only to accomplish this study, and will not use it for other purposes without the 
sponsor's prior written consent.
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The investigator understands that the information developed in the study will be used by the 
sponsor in connection with the continued development of guselkumab, and thus may be 
disclosed as required to other clinical investigators or regulatory agencies. To permit the 
information derived from the clinical studies to be used, the investigator is obligated to provide 
the sponsor with all data obtained in the study.
The results of the study will be reported in a Clinical Study Report (CSR) generated by the 
sponsor and will contain data from all study sites that participated in the study as per protocol. 
Recruitment performance or specific expertise related to the nature and the key assessment 
parameters of the study will be used to determine a coordinating investigator. Results of genetic 
or exploratory biomarker analyses performed after the CSR has been issued will be reported in a 
separate report and will not require a revision of the CSR. Study subject identifiers will not be 
used in publication of results. Any work created in connection with performance of the study and 
contained in the data that can benefit from copyright protection (except any publication by the 
investigator as provided for below) shall be the property of the sponsor as author and owner of 
copyright in such work.
Consistent with Good Publication Practices and International Committee of Medical Journal 
Editors guidelines, the sponsor shall have the right to publish such primary (multicenter) data 
and information without approval from the investigator. The investigator has the right to publish 
study site-specific data after the primary data are published. If an investigator wishes to publish 
information from the study, a copy of the manuscript must be provided to the sponsor for review 
at least 60 days before submission for publication or presentation. Expedited reviews will be 
arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in 
writing, the investigator will withhold such publication for up to an additional 60 days to allow 
for filing of a patent application. In the event that issues arise regarding scientific integrity or 
regulatory compliance, the sponsor will review these issues with the investigator. The sponsor 
will not mandate modifications to scientific content and does not have the right to suppress 
information. For multicenter study designs and substudy approaches, secondary results generally 
should not be published before the primary endpoints of a study have been published. Similarly, 
investigators will recognize the integrity of a multicenter study by not submitting for publication 
data derived from the individual study site until the combined results from the completed study
have been submitted for publication, within 12 months of the availability of the final data (tables, 
listings, graphs), 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 Uniform Requirements for Manuscripts Submitted to 
Biomedical Journals, which state that the named authors must have made a significant 
contribution to the design of the study or analysis and interpretation of the data, provided critical 
review of the paper, and given final approval of the final version.
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.
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REFERENCES
1.
Blauvet A, Lebwohl M, Bissonnette R. IL-23/IL-17A dysfunction phenotypes inform possible clinical effects 
from anti-IL-17A therapies. J Invest Dermatol. 2015;135(8):1946-1953.
2.
Bowes J, Orozco G, Flynn E, et al. Confirmation of TNIP1 and IL23A as susceptibility loci for psoriatic 
arthritis. 70, no. 9 (2011): 1641-1644.
3.
Danesh MJ, Kimball AB. Brodalumab and suicidal ideation in the context of a recent economic crisis in the 
United States. J Am Acad Dermatol. 2016;74(1):190-192.
4.
Duerr RH, Taylor KD, Brant SR, et al. A genome-wide association study identifies IL23R as an inflammatory 
bowel disease gene. Science. 2006;314(5804):1461-1463.
5.
Fredriksson T, Pettersson U. Severe psoriasis - oral therapy with a new retinoid. Dermatologica.
1978;157:238–244.
6.
Langley RG, Elewski BE, Lebwohl M, et al; ERASURE Study Group; FIXTURE Study Group. Secukinumab 
in plaque psoriasis--results of two phase 3 trials. N Engl J Med. 2014;371(4):326-338. doi: 
10.1056/NEJMoa1314258.
7.
Liu Y, Helms C, Liao W, et al. A genome-wide association study of psoriasis and psoriatic arthritis identifies 
new disease loci. PLoS Genet. 2008;4(3):e1000041.
8.
Lowes MA, Bowcock AM, Krueger JG. Pathogenesis and therapy of psoriasis. Nature 2007;445(7130):866-
873.
9.
Lowes MA, Suarez-Farina M, Krueger JG. Immunology of Psoriasis.. Ann Rev Immunol. 2014;32: 227–255.
10.
Mundt, JC, Greist, JH, Jefferson, JW, et al. Prediction of suicidal behavior in clinical research by lifetime 
suicidal ideation and behavior ascertained by the electronic Columbia-Suicide Severity Rating Scale. J Clin 
Psych. 2013;74(9):887-893.
11.
Nair RP, Duffin KC, Helms C, et al. Genome-wide scan reveals association of psoriasis with IL-23 and NF κB 
pathways. Nat Genet. 2009;41(2):199-204.
12.
Ness-Schwickerath K, Jin C, Morita, C. Cytokine requirements for the differentiation and expansion of IL-
17A- and IL-22-producing hunab V(gamma)2V(delta) 2 T cells. J. Immun. 2010;184:7268-7280.
13.
O'Rielly DD, Rahman P. Genetics of susceptibility and treatment response in psoriatic arthritis. Nat Rev 
Rheumatol. 2011;7(12):718-732.
14.
Ouyang W, Kolls JK, Zheng Y. The biological functions of T helper 17 cell effector cytokines in 
inflammation. Immunity. 2008;28(4):454-467.
15.
Posner, K, Brown, GK, Stanley, B, et al. The Columbia-Suicide Severity Rating Scale: Initial validity and 
internal consistency findings from three multisite studies with adolescents and adults. Am J Psychiatry. 
2011;168(12):1266-1277.
16.
Revicki DA, Willian MK, Menter A, Saurat J-H, Harnam N, Kaul M. Relationship between clinical tesponse to 
therapy and health-related quality of life outcomes in patients with moderate to severe plaque psoriasis. 
Dermatology. 2008;216:260–270.
17.
Strober B, Papp KA, Lebwohl M, et al. Clinical meaningfulness of complete skin clearance in psoriasis. J Am 
Acad Dematol. 2016;75(1):77-82.
18.
Takeshita J, Callis Duffin K, Shin DB, et al. Patient-reported outcomes for psoriasis patients with clear versus 
almost clear skin in the clinical setting. J Am Acad Dematol. 2014;70:633-641.
19.
Tato CM, O'Shea JJ. Immunology: what does it mean to be just 17? Nature. 2006;441(7090):166-168.
20.
Thaçi D, Blauvelt A, Reich K, et al. Secukinumab is superior to ustekinumab in clearing skin of subjects with 
moderate to severe plaque psoriasis: CLEAR, a randomized controlled trial. J Am Acad Dematol. 
2015;73(3):400-409.
21.
Viswanathan HN, Chau D, Milmont CF, et al. Total skin clearance results in improvements in health-related
quality of life and reduced symptom severity among patients with moderate to severe psoriasis. Journal of 
Dermatological Treatment. 2015;26(3):235-239.
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Attachment 1: Investigator’s Global Assessment
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
Total Average = ( I + E + S) / 3
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.
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Attachment 2: 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. 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, trunk, upper extremities, and lower 
extremities, 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) are: 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, A = area,
h = head, t = trunk, u = upper extremities, and l = lower extremities
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Attachment 3: 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 subjects 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).
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 subject, 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 laboratory. The laboratory will perform an ELISA to quantify the amount of IFN-
present in the plasma using spectrophotometry and computer software analysis.
The laboratory will analyze and report results for each subject, and sites will be informed of the results. Subjects 
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 antituberculous 
treatment regimens for latent TB. If no local country guidelines for immunocompromised patients exist, US 
guidelines must be followed.
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In countries in which the QuantiFERON®-TB Gold test is not considered approved/registered, a tuberculin skin test 
is additionally required.
References
Barnes PF. Diagnosing latent tuberculosis infection: Turning glitter to gold [editorial]. Amer J Respir Crit Care 
Med. 2004;170:5-6.
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.
Cellestis. QuantiFERON-TB Gold clinicians guide and QuantiFERON-TB Gold In-Tube Method package insert. 
Downloaded from www.cellestis.com, February 2009.
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.
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.
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.
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.
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.
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.
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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Attachment 4: Tuberculin Skin Testing
Administering the Mantoux Tuberculin Skin Test
The Mantoux tuberculin skin test (CDC, 2000) is the standard method of identifying persons infected with 
Mycobacterium tuberculosis. Multiple puncture tests (Tine and Heaf) should not be used to determine whether a 
person is infected because the amount of tuberculin injected intradermally cannot be precisely controlled. Tuberculin 
skin testing is both safe and reliable throughout the course of pregnancy. The Mantoux tuberculin test is performed 
by placing an intradermal injection of 0.1 mL of tuberculin into the inner surface of the forearm. The test must be 
performed with tuberculin that has at least the same strength as either 5 tuberculin units (TU) of standard purified 
protein derivative (PPD)-S or 2 TU of PPD-RT 23, Statens Seruminstitut, as recommended by the World Health 
Organization. PPD strengths of 1 TU or 250 TU are not acceptable (Menzies, 2000). Using a disposable tuberculin 
syringe with the needle bevel facing upward, the injection should be made just beneath the surface of the skin. This 
should produce a discrete, pale elevation of the skin (a wheal) 6 mm to 10 mm in diameter. To prevent needle-stick 
injuries, needles should not be recapped, purposely bent or broken, removed from disposable syringes, or otherwise 
manipulated by hand. After they are used, disposable needles and syringes should be placed in puncture-resistant 
containers for disposal. Institutional guidelines regarding universal precautions for infection control (eg, the use of 
gloves) should be followed. A trained health care worker, preferably the investigator, should read the reaction to the 
Mantoux test 48 to 72 hours after the injection. Subjects should never be allowed to read their own tuberculin skin 
test results. If a subject fails to show up for the scheduled reading, a positive reaction may still be measurable up to 
1 week after testing. However, if a subject who fails to return within 72 hours has a negative test, tuberculin testing 
should be repeated. The area of induration (palpable raised hardened area) around the site of injection is the reaction 
to tuberculin. For standardization, the diameter of the induration should be measured transversely (perpendicular) to 
the long axis of the forearm. Erythema (redness) should not be measured. All reactions should be recorded in 
millimeters, even those classified as negative.
Interpreting the Tuberculin Skin Test Results
In the US and many other countries, the most conservative definition of positivity for the tuberculin skin test is 
reserved for immunocompromised patients, and this definition is to be applied in this study to maximize the 
likelihood of detecting latent TB, even though the subjects may not be immunocompromised at baseline.
In the US and Canada, an induration of 5 mm or greater in response to the intradermal tuberculin skin test is 
considered to be a positive result and evidence for either latent or active TB.
In countries outside the US and Canada, country-specific guidelines for immunocompromised patients should be 
consulted for the interpretation of tuberculin skin test results. If no local country guidelines for 
immunocompromised patients exist, US guidelines must be followed.
Treatment of Latent Tuberculosis
Local country guidelines for immunocompromised patients should be consulted for acceptable antituberculous 
treatment regimens for latent TB. If no local country guidelines for immunocompromised patients exist, US 
guidelines must be followed.
References
Centers for Disease Control and Prevention. Core curriculum on tuberculosis: What the clinician should know 
(Fourth Edition). Atlanta, GA: Department of Health and Human Services; Centers for Disease Control and 
Prevention; National Center for HIV, STD, and TB Prevention; Division of Tuberculosis Elimination; 2000:25-86.
Menzies RI. Tuberculin skin testing. In: Reichman LB, Hershfield ES (eds). Tuberculosis, a comprehensive 
international approach. 2nd ed. New York, NY: Marcel Dekker, Inc; 2000:279-322.
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Attachment 5: Hepatitis B Virus (HBV) Screening With HBV DNA Testing
Subjects must undergo screening for hepatitis B virus (HBV). At a minimum, this includes 
testing for HBsAg (HBV surface antigen), anti-HBs (HBV surface antibody), and anti-HBc total 
(HBV core antibody total):

Subjects who test negative for all HBV screening tests (ie, HBsAg-, anti-HBc-, and 
anti-HBs-) are eligible for this study.

Subjects who test negative for surface antigen (HBsAg-) and test positive for core 
antibody (anti-HBc+) and surface antibody (anti-HBs+) are eligible for this study.

Subjects who test positive only for surface antibody (anti-HBs+) are eligible for this 
study.

Subjects who test positive for surface antigen (HBsAg+) are NOT eligible for this study, 
regardless of the results of other hepatitis B tests.

Subjects who test positive only for core antibody (anti-HBc+) must undergo further 
testing for the presence of hepatitis B virus deoxyribonucleic acid (HBV DNA test). If 
the HBV DNA test is positive, the subject is NOT eligible for this study. If the HBV 
DNA test is negative, the subject is eligible for this study. In the event the HBV DNA 
test cannot be performed, the subject is NOT eligible for this study.
For subjects who are not eligible for this study due to HBV test results, consultation with a 
physician with expertise in the treatment of hepatitis B virus infection is recommended.
Eligibility based on hepatitis B virus test results
Hepatitis B test result
Action
Hepatitis B 
surface antigen
(HBsAg)
Hepatitis B 
surface antibody
(anti-HBs)
Hepatitis B core 
antibody
(anti-HBc total)
Include
—
—
—
—
+
—
—
+
+
Exclude
+
— or +
— or +
Require testing for presence 
HBV DNA*
—
—
+
* If HBV DNA is detectable, exclude from the clinical study. If HBV DNA testing cannot be 
performed, or there is evidence of chronic liver disease, exclude from the clinical study. 
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Attachment 6: Anticipated Events
Anticipated Event
An anticipated event is an AE (serious or non-serious) that commonly occurs as a consequence of the 
underlying disease or condition under investigation (disease related) or background regimen.
For the purposes of this study the event of psoriasis will be considered anticipated event.
Reporting of Anticipated Events
All AEs will be recorded in the eCRF regardless of whether considered to be anticipated events and will 
be reported to the sponsor as described in Section 12.3.1, All Adverse Events. Any anticipated event that 
meets SAE criteria will be reported to the sponsor as described in Section 12.3.2, Serious Adverse Events. 
These anticipated events are exempt from expedited reporting as individual single cases to Health 
Authorities. However, if based on an aggregate review, it is determined that an anticipated event is 
possibly related to study drug, the sponsor will report these events in an expedited manner.
Anticipated Event Review Committee (ARC)
An Anticipated Event Review Committee (ARC) will be established to perform reviews of pre-specified 
anticipated events at an aggregate level. The ARC is a safety committee within the sponsor’s organization 
that is independent of the sponsor’s study team. The ARC will meet to aid in the recommendation to the 
sponsor’s study team as to whether there is a reasonable possibility that an anticipated event is related to 
the study drug.
Statistical Analysis
Details of statistical analysis of anticipated events, including the frequency of review and threshold to 
trigger an aggregate analysis of anticipated events will be provided in a separate Anticipated Events 
Safety Monitoring Plan (ASMP).
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INVESTIGATOR AGREEMENT
NCT03090100

SAP_001.pdf: 
1
Approved, Date: 8 February 2018
Janssen Research & Development *
Statistical Analysis Plan
A Phase 3, Multicenter, Randomized, Double-blind Study Evaluating the Efficacy the 
Comparative Efficacy of CNTO 1959 (Guselkumab) and Secukinumab for the Treatment 
of Subjects with Moderate to Severe Plaque-Type Psoriasis
Protocol CNTO1959PSO3009; Phase 3
AMENDMENT 1
CNTO 1959  (Guselkumab)
Status:
Approved
Date:
8 February 2018
Prepared by:
Janssen Research & Development, LLC
Document No.: EDMS-ERI-142776698, 2.0
Compliance: The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement
The information in this document contains trade secrets and commercial information that are privileged or confidential and 
may not be disclosed unless such disclosure is required by applicable law or regulations. In any event, persons to whom the 
information is disclosed must be informed that the information is privileged or confidential and may not be further disclosed 
by them. These restrictions on disclosure will apply equally to all future information supplied to you that is indicated as 
privileged or confidential.
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CNTO 1959  (Guselkumab)
Statistical Analysis Plan CNTO1959PSO3009 Amendment 1
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Approved, Date: 8 February 2018
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 3
AMENDMENT HISTORY.............................................................................................................................. 4
ABBREVIATIONS ........................................................................................................................................ 5
1.
INTRODUCTION.................................................................................................................................. 6
1.1.
Trial Objectives ................................................................................................................................ 6
1.2.
Trial Design ...................................................................................................................................... 6
1.3.
Statistical Hypotheses for Trial Objectives....................................................................................... 7
1.4.
Sample Size Justification ................................................................................................................. 8
1.5.
Randomization and Blinding ............................................................................................................ 9
1.5.1.
Procedures for Randomization and Stratification ......................................................................... 9
1.5.2.
Blinding ....................................................................................................................................... 10
2.
GENERAL ANALYSIS DEFINITIONS .............................................................................................. 10
2.1.
Imputation Rules for Partial or Missing AE Dates.......................................................................... 10
2.2.
Visit Windows................................................................................................................................. 11
2.3.
Pooling Algorithm for Analysis Centers.......................................................................................... 12
2.4.
Analysis Sets.................................................................................................................................. 12
2.4.1.
Efficacy Analysis Set .................................................................................................................. 12
2.4.1.1.
Full Analysis Set ...................................................................................................................... 12
2.4.1.2.
Per Protocol Analysis Set........................................................................................................ 12
2.4.2.
Safety Analysis Set..................................................................................................................... 14
2.4.3.
Pharmacokinetics Analysis Set .................................................................................................. 14
2.4.4.
Immunogenicity Analysis Set...................................................................................................... 14
2.5.
Definition of Subgroups.................................................................................................................. 14
2.6.
Statistical Methods......................................................................................................................... 15
2.6.1.
Study Day ................................................................................................................................... 15
2.6.2.
Baseline ...................................................................................................................................... 16
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW....................................... 16
4.
SUBJECT INFORMATION................................................................................................................ 16
4.1.
Demographics and Baseline Characteristics ................................................................................. 16
4.1.1.
Demographics............................................................................................................................. 16
4.1.2.
Baseline Characteristics ............................................................................................................. 17
4.2.
Disposition Information................................................................................................................... 17
4.3.
Treatment Compliance................................................................................................................... 18
4.4.
Extent of Exposure......................................................................................................................... 18
4.5.
Protocol Deviations ........................................................................................................................ 18
4.6.
Prior and Concomitant Medications ............................................................................................... 19
5.
EFFICACY ......................................................................................................................................... 19
5.1.
Analysis Specifications................................................................................................................... 19
5.1.1.
Level of Significance................................................................................................................... 19
5.1.1.1.
Multiplicity Adjustment for Testing Procedures ....................................................................... 19
5.1.2.
Definition of the Efficacy Endpoints and Calculation of the Efficacy Instruments ...................... 20
5.1.2.1.
Investigator’s Global Assessment ........................................................................................... 20
5.1.2.2.
Psoriasis Area and Severity Index .......................................................................................... 21
5.1.3.
Data Handling Rules................................................................................................................... 21
5.1.3.1.
Treatment Failure Criteria........................................................................................................ 21
5.1.3.2.
Treatment Failure Rules .......................................................................................................... 22
5.1.3.3.
Missing Data Imputation.......................................................................................................... 22
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Statistical Analysis Plan CNTO1959PSO3009 Amendment 1
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5.2.
Primary Efficacy Endpoint(s).......................................................................................................... 22
5.2.1.
Definition..................................................................................................................................... 22
5.2.2.
Estimand..................................................................................................................................... 22
5.2.3.
Analysis Methods........................................................................................................................ 23
5.2.4.
Data Handling ............................................................................................................................. 24
5.2.5.
Sensitivity Analysis ..................................................................................................................... 24
5.2.6.
Subgroup Analysis...................................................................................................................... 25
5.2.7.
Per Protocol Analyses ................................................................................................................ 25
5.3.
Major Secondary Endpoints........................................................................................................... 25
5.3.1.
Definition..................................................................................................................................... 25
5.3.2.
Analysis Methods........................................................................................................................ 25
5.3.3.
Data Handling ............................................................................................................................. 26
5.4.
Other Efficacy Variable(s) .............................................................................................................. 26
5.4.1.
Definition..................................................................................................................................... 27
5.4.2.
Analysis Methods........................................................................................................................ 27
5.4.2.1.
Analyses Related to IGA ......................................................................................................... 27
5.4.2.2.
Analyses Related to PASI ....................................................................................................... 27
5.4.3.
Data Handling ............................................................................................................................. 28
6.
SAFETY............................................................................................................................................. 28
6.1.
Adverse Events .............................................................................................................................. 29
6.2.
Clinical Laboratory Tests................................................................................................................ 30
6.3.
Vital Signs and Physical Examination Findings ............................................................................. 30
6.4.
Electrocardiogram.......................................................................................................................... 30
6.5.
Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) ................................................... 31
7.
PHARMACOKINETICS/IMMUNOGENICITY.................................................................................... 32
7.1.
Pharmacokinetics........................................................................................................................... 32
7.2.
Immunogenicity (Antibodies to Guselkumab) ................................................................................ 33
REFERENCES............................................................................................................................................ 34
ATTACHMENT ........................................................................................................................................... 35
LIST OF IN-TEXT TABLES AND FIGURES 
TABLES
Table 1:
Power to Detect a Treatment Effect Based on Different Proportions of Subjects 
Achieving the Primary Endpoint PASI 90 at Week 48 and the Major Secondary 
Endpoint PASI 100 at Week 48 .................................................................................................. 9
Table 2:
Demographic Variables............................................................................................................. 17
FIGURES
Figure 1:
Schematic Overview of the Study............................................................................................... 7
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Statistical Analysis Plan CNTO1959PSO3009 Amendment 1
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Approved, Date: 8 February 2018
AMENDMENT HISTORY
Summary of the Amendment 1
This statistical analysis plan (SAP) was amended to implement the following modifications to 
the original SAP:
1.
To remove the database lock (DBL) at Week 48 and the associated analyses specifically
related to Week 48 DBL since the protocol was amended to remove the Week 48 DBL.
2.
To clarify the per-protocol analysis set in terms of the definition of subjects who violated the 
specified exposure to study agent
3.
To modify the sensitivity analysis based on multiple imputation (MI) by first imputing 
intermittent missing data and then using regression method to impute the remaining missing 
data. In addition, to spell out details about the MI including number of imputations and 
seeds.
4.
To add sensitivity analyses for all the major secondary endpoints.
5.
To add the detailed investigator site pooling strategy given the enrollment has completed.
Additionally, minor grammatical, formatting, or spelling changes were made.
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Statistical Analysis Plan CNTO1959PSO3009 Amendment 1
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ABBREVIATIONS
AE
adverse event
CI
confidence interval
CRF
case report form
CSR
Clinical Study Report
DBL
Database lock
DC
Discontinuation
DMC
Data Monitoring Committee
ECG
Electrocardiogram
eCRF
electronic case report form
eC-SSRS
Electronic Columbia-Suicide Severity Rating Scale
FDA
Food and Drug Administration
IgG1λ
immunoglobulin G1 lambda
IGA
Investigator’s Global Assessment
IWRS
interactive web response system
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
NAbs
neutralizing antibodies
NCI-CTCAE
National Cancer Institute-Common Terminology Criteria for Adverse Events
PASI
Psoriasis Area and Severity Index
PK
pharmacokinetic(s)
SAE
serious adverse event
SAP
Statistical Analysis Plan
SD
standard deviation
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1.
INTRODUCTION
This statistical analysis plan (SAP) contains definitions of analysis sets, derived variables, and 
statistical methods for the analysis of efficacy, safety and pharmacokinetics for the guselkumab 
(CNTO
1959) clinical study CNTO1959PSO3009. Guselkumab is a fully human 
immunoglobulin G1 lambda (IgG1λ) monoclonal antibody (mAb) that inhibits the biological 
activity of IL-23 and therefore has the potential for the treatment of psoriasis.
1.1.
Trial Objectives
Primary Objectives
The primary objective is to evaluate the efficacy of guselkumab compared with secukinumab for 
the treatment of subjects with moderate to severe plaque-type psoriasis.
Secondary Objectives
The secondary objectives are to evaluate:

The safety and tolerability of guselkumab in subjects with moderate to severe plaque-type 
psoriasis.

The PK and immunogenicity of guselkumab after subcutaneous (SC) administrations in 
subjects with moderate to severe plaque-type psoriasis.
1.2.
Trial Design
This is a Phase 3, randomized, double-blind, multicenter, active-comparator-controlled study in 
subjects with moderate to severe plaque-type psoriasis. The target population is adult men or 
women, with a diagnosis of plaque-type psoriasis (with or without PsA) for at least 6 months 
before the first administration of study drug. Subjects must have moderate to severe plaque-type 
psoriasis defined by IGA 3, PASI 12, and involved body surface area (BSA) 10%. Subjects 
must be candidates for either systemic therapy or phototherapy for psoriasis, and may have 
previously received some systemic therapies or phototherapy for psoriasis. Subjects with 
nonplaque forms of psoriasis (eg, erythrodermic, guttate, or pustular) or with drug-induced 
psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from beta blockers, calcium 
channel blockers, or lithium) are excluded. Subjects who have ever received guselkumab or 
secukinumab are also excluded.
Key features of study drug administration for each treatment group are outlined below.
Week 0 through Week 44 (Blinded Treatment Period)
As depicted in Figure 1, approximately 1,040 subjects who satisfy all inclusion and exclusion
criteria will be randomized in a 1:1 ratio to 1 of 2 treatment arms:

Group I (n=520): guselkumab 100 mg SC at Weeks 0, 4, 12, and q8w thereafter through 
Week 44.

Group II (n=520): secukinumab 300 mg SC at Weeks 0, 1, 2, 3, 4 and q4w thereafter 
through Week 44.
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CNTO 1959  (Guselkumab)
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After Week 44 through Week 56 (Follow-up Period)
The follow-up period will begin after Week 44 and extend through Week 56.
There is one database locks (DBL) in this study at Week 56.  The Sponsor, the investigators, 
subjects, and site monitors will be unblinded after the Week 56 DBL has occurred. The end of 
the study is defined as the timepoint when the last subject completes the Week 56 visit.
A diagram of the study design is provided in Figure 1.
Figure 1:
Schematic Overview of the Study
1.3.
Statistical Hypotheses for Trial Objectives
The proposed randomized, blinded, two-active-arm trial will evaluate the relative performance of
guselkumab and secukinumab utilizing a comprehensive battery of endpoints (eg, PASI 75, 90 ,
and 100) at various timepoints (eg, Week 12 and Week 48) using rigorous statistical 
methodology to control for multiplicity.
While the ultimate goal of the trial is to demonstrate that the efficacy of guselkumab is superior 
to secukinumab for PASI 90 at Week 48, initial testing for non-inferiority is included for this 
endpoint because the overall profile of guselkumab will likely be favorable compared with 
secukinumab (in terms of potential for increased compliance and lesser patient burden), even if 
final results only indicate the relative efficacy is no worse for this endpoint.
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Primary Hypothesis:
The primary hypotheses are that guselkumab treatment is non-inferior to secukinumab as 
assessed by the proportion of subjects achieving a PASI 90 response at Week 48 with a 
noninferiority margin of 10% and, once non-inferiority is established, that guselkumab is 
superior to secukinumab as assessed by the proportion of subjects achieving a PASI 90 response 
at Week 48.
Major secondary hypotheses are that guselkumab treatment is:

Non-inferior to secukinumab for the maintenance of a PASI 75 response as assessed by the 
proportion of subjects who achieve a PASI 75 response at both Week 12 and Week 48 with 
a non-inferiority margin of 10% and, once non-inferiority is established, that guselkumab is 
superior to secukinumab as assessed by the proportion of subjects who achieve a PASI 75 
response at both Week 12 and Week 48.

Non-inferior to secukinumab at Week 12 as assessed by the proportion of subjects who 
achieve PASI 90 at Week 12 with a non-inferiority margin of 10%.

Non-inferior to secukinumab at Week 12 as assessed by the proportion of subjects who 
achieve PASI 75 at Week 12 with a non-inferiority margin of 10%.

Non-inferior to secukinumab at Week 48 as assessed by the proportion of subjects who 
achieve PASI 100 at Week 48 with a non-inferiority margin of 10% and, once noninferiority 
is established, that guselkumab is superior to secukinumab as assessed by the proportion of 
subjects who achieve a PASI 100 response at Week 48.

Non-inferior to secukinumab at Week 48 as assessed by the proportion of subjects who 
achieve an IGA score of cleared (0) at Week 48 with a non-inferiority margin of 10% and, 
once non-inferiority if established, that guselkumab is superior to secukinumab as assessed 
by the proportion of subjects who achieve an IGA score of cleared (0) at Week 48.

Non-inferiority test to secukinumab at Week 48 as assessed by the proportion of subjects 
who achieve an IGA score of cleared (0) or minimal (1) at Week 48 with a non-inferiority 
margin of 10% and, once non-inferiority if established, that guselkumab is superior to 
secukinumab as assessed by the proportion of subjects who achieve an IGA score of cleared 
(0) or minimal (1) at Week 48.
1.4.
Sample Size Justification
This study is designed to evaluate the efficacy of guselkumab 100 mg vs secukinumab 300 mg. 
The power and sample size were evaluated for the primary endpoint of PASI 90 at Week 48. In 
addition, since the response rate for guselkumab for PASI 100 at Week 48 is around 50% where 
the variability is the highest, the power and sample size were also evaluated for this major 
secondary endpoint. The assumptions for the sample size and power calculations were based on 
the data from the guselkumab CNTO1959PSO3001 and CNTO1959PSO3002 and the 
secukinumab Phase 3 studies (ERASURE and FIXTURE).1 The assumptions used are as
follows:
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Statistical Analysis Plan CNTO1959PSO3009 Amendment 1
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
The proportion of subjects who achieve a PASI 90 response at Week 48 is 70% to 80% in 
subjects receiving guselkumab and 60% to 70% for subjects receiving secukinumab.

The proportion of subjects who achieve a PASI 100 response at Week 48 is 44% to 51% in 
subjects receiving guselkumab and 35% to 40% for subjects receiving secukinumab.
Approximately 1,040 subjects are planned to be randomized in a 1:1 ratio to either guselkumab
100 mg (n=520) (administered at Weeks 0, 4, 12 and q8w thereafter until Week 44) or
secukinumab 300 mg (n=520) (administered at Weeks 0, 1, 2, 3, and 4 and q4w thereafter until
Week 44).
Based on the above assumptions, the planned sample size, and a noninferiority margin of 10%,
the power to demonstrate the non-inferiority for the primary endpoint of PASI 90 at Week 48
and the major secondary endpoint of PASI 100 at Week 48 will be > 99%.
Table 1 provides the power for detecting a treatment difference (superiority of guselkumab over
secukinumab) under varying assumptions at a significance level of 0.05 for the primary endpoint
PASI 90 at Week 48 and the major secondary endpoint of PASI 100 at Week 48.
Table 1:
Power to Detect a Treatment Effect Based on Different Proportions of Subjects Achieving the 
Primary Endpoint PASI 90 at Week 48 and the Major Secondary Endpoint PASI 100 at 
Week 48
Primary Endpoint
PASI 90 at Week 48
Secukinumab 300 mg (n=520)
Guselkumab 100 mg (n=520)
60%
70%
92%
75%
>99%
65%
75%
94%
80%
>99%
70%
80%
96%
Selected Major Secondary Endpoint
PASI 100 at Week 48
35%
44%
84%
45%
91%
46%
95%
40%
49%
83%
50%
90%
51%
95%
PASI = Psoriasis Area and Severity Index.
1.5.
Randomization and Blinding
1.5.1.
Procedures for Randomization and Stratification
Central randomization will be implemented in this study. Subjects will be randomly assigned to
1 of 2 treatment groups based on a computer-generated randomization schedule prepared before
the study under the supervision of the sponsor. The randomization will be balanced by using 
randomly permuted blocks and will be stratified by study site. The interactive web response 
system (IWRS) will assign a unique treatment code, which will dictate the treatment assignment 
and matching study drug kit for the subject. The requestor must use his or her own user 
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identification and personal identification number when contacting the IWRS, and will then give 
the relevant subject details to uniquely identify the subject.
1.5.2.
Blinding
The investigator will not be provided with randomization codes. The codes will be maintained
within the IWRS, which has the functionality to allow the investigator to break the blind for an
individual subject.
Data that may potentially unblind the treatment assignment (eg, treatment allocation, study drug
preparation/accountability data [including unblinded personnel], and administration of study
drug (see details in Section 6 of the protocol) will be handled with special care to ensure that the 
integrity of the blind is maintained and the potential for bias is minimized. This can include 
making special provisions, such as segregating the data in question from view by the 
investigators, clinical team, or others as appropriate until the time of DBL and unblinding.
Under normal circumstances, the blind should not be broken for subjects, investigators, or site
monitors until the Week 56 database is locked and finalized. Otherwise, the blind should be
broken only if specific emergency treatment/course of action would be dictated by knowing the
treatment status of the subject. In such cases, the investigator may in an emergency determine the
identity of the treatment by contacting the IWRS. It is recommended that the investigator contact
the sponsor or its designee if possible to discuss the particular situation, before breaking the
blind. Telephone contact with the sponsor or its designee will be available 24 hours per day,
7 days per week. In the event the blind is broken, the sponsor must be informed as soon as
possible. The date and reason for the unblinding must be documented by the IWRS, in the
appropriate section of the electronic case report form (eCRF), and in the source document. The
documentation received from the IWRS indicating the code break must be retained with the 
subject's source documents in a secure manner.
Subjects who have had their treatment assignment unblinded should continue to return for
scheduled evaluations. The decision to continue or discontinue study treatment for these subjects
will be based upon consultation of the investigator with the medical monitor.
2.
GENERAL ANALYSIS DEFINITIONS
This analysis plan provides the general analysis definitions and describes the planned subject
information, efficacy, safety, pharmacokinetics, and antibody analyses for the two planned
DBLs.
2.1.
Imputation Rules for Partial or Missing AE Dates
Partial AE onset dates will be imputed as follows:

If the onset date of an adverse event is missing day only, it will be set to:

First day of the month that the AE occurred, if month/year of the onset of AE is 
different than the month/year of the study agent start 
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
The day of study agent start, if the month/year of the onset of AE is the same as 
month/year of the study agent start date and month/year of the AE resolution date is 
different

The day of study agent start or day of AE resolution date, whichever is the earliest, if 
month/year of the onset of AE and month/year of the study agent start date and 
month/year of the AE resolution date are same

If the onset date of an adverse event is missing both day and month, it will be set to the 
earliest of:

January 1 of the year of onset, as long as this date is on or after the study agent start 
date 

Month and day of the study agent start date, if this date is in the same year that the AE 
occurred

Last day of the year if the year of the AE onset is prior to the year of the study agent 
start date, 

The AE resolution date.

Completely missing onset dates will not be imputed.
Partial AE resolution dates not marked as ongoing will be imputed as follows:

If the resolution date of an adverse event is missing day only, it will be set to the earliest of 
the last day of the month of occurrence of resolution or the date of death, if the death 
occurred in that month.

If the resolution date of an adverse event is missing both day and month, it will be set to the 
earliest of December 31 of the year or the day and month of the date of death, if the death 
occurred in that year.
Completely missing resolution dates will not be imputed.
2.2.
Visit Windows
Nominal visits will be used for all by-visit analyses in the study unless otherwise specified, 
regardless of the scheduled visit window. The study visits scheduled should occur at the times 
delineated in the Time and Events Schedule of the protocol. From Weeks 0 to 4 it is expected 
that all subjects will attend visits within a range of ± 3 days. After Week 4 and through Week 44, 
it is expected that all visits will occur within a range of ± 7 days. Any visits outside of these 
ranges should be discussed with the sponsor. If a study visit occurs outside the specified visit 
window, the subject should then resume his or her normal dose schedule relative to the baseline 
visit (Week 0) as soon as possible. All other follow-up study visits should occur within ± 14 days 
of the scheduled study visit. Any out-of-range visit should be documented in the subject’s source 
notes.
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2.3.
Pooling Algorithm for Analysis Centers
For efficacy analyses, investigator sites may be pooled as a stratification factor if there are sites 
with less than 10 subjects randomized. Sites with small number of subjects randomized will be 
pooled with the sites with larger number of randomized subjects by similar region/location when 
appropriate, so the number of subjects within the aggregated sites is at least 10. Note that site 
size and geography were considered when aggregating site sizes. Specific pooling strategy can 
be found in Attachment 1. 
2.4.
Analysis Sets
2.4.1.
Efficacy Analysis Set
2.4.1.1.
Full Analysis Set
For the efficacy analyses in this study, the full analysis set (FAS) will be used according to 
subjects’ assigned treatment to which they were randomized, regardless of the treatment they 
actually received. The FAS includes all randomized subjects. The full analysis set will be used 
for all primary and secondary efficacy analyses. In addition, for endpoints that include a non-
inferiority test, analyses will also be performed using the per protocol analysis set as defined 
below.
2.4.1.2.
Per Protocol Analysis Set
The per protocol population includes subjects in full analysis set except those

who did not meet the inclusion criteria 3, 4 or 5 in the protocol as listed below:

Have a PASI 12 at screening and at baseline.

Have an IGA 3 at screening and at baseline.

Have an involved BSA 10% at screening and at baseline.

who violated the exclusion diagnosis criteria 7 or 8:

Has a nonplaque form of psoriasis (eg, erythrodermic, guttate, or pustular).

Has current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of 
psoriasis from beta blockers, calcium channel blockers, or lithium).

who violated the concomitant or previous psoriasis medications or therapies-related 
exclusion criteria (12, 13, and 15 through 22) as listed below:

Has previously received guselkumab or secukinumab.

Has any contraindications to the use of secukinumab per local prescribing information.

Has received any anti-tumor necrosis factor α biologic therapy within 3 months before
the first administration of study drug.
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
Has received any therapeutic agent directly targeted to IL-12, IL-17A, IL-17R, or IL-23 
within 6 months of the first administration of study drug (including but not limited to 
ustekinumab, tildrakizumab [MK3222], risankizumab [BI-655066], ixekizumab 
[LY2439821], or brodalumab [AMG 827]) with the exception of secukinumab (which is 
completely excluded).

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 study drug.

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 study drug.

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 
and 
analogues, 
psoralens,sulfasalazine, hydroxyurea, fumaric acid derivatives, herbal treatments, or 
traditional Taiwanese, Korean, or Chinese medicines) within 4 weeks of the first 
administration of study drug.

Has used topical medications/treatments that could affect psoriasis or IGA evaluations 
(including, but not limited to, corticosteroids, anthralin, calcipotriene, topical vitamin D 
derivatives, 
retinoids, 
tazarotene, 
methoxsalen, 
trimethylpsoralens, 
pimecrolimus,tacrolimus, or topical traditional Taiwanese, Korean, or Chinese 
medicines) within 2 weeks of the first administration of study drug.

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 
study drug.

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 study drug administration or 
is currently enrolled in another study using an investigational agent or procedure.

who did not complete the specified exposure to study agent as outline below

subjects randomized to guselkumab at Week 0 but did not receive all scheduled 
guselkumab administrations, received one or more extra guselkumab administrations, or 
received one or more secukinumab administrations prior to the specified time period for 
the endpoints (eg, Week 12 or Week 48).

subjects randomized to secukinumab at Week 0 but did not receive all scheduled
secukinumab administrations, received one or more extra secukinumab administrations,
or received one or more guselkumab administrations prior to the specified time period 
for the endpoints.
However, for those who did not complete the specified exposure to study agent as outline above, 
subjects who discontinued the study agent due to unsatisfactory therapeutic effect or an adverse 
event (AE) of worsening of psoriasis, or subjects who started prohibited medications and 
continued receiving study agents prior to the specified timepoint for the endpoints will be 
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included in the per protocol analysis and the treatment failure rules specified in Section 5.1.3.2
will apply.
Subjects who were excluded from the per protocol analyses will also be summarized.
2.4.2.
Safety Analysis Set
In contrast to the efficacy analysis set, safety analyses will be performed on the safety analysis 
set, which is defined as all randomized and treated subjects who received at least 1 injection of 
study agent (partial or complete) according to the actual treatment received during the study,
irrespective of the treatment assigned at randomization.  
2.4.3.
Pharmacokinetics Analysis Set
The PK analysis set is defined as subjects who received at least one injection of guselkumab and 
have at least one valid blood sample drawn for PK analysis.
2.4.4.
Immunogenicity Analysis Set
The immunogenicity analysis set is defined as all subjects who received at least one injection of 
guselkumab and have at least one appropriate sample collected post guselkumab administration 
for the detection of antibodies to guselkumab. 
In both PK and immunogenicity analyses, subjects will be analyzed according to the treatment 
they actually receive, regardless of the treatment they are randomized to.
2.5.
Definition of Subgroups
To evaluate the consistency of efficacy based on demographic characteristics, baseline disease 
characteristics, and psoriasis medication history, subgroup analyses will be performed for the 
primary endpoint, PASI 90, and the major secondary endpoints of PASI 100 and IGA score of 
cleared (0), all assessed at Week 48. The subgroups for subgroup analyses include the following:
Baseline demographics:

Sex (male, female)

Race 

Baseline Age (<45 years, 45 to <65 years, 65 years)

Baseline weight (90 kg, >90 kg) 

BMI (Normal [<25], Overweight [25 -<30], Obese [30])
Baseline disease characteristics:

Age at diagnosis (years) (<25, 25)

Psoriasis disease duration (years) (<15, 15)

Baseline PASI (<20, 20)

Baseline IGA (<4, =4)
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
Baseline BSA (<20%, 20%)

Psoriatic arthritis (Yes, No)
Psoriasis medication history:

Phototherapy (ultraviolet B light [UVB] or psoralen and ultraviolet A light therapy [PUVA]) 

Never used

Ever used

Non-biologic systemics (PUVA, MTX, cyclosporine, acitretin, apremilast, or tofacitinib)

Never used

Ever Used

Biologics (etanercept, infliximab, alefacept, efalizumab, ustekinumab, briakinumab, 
ixekizumab, brodalumab, adalimumab, tildrakizumab, or risankizumab)

Never used

Ever Used

Non-biologic systemics or biologics (as defined above)

Never used

Ever used

Anti-TNFα agent (etanercept, infliximab, adalimumab)

Never used

Ever used

IL-12/23 inhibitors (ustekinumab, briakinumab, tildrakizumab, or risankizumab)

Never used

Ever used

IL-17 inhibitors (ixekizumab, or brodalumab)

Never used

Ever used

Subjects who had an inadequate response to, were intolerant to, or had a contraindication to 
any of the following four biologic therapies: etanercept, infliximab, adalimumab or 
ustekinumab
2.6.
Statistical Methods
2.6.1.
Study Day
Study Day 1 refers to the first study agent administration date. The study day for an event is 
defined as:
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
Event date - (date of Study Day 1) +1, if event date is date of Day 1

Event date - date of Day 1, if event date < date of Day 1 
2.6.2.
Baseline
In general, the baseline measurement is defined as the closest measurement taken prior to or at 
the time of the first study agent administration date unless otherwise specified.
3.
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW
No formal interim analysis is planned for this study. There is no Data Monitoring Committee for 
this study.
4.
SUBJECT INFORMATION
Either the full analysis set or the safety analysis set will be used for the subject information 
analyses as specified below unless otherwise noted. The number of subjects in each analysis set 
will be summarized by treatment group and overall. In addition, the distribution of subjects by 
country, and site will be presented. 
Simple descriptive statistics, such as mean, median, standard deviation, interquartile range, 
maximum, and minimum for continuous variables, and counts and percentages for discrete 
variables will be used to summarize most data and no formal statistical analyses for treatment 
comparisons will be performed. In addition, subject listings will also be used to present the data.
4.1.
Demographics and Baseline Characteristics
4.1.1.
Demographics
Table 2 presents a list of the demographic variables that will be summarized by treatment group, 
and overall for the full analysis set.  
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Table 2:
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) (<= 90 kg, > 90 kg)
Height (cm)
Categorical Variables:
Age (<45 years, 45 to <65 years, and 65 years)  
Frequency distribution with the 
number and percentage of subjects 
in each category.
Sex (male, female)
Racea (American Indian or Alaska Native, Asian, Black or African 
American, Native Hawaiian or other Pacific Islander, White, Other, 
Multiple, Unknown, Not reported)
Ethnicity (Hispanic or Latino, Not Hispanic or Latino, Not Reported, 
Unknown)
BMI (Normal [<25], Overweight [25 -<30], Obese [30])
a
If multiple race categories are indicated, then Race is recorded as “Multiple.”
4.1.2.
Baseline Characteristics
Psoriasis baseline disease characteristics (ie, psoriasis disease duration [years], age at diagnosis 
[years], BSA [%], psoriatic arthritis, baseline IGA score, and baseline PASI score [0-72]) will be 
summarized by treatment group for the full analysis set.
4.2.
Disposition Information
Screened subjects will be summarized overall.
The number of subjects in the following disposition categories will be summarized by treatment 
group and overall:

Subjects randomized 

Subjects who received study agent

Subjects who completed the study

Subjects who discontinued study agent 

Reasons for discontinuation of study agent 

Subjects who terminated study prematurely

Reasons for termination of study
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The above categories will include summaries over the period of Week 44 (the last study agent 
administration) and Week 56 if appropriate.
Listings of subjects will be provided for the following categories:

Subjects who discontinued study agent

Subjects who terminated study prematurely

Subjects who were unblinded during the study period 

Subjects who were randomized yet did not receive study agent
4.3.
Treatment Compliance
Study agent compliance will be summarized descriptively through Week 44 for the full analysis 
set. Number of subjects by randomized treatment versus actual treatment will be presented in a 
summary table. 
4.4.
Extent of Exposure
The exposure data will be summarized through Week 44. The number and percentage of subjects 
who receive study agent will be summarized by treatment group for the safety analysis set.
Descriptive statistics will be presented for the following parameters:

Number of administrations

Cumulative total dose 
In addition, the study agent lots received by treatment, including matching placebo for active 
treatment will be summarized.
4.5.
Protocol Deviations
In general, the following list of major protocol deviations may have the potential to impact 
subjects’ rights, safety or well-being, or the integrity and/or result of the clinical trial. Subjects 
with major protocol deviations will be identified prior to database lock and will be summarized 
by category by treatment group through Week 56 for the full analysis set.

Entered but did not satisfy criteria

Developed withdrawal criteria but not withdrawn

Received a disallowed concomitant treatment

Received wrong treatment or incorrect dose

Other: to be defined in the major protocol deviation criteria document
A listing of subjects with major protocol deviations will also be provided by randomized 
treatment group.
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4.6.
Prior and Concomitant Medications
Subjects’ prior psoriasis medication history with topical agents, phototherapy, non-biologic 
systemic therapies, and biologic medications will be summarized by treatment group for the full 
analysis set. See Section 2.5 for list of medications in each category. In addition, reasons for 
which subjects discontinued previous systemic therapies including PUVA, methotrexate, 
cyclosporine, etanercept, infliximab, adalimumab and ustekinumab (contraindication, inadequate 
response, intolerance [ie, AEs], or other) will be summarized by randomized treatment group for 
the full analysis set.
The number of subjects who received concomitant treatment with a moisturizer for psoriasis will 
be summarized by randomized treatment group for the full analysis set.
Listings of subjects who received concomitant corticosteroids for indications other than psoriasis 
and/or psoriatic arthritis and of subjects who received concomitant prophylactic treatment for 
latent TB infection will be provided.
5.
EFFICACY
In general, efficacy data summaries will be provided by treatment group for the full analysis set. 
In order to compare the proportion of subjects responding to the two treatments, the Cochran-
Mantel-Haenszel chi-square test stratified by investigator site will be used. To test the 
noninferiority of guselkumab to secukinumab, a 1-sided (=0.025) Z-test2 with Mantel-Haenszel 
weights adjusted by investigator site after pooling will be used. All statistical testing will be 
performed 2-sided for superiority and 1-sided for non-inferiority.
Descriptive statistics, such as mean, median, standard deviation, minimum and maximum,
interquartile range for continuous variables, and counts and percentages for categorical variables 
will be used to summarize the data. Graphical data displays and subject listings may also be used 
to summarize the data.
5.1.
Analysis Specifications
5.1.1.
Level of Significance
All statistical procedures to test superiority hypotheses will be performed at a 2-sided
significance level of 0.05 and 1-sided at a significance level of 0.025 for non-inferiority. This 
study is designed to maintain an overall Type I error of 0.05 or less for the primary analysis and 
major secondary analyses. Nominal p-values will be reported for other secondary analyses.
5.1.1.1.
Multiplicity Adjustment for Testing Procedures
The primary endpoint in this study is the proportion of subjects who achieve a PASI 90 response
at Week 48. The primary analyses will be evaluated by a non-inferiority test with a non-
inferiority margin of 10% followed by a superiority test between the guselkumab 100 mg 
treatment group and the secukinumab 300 mg group. 
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In addition, there are 6 major secondary endpoints in this study to be compared between the 
guselkumab 100 mg group and the secukinumab 300 mg group:

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 75 response at both Week 12 and Week 48 will be performed. If 
non-inferiority is established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 90 response at Week 12 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 75 response at Week 12 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 100 response at Week 48 will be performed. If non-inferiority is 
established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving an IGA score of cleared (0) at Week 48 will be performed. If non-
inferiority is established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving an IGA score of cleared (0) or minimal (1) at Week 48 will be performed. 
If non-inferiority is established, the superiority test on this endpoint will be performed.
In order to control the overall Type 1 error rate, the primary analysis and major secondary
analyses will be tested in a fixed sequence as ordered above. That is, the first major secondary
analysis will be performed only if the primary endpoint is positive for both non-inferiority and
superiority, and each subsequent analysis will be performed only if the preceding analysis in the
sequence is positive.
5.1.2.
Definition of the Efficacy Endpoints and Calculation of the Efficacy 
Instruments
5.1.2.1.
Investigator’s Global Assessment 
The Investigator’s Global Assessment (IGA) documents the investigator’s assessment of the 
subject’s psoriasis at a given time point. Overall lesions are graded for induration, erythema, and 
scaling. The patient’s psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or 
severe (4).
Efficacy endpoints related to the IGA score are defined below:
IGA cleared responder 
Subjects who achieve an IGA score of cleared (0) will be considered IGA cleared responders.
IGA cleared or minimal responder
Subjects who achieve an IGA score of cleared (0) or minimal (1) will be considered IGA cleared 
or minimal responders.
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IGA mild or better responder
Subjects who achieve an IGA score of cleared (0), minimal (1), or mild (2) will be considered 
IGA mild or better responders.
5.1.2.2.
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. 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.
Efficacy endpoints related to the PASI score are defined below:
PASI 50 Responder
Subjects with 50% improvement in PASI from baseline will be considered PASI 50 responders.
PASI 75 Responder
Subjects with 75% improvement in PASI from baseline will be considered PASI 75 responders.
PASI 90 Responder
Subjects with 90% improvement in PASI from baseline will be considered PASI 90 responders.
PASI 100 Responder
Subjects with 100% improvement in PASI from baseline (ie, a PASI score of 0) will be 
considered PASI 100 responders.
5.1.3.
Data Handling Rules
The following treatment failure rules and data handling rules will be applied to the PASI and 
IGA related efficacy analyses in this study. 
5.1.3.1.
Treatment Failure Criteria
Subjects who discontinue study agent due to lack of efficacy, an adverse event (AE) of
worsening of psoriasis, or who started a protocol-prohibited medication/therapy during the study
that could affect their psoriasis are considered as treatment failures.
The protocol-prohibited medications/therapies include:
Topical Therapies:

Any topical therapies used for psoriasis (with the exception of topical moisturizers and 
shampoos containing tar or salicylic acid only)
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Phototherapy or Systemic Therapies:

Any systemic corticosteroid used for psoriatic arthritis or psoriasis with the exception of 
intra-articular corticosteroids.

Any other anti-psoriatic systemic therapy or biologic therapy.

Phototherapy of UVB or PUVA.

Any other phototherapy for psoriasis.
5.1.3.2.
Treatment Failure Rules
A subject who meets one or more of the treatment failure criteria specified in Section 5.1.3.1 will 
be considered a treatment failure from that point onward. The baseline values will be used for all 
directly measured endpoints regardless of the actual measurements. Zero will be assigned to 
improvement and percent improvement, and non-responder status will be assigned to binary 
response variables. 
Treatment failure is assumed to have occurred at the earlier of the following dates:  

Date of discontinuation (DC) of study treatment due to lack of efficacy or an AE of 
worsening of psoriasis or 

Date of initiation of a protocol-prohibited medication/therapy during the study that could 
improve psoriasis
5.1.3.3.
Missing Data Imputation
After the treatment failure rules are applied, the remaining missing data will be handled as 
follows for all of the efficacy analyses including the analyses at key visits (eg, Week 12 and 
Week 48) and over time:

Non-responder imputation will be applied for binary endpoints.

No imputation will be performed for continuous endpoints and the values will remain as 
missing. 
5.2.
Primary Efficacy Endpoint(s)
5.2.1.
Definition
The primary endpoint in this study is the proportion of subjects who achieve a PASI 90 response 
at Week 48. Refer to Section 5.1.2.2 for the definition of a PASI 90 responder.
5.2.2.
Estimand
Population: subjects with moderate-to-severe plaque psoriasis who are randomized and treated 
with guselkumab 100 mg or secukinumab 300 mg.
Endpoint: the proportion of subjects who achieve a PASI 90 response at Week 48
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Measure of Intervention: the effect of the initially randomized treatment regardless of what 
treatments are actually received. Non-responder status will be assigned if treatment failure 
criteria are met or data are missing.
5.2.3.
Analysis Methods
The primary endpoint will be compared between the guselkumab 100 mg group and the 
secukinumab 300 mg group. In the primary efficacy analysis, data from all randomized will be 
analyzed according to their assigned treatment group (ie, full analysis set). The number and 
proportion of subjects who achieve a PASI 90 response at Week 48 will be summarized for each 
treatment group respectively.
To address the primary efficacy objective, the proportion of subjects achieving a PASI 90
response at Week 48 will be evaluated with a non-inferiority test followed by a superiority test.
The following stepwise comparisons will be made to compare the efficacy of guselkumab to that
of secukinumab at Week 48:
a.
First a non-inferiority test with a non-inferiority margin of 10% will be conducted. A 
non-inferiority margin of 10% was chosen based on a minimal clinically meaningful
difference. This margin was also used as the non-inferiority margin for the ustekinumab
psoriasis study C0743T12 and the guselkumab psoriasis CNTO1959PSO3001 and
CNTO1959PSO3002 studies. In addition, in studies with biologic agents, placebo 
response rates for PASI 90 are consistently low (eg, <5% Cosentyx® SmPC, <5% 
STELARA SmPC, <5% guselkumab). Further, there is no placebo data at Week 48 for 
any clinical study of biologics. Therefore, the preservation of benefit for the Week 48 
endpoints is based on the historic response rates of the active comparator, 
ie, secukinumab. Based on the 2 placebo-controlled Phase 3 secukinumab studies 
(FIXTURE and ERASURE), a PASI 90 response was estimated to occur in 64.6% 
(95% confidence interval [CI]: 60.7%, 68.6%) of subjects receiving secukinumab 
300 mg at Week 48, whereby a 10% non-inferiority margin would preserve at least 80% 
of the secukinumab benefit.
To claim the non-inferiority of guselkumab to secukinumab, a 1-sided (=0.025) Z-test 
with Mantel-Haenszel (MH) weights adjusting for investigator site2 will be used. That 
is, the lower bound of the 2-sided 95% confidence interval (CI) of P1 – P2 must be
-10%, where P1 and P2 are the proportions of subjects achieving a PASI 90 response 
at Week 48 in the guselkumab 100 mg and the secukinumab 300 mg groups, 
respectively. The 2-sided 95% CI on the difference between guselkumab 100 mg and 
the secukinumab 300 mg groups will be calculated adjusting for investigator site after 
pooling using Mantel-Haenszel weights.2 If non-inferiority is not established, no further 
test will be conducted and Step b will be skipped.
b.
If non-inferiority is established in Step a, the superiority test of guselkumab to 
secukinumab using the CMH chi-square test stratified by investigator site after pooling 
will be performed at a significance level of 0.05. The proportion difference between 
guselkumab 100 mg and the secukinumab 300 mg groups and its 2-sided 95% CI will 
be provided based on normal approximation with Mantel-Haenszel weights adjusting 
for investigator site.
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If both the non-inferiority test and the superiority test are positive, the major secondary 
hypotheses comparing the guselkumab group and the secukinumab group will be tested 
sequentially. Otherwise, all remaining p-values will be considered nominal.
5.2.4.
Data Handling
Subjects who meet treatment failure criteria specified in Section 5.1.3.1 prior to Week 48 will be 
considered PASI 90 nonresponders at Week 48. In addition, subjects with a missing PASI score 
at Week 48 or who do not return for evaluation at Week 48 will be considered PASI 90 
nonresponders at Week 48.
5.2.5.
Sensitivity Analysis
To assess the robustness of the primary endpoint analysis results, the following three sensitivity 
analyses will be conducted.
Sensitivity Analysis 1
For subjects who have a missing PASI score at Week 48, the score will not be imputed. That is, 
the analysis will be performed using observed data, after applying treatment failure rules (as 
defined in Section 5.1.3.2).
Sensitivity Analysis 2
The second sensitivity analysis will be performed by using multiple imputations (MI), after 
applying treatment failure rules (as defined in Section 5.1.3.2). The intermittent missing PASI 
scores which include PASI scores at Week 0, Week 4 through Week 48 will be imputed using 
the Markov Chain Monte Carlo (MCMC) algorithm with 200 imputed data sets and seed = 123 
to make the missing data pattern monotone. The PASI 90 responses will then be derived based 
on the imputed score at or before Week 48. The remaining missing data for the PASI 90 response 
will be imputed with monotone logistic regression with treatment group, baseline PASI,
investigator site and PASI 90 response status starting from Week 4 in the model with one 
imputed dataset and seed = 789 to fill in the remaining missing items in each of the 200 copies of 
datasets. If the model fails to converge, investigator site will not be included as an explanatory 
variable. The proportion difference of PASI 90 response at Week 48 adjusted for investigator site 
(pooling) using Mantel-Haenszel weight between the guselkumab 100 mg and the secukinumab 
300 mg groups and its 95% CI combining multiple datasets will also be provided. In addition, the 
superiority test of guselkumab to secukinumab combining all the multiple imputation datasets
using the CMH chi-square test stratified by investigator site will be performed at a significance 
level of 0.05.
Sensitivity Analysis 3
A generalized linear model with logit link for binary repeated measurement data will also be
performed as a sensitivity analysis to compare the proportion of subjects responding to 
treatments at Week 48, after applying treatment failure rules (as defined in Section 5.1.3.2). The 
model will include baseline PASI score, treatment group, investigator site, visit starting from 
Week 4, the interaction of treatment group and visit, and the interaction of baseline PASI score 
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and visit as explanatory variables. If the model fails to converge, investigator site will not be 
included as an explanatory variable. The derived odds ratio on PASI 90 at Week 48 and its 95% 
CI will be provided. In addition, the proportion difference of PASI 90 response at Week 48
between the guselkumab 100 mg and the secukinumab 300 mg groups and its 95% CI will also 
be provided. For subjects who do not return for evaluation at any visit, the missing PASI score
will not be imputed.
5.2.6.
Subgroup Analysis
For each of the subgroups defined in Section 2.5, the proportion of subjects achieving a PASI 90 
response at Week 48 by treatment group will be summarized, respectively. Under the assumption 
of normal distributions, the 95% confidence interval without adjusting for investigator site of the
difference between the guselkumab 100 mg and the secukinumab 300 mg groups for the primary 
endpoint will also be provided. In addition, the proportion of PASI 90 responders at Week 48 by 
investigator site will be summarized.
5.2.7.
Per Protocol Analyses 
The primary analysis will also be performed on the per protocol analysis set defined in 
Section 2.4.1.2.
5.3.
Major Secondary Endpoints
The analyses for the major secondary endpoints will be performed in the order listed in 
Section 5.1.1.1.
The sections below outline the analysis methods and the data imputation rules for the major 
secondary analyses to be performed.
5.3.1.
Definition
There are 6 major secondary endpoints in this study to be compared between the guselkumab 
100 mg group and the secukinumab 300 mg group:

A PASI 75 response at both Week 12 and Week 48.

A PASI 90 response at Week 12.

A PASI 75 response at Week 12.

A PASI 100 response at Week 48.

An IGA score of cleared (0) at Week 48.

An IGA score of cleared (0) or minimal (1) at Week 48.
5.3.2.
Analysis Methods
The major secondary efficacy analyses described in this section will be performed using the full 
analysis set. For the major secondary analyses, all non-inferiority tests will be performed 1-sided 
(=0.025) with a non-inferiority margin of 10%. The margin of 10% was similarly determined as 
for the primary endpoint. All superiority statistical testing will be performed at a two-sided 
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significance level of 0.05. In addition, all the major secondary analyses will also be performed on 
the per protocol analysis set defined in Section 2.4.1.2. The same statistical methods used for the 
primary endpoint will also be used to analyze the major secondary endpoints. In addition, similar
Sensitivity Analyses 1 and 2 as performed for the primary endpoint will be performed for the 
major secondary endpoints. For the Sensitivity Analysis 2 for the endpoints of PASI 75 response 
and PASI 90 response at Week 12 where non-inferiority test only is specified for these 2 
endpoints, 1-side Wald test with Mantel-Haenszel weights adjusted by investigator site will be 
performed. The sensitivity analyses using MI will be performed similarly as that done for the 
primary endpoint including using the same seeds and same number of imputations. 
In addition, subgroup analyses for the IGA score of cleared (0) at Week 48 and PASI 100 at 
Week 48 will be performed similarly as for the primary endpoint.
The major secondary analyses are:

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 75 response at both Week 12 and Week 48 will be performed. If 
non-inferiority is established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 90 response at Week 12 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 75 response at Week 12 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 100 response at Week 48 will be performed. If non-inferiority is 
established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving an IGA score of cleared (0) at Week 48 will be performed. If non-
inferiority is established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving an IGA score of cleared (0) or minimal (1) at Week 48 will be performed. 
If non-inferiority is established, the superiority test on this endpoint will be performed.
5.3.3.
Data Handling
Unless otherwise specified, data handling rules specified in Section 5.1.3 will be applied to the 
major secondary analyses.
5.4.
Other Efficacy Variable(s)
Other secondary efficacy endpoints include the endpoints related to 

PASI 

IGA 
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5.4.1.
Definition
Refer to Section 5.1.2 for the definitions of the other efficacy endpoints described in the 
following section.
5.4.2.
Analysis Methods
Most of the other secondary efficacy analyses described in this section will be performed using 
the full analysis set. For the other secondary analyses, all non-inferiority tests will be performed 
1-sided (=0.025) with a non-inferiority margin of 10%. The margin of 10% was similarly 
determined as for the primary endpoint. All the non-inferiority analyses will also be repeated for 
the per protocol population (Section 2.4.1.2). All superiority statistical testing will be performed 
2-sided (=0.05). Nominal p-values will be presented. The same statistical methods used for the 
primary endpoint will also be used to analyze the secondary endpoints.
5.4.2.1.
Analyses Related to IGA

The non-inferiority test comparing guselkumab with secukinumab for the proportion of
subjects achieving an IGA score of cleared (0) or minimal (1) at Week 16 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of
subjects achieving an IGA score of cleared (0) or minimal (1) at Week 12 will be performed. 

The proportions of subjects who achieve an IGA score of cleared (0) response, IGA score of 
cleared (0) or minimal (1) response, and IGA score of mild or better (2) response over time 
through Week 56 will be summarized by treatment group. Line plots will be provided 
displaying the proportions and 95% CIs of subjects achieve an IGA score of cleared (0); and 
an IGA score of cleared (0) or minimal (1) through Week 48. The 95% CI will be calculated 
based on normal approximation.

The proportions of subjects achieving an IGA score of cleared (0) response, IGA score of 
cleared (0) or minimal (1) response, and IGA score of mild or better (2) response will also 
be summarized over time through Week through Week 56 by treatment group using 
observed data after applying treatment failure rules.
5.4.2.2.
Analyses Related to PASI

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 90 response at both Week 16 and Week 48 will be performed. If 
non-inferiority is established, the superiority test on this endpoint will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 75 response at Week 16 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 90 response at Week 16 will be performed.

The non-inferiority test comparing guselkumab with secukinumab for the proportion of 
subjects achieving a PASI 90 response at all 7 visits from Week 24 through Week 48 will be 
performed. If non-inferiority is established, the superiority test on this endpoint will be 
performed.
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
The proportions of subjects who achieve a PASI 75 response at Week 48 among PASI 75 
responders at Week 12 will be summarized by treatment group.

The proportions of subjects who achieve a PASI 90 response at Week 48 among PASI 90 
responders at Week 16 will be summarized by treatment group.

The proportions of PASI 100 responders, PASI 90 responders, PASI 75 responders, and 
PASI 50 responders will be summarized over time through Week 56 by treatment group. 
Line plots will be provided displaying proportions and 95% CIs of PASI 100 responders and 
PASI 90 responders through Week 48. The 95% CI will be calculated based on normal 
approximation.

The proportions of PASI 100 responders, PASI 90 responders, PASI 75 responders, and 
PASI 50 responders, will be summarized over time through Week 56 by treatment group 
using observed data after applying treatment failure rules.

The percent improvement from baseline in PASI will be summarized over time through 
Week 56 by treatment group.

The proportion of subjects who achieve 100% improvement, 90%, 75%, or 50% 
improvement from baseline in PASI component (induration, erythema, and scaling) and 
region component (head, trunk, upper extremities, and lower extremities) will be 
summarized at Week 48 by treatment group. 
5.4.3.
Data Handling
Data handling rules specified in Section 5.1.3 will be applied to all IGA related and PASI related 
analyses.
6.
SAFETY
Safety will be assessed by summarizing the incidence and type of AEs and examining changes in 
laboratory parameters (hematology and chemistry), vital signs and electrocardiogram (ECG)
parameters, and suicidal ideation and behavior as measured by the eC-SSRS (electronic 
Columbia-Suicide Severity Rating Scale).
In all the safety analysis, subjects who were randomized and received at least 1 (partial or 
complete) dose of study agent will be included and analyzed according to the treatment they 
actually received, regardless of the treatment they are randomized to. No formal hypothesis 
testing is planned. 
Depending on the safety data categories, the cumulative safety data will be analyzed through 
Week 56. Unless otherwise specified, tabular summaries of safety events for the study periods
are presented as follows:
o
Guselkumab 100 mg
o
Secukinumab 300 mg   
This allows between-group comparisons of safety between the guselkumab 100 mg group and 
the secukinumab 300 mg group based on the same follow-up period in each group.
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6.1.
Adverse Events
The verbatim terms used in the CRF by investigators to identify adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Any AE starting at or after 
the initial administration of study agent through the end of the trial is considered to be treatment 
emergent. If the event occurs on the day of the initial administration of study agent, and either 
event time or time of administration are missing, then the event will be assumed to be treatment 
emergent. If the event date is recorded as partial or completely missing, then the event will be 
considered to be treatment emergent unless it is known to be prior to the first administration of 
study agent based on partial onset date or resolution date. All reported treatment-emergent 
adverse events will be included in the analysis. For each adverse event, the number and 
percentage of subjects who experience at least 1 occurrence of the given event will be 
summarized by treatment group. In addition, event rate per 100 subject-years of follow-up for 
serious infections will be provided.
Summary tables will be provided for:

AEs

Serious AEs (SAEs)

AEs leading to discontinuation of study agent administration

AEs by severity

AEs by relationship to study agent

Infections

Serious infections

Infections treated with oral or parenteral antimicrobial treatment parenteral antibiotics 

Injection-site reactions

AEs of psoriasis
In addition to the summary tables, listings will be provided for subjects who:

Had SAEs

Had AEs leading to discontinuation of study agent administration

Had AEs of severe intensity

Had serum sickness-like reactions or anaphylactic reactions
Any unfavorable or unintended sign that occurs at the injection site is an injection site reaction 
and will be recorded as an injection site reaction by the investigator on the eCRF. An infection is 
defined as any AE that was recorded as an infection by the investigator on the eCRF. 
The treatment-emergent adverse events of psoriasis include any event of erythrodermic psoriasis, 
pustular psoriasis, guttate psoriasis, and worsening or exacerbation of psoriasis. Incidence of 
these events will be summarized.
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Since safety should be assessed relative to exposure and follow-up, most AE summary tables 
will include average weeks of follow-up and average number of study agent administrations for 
each treatment group.
6.2.
Clinical Laboratory Tests
All clinical laboratory reports will be displayed for the subjects included in the safety analysis 
set. The clinical laboratory parameters to be evaluated by the central laboratory include but are 
not limited to:

Hematology: hemoglobin, hematocrit, lymphocytes, neutrophils, platelets, red blood cell 
(RBC) count and white blood cell (WBC) count.

Chemistry: 
albumin, 
alkaline 
phosphatase, 
alanine 
aminotransferase, 
aspartate 
aminotransferase, total carbon dioxide (CO2), total bilirubin, blood urea nitrogen/urea, 
calcium, chloride, creatinine, glucose, potassium, total protein, sodium.
Box plots of laboratory measurements and change from baseline will be provided for the selected 
laboratory measurement. 
Applicable laboratory results will be graded according to National Cancer Institute’s Common 
Terminology Criteria for Adverse Events (NCI-CTCAE version 4.03). The worst NCI-CTCAE 
will be summarized by treatment group. 
For non-fasting glucose, the screening measurement will be used as the baseline measurement. A 
listing of subjects with 1 or more NCI-CTCAE toxicity grade 2 in hematology and clinical 
chemistry laboratory measurements will be provided.
6.3.
Vital Signs and Physical Examination Findings
Vital signs variables including heart rate, blood pressure (systolic and diastolic) will be measured 
at visits as per the schedule of events in the protocol. Descriptive statistics of the observed value 
and change from baseline of the vital signs will be summarized by treatment group.
Physical exam findings will not be analyzed except that they are captured as AEs and are 
included in the analyses of AEs.  
6.4.
Electrocardiogram
A supine 12-lead ECG will be performed at Weeks 0, 16, and 48, as specified in the Time and 
Events Schedule. Electrocardiogram data will be summarized by ECG parameter. Descriptive 
statistics will be calculated at baseline and for observed values and change from baseline at each 
scheduled time point.
In addition, summary of post-baseline ECG abnormalities different from Week 0 and a listing of 
subjects with any post-baseline ECG abnormalities different from Week 0 measurement will be 
provided.
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6.5.
Electronic Columbia-Suicide Severity Rating Scale (eC-SSRS)
The electronic Columbia-Suicide Severity Rating Scale (eC-SSRS) will be used as a screening 
tool to prospectively evaluate the potential of guselkumab to induce suicidal ideation and 
behavior. The eC-SSRS defines five subtypes of suicidal ideation and behavior in addition to 
self-injurious behavior with no suicidal intent, and is a fully-structured subject self-report 
questionnaire, including standardized questions, follow-up prompts, error handling routines, and 
scoring conventions. The Screening version of the eC-SSRS will be conducted at Screening
followed by the Since Last Visit version of the eC-SSRS at all other visits through Week 56
except at Week 1, 2, and 3.
The eC-SSRS will be performed during each evaluation visit according to the assessment 
schedule. The eC-SSRS will be performed at screening after signing informed consent, and 
before study agent administration, and as the first assessment for all post-baseline visits. The
baseline is defined as the most severe/maximum eC-SSRS score at either screening or Week 0.
In addition, potential suicide related adverse events including suicidal ideation, suicidal behavior
excluding completed suicide, and completed suicide will be identified by the investigators and 
collected in the eCRF. 
The following are eC-SSRS categories and have binary responses (yes/no). A “yes” response to 
any eC-SSRS category will be assigned a score as below:
Suicidal Ideation (1-5)
1 = Wish to be Dead
2 = Non-specific Active Suicidal Thoughts
3 = Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act
4 = Active Suicidal Ideation with Some Intent to Act, without Specific Plan
5 = Active Suicidal Ideation with Specific Plan and Intent
Suicidal Behavior (6-10)
6 = Preparatory Acts or Behavior
7 = Aborted Attempt
8 = Interrupted Attempt
9 = Actual Attempt (non-fatal)
10 = Completed Suicide
If no events qualify for a score of 1 to 10, a score of 0 will be assigned (0 = “Negative result [no 
suicidal ideation or behavior]”). Higher scores indicate greater severity.
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The summary for suicidal ideation and behavior will be based on the safety analysis set. Suicidal 
ideation and behavior will be summarized based on the most severe/maximum post baseline 
eC-SSRS outcome or AE of suicidal ideation, suicidal behavior excluding completed suicide, or 
completed suicide through Week 56. 
The maximum score assigned for each subject will also be summarized into one of three broad 
categories: No suicidal ideation or behavior, suicidal ideation, suicidal behavior. A shift table for 
change in eC-SSRS categories of no suicidal ideation or behavior, suicidal ideation, and suicidal 
behavior from baseline through Week 56 will be presented, where the baseline category is based 
on eC-SSRS score and the post baseline is based on eC-SSRS or AE data.
7.
PHARMACOKINETICS/IMMUNOGENICITY
7.1.
Pharmacokinetics
Blood samples for measuring serum guselkumab concentrations (pre-injection if it is injection 
visit) will be collected from all subjects at scheduled visits as indicated in the Time and Events
Schedule in the protocol.  
The PK analysis will be based on subjects who received at least 1 administration of guselkumab 
and had at least one evaluable serum sample. No imputation of missing concentration data will 
be performed, that is, data summaries will be based on the observed data.
All concentrations below the lowest quantifiable concentration in a sample or missing data will 
be labeled as such in the concentration data listings or Statistical Analysis Softwaredataset. 
Concentrations below the lowest quantifiable concentration in a sample will be treated as zero in 
the summary statistics. All subjects and samples excluded from the analysis will be clearly 
documented.
For analysis of serum guselkumab concentrations, descriptive statistics, including arithmetic 
mean, SD, median, interquartile range, minimum, and maximum will be calculated at each 
scheduled sampling time point for the guselkumab group. The PK concentration data may be 
displayed graphically.  
All summaries for serum guselkumab concentration will exclude data collected after subjects 
(1) did not receive a scheduled guselkumab administration within ± 14 days of the protocol 
scheduled dosing date, or those subjects who discontinued study agent, (2) received a partial, 
incorrect, or an additional guselkumab administration, (3) or have invalid sample data if the 
sample is taken after study agent administration or a concentration value falls outside the 
predefined range (±10*SD). Of note, serum guselkumab concentrations prior to the first of such 
events will be included in the summaries. 
If needed, a population PK analysis using a nonlinear mixed-effects modeling approach will be 
used to characterize the disposition characteristics of guselkumab in the current study. Data may 
be combined with those from pivotal Phase 3 studies (CNTO1959PSO3001 and 
CNTO1959PSO3002) to support a relevant structural model. Details will be given in a 
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population PK analysis plan and results of the population PK analysis will be presented in a 
separate technical report.
The effect of serum guselkumab concentrations on efficacy of guselkumab will be explored.
7.2.
Immunogenicity (Antibodies to Guselkumab)
Blood samples will be collected for the detection of antibodies to guselkumab at the specified 
visits as shown in the Time and Events schedule in the protocol. 
The antibodies to guselkumab analysis will be based on subjects who receive at least 1 dose of 
guselkumab and have at least one samples collected post guselkumab administration for the
detection of antibodies to guselkumab. No imputation of missing data will be performed, that is, 
data summaries will be based on the observed data.
The following analyses will be performed for guselkumab group as appropriate:

Summary of antibodies to guselkumab status (incidence of positive antibodies to 
guselkumab and antibody titers)

List of subjects positive for antibodies to guselkumab
In addition, the incidence of neutralizing antibodies (NAbs) to guselkumab will be summarized 
for subjects who are positive for antibodies to guselkumab and have samples evaluable for 
NAbs.
The effect of antibodies to guselkumab on PK, efficacy, and safety will be explored.
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REFERENCES
1.
Langley RG, Elewski BE, Lebwohl M, et al; ERASURE Study Group; FIXTURE Study Group. Secukinumab 
in plaque psoriasis - results of two phase 3 trials. N Engl J Med. 2014;371(4):326-338. 
2.
Miettinen O, Nurminen M. Comparative analysis of two rates. Statistics in Medicine. 1985; 4:213-226.
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ATTACHMENT
Attachment 1 Summary of Pooling Centers for Analysis
Site #
City
State/
Provin
ce
Country/ US
Region
Number of 
Subjects 
Randomized
Sites to be 
combined
Number 
of 
Subjects 
per 
Pooled 
Site
Site 
Group
Australia
5
15
Australia
2
Australia
3
Australia
5
Australia
7
14
Australia
7
Australia
3
11
Australia
8
Australia
1
18
Australia
17
Australia
13
Canada
7
15
Canada
8
Canada
10
Canada
10
Canada
10
Canada
15
Canada
9
19
Canada
5
Canada
5
Canada
10
Canada
24
Canada
25
Canada
10
Canada
10
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Site #
City
State/
Provin
ce
Country/ US
Region
Number of 
Subjects 
Randomized
Sites to be 
combined
Number 
of 
Subjects 
per 
Pooled 
Site
Site 
Group
Czech 
Republic
4
11
Czech 
Republic
7
Czech 
Republic
5
16
Czech 
Republic
7
Czech 
Republic
4
Czech 
Republic
10
17
Czech 
Republic
7
Czech 
Republic
11
Spain
4
13
Spain
6
Spain
3
Spain
8
17
Spain
4
Spain
4
Spain
1
Spain
3
12
Spain
6
Spain
3
Spain
12
Spain
8
14
Spain
3
Spain
3
France
11
France
16
France
8
13
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Site #
City
State/
Provin
ce
Country/ US
Region
Number of 
Subjects 
Randomized
Sites to be 
combined
Number 
of 
Subjects 
per 
Pooled 
Site
Site 
Group
France
2
France
3
France
18
Germany
7
19
Germany
12
Germany
5
15
Germany
4
Germany
6
Germany
9
22
Germany
5
Germany
8
Germany
4
15
Germany
8
Germany
3
Germany
7
13
Germany
6
Germany
15
Germany
10
Germany
5
13
Germany
8
Hungary
3
13
Hungary
9
Hungary
1
Hungary
6
16
Hungary
4
Hungary
6
Hungary
6
16
Hungary
7
NCT03090100


CNTO 1959  (Guselkumab)
Statistical Analysis Plan CNTO1959PSO3009 Amendment 1
38
Approved, Date: 8 February 2018
Site #
City
State/
Provin
ce
Country/ US
Region
Number of 
Subjects 
Randomized
Sites to be 
combined
Number 
of 
Subjects 
per 
Pooled 
Site
Site 
Group
Hungary
3
Poland
20
Poland
20
Poland
10
Poland
10
Poland
10
13
Poland
3
Poland
30
Poland
11
Poland
10
Poland
18
Poland
15
Poland
20
Poland
29
Poland
4
13
Poland
9
Poland
19
United 
States
2
10
United 
States
8
United 
States
1
10
United 
States
4
United 
States
5
United 
States
9
10
United 
States
1
United 
States
5
11
NCT03090100


CNTO 1959  (Guselkumab)
Statistical Analysis Plan CNTO1959PSO3009 Amendment 1
39
Approved, Date: 8 February 2018
Site #
City
State/
Provin
ce
Country/ US
Region
Number of 
Subjects 
Randomized
Sites to be 
combined
Number 
of 
Subjects 
per 
Pooled 
Site
Site 
Group
United 
States
6
United 
States
9
23
United 
States
2
United 
States
4
United 
States
8
United 
States
4
25
United 
States
21
United 
States
3
14
United 
States
11
United 
States
4
14
United 
States
5
United 
States
2
United 
States
3
United 
States
4
16
United 
States
8
United 
States
4
United 
States
5
15
United 
States
7
United 
States
3
United 
States
1
19
NCT03090100


CNTO 1959  (Guselkumab)
Statistical Analysis Plan CNTO1959PSO3009 Amendment 1
40
Approved, Date: 8 February 2018
Site #
City
State/
Provin
ce
Country/ US
Region
Number of 
Subjects 
Randomized
Sites to be 
combined
Number 
of 
Subjects 
per 
Pooled 
Site
Site 
Group
United 
States
3
United 
States
4
United 
States
5
United 
States
1
United 
States
5
United 
States
3
13
United 
States
10
United 
States
19
United 
States
5
20
United 
States
3
United 
States
10
United 
States
2
United 
States
9
14
United 
States
4
United 
States
1
NCT03090100