Conditions: Psoriasis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 880
Healthy volunteers: no

Brief summary:
The purpose of this study is to demonstrate that Super-Responders (SRe; defined as psoriasis participants who receive on-label guselkumab treatment until week 20 and respond with a Psoriasis Area and Severity Index score (PASI) = 0 at weeks 20 and 28) maintain control of disease until week 68 with prolonged treatment intervals of 16 weeks (guselkumab 100 mg every 16 weeks).

Detailed description:

Arms:
arm 1: Participants in group 1 (Part 1) will receive 100 milligram (mg) guselkumab subcutaneously (SC) at Weeks 0, 4, 12 and 20. arm 2: Eligible participants from Part 1 will continue to participate in Part 2. Participants (super responder \[SRe\]) with a Psoriasis Area and Severity Index (PASI) score = 0 at weeks 20 and 28 will be randomized to guselkumab 100 mg every 8 weeks (q8w) (group 2a) or guselkumab 100 mg q16w (group 2b), at weeks 28 to 60. Group 2b will receive placebo injection at weeks 28, 44 and 60 to keep the comparison double blind. Participants losing control of disease (PASI score \>5) during study Part 2 (until week 60), will enter the re-treatment arm (group 2d) and receive guselkumab 100mg q8w (at re-treatment week 0), followed by administration at re-treatment-weeks 8 and 16. arm 3: Participants (Non SRe) in group 2c with a PASI score greater than (\>) 0 at week 20 and/or 28 will continue to receive guselkumab 100 mg q8w until week 60. arm 4: Participants from groups 2a and 2b with a PASI score \<3 at week 68 will be included in Part 3 (group 3a and 3b) and be withdrawn from guselkumab. Study visits will be conducted every 12 weeks until week 220 (follow-up). Participants with fluctuating disease (PASI score greater than or equal to \[\>=\] 3) at week 68 or PASI \>5 (participants losing control of disease) at any visit during part 3 after week 68 will get an opportunity to enter the re-treatment-arm (group 3c) in which participants will receive three guselkumab injections of 100 mg q8w.

Interventions: intervention 1: Guselkumab intervention 2: Placebo Injection
Intervention descriptions: intervention 1: Participants will receive 100 mg guselkumab subcutaneously at Weeks 0, 4, 12 and 20 (group 1), at weeks 28, 36, 44, 52, 60 (group 2a and 2c), and at weeks 36 and 52 (group 2b). Group 2d and 3c are the re-treatment groups and will receive three injections after loss of disease control. intervention 2: Participants of group 2b will receive matching placebo injection subcutaneously at weeks 28, 44 and 60.

Protocol document:
Prot_000.pdf: 
Janssen-Cilag GmbH*
Clinical Protocol
A Phase 3b, Randomized, Double-blind, Parallel Group, Multicenter Study to Evaluate 
Further Therapeutic Strategies with Guselkumab in Patients with Moderate-to-Severe 
Plaque-Type Psoriasis
GUIDE
Protocol CNTO1959PSO3012; Phase 3b
AMENDMENT 5
TREMFYA®
(guselkumab)
*Janssen-Cilag is a regional organization that operates through different legal entities in various countries.
The legal entity acting as the Sponsor for Janssen-Cilag studies may vary, such as, but not limited to
Janssen-Cilag International NV or Janssen Pharmaceuticals NV. The term “Sponsor” is used throughout
the protocol to represent these various legal entities. The Sponsor is identified on the Contact Information
page that accompanies the protocol.
EudraCT NUMBER: 2018-001238-16
Status:
Approved
Date:
14 June 2021
Prepared by:
Janssen-Cilag GmbH, Germany
EDMS number:
EDMS-ERI-165008226
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.
NCT03818035


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
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Approved, Date: 14 June 2021
TABLE OF CONTENTS
TABLE OF CONTENTS ............................................................................................................................... 2 
LIST OF ATTACHMENTS............................................................................................................................ 4 
LIST OF IN-TEXT TABLES AND FIGURES................................................................................................ 4 
PROTOCOL AMENDMENTS....................................................................................................................... 5 
SYNOPSIS.................................................................................................................................................... 6 
TIME AND EVENTS SCHEDULE .............................................................................................................. 17 
ABBREVIATIONS ...................................................................................................................................... 23 
DEFINITIONS OF TERMS.......................................................................................................................... 23 
1. 
INTRODUCTION................................................................................................................................ 24 
1.1. 
Background .................................................................................................................................... 24 
1.2. 
Overall Rationale for the Study ...................................................................................................... 25 
1.3. 
Benefit/Risk Assessment ............................................................................................................... 26 
2. 
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS........................................................................... 27 
2.1. 
Objectives and Endpoints .............................................................................................................. 27 
2.1.1. 
Objectives ................................................................................................................................... 27 
2.1.2. 
Endpoints.................................................................................................................................... 28 
2.2. 
Hypothesis ..................................................................................................................................... 30 
3. 
STUDY DESIGN AND RATIONALE ................................................................................................. 30 
3.1. 
Overview of Study Design.............................................................................................................. 30 
3.2. 
Study Design Rationale.................................................................................................................. 35 
4. 
SUBJECT POPULATION.................................................................................................................. 37 
4.1. 
Inclusion Criteria ............................................................................................................................ 37 
4.2. 
Exclusion Criteria ........................................................................................................................... 39 
4.3. 
Prohibitions and Restrictions ......................................................................................................... 43 
5. 
TREATMENT ALLOCATION AND BLINDING................................................................................. 43 
6. 
DOSAGE AND ADMINISTRATION .................................................................................................. 45 
7. 
TREATMENT COMPLIANCE............................................................................................................ 46 
8. 
CONCOMITANT THERAPY.............................................................................................................. 47 
8.1. 
Concomitant Medications for Treatment of Psoriasis .................................................................... 47 
8.2. 
Concomitant Medications for Conditions other than Psoriasis ...................................................... 48 
9. 
STUDY EVALUATIONS .................................................................................................................... 48 
9.1. 
Study Procedures........................................................................................................................... 48 
9.1.1. 
Overview..................................................................................................................................... 48 
9.1.2. 
Screening Phase ........................................................................................................................ 49 
9.1.2.1. 
TB screening............................................................................................................................ 50 
9.1.2.2. 
Screening Failure/Rescreening ............................................................................................... 50 
9.1.3. 
Study Part 1: Open-label Treatment Phase................................................................................ 51 
9.1.4. 
Study Part 2: Double-blind Treatment Phase............................................................................. 51 
9.1.5. 
Study Part 3: Drug Withdrawal phase ........................................................................................ 51 
9.1.6. 
Re-treatment Phase.................................................................................................................... 52 
9.2. 
Efficacy Evaluations....................................................................................................................... 52 


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
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Approved, Date: 14 June 2021
9.2.1. 
Efficacy Assessor Assessments................................................................................................. 52 
9.2.1.1. 
Psoriasis Area and Severity Index .......................................................................................... 53 
9.2.1.2. 
Nail Assessment in Psoriasis and Psoriatic Arthritis ............................................................... 53 
9.2.1.3. 
Psoriasis-affected Body Surface Area..................................................................................... 53 
9.2.1.4. 
Target Lesion Severity Score .................................................................................................. 53 
9.2.2. 
Patient-reported Outcomes ........................................................................................................ 54 
9.2.2.1. 
Dermatology Life Quality Index ............................................................................................... 54 
9.2.2.2. 
Psoriasis Symptom and Sign Diary ......................................................................................... 54 
9.3. 
Pharmacokinetics (PK)................................................................................................................... 54 
9.4. 
Biomarkers ..................................................................................................................................... 55 
9.5. 
Pharmacogenomic (DNA) Evaluations .......................................................................................... 55 
9.6. 
Safety Evaluations ......................................................................................................................... 56 
9.7. 
Sample Collection and Handling.................................................................................................... 59 
10. 
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ WITHDRAWAL 
FROM THE STUDY ........................................................................................................................... 59 
10.1. 
Completion ..................................................................................................................................... 59 
10.2. 
Discontinuation of Study Treatment............................................................................................... 59 
10.3. 
Withdrawal From the Use of Research Samples........................................................................... 61 
11. 
STATISTICAL METHODS................................................................................................................. 62 
11.1. 
Subject Information ........................................................................................................................ 62 
11.2. 
Sample Size Determination ........................................................................................................... 62 
11.3. 
Efficacy Analyses........................................................................................................................... 64 
11.4. 
Pharmacokinetic Analyses............................................................................................................. 66 
11.5. 
Biomarker Analyses ....................................................................................................................... 66 
11.6. 
Pharmacogenomic Analyses ......................................................................................................... 66 
11.7. 
Safety Analyses ............................................................................................................................. 66 
11.8. 
Other Analyses............................................................................................................................... 67 
11.9. 
Statistical Analyses per Study Part................................................................................................ 68 
11.10. Subgroup and Sensitivity Analyses................................................................................................ 69 
11.11. Handling of Missing Data ............................................................................................................... 69 
12. 
ADVERSE EVENT REPORTING ...................................................................................................... 70 
12.1. 
Definitions ...................................................................................................................................... 70 
12.1.1. 
Adverse Event Definitions and Classifications ........................................................................... 70 
12.1.2. 
Attribution Definitions.................................................................................................................. 71 
12.1.3. 
Severity Criteria .......................................................................................................................... 71 
12.2. 
Special Reporting Situations.......................................................................................................... 72 
12.3. 
Procedures..................................................................................................................................... 72 
12.3.1. 
All Adverse Events...................................................................................................................... 72 
12.3.2. 
Serious Adverse Events ............................................................................................................. 73 
12.3.3. 
Pregnancy................................................................................................................................... 74 
12.4. 
Events of Special Interest .............................................................................................................. 74 
12.5. 
Contacting Sponsor Regarding Safety........................................................................................... 74 
13. 
PRODUCT QUALITY COMPLAINT HANDLING.............................................................................. 74 
13.1. 
Procedures..................................................................................................................................... 74 
13.2. 
Contacting Sponsor Regarding Product Quality ............................................................................ 75 
14. 
STUDY DRUG INFORMATION......................................................................................................... 75 
14.1. 
Physical Description of Study Drug(s) ........................................................................................... 75 
14.2. 
Packaging ...................................................................................................................................... 75 
14.3. 
Labeling.......................................................................................................................................... 75 
14.4. 
Preparation, Handling, and Storage............................................................................................... 75 
14.5. 
Drug Accountability ........................................................................................................................ 76 
15. 
STUDY-SPECIFIC MATERIALS....................................................................................................... 76 


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
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Approved, Date: 14 June 2021
16. 
ETHICAL ASPECTS ......................................................................................................................... 77 
16.1. 
Study-Specific Design Considerations........................................................................................... 77 
16.2. 
Regulatory Ethics Compliance....................................................................................................... 77 
16.2.1. 
Investigator Responsibilities ....................................................................................................... 77 
16.2.2. 
Independent Ethics Committee or Institutional Review Board ................................................... 77 
16.2.3. 
Informed Consent ....................................................................................................................... 78 
16.2.4. 
Privacy of Personal Data ............................................................................................................ 79 
16.2.5. 
Long-Term Retention of Samples for Additional Future Research ............................................ 80 
17. 
ADMINISTRATIVE REQUIREMENTS .............................................................................................. 80 
17.1. 
Protocol Amendments.................................................................................................................... 80 
17.2. 
Regulatory Documentation ............................................................................................................ 80 
17.2.1. 
Regulatory Approval/Notification ................................................................................................ 80 
17.2.2. 
Required Prestudy Documentation............................................................................................. 81 
17.3. 
Subject Identification, Enrollment, and Screening Logs ................................................................ 81 
17.4. 
Source Documentation................................................................................................................... 82 
17.5. 
Case Report Form Completion ...................................................................................................... 82 
17.6. 
Data Quality Assurance/Quality Control ........................................................................................ 83 
17.7. 
Record Retention ........................................................................................................................... 83 
17.8. 
Monitoring ...................................................................................................................................... 83 
17.9. 
Study Completion/Termination....................................................................................................... 84 
17.9.1. 
Study Completion/End of Study.................................................................................................. 84 
17.9.2. 
Study Termination....................................................................................................................... 84 
17.10. On-Site Audits ................................................................................................................................ 84 
17.11. Use of Information and Publication................................................................................................ 85 
REFERENCES............................................................................................................................................ 87 
INVESTIGATOR AGREEMENT ............................................................................................................... 103 
LIST OF ATTACHMENTS
Attachment 1: 
Assessment of Induration. Erythema and Scaling for Target Lesion Severity 
Score (TLSS) and Investigator’s Global Assessment (IGA)..................................................... 89 
Attachment 2: 
Psoriasis Area and Severity Index................................................................................. 90 
Attachment 3: 
Hepatitis B Virus (HBV) Screening with HBV DNA........................................................ 91 
Attachment 4: 
Instructions for the Completion of PRO Assessments................................................... 92 
Attachment 5: 
Contraception................................................................................................................. 93 
Attachment 6: 
Guidance on Study Conduct during the COVID-19 Pandemic...................................... 94 
Attachment 7: 
Protocol Amendment History ......................................................................................... 96 
Attachment 8: 
Liver Stopping Criteria and Follow-up Assessments ................................................... 100 
LIST OF IN-TEXT TABLES AND FIGURES
TABLES
Table 9.1-1: Required Blood Volume per Subject ...................................................................................... 49 
FIGURES
Figure 3.1-1: Overview of Study Design ..................................................................................................... 33 


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
5
Approved, Date: 14 June 2021
PROTOCOL AMENDMENTS
Protocol Version 
Date
Original Protocol
5 July 2018
Amendment 1
Amendment 2
Amendment 3
Amendment 4
06 December 2018
29 May 2019
15 April 2020 (COVID-19 amendment)
15 June 2020
Amendment 5
10 June 2021
Key changes in Amendment 5 are summarized below; minor changes of language and editorial items are not listed.
Amendment 5 (10 June 2021)
Overall Rationale for the Amendment: The overall reason for the amendment is the prolongation of study part 3
by two years (ie, 104 weeks) for all subjects regularly and successfully enrolled at study beginning.
Section Number / Name Description of Changes and Brief Rationale
Synopsis,
2.1.1 Objectives
Description of Change: Two new secondary objectives were defined to evaluate 
whether super responders (SRe) will show sustained remission, continued loss of 
response, or stabilization of disease worsening over two additional years of observation.
Rationale: To determine additional objectives for the prolonged study part 3
Synopsis,
2.7 Endpoints
Description of Change: Various endpoints were adapted to include week 164 (~2 years 
after drug withdrawal) and week 220 (~3 years after drug withdrawal, final study visit),
respectively, including the whole period from week 68 to week 220.
Rationale: To allow evaluation of the prolonged study part 3
Synopsis,
3.1 Study Design,
7 Treatment Compliance,
9.1.5 Study Evaluations -
Study Part 3, Time and 
Events Schedule
Description of Change: Text, study design diagram and time and events schedule were 
adapted to include the prolonged study part 3. Additional on-site visits will occur every 
3 months, i.e. at weeks 128, 140, 152, 164, 176, 188, 200, 212 and 220. In between there 
will be a telephone-visit 6 weeks after each visit (ie, telephone visits at weeks 74, 86, 98, 
110, 122, 134, 146, 158, 170, 182, 194, and 206.
Rationale: To display prolongation of study part 3
Synopsis,
3.1 Study Design:
Substudies
Description of Change: The novel measure tape stripping will be performed for all 
participants in part 3 (SRe). It is a less invasive collection method to allow measurements 
of gene expression and levels of proteins or other biomarkers in the stratum corneum.
Rationale: To implement a novel investigational method to the prolonged study part 3
Synopsis,
11.9 Statistical Analyses 
per Study Part
Description of Change: Two interim analyses of study part 3 were added. They are
planned after all subjects have completed their visit at week 116 (or at week 144 in case 
of subjects entering the re-treatment arm in week 116) and at week 164 (or at week 192 
in case of subjects entering re-treatment arm in week 164). The final analysis will be 
performed after all subjects have completed their visit at week 220 (or at week 248 in 
case of subjects entering the re-treatment arm in week 220).
Rationale: To allow two interim analyses of study part 3
10.2 Discontinuation of 
Study Treatment, 12.3.2. 
Serious Adverse Events,
Appendix
Description of Change: Section 10.2 was adapted to include that study treatment must 
be discontinued in case of abnormal liver tests. Corresponding appendices (8A and 8B) 
were added to provide liver stopping criteria and guidance for follow-up assessments.
Section 12.3.2 was adapted to emphasL]H WKDW DQ\ SRVVLEOH +\¶V ODZ FDVH $67 RU $/7 
[ 8/1 WRJHWKHU ZLWK ELOLUXELQ  ; 8/1 RU ,15 ! KDV WR EH UHSRUWHG WR WKH
sponsor in an expedited manner using the Serious Adverse Event form.
Rationale: To incorporate Hy’s law language into the protocol


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
6
Approved, Date: 14 June 2021
SYNOPSIS
A Phase 3b, Randomized, Double-blind, Parallel Group, Multicenter Study to Evaluate Further 
Therapeutic Strategies with Guselkumab in Patients with Moderate-to-Severe Plaque-Type Psoriasis
(GUIDE).
Protocol Number: CNTO1959PSO3012
EudraCT NUMBER: 2018-001238-16
Study drug: CNTO 1959 (guselkumab; LV D IXOO\ KXPDQ LPPXQRJOREXOLQ * ODPEGD ,J*Ȝ PRQRFORQDO
antibody (mAb) that binds to the p19 protein subunit of human interleukin (IL)-23 with high specificity and 
affinity. The binding of guselkumab to the IL-23 p19 subunit blocks the binding of extracellular IL-23 to 
the cell surface IL-23 receptor, inhibiting IL-23-specific intracellular signaling and subsequent Th17 (IL-
17 producing T helper cell), Tc17 (IL-17 producing cytotoxic T cell) and Th22 cell proliferation, cytokine 
production, and survival. In July 2017, guselkumab has been approved for the treatment of moderate-to-
severe psoriasis by the Food and Drug Administration (FDA) and in November 2017 by the European 
Medicines Agency (EMA).
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
Objectives
Primary objective
The primary objective of the study is to demonstrate that Super-Responders (SRe; defined as psoriasis 
subjects who receive on-label guselkumab treatment until week 20 and respond with a Psoriasis Area and 
Severity Index [PASI] score=0 at weeks 20 and 28) maintain control of disease until week 68 with 
prolonged treatment intervals of 16 weeks (100 mg q16w). To be demonstrated in Study Part 2 (see
Section 3.1 for study design).
Secondary objectives
Secondary objectives are to evaluate,
x
whether subjects with short disease duration  \HDUV show a more rapid and better guselkumab
response compared to subjects with longer disease duration and whether subjects with shorter disease
are more likely to maintain drug-free control of disease after guselkumab withdrawal. To be evaluated 
in Study Parts 1, 2, and 3.
x
whether SRe with short disease duration and PASI=0 at week 116 (ie, remission for one year after 
withdrawal) will show sustained remission (ie, PASI=0) over two additional years compared to
subjects with longer disease duration. To be evaluated in Study Part 3.
x
whether SRe with short disease duration and PASI>0 to  DW ZHHN  LH SDUWLDO UHODSVH IRU one year 
after withdrawal) will show continued loss of response or stabilization of disease worsening over two
additional years compared to subjects with longer disease duration. To be evaluated in Study Part 3.
x
whether different treatment intervals (weeks 28 to 60: guselkumab 100 mg q8w vs. guselkumab 
100 mg q16w) affect the maintenance of drug-free control of disease after 68 weeks of guselkumab 
treatment. To be evaluated in Study Part 3.
x
the safety and tolerability of guselkumab in subjects with moderate-to-severe plaque-type psoriasis.
Note: disease duration will be calculated from date at which first symptoms (plaque) were reported by 
subject to date of screening visit.


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
7
Approved, Date: 14 June 2021
Exploratory objectives
The following objectives are to be explored in the mechanistic biomarker substudies:
x
characterization of the immune cellular and molecular composition at baseline (week 0) and changes 
(quantitative and qualitative characterization) in the lesional skin of subjects during treatment with 
guselkumab as determined by fluorescence activated cell sorting (FACS)-based analysis. To be 
explored in substudy 1
x
characterization of the immune cellular changes (quantitative and qualitative characterization) in the 
blood of subjects at baseline (week 0), during and after treatment with guselkumab as determined by 
FACS-based analysis. To be explored in substudy 1
x
characterization of molecular (gene expression) changes during treatment with guselkumab in the skin 
of subjects treated with guselkumab as determined by RNA sequencing (RNAseq) and quantitative 
polymerase chain reaction (qPCR). To be explored in substudies 2 and 3
x
characterization of the tissue immunopathological changes  in the skin of subjects during and after 
treatment with guselkumab as determined by immunohistochemistry (IHC)/ immunofluorescence (IF)/
in situ hybridization (ISH). To be explored in substudy 2
x
characterization of the effects of guselkumab treatment on serum biomarkers as determined by 
immunoassays. To be explored in substudy 3
x
characterization of the association between changes in the various exploratory biomarker endpoints 
and 1) efficacy of guselkumab, 2) duration of psoriasis, 3) maintenance of response after stopping 
guselkumab treatment, and 4) ability to achieve a PASI 100 response at weeks 20 and 28 (super 
responder status). To be explored in all substudies
Endpoints
For the endpoints, the following terms were defined:
x
Control of disease: PASI score <3
x
Fluctuating disease: PASI score 3 to 5
x
Loss of disease control: PASI score >5.
Study groups are defined as follows:
x
1: All participating subjects who are enrolled and are scheduled to receive guselkumab 100 mg at
weeks 0, 4, q8w until week 28 (Study Part 1)
x
2a: SRe (PASI score=0 at weeks 20 and 28) randomized to guselkumab 100 mg q8w at weeks 28 to 
60 (Study Part 2)
x
2b: SRe randomized to guselkumab 100 mg q16w at weeks 28 to 60 (Study Part 2)
x
2c: non-SRe with a PASI score >0 at week 20 and/or 28 who will receive guselkumab 100 mg q8w at 
weeks 28 to 60 (Study Part 2)
x
2d: SRe with loss of disease control between week 28 and 68, who will enter the re-treatment arm and 
receive guselkumab 100 mg at weeks 0, 8, and 16 calculated from the date of loss of disease control 
(Study Part 2)
x
3a: SRe randomized to guselkumab 100 mg q8w in Study Part 2 with withdrawal of guselkumab at 
week 68 (Study Part 3)
x
3b: SRe randomized to guselkumab 100 mg q16w in Study Part 2 with withdrawal of guselkumab at 
week 68 (Study Part 3)
x
3c: SRe with fluctuating disease at week 68 or loss of disease control at any other visit after week 68,
who will enter the re-treatment arm and receive guselkumab 100 mg at weeks 0, 8, and 16 calculated 
from the date of loss of disease control (Study Part 3).


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
8
Approved, Date: 14 June 2021
Endpoints of the main study
Primary endpoint
The primary endpoint of the main study is the proportion of subjects in study groups 2a and 2b who achieve 
an absolute PASI score <3 at week 68.
Major secondary endpoints
Major secondary endpoints of this study are:
x
Time to improvement from baseline (week 0) in PASI (PASI 75/90/100 response and absolute PASI 
score=0) for subjectV ZLWK VKRUW   years) and longer (>2 years) disease duration per study group (1,
2a, 2b, and 2c)
x
Proportion of subjectV ZLWK VKRUW  \HDUV DQG ORQJHU ! \HDUV GLVHDVH GXUDWLRQ ZKR DFKLHYH DQ
DEVROXWH 3$6, VFRUH RI   DQG  DW ZHHNV   , 116, 164, and 220 per study group (1, 2a, 2b, 
2c, 3a, and 3b)
x
Proportion of subjects who retain disease control (ie, absolute PASI score <3 at all visits) from week 68
through week 116, from week 68 through week 164, and from week 68 through week 220 for subjects
ZLWK VKRUW   \HDUV DQG ORQJHU ! \HDUV GLVHDVH GXUDWLRQ per study group (3a and 3b).
Other secondary endpoints of this study are:
x
Proportion of subjects who achieve a PASI 75/90/100 response at weeks 20, 28, 68, 116, 164, and 220
per study group (1, 2a, 2b, 2c, 3a, and 3b)
x
Time to loss of disease control (absolute PASI score >5 at any visit) after treatment withdrawal beyond 
week 68 per study group (3a and 3b)
x
Proportion of subjects with an absolute PASI score=0 at all of the following visits: weeks 12, 16, 20,
and 28 (study group 1)
x
Change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at weeks 28, 68, 116, 
164, and 220 per study group (1, 2a, 2b, 2c, 3a, 3b, and 3c)
x
Proportion of subjects who achieve a DLQI score 0/1 and <5 at weeks 28, 68, 116, 164, and 220 per 
study group (1, 2a, 2b, 2c, 3a, 3b, and 3c)
x
Change from baseline (week 0) in affected Body Surface Area (BSA) at weeks 12, 28, 52, 68, 80, 104,
116, 140, 164, 188, 212, and 220 (all study groups)
x
Change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
score at weeks 28, 68, 116, 164, and 220 among subjects with nail psoriasis at baseline (week 0; 1, 2a, 
2b, 2c, 3a, and 3b).
x
Change from baseline (week 0) in the signs and symptoms aggregate scores of the Psoriasis Symptoms 
and Signs Diary (PSSD) at weeks 28, 68, 116, 164, and 220 (1, 2a, 2b, 2c, 3a, and 3b)
x
Proportion of subjects who achieve a PSSD sign score=0 at week 68 among subjects with a PSSD sign 
VFRUH  DW ZHHN 28 per study group (2a, 2b, and 2c).
x
Association between trough serum guselkumab concentration and efficacy or serum biomarker level
x
Association between trough serum guselkumab levels at weeks 20, 28, 36, and 68 and achieving a 
PASI score <3 at week 68 per study group (2a and 2b)
x
Proportion of subjects who were re-treated due to loss of disease control (PASI >5) and regain control 
of disease (PASI <3) 24 weeks after start of re-treatment (study groups 2d and 3c)
x
Safety and tolerability with regard to adverse events (AEs) and abnormal laboratory results (all study 
groups).


CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
9
Approved, Date: 14 June 2021
Hypothesis
In this study, Super-Responders (SRe) are defined as psoriasis subjects achieving clear skin (measured as 
absolute PASI score=0) at weeks 20 and 28 of treatment. SubjectV ZLWK VKRUWHU GLVHDVH GXUDWLRQ  years
calculated from date at which first symptoms [plaque] were reported by subject to date of screening visit)
are expected to have a higher likelihood to be SRe.
In Super-Responders, guselkumab treatment might have stronger modifying effects on immunopathological 
mechanisms of the disease than in non-SRe. Therefore, it is hypothesized that this subpopulation might not 
lose control of disease even with a longer dosing interval (q16w instead of q8w) and that this subpopulation 
will have higher probability of drug-free remission after 60 weeks of treatment.
The hypothesis of this study is that guselkumab q16w treatment is non-inferior to guselkumab q8w 
treatment in SRe as assessed by the proportion of subjects with an absolute PASI score <3 at week 68
(alternative hypothesis in a statistical sense). If the hypothesis is accepted, the study will be considered 
positive.
OVERVIEW OF STUDY DESIGN
The present trial is designed as a phase 3b, randomized, double-blind, parallel-group, multicenter, 
comparison study in subjects of at least 18 years of age with moderate to severe plaque-type psoriasis.
It is planned to achieve about 280 subjects categorized as Super-Responders (SRe, ie PASI score=0 at 
weeks 20 and 28) for randomization in Study Part 2 (140 subjects in study group 2a and 140 subjects in 
study group 2b). It is assumed that 900-1000 subjects are therefore needed to be screened at up to 90
German study sites and 10 French study sites and that 888 subjects are needed to be enrolled (based on a 
SRe rate of 30-35% of enrolled subjects). Screenings and enrollments will be adjusted if necessary (without 
protocol amendment) to achieve 280 SRe at week 28. Ongoing subjects in Study Part I will continue to Part 
II if eligible, irrespective of whether or not 280 SRe are already randomized. Only screenings will be closed.
Of the enrolled subjects approximately 40% must KDYH D GLVHDVH GXUDWLRQ RI  years calculated from date 
at which first symptoms (plaque) were reported by subject to date of screening visit. Subjects with a disease 
GXUDWLRQ RI  years are expected to have a higher likelihood to be SRe. At randomization two stratification 
criteria apply: (i) 65H ZLWK D GLVHDVH GXUDWLRQ RI  years will be stratified equally to study group 2a and 
2b. Further, (ii) SRe who are participating in the mechanistical substudy 1 will be stratified equally to study 
group 2a and 2b.
The study will feature the following structure and design:
Study Part 1: Screening through Week 28:
This will be screening phase lasting up to four weeks (+ 7 calendar days) prior to first administration of 
guselkumab (week 0) followed by a 28-week run-in period with visits and administration of 100 mg 
guselkumab at weeks 4, 12, and 20. In case of a PASI score=0 at weeks 20 and 28 subjects are qualified to 
be randomized either to study group 2a or 2b of Study Part 2. In case of PASI score >0 at weeks 20 and/or 
28 the subjects will continue to receive guselkumab 100 mg q8w until week 60 (last administration at
week 60 visit) with final study assessments at week 68 and final safety follow-up visit at week 72 (defined 
as study group 2c).
Study Part 2: Week 28 through Week 68:
Subjects with a PASI score=0 at weeks 20 and 28 will be defined as SRe and randomly assigned to the 
following two treatment groups: 2a) guselkumab 100 mg q8w or 2b) guselkumab 100 mg q16w. In 
addition, subjects ZLWK GLVHDVH GXUDWLRQ  years will be equally distributed to either group. Study visits of 
Study Part 2 will be conducted every 8 weeks.
To blind the study, study treatment (guselkumab or Placebo) will be administered q8w starting at week 28
until the end of study therapy (last administration in week 60). The q16w group will receive Placebo at 
weeks 28, 44 and 60. Subjects losing control of disease, defined as PASI score >5 at any visit during Study 
Part 2 (ie, until week 60), will enter the Re-treatment arm (group 2d, see section Re-treatment below).


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The assessment for the primary endpoint (EP) will be at week 68 for both study groups (2a and 2b).
In case of PASI <3 at week 68 the subject will not receive any study medication and enter the drug 
ZLWKGUDZDO SDUW 6WXG\ 3DUW  ,Q FDVH RI 3$6,   DW YLVLW ZHHN  WKH subject will enter the re-treatment 
arm 3c (see section Re-treatment below).
In case of PASI score >0 at weeks 20 and/or 28 the subjects will continue to receive guselkumab 100 mg 
q8w until week 60 (last administration of study treatment) with final study assessments at week 68 and final 
safety follow-up visit at week 72 (defined as study group 2c). At visit week 68 (for group 2c), the 
investigator may continue treatment with commercially available guselkumab (ie, not provided by Sponsor) 
to maintain a q8w interval. Due to the half-life of guselkumab, it is recommended not to start a new therapy 
during safety follow-up period (ie, 12 weeks after last dose). If the investigator feels strongly that additional 
therapy is needed, this should be discussed with the sponsor before initiation of the new therapy.
Study Part 3: Week 68 through Week 220:
Subjects of group 2a and 2b with a PASI score <3 at week 68 will enter Study Part 3 and be withdrawn 
from the study medication and followed-up until week 220. Study visits of Study Part 3 will be conducted 
every 12 weeks (ie, at weeks 80, 92, 104, 116, 128, 140, 152, 164, 176, 188, 200, and 212; ± 14 days). In 
between the 12-weekly on-site visits, a telephone-visit 6 weeks (± 7 days) will be done after each on-site 
visit (ie, telephone visits at weeks 74, 86, 98, 110, 122, 134, 146, 158, 170, 182, 194, and 206) to assess 
whether the subject notices a worsening of his/her psoriasis. If so, the subject must attend an on-site visit 
for efficacy assessment by the assessor as soon as possible but not later than 2 weeks after the phone call.
For patients not starting re-treatment, the final visit will take place at week 220.
Re-treatment
Subjects losing control of disease, defined as PASI score >5 at any visit during Study Part 2 or 3 (ie, until 
week 220), will enter the re-treatment-arms (2d or 3c) with three guselkumab 100 mg administrations 
starting at that visit (= re-treatment-week 0, followed by administration at re-treatment-weeks 8 and 16).
If re-treatment is started at a visit which would usually not require all PROs needed at the first re-treatment
visit, those PROs will be obtained immediately after efficacy assessments (basis for re-treatment-decision) 
and prior to drug administration at that visit.
The final efficacy assessment for all subjects in the re-treatment-arms will take place 24 weeks after loss of 
control and study termination will be 28 weeks after loss of control (final study visit/safety follow-up). At 
visit week 24 of the re-treatment, the investigator may continue actual treatment with commercially
available guselkumab (ie, not supplied by Sponsor) to maintain a q8w interval. Due to the half-life of 
guselkumab, it is recommended not to start a new therapy during safety follow-up period (ie, 12 weeks after 
last dose). If the investigator feels strongly that an additional therapy is needed, this should be discussed 
with the Sponsor before initiation of the new therapy.
Subjects with fluctuating disease (ie, PASI score 3 to 5) at the week 68 visit will also get the opportunity 
to enter the re-treatment-arm (3c).
The last chance to start re-treatment will be the visit week 220 (ie, final efficacy assessment at week 244
with final study visit/safety follow-up at week 248).


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A schematic diagram of the study design is provided below:
Treatment compliance
Week 0 can be done once all screening activities are completed, results are available, and the subject is 
eligible, but latest 4 weeks (+7 calendar days) after screening visit. From weeks 4 to 68 it is expected that 
all subjects will attend visits within a range of ±7 calendar days. Visits during the re-treatment period (study 
groups 2d and 3c) are also expected to occur within a range of ±7 days. Visits from week 68 through 
week 220 are to be conducted within ±14 calendar days of the anticipated visit date. The week 220 visit 
should be conducted at least 160 weeks after the last study agent injection.
Efficacy of treatment will be assessed before any tests, procedures or other evaluations, first by the subject
him/herself (1st DLQI, 2nd 7-day version of PSSD, 3rd NAPPA-QoL and 4th NAPPA-PBI), and subsequently 
by the investigator (PASI, BSA and NAPPA-CLIN). 
An exception to this order is the entrance into a re-treatment arm at a visit which would normally not require 
all PROs needed at the first visit of the re-treatment arm (R0). In this case, PROs will be obtained 
immediately after efficacy assessments (which are the basis for re-treatment-decision) and prior to drug 
administration at that visit.
Safety evaluations will include the monitoring of adverse events (AEs; including injection site and allergic 
reactions), clinical laboratory tests (hematology, chemistry and pregnancy testing), physical examinations, 
vital signs, concomitant medication review, and early detection of tuberculosis (TB). Venous blood samples 
will be collected for the determination of serum guselkumab concentrations (pharmacokinetics).
The first study drug injection will be administered at week 0, and the last regular injection will be given at 
week 60. For subjects entering the re-treatment arm the last possible drug injection will be week 84 (arm 
2d) and week 236 respectively (please refer to re-treatment section).
Including a 4-week screening phase and a 12-week safety follow-up, the minimum duration of a subject’s 
regular participation in this study will be 75 weeks and the maximum duration will be 252 weeks.
The study is considered completed with the last visit for the last subject participating in the study. The final 
data from the study site will be sent to the Sponsor (or designee) after completion of the final visit at that 
study site, in the time frame specified in the Clinical Trial Agreement. The overall duration of the study is 
expected to be approximately 84 months (start in Q4 2018, stop in Q1 2025). The estimated frequency and 
timing of the study visits are summarized in the 'Time and Events Schedule' (TES).


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Substudies:
Four substudies are planned to further evaluate pharmacologic effects of guselkumab and evaluate various 
pharmacologic/clinical response relationships allowing assessment of inter-individual variability in clinical 
outcomes and possible identification of subject population groups that may respond differently to 
guselkumab. The substudies will also aim to further define the mechanism of action (MoA) of guselkumab
at the molecular and cellular levels during and after treatment. Changes in gene expression as well as 
quantitative and qualitative changes in different types of immune cells will be evaluated in skin biopsies 
and blood.
Substudy 1 (Cellular MoA substudy):
Few sites will be identified that have expertise to conduct fluorescence activated cell sorting (FACS)-based 
cellular immunophenotypic characterization of freshly isolated skin biopsies. Participation in this study is 
optional. Subjects recruited to the selected sites will be asked to agree to the cellular MoA substudy (target 
n=60). 6 mm skin biopsy samples will be collected as follows: 1 non-lesional (NL) and 1 lesional (L) biopsy 
at weeks 0 and 116 (only SRe), and 1 L biopsy at weeks 4, 28, 68, and 220. In addition, when subjects lose 
control of disease (PASI >5) in Study Parts 2 or 3 and go into re-treatment, an additional biopsy will be 
taken from a lesional plaque that shows disease activity. Biopsies will be dissociated into single cell 
suspension and subjected to FACS-based immunophenotyping analyses. Whole blood samples for the 
isolation of peripheral blood mononuclear cells (PBMCs) will also be collected from consenting subjects
for subsequent immunophenotyping analyses by FACS (according to TES at weeks 0, 4, 28, 68, 80, 116, 
and 220).
Substudy 2 (Gene expression substudy):
Skin biopsies will be collected in a subset of subjects (target n=100) at selected sites (capable of performing 
the skin biopsy collection and processing procedure) to evaluate gene and protein expression profiles and 
cellular content. Participation in this skin biopsy substudy is optional. 6 mm skin biopsy samples will be 
collected as follows: 1 NL and 1 L biopsy at weeks 0 and 116 (only SRe), and 1 L biopsy at weeks 4, 28, 68,
and 220. In addition, when subjects lose control of disease (PASI >5) in Study Part 2 or 3, and go into re-
treatment, an additional biopsy will be taken from a lesional plaque that shows disease activity. Each biopsy 
will be split in two parts; one part will be stored in RNA later preservative for RNA gene expression 
analysis, while the other part will be stored frozen in optimal cutting temperature (OCT) media for
hematoxylin and eosin stain (H&E), immunohistochemistry (IHC) and immunofluorescence (IF) analysis. 
Two 3 mm biopsies may be taken instead of the 6 mm biopsy if preferred by the investigator and consented 
by the patient. The splitting step is not applicable in that case.
In addition to the biopsy collection for the selected patients taking part in the substudy 2, the novel method 
tape stripping (non-invasive) will be done for all participants in part 3 (SRe). Tape stripping is a less 
invasive collection method that may allow measurement of gene expression as well as levels of proteins or 
other biomarkers in the stratum corneum. The tape strip approach will be done to gain epidermal cells for 
biomarker analysis (transcriptomics via RNA seq; proteomics) and to validate tape stripping results by 
comparison with available skin biopsies. Tape stripping will be performed, where feasible, at week 116 for 
all participants, and at R0 visit or week 220 visit for those, who do or do not relapse. Tape strip samples 
will be collected from both lesional and adjacent non-lesional areas during the sampling period starting at 
week 116.
The samples will be shipped to the central lab and will be analyzed later.
Substudy 3 (Serum analysis):
Participation in this substudy is mandatory. Serum samples will be collected from all subjects to assess PD 
markers associated with the response to guselkumab as well as markers related to psoriasis. Measurements 
may include but are not limited to serum IL-17A, IL-17F, IL-22 levels and beta defensin-2 (BD-2). The 
samples) will be collected according to the TES at weeks 0, 4, 28, 68, 80, 116, 164, and 220 (and R0, if 
applicable) and analyzed by immunoassays.


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Substudy 4 (Genetic analyses):
It is recognized that genetic variation can be an important contributing 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 identify population subgroups that respond differently to a drug. The 
goal of the genetic (DNA) analysis is to collect a single DNA sample at week 0 as specified in the TES to 
search for genetic factors that may influence molecular effects, clinical efficacy, or tolerability of 
guselkumab and to identify genetic factors associated with psoriasis. Participation in this study is optional.
Only subjects who sign the consent form to participate in the genetic assessment will have whole blood 
DNA samples collected.
Note: One additional blood sample for biomarker assessments will be taken at the time when the subject
loses control of disease (defined as PASI >5 at any visit during Study Part 2 or 3 = R0).
Altogether, these substudies will provide crucial information about possible subject-optimized guselkumab
treatment algorithms and may relate immunopathological mechanisms to clinical course and characteristics 
of plaque psoriasis.
SUBJECT POPULATION
The target population comprises adults with a diagnosis of plaque-type psoriasis (approximately 40% 
subjects with disease duration  \HDUV calculated from date at which first symptoms (plaque) were reported 
by subject to date of screening visit). Subjects must have moderate-to-severe plaque-type psoriasis defined 
by PASI >10 or affected body surface area (BSA) >10% and additionally a DLQI >10. Subjects must be 
candidates for systemic therapy for psoriasis. Subjects with a clinical active psoriasis arthritis (PsA) which 
needs treatment beyond NSAIDs, non-plaque 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) will be excluded.
DOSAGE AND ADMINISTRATION
A guselkumab-prefilled syringe assembled with the UltraSafe Plus™ Passive Needle Guard (PFS-U) 
device, designed to deliver a single, fixed dose of 100 mg and a matched PFS-U containing Placebo will be 
used. Products will be labeled in a blinded manner; it will not be possible to differentiate between active 
and Placebo-prefilled syringes.
For Study Part 1 all enrolled subjects will receive one injection of guselkumab according to the TES, ie at 
weeks 0, 4, 12, and 20.
Subjects with a PASI score=0 at weeks 20 and 28 are qualified for randomization in Study Part 2. In case 
of PASI score >0 at weeks 20 or/and 28, subjects will continue to get guselkumab 100 mg q8w with last 
administration in week 60 (study group 2c).
Randomized subjects of Study Part 2 (study groups 2a and 2b) will receive one injection of either 
guselkumab or matching Placebo solution for injection (ie, identical to guselkumab in color, smell, and 
shape) according to the following schemes:
x
Study group 2a: guselkumab 100 mg q8w, ie at weeks 28/36/44/52/60
x
Study group 2b: guselkumab 100 mg q16w, ie guselkumab at weeks 36 and 52; Placebo at weeks
28/44/60 (guselkumab and placebo will be provided blinded, IWRS will assure correct assignment).
Subjects (from groups 2a and 2b) with a PASI score <3 at week 68 are qualified for entering Study Part 3
and will be withdrawn from the study medication.
Subjects (from groups 2a, 2b, 3a and 3b) losing control of disease, defined as PASI score >5 at any visit of 
Study Parts 2 or 3 (ie, until week 220), will enter the re-treatment-arm with guselkumab 100 mg q8w for 
further 3 administrations (starting at that visit = re-treatment week 0, followed by administration at re-
treatment-weeks 8 and 16). The final efficacy assessment for all subjects in the re-treatment arm will take 
place 24 weeks after loss of control and study termination will be 28 weeks after loss of control (final study 
visit). Subjects with fluctuating disease (ie, PASI score 3 to 5) or PASI >5 (subjects losing control of 
disease) at week 68 will also get the opportunity to enter the re-treatment-arm.


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All study procedures should be completed prior to administering the study drug. Sub-cutaneous injections 
should be administered by qualified study site staff during the study visit, if possible. However, in cases 
where a site visit is not possible, subjects who have appropriate experience or have received required 
training may self-administer study drug at the times instructed by the investigator. Study site staff must 
ensure that those subjects have the appropriate experience or have received the required training to perform 
self-administration of SC injections.
Self-administration at home is only allowed subsequent to performance of a phone or video visit. 
Application of study drug at home can also be performed by a Home Health Care service provider if agreed
by the sponsor, investigator and subject. Self-administration cannot take place on 2 consecutive visits.
Site personnel and subjects will remain blinded to the treatment assignments until the last subject completes 
week 220 evaluations and the database has been locked.
EFFICACY EVALUATIONS
Efficacy evaluations chosen for this study are consistent with those used to evaluate other therapies for 
psoriasis and include:
x
Psoriasis Area and Severity Index (PASI) 
x
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA-CLIN)
x
Psoriasis-affected Body Surface Area (BSA)
x
Dermatology Life Quality Index (DLQI) [PRO]
x
Psoriasis Symptom and Sign Diary (PSSD, 7-day version) [PRO]
x
Nail associated quality of life (NAPPA-QoL) and patient- relevant treatment benefit (NAPPA-PBI) 
[PRO]
x
Target Lesion Severity Scores (TLSS; only for subjects participating in substudies 1 and 2).
The efficacy assessments PASI, affected BSA and NAPPA-CLIN will be performed at the site by an 
efficacy assessor (preferably a dermatologist) trained by the Sponsor and at the appropriate visits as outlined 
in the TES.
PHARMACOKINETIC EVALUATIONS
Venous blood samples will be collected at the points in time shown in the TES for the determination of 
serum guselkumab concentrations. Each sample will be divided into 2 aliquots (1 aliquot for serum 
guselkumab concentration and 1 aliquot as back-up sample). Samples must be collected before study drug 
administration at visits when a study drug administration is scheduled. The exact dates and times of blood 
sampling must be recorded in the laboratory requisition form. The samples will be shipped to the central 
laboratory and will be analyzed later.
Please refer to the Laboratory Manual for further information regarding collection, handling, and shipment 
of biological samples. The Sponsor, or its designee, will assay these samples using a validated, specific, 
and sensitive immunoassay method under conditions in which the subjects’ identity remains blinded.
Note: One additional blood sample for PK assessments will be taken at the time when the subject loses 
control of disease (PASI score >5 at any visit during Study Parts 2 or 3, RU 3$6,  DW ZHHk 68). However 
at R0, PK-samples will only be taken for Study Part 2d (ie, not for Study Part 3c).
SAFETY EVALUATIONS
Safety and tolerability of guselkumab will be monitored until 12 weeks after last administration of study 
drug by collecting information on AEs (including injection site and allergic reactions), clinical laboratory 
tests (hematology, chemistry and pregnancy testing), physical examinations, vital signs, concomitant 
medication review, and early detection of tuberculosis (TB). Subjects participating in Study Part 3 and not 
treated in the re-treatment arm will be monitored through week 220 by collecting information on AEs 
(including injection site and allergic reactions), vital signs, weight, and concomitant medication review.


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STATISTICAL METHODS
The statistical analyses in this study will be performed separately for each Study Part and will focus on the 
comparison of the two randomized treatment groups (ie, 2a: guselkumab 100 mg q8w vs. 2b: guselkumab
100 mg q16w) in Study Part 2. The analyses will be confirmatory for the primary endpoint, and exploratory 
for the major secondary endpoints and for all other secondary endpoints.
Descriptive statistics will include counts and proportions for categorical data, and mean, standard deviation, 
median, interquartile range, and range for continuous data. Graphical data displays may also be used to 
summarize the data. The two-group large-sample normal approximation Wald Z-test with Mantel-Haenszel 
stratum weights for 'disease duration' will be used to compare the proportion of subjects responding to 
treatment. Continuous response parameters will be compared using an analysis of variance model with fixed 
effects for treatment group and disease duration and baseline (week 0) value as a covariate. Time-to-event 
endpoints will be analyzed using Kaplan-Meier product limit methods to estimate the survival distributions 
and the median time-to-event. The confirmatory significance level for non-inferiority testing is fixed to a 
one-sided D=0.05. Besides the confirmatory testing of the primary endpoint all other inferential statistical 
testing (including calculation of confidence intervals) is to be interpreted in the exploratory sense only.
Sample Size Determination
The present trial is designed to demonstrate that guselkumab 100 mg q16w treatment is non-inferior to 
guselkumab 100 mg q8w treatment in SRe as assessed by the proportion of subjects with an absolute PASI 
score <3 at week 68. A non-inferiority margin of 10% was chosen based on a minimally clinically 
meaningful difference. Based on data from CNTO1959PSO3002 (IB, Section 4.3.1.5) the proportion of 
subjects with an absolute PASI score <3 at week 68 is assumed to be 90% for guselkumab 100 mg q8w. 
The expected difference in proportions between the treatment groups is 0%.
The sample size estimation using the power approach is performed for the per-protocol analysis set as 
described below. No formal adjustment of the significance level is necessary. 
When the sample size in each group is 112, a two-group large-sample normal approximation Wald Z-test 
of proportions with a one-sided 0.05 significance level will have 80% power to reject the null hypothesis 
that the guselkumab 100 mg q16w treatment is inferior to the guselkumab 100 mg q8w treatment (the 
difference in proportions, Pguselkumab 100mg q16w – P guselkumab 100mg q8w  LV  -10%) in favor of the alternative 
hypothesis that the guselkumab 100 mg q16w treatment is non-inferior to the guselkumab 100 mg q8w 
treatment (the difference in proportions is > -10%), assuming that the expected difference in proportions is 
0 and the proportion in the guselkumab 100 mg q8w treatment group is 90% (nQuery Advisor® 7.0).
Considering the frequency of drop-out rates and protocol violations from previous trials, it is assumed that 
about 20% randomized subjects will not be evaluable for the per-protocol analysis in Study Part 2. Hence, 
280 subjects (140 subjects per treatment group) are planned to be randomized in a ratio of 1:1 to meet the 
required sample size of 224 subjects (112 subjects per treatment group) for the per-protocol analysis.
Based on data from CNTO1959PSO3001 and CNTO1959PSO3002, it is anticipated that approximately 
35% of enrolled subjects in Study Part 1 will be eligible for randomization at week 28 in Study Part 2. Thus, 
a total of 800 subjects should be enrolled in Study Part 1 to ensure that at least 280 subjects are eligible for 
randomization in Study Part 2. Accounting for a 10% drop-out rate of subjects ineligible for randomization 
at week 28 because of study discontinuation prior to week 28, it is therefore planned to enroll a total of 
888 subjects in Study Part 1.
Note: Screenings and enrollments will be adjusted if necessary (without protocol amendment) to achieve 
280 SRe at week 28. Ongoing subjects in Study Part I will continue to Part 2 if eligible, irrespective of 
whether or not 280 SRe are already randomized. Only screenings will be closed.


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Efficacy Analyses
The efficacy analyses will be performed separately for each Study Part. For all efficacy analyses to compare 
guselkumab 100 mg q8w vs. guselkumab 100 mg q16w in Study Part 2, all randomized subjects at week 28 
will be included. In Study Part 2 subjects will be analyzed according to the group to which they were 
randomized regardless of the treatment they actually received (intent-to-treat analysis set).
The per-protocol analysis set will consist of all subjects in the intent-to-treat analysis set terminating the 
study without any major deviation of the protocol and its procedures. Subjects with major protocol 
deviations will be excluded from the per-protocol analysis. 
The confirmatory analysis of the primary endpoint variable will be performed both for the intent-to-treat 
analysis set and the per-protocol analysis set. In Study Part 1 and Study Part 3 all subjects treated with at 
least one dose of study drug will be included in the efficacy analyses. For all efficacy analyses in Study 
Part 1 and Study Part 3, subjects will be analyzed according to the treatment they actually received.
All analyses as described in detail in the statistical analysis plan (SAP) will be performed after DBL.
Safety Analyses
Safety data, including but not limited to, AEs, SAEs, infections, serious infections, changes in laboratory 
assessments, and changes in vital signs will be summarized. Treatment-emergent AEs (TEAEs) will be 
summarized by treatment group and Medical Dictionary for Regulatory Activities (MedDRA) system organ 
class and preferred terms.
Pharmacokinetic Analyses
Serum guselkumab concentrations at specified visits will be summarized by efficacy response status for 
each treatment group. Descriptive statistics, including arithmetic mean, SD, median, interquartile range, 
minimum, and maximum will be calculated at each sampling time. All concentrations below the lowest
quantifiable sample concentration of the assay (below the quantifiable limit; BQL) or missing data will be 
labeled as such in the concentration data listing or statistical analysis system dataset. The BQL 
concentrations will be treated as zero in the summary statistics. 
Biomarker Analyses
Biomarker samples will be used to define serum markers, skin gene expression and cellular profiles, and 
genetic (DNA) data for correlative analyses to better understand the molecular effects of guselkumab on
the pathogenesis of psoriasis including the differences between >2 years and 2 years disease duration and 
to understand why people may respond differently to guselkumab. These analyses are considered 
exploratory and will be summarized in a separate technical manual.
Statistical Analyses per Study Part
Statistical analyses will be performed for each Study Part.
The confirmatory analysis is planned to be performed at the end of Study Part 2, ie, after all subjects have 
completed their visit at week 68 (ie, 40 weeks after randomization) or discontinued earlier. This analysis 
will include the confirmatory analysis of the primary endpoint, and the exploratory analyses of the major 
secondary endpoints and all other predefined efficacy and safety analyses from week 28 until week 68.
The analyses of Study Part 1 and Study Part 3 will be exploratory. The exploratory analysis of Study Part 1
will occur after all subjects have completed their visit at week 28 (ie, 28 weeks after study inclusion) or 
discontinued earlier. This analysis will include the safety analysis and all efficacy measures after Week 0 
and will cover the time until the week 28 visit. The exploratory analysis of Study Part 3 will occur after all 
subjects have completed their visits at week 116 (ie, 48 weeks after inclusion in Study Part 3 at week 68)
or week 144 in case of subjects entering the re-treatment arm in week 116, at week 164 (ie, 96 weeks after 
inclusion in Study Part 3 at week 68) or week 192 in case of subjects entering the re-treatment arm in week 
164, and at week 220 (ie, 152 weeks after inclusion in Study Part 3 at week 68) or week 248 in case of 
subjects entering the re-treatment arm in week 220 or discontinued earlier. These analyses will include the 
safety analyses and all efficacy measurements after week 68 and will cover the time until week 116/164/220
and week 144/192/248, respectively.








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BSA = body surface area; DLQI = Dermatology Life Quality Index; ETV = Early Termination Visit; FSV = Final Study Visit; NAPPA = Nail Assessment in Psoriasis and Psoriatic Arthritis
(CLIN, PBI and QoL); PASI = Psoriasis Area and Severity Index; PBMC = peripheral blood mononuclear cells; PSSD = Psoriasis Symptom and Sign Diary 7-day version; SFU = Safety-
Follow-up visit; TLSS = Target Lesion Severity Scores
Visits through week 68 are to be conducted within ±7 calendar days and visits after week 68 are to be conducted within ±14 calendar days; please prospectively contact the Sponsor 
for further instructions if it is anticipated that a visit may fall outside this window. In the event of early discontinuation of study agent, the assessments should be conducted at the 
time of discontinuation of study agent (ETV). After ETV, safety follow-up should be conducted for 12 weeks after the last administration of study drug. Subjects who discontinue 
study agent may or may not continue in the study depending on the reason for discontinuation of study agent; refer to Section 10.2 for further details.
*): Only for subjects reaching a PASI score=0 at weeks 20 and 28
**): Subjects who will not reach a PASI score=0 at week 20 or week 28 will receive further q8w guselkumab 100 mg treatment until week 60 (last guselkumab administration), with final study 
assessment at week 68 and final Safety Follow-Up Visit at week 72. 
***): Study Part 3 will last about 152 weeks until week 220 (Final Study Visit) and will not require any administrations of guselkumab. In between the 12-weekly on-site visits, telephone-visits 
will be done 6 weeks (± 7 days) after each on-site visit (ie, telephone visits at weeks 74, 86, 98, 110, 122, 134, 146, 158, 170, 182, 194, and 206) to notice a possible worsening of psoriasis.
****): For subjects, who withdraw from study participation, every effort should be made to conduct the ETV.
*****): For all subjects (part 1 and part 2) who discontinue study treatment prematurely, every effort should be made to conduct the SFU 12 weeks after the last study drug administration.
a.
All study procedures and evaluations are to be completed before study drug injection. Assessments for subjects who discontinue study agent administration or withdraw from the study are 
described in Section 10.2 and 10.3, respectively. 
b.
To occur within 4 weeks prior to week 0.
c.
Informed consent form must be signed before any study-related activity
d.
All subjects reaching a PASI=0 at week 20 and 28 will be determined as Super-Responders (SRe) and will be randomized at week 28 in Study Part 2.
e.
Subjects will receive guselkumab 100 mg at the weeks 0, 4, 12 and 20 (Study Part 1), and guselkumab or Placebo q8w at the weeks 28 to 60 (Study Part 2). 
f.
Women of childbearing potential must have a negative urine pregnancy test result at all study visits before study treatment drug administration.
g.
Performed by the subject (PRO) before any tests, procedures, or other evaluations (eg, PASI, affected BSA or NAPPA-CLIN) are performed for that visit.
h.
TLSS for the selected target lesion will be recorded at each biopsy collection time.
i.
Photo-documentation will be done standardized and professionally at few selected sites equipped with an appropriate photography laboratory (described in photo-documentation manual).
j.
All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled. Details will be provided in the Laboratory Manual.
k.
Laboratory assessments can be non-fasting and are listed in Section 9.6.
l.
One additional blood sample for pharmacokinetic and serum biomarker assessments will be taken at the time when the subject loses control of disease (defined as PASI score >5 at any 
visit during Study Parts 2 or 3, or PASI  DW ZHHN ).
m.
Biopsy samples for molecular and cellular analyses will be collected only from subjects who consent to participate in the optional biopsy substudy. A total of six 6 mm biopsy samples (or 
twelve 3 mm biopsy samples in substudy 2, if applicable; refer to Section 3.1) will be collected (1 NL at week 0, 1 L at weeks 0, 4, 28, and 68, and where feasible, 1 biopsy from a relapsing 
plaque at the time a subject in Study Part 2 or 3 requires re-treatment (see l). For further details regarding these evaluations, refer to Section 9.4. The target lesion will be photo-documented 
in a standardized manner (described in the Biopsy manual) if the subject agrees to photo-documentation.
n.
Blood samples to isolate PBMC for immunophenotyping analyses will be collected only from subjects who consent to participate in the optional substudy 1. For further details regarding 
these evaluations, refer to Section 9.4.
o.
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. For further details 
regarding these evaluations, refer to Section 9.4.
p.
Only if no chest radiograph done within the last 3 months before administration of first study drug.




CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
22
Approved, Date: 14 June 2021
BSA = body surface area; DLQI = Dermatology Life Quality Index; NAPPA = Nail Assessment in Psoriasis and Psoriatic Arthritis (CLIN, PBI and QoL); PASI = Psoriasis Area and Severity 
Index; PSSD = Psoriasis Symptom and Sign Diary 7-day version; SFU = Safety-Follow-up visit; TLSS = Target Lesion Severity Scores
Re-treatment visits are to be conducted within ±7 calendar days; please prospectively contact the Sponsor for further instructions if it is anticipated that a visit may fall outside this 
window. In the event of early discontinuation of study agent, these assessments should be conducted at the time of discontinuation of study agent (ETV). After ETV, safety follow-up 
should be conducted for 12 weeks after the last administration of study drug. Subjects who discontinue study agent may or may not continue in the study depending on the reason 
for discontinuation of study agent; refer to Section 10.2 for further details.
*): 6XEMHFWV 65H ZLWK 3$6, VFRUH ! DW DQ\ YLVLW LQ 6WXG\ 3DUW  RU  RU D 3$6, VFRUH  DW ZHHN  ZLOO UHFHLYH JXVHONXPDE 0 mg q8w for further 3 administrations (at that visit = re-
treatment weeks 0, 8 and 16) and study termination after 28 weeks (Safety-Follow Up visit)
a.
All study procedures and evaluations are to be completed before study drug injection. Assessments for subjects who discontinue study agent administration or withdraw from the study are 
described in Section 10.2 and 10.3, respectively. 
b.
Subjects will receive guselkumab 100 mg q8w for further 3 administrations (re-treatment weeks 0, 8 and 16).
c.
Women of childbearing potential must have a negative urine pregnancy test result at all study visits before study treatment drug administration.
d.
Performed by the subject (PRO) before any tests, procedures, or other evaluations (eg, PASI, affected BSA or NAPPA-CLIN) are performed for that visit.
e.
TLSS for the selected target lesion will be recorded at each biopsy collection time.
f.
Photo-documentation will be done standardized and professionally at few selected sites equipped with an appropriate photography laboratory (described in Photo-documentation manual).
g.
All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled. Details will be provided in the Laboratory Manual.
h.
Laboratory assessments can be non-fasting and are listed in Section 9.6.
i.
One additional blood sample for pharmacokinetic and serum biomarker assessments will be taken at the time when the subject loses control of disease (defined as PASI score >5 at any 
visit during Study Parts 2 or 3, or PASI  DW ZHHN ). However at R0, PK-samples will only be taken for Study Part 2d (ie, not for Study Part 3c).
j.
Biopsy samples for molecular and cellular analyses will be collected only from subjects who consent to participate in the optional biopsy substudy. A total of six 6 mm biopsy samples (or 
twelve 3 mm biopsy samples in sub 2 if appl., refer to Section 3.1). will be collected (1 NL at week 0, 1 L at weeks 0, 4, 28, and 68, and where feasible, 1 biopsy from a relapsing plaque 
at the time a subject in Study Part 2 or 3 requires re-treatment (see l).  For further details regarding these evaluations, refer to Section 9.4. The target lesion will be photo-documented in a 
standardized manner (described in the Biopsy manual), if the subject agrees to photo-documentation.
k.
Blood samples to isolate PBMC for immunophenotyping analyses will be collected only from subjects who consent to participate in the optional substudy 1. For further details regarding 
these evaluations, refer to Section 9.4.


23
Approved, Date: 14 June 2021
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
ABBREVIATIONS
AE
adverse event
ALT
alanine aminotransferase
APC
antigen presenting cell
AST
aspartate aminotransferase
BSA
body surface area
CLIN
Clinical
CRF
case report form(s)
DBL
database lock
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
eDC
electronic data capture
eg
example given
FSV
Final study visit
GCP
Good Clinical Practice
HBV/HCV
Hepatitis B virus/ Hepatitis C Virus
HIV
human immunodeficiency virus
IB
Investigators Brochure
ICF
informed consent form
ICH
International Council for Harmonisation
ie
that is
IEC
Independent Ethics Committee
IGRA
interferon-gamma-release-assay
IL
Interleukin
IL-23-R
interleukin-23 receptor
IRB
Institutional Review Board
ISR
injection site reaction
IWRS
interactive web response system
mAb
monoclonal antibody
MedDRA
Medical Dictionary for Regulatory Activities
MTX
Methotrexate
NAPPA
Nail Assessment in Psoriasis and Psoriatic Arthritis
NCI-CTCAE
National Cancer Institute Common Terminology Criteria for Adverse Events
PASI
Psoriasis Area and Severity Index
PBI
Patient Benefit Index
PFS-U
Prefilled Syringe assembled with the UltraSafe PLUSTM Passive Needle Guard
PQC
Product Quality Complaint
PRO
patient-reported outcome(s) 
PSSD
Psoriasis Symptom and Sign Diary
QoL
quality of life
q8w/q16w
every 8/16 weeks
RNA
ribonucleic acid
SAE
Serious Adverse Event
SAP
Statistical Analysis Plan
SC
Subcutaneous
SRe
Super-Responder(s)
SUSAR
suspected unexpected serious adverse reaction
TB
Tuberculosis
Tc17 cell
IL-17 producing cytotoxic T cell
TES
Time and Events Schedule
Th17 cell
IL-17 producing T helper cell
TLSS
Total Lesion Severity Score
ULN
upper limit normal
DEFINITIONS OF TERMS
PASI < 3: controlled disease
PASI 3 to 5: fluctuating disease
PASI >5: loss of control/re-treatment


24
Approved, Date: 14 June 2021
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
1.
INTRODUCTION
1.1.
Background
Psoriasis is a chronic inflammatory immune-mediated disease characterized by patches of 
inflamed skin covered with silvery-white scaly skin. Psoriasis pathogenesis involves the 
dysregulation of interleukin (IL)-23 mediated immune responses (Kollipara, et al. 2015). IL-23 is 
a key regulatory cytokine produced by macrophages and dendritic cells (DCs), which directs the 
differentiation, expansion and maintenance of CD4+ IL-17 producing T helper (Th17) cells, CD8+ 
IL-17 producing cytotoxic T (Tc17) cells, and CD4+ Th22 cells. It is probably also involved in the 
pathological differentiation and survival of tissue resident memory T cells (TRMs) (Cheuk, Wikén, 
et al. 2014).
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 generated by CD8+ Tc17 cells and 
various other immune cells, which are also to some extent regulated by IL-23 (Ness-Schwickerath, 
Jin und Morita 2010). The numbers of Th17 and Tc17 cells have been shown to be increased in 
psoriatic plaques (Cheuk, Wikèn, et al. 2014, Cheuk, Martini, et al. 2017) , and blockage of either 
IL-23 or IL-17 has demonstrated clinical benefit in psoriasis (Blauvelt, Lebwohl und Bissonnette 
2015). Inhibition of IL-23 has shown to normalize transcriptional signatures associated with Th17, 
and to normalize the levels of IL17A, IL17F and IL22 in psoriatic patients’ serum (Branigan et al., 
2016 SID; Liu et al., 2017, Gene to Clinic). In 2014, IL-23 inhibition was shown to result in clinical 
efficacy that was superior to that seen after TNF-Į LQKLELWLRQ (Sofen, et al. 2014, Blauvelt, Papp, 
et al. 2017, Reich, et al. 2017).
Guselkumab (CNTO 1959) is a fully KXPDQ LPPXQRJOREXOLQ * ODPEGD ,J*Ȝ PRQRFORQDO
antibody (mAb) that binds selectively to human IL-23 with high specificity and affinity. In in vitro 
models, guselkumab was shown to inhibit the bioactivity of IL-23 by blocking its interaction with 
cell surface IL-23 receptor, disrupting IL-23-mediated signaling, activation and cytokine cascades
and subsequent Th17, Tc17 and Th22 cell proliferation, cytokine production and survival. Other 
cells likely affected by guselkumab treatment include innate lymphoid cells type 3 (ILC3s) which 
also produce IL17 and IL22, are activated by IL-1 and IL-23 and are thought to be involved in 
psoriasis pathogenesis particularly during initiation of disease (Villanova, et al. 2014, Teunissen, 
et al. 2014).
Clinical studies with guselkumab have shown clearance rates that exceeded those afforded by other 
non-biologic and most biologic systemic psoriasis treatments, with ~30-45% of patients reaching 
complete clearance (Psoriasis Area and Severity Index [PASI] score=0) and approximately 70% 
RI SDWLHQWV UHDFKLQJ QHDUO\ FRPSOHWH FOHDUDQFH 3$6, VFRUH   ZHHNV DIWHU VWDUW RI guselkumab
treatment (Blauvelt, Papp, et al. 2017, Reich, et al. 2017, Papp, et al. 2018).
Additionally, blocking of IL-23 may have the potential to achieve a profound effect in the 
pathophysiology of the disease that goes beyond temporary clearance of psoriatic skin lesions. The 
induction of a sustained response with longer dosing intervals in a subset of patients will be 
investigated in this study.


25
Approved, Date: 14 June 2021
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
1.2.
Overall Rationale for the Study
Previous guselkumab studies suggest that after achieving a PASI 90 response some patients were 
still able to keep their responses for months after stopping the treatment. Several parameters 
including shorter disease duration, absolute PASI of 0 at week 28 and inflammatory cytokine 
serum levels at baseline (week 0) might be associated with higher drug-free remission rates.
Indeed, 
in 
exploratory 
analyses 
(unpublished 
data 
from 
CNTO1959PSO3001 and 
CNTO1959PSO3002), subjectV ZLWK VKRUWHU GLVHDVH GXUDWLRQ  \HDUV seem to have a higher 
maintenance of response rate after drug withdrawal than subjects with a longer history of disease 
(ie, >10 years) and achieving an absolute PASI of 0 at week 28 was associated with long-term 
maintenance of PASI 90 response (45.8% of subjects who achieved an absolute PASI of 0 at week 
28 achieved long-term maintenance of PASI 90 response; compared to 24% of subjects who didn’t 
achieve an absolute PASI of 0 at week 28 achieved long-term maintenance of PASI 90 response 
odds ratio of 2.66, p<0.005, Fisher’s exact test).
Whether there is a distinct subset of subjects, here termed Super Responders (SRe), who are more 
likely to show a more profound response of guselkumab on the pathophysiology of disease 
establishment, maintenance and relapse shall be investigated in this study. 
More precisely, the present study aims to define the subset of SRe (ie, subjects who achieve an
absolute PASI score=0 at weeks 20 and 28) and is intended to evaluate whether these subjects
maintain disease control during extended dosing intervals as well as after drug withdrawal.
To evaluate these points one after the other the study is divided into three parts:
Part 1 – Identification of SRe

SRe are defined by an absolute PASI score=0 at weeks 20 and 28
Part 2 – Comparison of treatment algorithms for SRe

Non-inferiority of q16w vs. q8w dosing of guselkumab
Part 3 – Maintenance of drug-free remission

Evaluation of drug-free maintenance of response following drug withdrawal in SRe.
All parts of the study are accompanied by investigations (4 substudies) on whether changes in 
clinical response are associated with distinct molecular or cellular changes in serum or skin 
biopsies.
To better understand the underlying immunological mechanisms of the profound effect of IL-23 
inhibition on disease establishment and chronicity of plaque psoriasis, a significant proportion 
(approximately 40%) of the subjects to be included in the study will have a disease history of 
 years.


26
Approved, Date: 14 June 2021
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
The following points were considered for design and conduct of the present clinical study:
x
Specific therapeutic algorithms/regimens are to be established to achieve subject-optimized 
guselkumab treatment: A dose regimen of 100 mg guselkumab at weeks 0, 4, and q8w 
thereafter has been shown to be most suitable regarding efficacy and safety for the overall 
population of subjects suffering from moderate-to-severe plaque psoriasis and was therefore 
approved by EMA and FDA (SmPC Tremfya® 2017). This regimen will also be used for 
Study Part 1 (lasting 28 weeks) and as comparative dosing regimen in Study Part 2.
x
As described above, SRe are presumed to respond better to guselkumab treatment even with 
extended dosing intervals and to show more profound changes in immunopathophysiology of 
the disease. Therefore, the primary objective of this study is to demonstrate non-inferiority of 
q16w treatment to q8w treatment in SRe in Study Part 2.
1.3.
Benefit/Risk Assessment
A large global Phase 3 program consisting of 3 studies (CNT1959PSO3001, CNTO1959PSO3002, 
and CNTO1959PSO3003) has been conducted to investigate the efficacy and safety of sc
guselkumab in adult patients with moderate to severe plaque psoriasis. The longer-term efficacy 
and safety of guselkumab is being assessed in 4-year extensions of studies CNTO1959PSO3001 
and CNTO1959PSO3002 (ie, both studies will have an overall study duration of 5 years). In the 
EU, approval was obtained for the use of Tremfya® in adults with moderate to severe plaque 
psoriasis on 10 November 2017. As such, the benefit-risk profile for guselkumab in the treatment 
of plaque psoriasis is considered to be favorable.
Extensive clinical development is also ongoing in other inflammatory diseases such as psoriatic 
arthritis (PsA), Crohn’s disease, generalized pustular psoriasis, erythrodermic psoriasis, and 
palmoplantar pustulosis, as summarized in the latest version of the IB.
Dosing in the current study is either at the approved dosing regimen for guselkumab in psoriasis 
(100 mg sc at Week 0 and Week 4, and then q8w) or at an extended interval (100 mg sc q16w). 
Details about the design and rationale of the study are provided in Section 3.
Potential risks of the study, including those of serious infection and malignancy, are being 
addressed via judicious inclusion/exclusion criteria, guidelines for subject management (including 
for discontinuation of study treatment), prohibited concomitant medications, and comprehensive 
medical monitoring of data by the sponsor during the conduct of the trial. Further details about the 
safety evaluations that will be utilized in the study are provided in Section 9.6.
Based on the available data and the proposed safety measures, the potential risks for subjects in 
the current study appear to be acceptable relative to the potential benefits of the study.


27
Approved, Date: 14 June 2021
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
2.
OBJECTIVES, ENDPOINTS, AND HYPOTHESIS
2.1.
Objectives and Endpoints
2.1.1.
Objectives
Primary objective
The primary objective of the study is to demonstrate that Super-Responders (SRe; defined as 
psoriasis subjects who receive on-label guselkumab treatment until week 20 and respond with a 
Psoriasis Area and Severity Index [PASI] score=0 at weeks 20 and 28) maintain control of disease 
until week 68 with prolonged treatment intervals of 16 weeks (100 mg q16w). To be demonstrated 
in Study Part 2 (see Section 3.1 for study design).
Secondary objectives
Secondary objectives are to evaluate
x
whether subjectV ZLWK VKRUW GLVHDVH GXUDWLRQ  \HDUV VKRZ D PRUH UDSLG DQG EHWWHU
guselkumab response compared to subjects with longer disease duration and whether subjects
with shorter disease are more likely to maintain drug-free control of disease after guselkumab 
withdrawal. To be evaluated in Study Parts 1, 2, and 3.
x
whether SRe with short disease duration and PASI=0 at week 116 (ie, remission for one year 
after withdrawal) will show sustained remission (ie, PASI=0) over two additional years 
compared to subjects with longer disease duration. To be evaluated in Study Part 3.
x
whether SRe with short disease duration and PASI>0 to  DW ZHHN  LH SDUWLDO UHODSVH IRU
one year after withdrawal) will show continued loss of response or stabilization of disease 
worsening over two additional years compared to subjects with longer disease duration.
To be evaluated in Study Part 3.
x
whether different treatment intervals (weeks 28 to 60: guselkumab 100 mg q8w vs. 
guselkumab 100 mg q16w) affect the maintenance of drug-free control of disease after 
68 weeks of guselkumab treatment. To be evaluated in Study Part 3.
x
the safety and tolerability of guselkumab in subjects with moderate-to-severe plaque-type 
psoriasis.
Note: disease duration will be calculated from date at which first symptoms (plaque) were reported 
by subject to date of screening visit.
Exploratory objectives
The following objectives are to be explored in the mechanistic biomarker substudies:
x
characterization of the immune cellular and molecular composition at baseline (week 0) and 
changes (quantitative and qualitative characterization) in the lesional skin of subjects during 
treatment with guselkumab as determined by fluorescence activated cell sorting (FACS)-
based analysis. To be explored in substudy 1
x
characterization of the immune cellular changes (quantitative and qualitative characterization) 
in the blood of subjects at baseline (week 0), during and after treatment with guselkumab as 
determined by FACS-based analysis. To be explored in substudy 1


28
Approved, Date: 14 June 2021
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
x
characterization of molecular (gene expression) changes during treatment with guselkumab in 
the skin of subjects treated with guselkumab as determined by RNA sequencing (RNAseq) 
and quantitative polymerase chain reaction (qPCR). To be explored in substudy 2
x
characterization of the tissue immunopathological changes in the skin of subjects during and 
after treatment with guselkumab as determined by immunohistochemistry (IHC)/ 
immunofluorescence (IF)/ in situ hybridization (ISH). To be explored in substudy 2 
x
characterization of the effects of guselkumab treatment on serum biomarkers as determined 
by immunoassays. To be explored in substudy 3
x
characterization of the association between changes in the various exploratory biomarker 
endpoints and 1) efficacy of guselkumab, 2) duration of psoriasis, 3) maintenance of response 
after stopping guselkumab treatment, and 4) ability to achieve a PASI 100 response at weeks 
20 and 28 (super responder status). To be explored in all substudies
2.1.2.
Endpoints
For the endpoints, the following terms were defined:
x
Control of disease: PASI score <3
x
Fluctuating disease: PASI score 3 to 5
x
Loss of disease control: PASI score >5.
Study groups are defined as follows:
x
1: All participating subjects who are enrolled and are scheduled to receive guselkumab 100 mg 
at weeks 0, 4, q8w until week 28 (Study Part 1)
x
2a: SRe (PASI score=0 at weeks 20 and 28) randomized to guselkumab 100 mg q8w at weeks 
28 to 60 (Study Part 2)
x
2b: SRe randomized to guselkumab 100 mg q16w at weeks 28 to 60 (Study Part 2)
x
2c: non-SRe with a PASI score >0 at week 20 and/or 28 who will receive guselkumab 100 mg 
q8w at weeks 28 to 60 (Study Part 2)
x
2d: SRe with loss of disease control between week 28 and 68, who will enter the re-treatment 
arm and receive guselkumab 100 mg at weeks 0, 8, and 16 calculated from the date of loss of 
disease control (Study Part 2)
x
3a: SRe randomized to guselkumab 100 mg q8w in Study Part 2 with withdrawal of 
guselkumab at week 68 (Study Part 3)
x
3b: SRe randomized to guselkumab 100 mg q16w in Study Part 2 with withdrawal of 
guselkumab at week 68 (Study Part 3)
x
3c: SRe with fluctuating disease at week 68 or loss of disease control at any other visit after 
week 68, who will enter the re-treatment arm and receive guselkumab 100 mg at weeks 0, 8 
and 16 calculated from the date of loss of disease control (Study Part 3).
Primary endpoint
The primary endpoint of the main study is the proportion of subjects in study groups 2a and 2b
who achieve an absolute PASI score <3 at week 68.


29
Approved, Date: 14 June 2021
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
Major secondary endpoints
Major secondary endpoints of this study are:
x
Time to improvement from baseline (week 0) in PASI (PASI 75/90/100 response and absolute PASI 
VFRUH  IRU VXEMHFWV ZLWK VKRUW   years) and longer (>2 years) disease duration per study group (1,
2a, 2b, and 2c)
x
Proportion RI VXEMHFWV ZLWK VKRUW  \HDUV DQG ORQJHU ! \HDUV GLVHDVH GXUDWLRQ ZKR DFKLHYH DQ
DEVROXWH 3$6, VFRUH RI   DQG  DW ZHHNV     , and 220 per study group (1, 2a, 2b, 
2c, 3a, and 3b)
x
Proportion of subjects who retain disease control (ie, absolute PASI score <3 at all visits) from week 68
through week 116, from week 68 through week 164, and from week 68 through week 220 for subjects 
ZLWK VKRUW   \HDUV DQG ORQJHU ! \HDUV GLVHDVH GXUDWLRQ SHU VWXG\ JURXS 3a and 3b)
Other secondary endpoints of this study are:
x
Proportion of subjects who achieve a PASI 75/90/100 response at weeks 20, 28, 68, 116, 164, and 220
per study group (1, 2a, 2b, 2c, 3a, and 3b)
x
Time to loss of disease control (absolute PASI score >5 at any visit) after treatment withdrawal beyond 
week 68 per study group (3a and 3b)
x
Proportion of subjects with an absolute PASI score=0 at all of the following visits: weeks 12, 16, 20,
and 28 (study group 1)
x
Change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at weeks 28, 68, 116, 
164, and 220 per study group (1, 2a, 2b, 2c, 3a, 3b, and 3c)
x
Proportion of subjects who achieve a DLQI score 0/1 and <5 at weeks 28, 68, 116, 164, and 220 per 
study group (1, 2a, 2b, 2c, 3a, 3b, and 3c)
x
Change from baseline (week 0) in affected Body Surface Area (BSA) at weeks 12, 28, 52, 68, 80, 104,
116, 140, 164, 188, 212, and 220 (all study groups)
x
Change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
score at weeks 28, 68, 116, 164, and 220 among subjects with nail psoriasis at baseline (week 0; 1, 2a, 
2b, 2c, 3a, and 3b).
x
Change from baseline (week 0) in the signs and symptoms aggregate scores of the Psoriasis Symptoms 
and Signs Diary (PSSD) at weeks 28, 68, 116, 164, and 220 (1, 2a, 2b, 2c, 3a and 3b)
x
Proportion of subjects who achieve a PSSD sign score=0 at week 68 among subjects with a PSSD sign 
VFRUH  DW ZHHN 28 per study group (2a, 2b, and 2c).
x
Association between trough serum guselkumab concentration and efficacy or serum biomarker level
x
Association between trough serum guselkumab levels at weeks 20, 28, 36, and 68 and achieving a 
PASI score <3 at week 68 per study group (2a and 2b)
x
Proportion of subjects who were re-treated due to loss of disease control (PASI >5) and regain control 
of disease (PASI <3) 24 weeks after start of re-treatment (study groups 2d and 3c)
x
Safety and tolerability with regard to adverse events (AEs) and abnormal laboratory results (all study 
groups).
Refer to Section 9 for evaluations related to these endpoints.


30
Approved, Date: 14 June 2021
CNTO 1959 (guselkumab)
Clinical Protocol CNTO1959PSO3012 Amendment 5
2.2.
Hypothesis
In this study, Super-Responders (SRe) are defined as psoriasis subjects achieving clear skin 
(measured as absolute PASI score=0) at weeks 20 and 28 of treatment. Subjects with shorter 
GLVHDVH GXUDWLRQ  years calculated from date at which first symptoms [plaque] were reported by 
subject to date of screening visit) are expected to have a higher likelihood to be SRe.
In Super-Responders, guselkumab treatment might have stronger modifying effects on 
immunopathological mechanisms of the disease than in non-SRe. Therefore, it is hypothesized that 
this subpopulation might not lose control of disease even with a longer dosing interval (q16w 
instead of q8w) and that this subpopulation will have higher probability of drug-free remission 
after 60 weeks of treatment.
The hypothesis of this study is that guselkumab q16w treatment is non-inferior to guselkumab q8w 
treatment in SRe as assessed by the proportion of subjects with an absolute PASI score <3 at 
week 68 (alternative hypothesis in a statistical sense).
If the hypothesis is accepted, the study will be considered positive.
3.
STUDY DESIGN AND RATIONALE
3.1.
Overview of Study Design
The present trial is designed as a phase 3b, randomized, double-blind, parallel-group, multicenter, 
comparison study in subjects of at least 18 years of age with moderate to severe plaque-type 
psoriasis.
It is planned to achieve about 280 subjects categorized as Super-Responders (SRe, ie, PASI 
score=0 at weeks 20 and 28) for randomization in Study Part 2 (140 subjects in study group 2a 
and 140 subjects in study group 2b). It is assumed that 900-1000 subjects are therefore needed to 
be screened at up to 90 German study sites and 10 French study sites and that 888 subjects are 
needed to be enrolled (based on a SRe rate of 30-35% of enrolled subjects). Screenings and 
enrollments will be adjusted if necessary (without protocol amendment) to achieve 280 SRe at 
week 28. Ongoing subjects in Study Part I will continue to Part II if eligible, irrespective of whether 
or not 280 SRe are already randomized. Only screenings will be closed.
Of the enrolled subjectV DSSUR[LPDWHO\  PXVW KDYH D GLVHDVH GXUDWLRQ RI  years calculated 
from date at which first symptoms (plaque) were reported by subject to date of screening visit. 
SubjectV ZLWK GLVHDVH GXUDWLRQ RI  years are expected to have a higher likelihood to be SRe. At 
UDQGRPL]DWLRQ WZR VWUDWLILFDWLRQ FULWHULD DSSO\ L 65H ZLWK GLVHDVH GXUDWLRQ RI  years will be 
stratified equally to study group 2a and 2b. Further, (ii) SRe who are participating in the 
mechanistical substudy 1 will be stratified equally to study group 2a and 2b.
The study will feature the following structure and design:
Study Part 1: Screening through Week 28:
This screening phase will last up to four weeks (+ 7 calendar days) prior to first administration of 
guselkumab (week 0) followed by a 28-week run-in period with visits and administration of 
100 mg guselkumab at weeks 4, 12, and 20. In case of a PASI score=0 at weeks 20 and 28 subjects
are qualified to be randomized either to study group 2a or 2b of Study Part 2. 


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In case of PASI score >0 at the weeks 20 and/or 28 the subjects will continue to receive 
guselkumab 100 mg q8w until week 60 (last administration at week 60 visit) with final study 
assessments at week 68 and final safety follow-up visit at week 72 (defined as study group 2c). 
Study Part 2: Week 28 through Week 68:
Subjects with a PASI score=0 at weeks 20 and 28 will be defined as SRe and randomly assigned 
to the following two treatment groups: 2a) guselkumab 100 mg q8w or 2b) guselkumab 100 mg 
q16w. In addition, subjectV ZLWK GLVHDVH GXUDWLRQ  years will be equally distributed to either 
group. Study visits of Study Part 2 will be conducted every 8 weeks.
To blind the study, study treatment (guselkumab or Placebo) will be administered q8w starting at 
week 28 until the end of study therapy (last administration in week 60). The q16w group will 
receive Placebo at weeks 28, 44 and 60. Subjects losing control of disease, defined as PASI score 
>5 at any visit during Study Part 2 (ie, until week 60), will enter the Re-treatment arm (group 2d,
see section Re-treatment below).
The assessment for the primary endpoint (EP) will be at week 68 for both study groups.
In case of PASI <3 at week 68 the subject will not receive any study medication and enter the drug 
ZLWKGUDZDO SDUW 6WXG\ 3DUW  ,Q FDVH RI 3$6,   DW YLVLW ZHHN  WKH subject will enter the re-
treatment arm 3c (see section Re-treatment below).
In case of PASI score >0 at the weeks 20 and/or 28 the subjects will continue to receive 
guselkumab 100 mg q8w until week 60 (last administration at week 60 visit) with final study 
assessments at week 68 and final safety follow-up visit at week 72 (defined as study group 2c). At 
visit week 68 (for group 2c), the investigator may continue treatment with commercially available 
guselkumab (ie, not provided by the Sponsor) to maintain a q8w interval. Due to the half-life of 
guselkumab, it is recommended not to start a new therapy during safety follow-up period (ie, 
12 weeks after last dose). If the investigator feels strongly that an additional therapy is needed, this 
should be discussed with the sponsor before initiation of the new therapy.
Study Part 3: Week 68 through Week 220:
Subjects of group 2a and 2b with a PASI score <3 at week 68 will enter Study Part 3 and be 
withdrawn from the study medication and followed-up until week 220. Study visits of Study Part 
3 will be conducted every 12 weeks (ie, at weeks 80, 92, 104, 116, 128, 140, 152, 164, 176, 188, 
200, and 212; ± 14 days). In between the 12-weekly on-site visits, a telephone-visit 6 weeks (± 
7 days) will be done after each on-site visit (ie, telephone visits at weeks 74, 86, 98, 110, 122, 134, 
146, 158, 170, 182, 194, and 206) to assess whether the subject notices a worsening of his/her 
psoriasis. If so, the subject must attend an on-site visit for efficacy assessment by the assessor as 
soon as possible but not later than 2 weeks after the phone call. For patients not starting re-
treatment, the final visit will take place at week 220.
Re-treatment
Subjects losing control of disease, defined as PASI score >5 at any visit during Study Part 2 or 3 
(ie, until week 220), will enter the re-treatment-arms (2d or 3c) with three guselkumab 100 mg 
administrations starting at that visit (= re-treatment-week 0, followed by administration at re-
treatment-weeks 8 and 16).


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If re-treatment is started at a visit which would usually not require all PROs needed at the first re-
treatment visit, those PROs will be obtained immediately after efficacy assessments (basis for re-
treatment-decision) and prior to drug administration at that visit.
The final efficacy assessment for all subjects in the re-treatment-arms will take place 24 weeks 
after loss of control and study termination will be 28 weeks after loss of control (final study 
visit/safety follow-up). At visit week 24 of the re-treatment, the investigator may continue actual 
treatment with commercially available guselkumab (ie, not supplied by Sponsor) to maintain a 
q8w interval. Due to the half-life of guselkumab, it is recommended not to start a new therapy 
during safety follow-up period (ie, 12 weeks after last dose). If the investigator feels strongly that 
an additional therapy is needed, this should be discussed with the Sponsor before initiation of the 
new therapy.
Subjects with fluctuating disease (ie, PASI score 3 to 5) at the week 68 visit will also get the 
opportunity to enter the re-treatment-arm (3c).
The last chance to start re-treatment will be the visit week 220 (ie, final efficacy assessment at 
week 244 with final study visit/safety follow-up at week 248).
Photo-documentation
At few selected sites equipped with professional photo-documentation laboratory, photos of
affected body areas and their changes will be performed after efficacy assessments (PASI, BSA, 
NAPPA-CLIN) are completed and if the subject agrees to photo-documentation. More details are 
described in a photo-documentation manual.
TLSS
For substudy 1 and 2, the TLSS for the selected target lesion will be recorded at each biopsy 
collection time. The target lesion will be photo-documented in a standardized manner (described 
in the Biopsy manual) if the subject agrees to photo-documentation.
Treatment compliance
Week 0 can be done once all screening activities are completed, results are available, and the 
subject is eligible, but latest 4 weeks after screening visit (+ 7 calendar days). From weeks 4 to 68 
it is expected that all subjects will attend visits within a range of ±7 calendar days. Visits from 
week 68 through week 220 are to be conducted within ±14 calendar days of the anticipated visit 
date. The week 220 visit should be conducted at least 160 weeks after the last study agent injection.
Visits during the re-treatment period (study groups 2d and 3c) are also expected to occur within a 
range of ±7 days.
Efficacy measurements
Efficacy of treatment will be assessed before any tests, procedures or other evaluations, first by 
the subject him/herself (1st DLQI, 2nd 7-day version of PSSD, NAPPA-QoL and NAPPA-PBI), 
and subsequently by the investigator (PASI, BSA and NAPPA-CLIN). 
An exception to this order is the start of re-treatment at a visit, which would usually not require all 
PROs needed at the visit week 0 of the re-treatment arm. In this case, PROs will be obtained 
immediately after efficacy assessments (which are the basis for re-treatment-decision) and prior to 
drug administration at that visit.


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Safety measurements
Safety evaluations will include the monitoring of adverse events (AEs, including injection site and 
allergic reactions), clinical laboratory tests (hematology, chemistry and pregnancy testing), 
physical examinations, vital signs, concomitant medication review, and early detection of 
tuberculosis (TB). Venous blood samples will be collected for the determination of serum 
guselkumab concentrations (pharmacokinetics).
Study duration
The first study drug injection will be administered at week 0, and the last regular injection will be 
given at week 60. For subjects entering the re-treatment arm last possible drug injection will be 
week 84 (group 2d) and week 236 (group 3c) respectively (please refer to re-treatment section). 
Including a 4-week screening phase and a 12-week safety follow-up, the minimum duration of a 
subject’s regular participation in this study will be 75 weeks and the maximum duration will be 
252 weeks.
The study is considered completed with the last visit for the last subject participating in the study. 
The final data from the study site will be sent to the Sponsor (or designee) after completion of the 
final visit at that study site, in the time frame specified in the Clinical Trial Agreement. The overall 
duration of the study is expected to be approximately 84 months (start in Q4 2018, stop in Q1
2025). The estimated frequency and timing of the study visits are summarized in the 'Time and 
Events Schedule' (TES).
A schematic diagram of the study design is provided below:
Figure 3.1-1: Overview of Study Design


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Substudies
Four substudies are planned to further evaluate pharmacologic effects of guselkumab and evaluate 
various pharmacologic/clinical response relationships allowing assessment of inter-individual 
variability in clinical outcomes and possible identification of subject population groups that may 
respond differently to guselkumab. The substudies will also aim to further define the mechanism 
of action (MoA) of guselkumab at the molecular and cellular levels during and after treatment. 
Changes in gene expression as well as quantitative and qualitative changes in different immune 
cells will be evaluated in skin biopsies and blood.
Substudy 1 (Cellular MoA substudy):
Few sites will be identified that have expertise to conduct fluorescence activated cell sorting 
(FACS)-based cellular immunophenotypic characterization of freshly isolated skin biopsies. 
Participation in this study is optional. Subjects recruited to the selected sites will be asked to agree 
to the cellular MoA substudy (target n=60). 6 mm skin biopsy samples will be collected as follows: 
1 non-lesional (NL) and 1 lesional (L) biopsy at weeks 0 and 116 (only SRe), and 1 L biopsy at 
weeks 4, 28, 68, and 220. In addition, when subjects lose control of disease (PASI >5) in Study 
Parts 2 or 3 and go into re-treatment, an additional biopsy will be taken from a lesional plaque that 
shows disease activity. Biopsies will be dissociated into single cell suspension and subjected to 
FACS-based immunophenotyping analyses. Whole blood samples for the isolation of peripheral 
blood mononuclear cells (PBMCs) will also be collected from consenting subjects for subsequent 
immunophenotyping analyses by FACS (according to TES at weeks 0, 4, 28, 68, 80, 116, and 220).
Substudy 2 (Gene expression substudy):
Skin biopsies will be collected in a subset of subjects (target n=100) at selected sites (capable of
performing the skin biopsy collection and processing procedure) to evaluate gene and protein 
expression profiles and cellular content. Participation in this skin biopsy substudy is optional. 
6 mm skin biopsy samples will be collected as follows: 1 NL and 1 L biopsy at weeks 0 and 116 
(only SRe), and 1 L biopsy at weeks 4, 28, 68, and 220. In addition, when subjects lose control of 
disease (PASI >5) in Study Part 2 or 3, and go into re-treatment, an additional biopsy will be taken 
from a lesional plaque that shows disease activity. Each biopsy will be split in two parts; one part 
will be stored in RNA later preservative for RNA gene expression analysis, while the other part 
will be stored frozen in optimal cutting temperature (OCT) media for hematoxylin and eosin stain 
(H&E), immunohistochemistry (IHC) and immunofluorescence (IF) analysis. Two 3 mm biopsies 
may be taken instead of the 6 mm biopsy if preferred by the investigator and consented by the 
patient. The splitting step is not applicable in that case.
In addition to the biopsy collection for the selected patients taking part in the substudy 2, the novel 
method tape stripping (non-invasive) will be done for all participants in part 3 (SRe). Tape 
stripping is a less invasive collection method that may allow measurement of gene expression as 
well as levels of proteins or other biomarkers in the stratum corneum. The tape strip approach will 
be done to gain epidermal cells for biomarker analysis (transcriptomics via RNA seq; proteomics) 
and to validate tape stripping results by comparison with available skin biopsies. Tape stripping 
will be performed, where feasible, at week 116 for all participants, and at R0 visit or week 220 
visit for those, who do or do not relapse. Tape strip samples will be collected from both lesional 
and adjacent non-lesional areas during the sampling period starting at week 116.
The samples will be shipped to the central lab and will be analyzed later.


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Substudy 3 (Serum analysis):
Participation in this substudy is mandatory. Serum samples will be collected from all subjects to 
assess PD markers associated with the response to guselkumab as well as markers related to 
psoriasis. Measurements may include but are not limited to serum IL-17A, IL-17F, IL-22 levels 
and beta defensin-2 (BD-2). The samples) will be collected according to the TES at weeks 0, 4, 
28, 68, 80, 116, 164, and 220 (and R0, if applicable), and analyzed by immunoassays.
Substudy 4 (Genetic analyses):
It is recognized that genetic variation can be an important contributing 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 identify population subgroups 
that respond differently to a drug. The goal of the genetic (DNA) analysis is to collect a single 
DNA sample at week 0 as specified in the TES to search for genetic factors that may influence 
molecular effects, clinical efficacy, or tolerability of guselkumab and to identify genetic factors 
associated with psoriasis. Participation in this study is optional. Only subjects who sign the consent 
form to participate in the genetic assessment will have whole blood DNA samples collected.
Note: One additional blood sample for biomarker assessments will be taken at the time when the 
subject loses control of disease (defined as PASI >5 at any visit during Study Part 2 or 3 = R0).
Altogether, these substudies will provide crucial information about possible subject-optimized 
guselkumab treatment algorithms and may relate immunopathological mechanisms to clinical 
course and characteristics of plaque psoriasis.
3.2.
Study Design Rationale
Dose rationale
A dose regimen of guselkumab 100 mg at weeks 0, 4 and q8w thereafter was selected for Study 
Part 1. This is the dose regimen, which is known to result in clinically meaningful improvement 
of the disease (SmPC TREMFYA®). In Study Part 2, subjects with a PASI score=0 at weeks 20 
and 28 will be randomly assigned to either guselkumab 100 mg q8w or q16w to evaluate if these 
subjects maintain their disease control (absolute PASI score <3 at week 68) under extended dosing 
intervals. A larger dosing interval would provide higher comfort and better economy for subjects
and physicians.
Duration of treatment period and whole study period
This study will have a 4-week screening phase, a 60-week treatment phase and a 12- to 160-week 
safety follow-up phase (depending on whether subjects are participating in Study Part 3). The 
duration of the regular subject’s participation allows for an adequate treatment period and provides 
sufficient time to perform follow-up on safety and maintenance of response.
Blinding and randomization
Randomization will be used to minimize bias in the assignment of subjects to guselkumab 100 mg 
q8w or q16w (Study Part 2), to increase the likelihood that known and unknown subject attributes 
(eg, demographic and baseline characteristics) are evenly balanced across treatment groups, and 
to enhance the validity of statistical comparisons across treatment groups. Double-blinded 
treatment (Placebo treatment at weeks 28, 44 and 60 for subjects assigned to guselkumab 100 mg 
q16w) will be used to reduce potential bias during data collection and evaluation of the endpoints. 
Week 28 was chosen as the time for randomization because it allows subjects to reach steady-state 


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Approved, Date: 14 June 2021
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guselkumab concentrations with a q8w dosing regimen as well as steady-state clinical response. 
Randomization will be stratified by disease duration at baseline  years vs. >2 years) and by 
participation in the mechanistical substudy 1 to allow for evaluation of similarities or differences 
regarding the response rates.
Biomarker and DNA collection
Besides assessing clinical parameters, biomarker and DNA samples will be collected to further 
evaluate i) the MoA and molecular effects of guselkumab, ii) psoriasis pathogenesis including 
differences between >2 \HDUV DQG  years disease duration, and iii) inter-individual variability in 
clinical outcomes. Furthermore, population subgroups may be identified who respond differently 
to guselkumab (iv).
Serum samples will be collected in all subjects (mandatory) to assess pharmacodynamic markers 
associated with the response to guselkumab (substudy 3). Skin biopsies and blood for 
immunophenotyping of PBMCs will be only collected in a subgroup of subjects who consent to 
participate in the optional biomarker substudies 1 or 2. The goal of these biopsy substudies is to 
analyze immunological parameters and biomarkers, and to compare the results between subjects
with long and short disease duration before starting, during and after withdrawal of the treatment 
with guselkumab.
Whole blood samples will be collected for genetic analyses in those subjects who sign the consent 
form to participate in the genetic (DNA) assessment. 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. Pharmacogenomic research
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 pharmacogenomic 
component is to collect DNA to allow identification of genetic factors that may influence the 
pharmacodynamics, efficacy, or tolerability of guselkumab and to find genetic factors associated 
with psoriasis.


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4.
SUBJECT POPULATION
Screening for eligible subjects will be performed within 4 weeks before administration of the study 
drug. The inclusion and exclusion criteria for enrolling subjects in this study are described in the 
following two 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 11.1.
4.1.
Inclusion Criteria
Each potential subject must satisfy all of the following criteria to be enrolled in the study:
1.
Male or female with at least 18 years of age.
2.
Has a GLVHDVH GXUDWLRQ RI SODTXH SVRULDVLV RI HLWKHU  years or >2 years calculated from date 
at which first symptoms [plaque] were reported by subject to date of screening visit at 
screening; approximately 40% subjects must have a GLVHDVH GXUDWLRQ  years.
3.
Has moderate-to-severe plaque-psoriasis defined by a) a PASI score >10 or affected BSA 
>10% 
and b) additionally a DLQI score >10 at baseline (week 0).
4.
Is a candidate for systemic treatment for psoriasis.
Reproduction-related inclusion criteria
Contraceptive (birth control) use by men or women should be consistent with local regulations 
regarding the acceptable methods of contraception for those participating in clinical studies.
Typical use failure rates may differ from those when used consistently and correctly. Use should 
be consistent with local regulations regarding the use of contraceptive methods for subjects in 
clinical studies.
5.
Before first administration of study drug, a woman must be (as defined in Attachment 5):
a.
Not of childbearing potential 
b.
Of childbearing potential and practicing a highly effective method of contraception 
(failure rate of <1% per year when used consistently and correctly) and agrees to remain 
on a highly effective method method while receiving study treatment and until 12 weeks 
after last dose - the end of relevant systemic exposure. Examples of highly effective 
methods of contraception are located in Attachment 5.
6.
A woman of childbearing potential must have a negative urine pregnancy test at baseline and 
agree to urine pregnancy testing before receiving injections and at safety follow-up.
7.
A woman must agree not to donate eggs (ova, oocytes) for the purposes of assisted 
reproduction during the study and for a period of 12 weeks after receiving the last 
administration of guselkumab.
8.
A male subject must wear a condom when engaging in any activity that allows for passage 
of ejaculate to another person.


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9.
A male subject must agree not to donate sperm for the purpose of reproduction during the 
study and for a minimum 12 weeks after receiving the last dose of study treatment.
10.
TB-related inclusion criteria:
Subjects are considered eligible according to the following TB screening criteria:
a. 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.
Note: It is the responsibility of the investigator to verify the adequacy of previous
anti-TB treatment and to provide appropriate documentation.
b. Have no signs or symptoms suggestive of active TB upon medical history and/or physical 
examination.
c. Have had no recent close contact with a person with active TB or, if there has been such 
contact, will be referred to a physician specializing in TB to undergo additional 
evaluation and, if warranted, receive appropriate treatment for latent TB before the first 
administration of study drug.
d. Within 2 months before baseline, have a negative QuantiFERON®-TB Gold test result, 
or have a newly identified positive QuantiFERON-TB Gold test result) in which active 
TB has been ruled out and for which appropriate treatment for latent TB has been initiated 
before baseline. Within 2 months before baseline, 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 baseline, 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 
baseline 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 
a documentation of having completed adequate treatment as described above are not 
required to initiate additional treatment for latent TB.
e. 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.
11.
Agrees not to receive a live virus or live bacterial vaccination during the study, or within 
3 months after the last administration of study drug.
12.
Agrees not to receive a BCG vaccination during the study, or within 12 months after the last 
administration of study drug.




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Approved, Date: 14 June 2021
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Clinical Protocol CNTO1959PSO3012 Amendment 5
6.
Is pregnant, nursing, or planning a pregnancy (both men and women) while enrolled in 
this study and within 16 weeks following the last administration of study drug.
7.
Has a non-plaque 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.
Had major surgery, (eg, requiring general anesthesia and hospitalization) within 8 weeks 
before screening, or will not have fully recovered from surgery at baseline, or has surgery 
planned during the time the subject is expected to participate in the study.
Note: Subjects with planned surgical procedures to be conducted under local anesthesia 
may participate.
10.
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 any therapeutic agent directly targeted to IL-23 (including but not 
limited to guselkumab, tildrakizumab [MK3222], risankizumab [BI-655066])
13.
Has received any anti-TNF-Į ELRORJLF WKHUDS\ ZLWKLQ  months before the first 
administration of study drug.
14.
Has received any therapeutic agent directly targeted to IL-12/23, IL-17A or IL-17R within 
3 months of the first administration of study drug (including but not limited to 
ustekinumab, ixekizumab [LY2439821], brodalumab [AMG 827], or secukinumab).
15.
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.
16.
Has received any systemic immunosuppressant (eg, methotrexate, azathioprine, 
cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate mofetil, tacrolimus, fumaric 
acid esters), or anakinra within 4 weeks of the first administration of study drug.
17.
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.
18.
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.




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Malignancy or increased potential for malignancy-related exclusion criteria:
34.
Currently has a known malignance or has a history of malignancy within 5 years before 
study start (with the exception of a non-melanoma skin cancer that has been adequately 
treated with no evidence of recurrence for at least 3 months before the first study 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).
35.
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:
36.
Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or 
lack of easy access to veins.
37.
Lives in an institution on court or authority order.
38.
Has a condition that, in the opinion of the investigator, would participation not be in the 
best interest of the subject (eg, compromise the well-being) or that could prevent, limit, or 
confound the protocol-specified assessments
39.
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.
40.
Criterion added per Amendment 4:
Exclusion: a potential participant with the following features will be excluded from 
participating in the study protocol:
o
During the 6 weeks prior to baseline, have had ANY of (a) confirmed SARS-CoV-
2 (COVID-19) infection (test positive), OR (b) suspected SARS-CoV-2 infection (clinical 
features without documented test results), OR (c) close contact with a person with known 
or suspected SARS-CoV-2 infection 
Exception: if recommended by local guidelines and as part of standard of care in the 
respective country, patients may be included with a documented negative result for a 
validated SARS-CoV-2 test (direct detection methods)
(i)
obtained at least 2 weeks after conditions (a), (b), (c) above (timed from resolution 
of key clinical features if present, e.g. fever, cough, dyspnea)
AND
(ii)
with absence of ALL conditions (a), (b), (c) above during the period between the 
negative test result and the baseline study visit 
NOTES on COVID-related exclusion:
Precaution: for those who may carry a higher risk for severe COVID-19 illness (eg, those 
aged over 65 years), follow guidance from local health authorities when weighing the 
potential benefits and risks of enrolling in the study, and during study participation


43
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NOTES:
Investigators should ensure that all study enrollment criteria have been met at baseline. If a 
subject's clinical status changes (including any available laboratory results or receipt of additional 
medical records) 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.
Prior to randomization at week 28 and again prior to entering Study Part 3 at week 68 exclusion 
criterion 1 (subject has a clinically active psoriasis arthritis which needs systemic therapy beyond 
NSAIDs) has to be re-evaluated and subjects with diagnosed PsA who need systemic therapy 
beyond NSAIDs are to be excluded from further participation in the trial.
SRe who already had their regular final study visit at week 116 before Study Amendment 5 was
implemented and have not yet completed the study for more than 12 weeks, will be asked by the 
investigator if they want to participate in the long-term extension (LTE) follow-up phase defined 
by Amendment 5. All SRe with PASI 5 at week 116 are allowed to enter LTE with the first visit 
in week 128 (12 weeks after last study visit). In case of PASI >5 at week 128, it will be possible 
to start re-treatment according to protocol. Subjects who have previously used an antipsoriatic 
medication prohibited by the protocol are not allowed to continue after week 116.
Section 17.4 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 entire course of the study to be eligible for participation:
1.
Refer to Section 8 for details regarding prohibited and restricted therapy during the study.
2.
Agree to follow all requirements that must be met during the study as noted in the Inclusion 
and Exclusion Criteria (eg, contraceptive requirements).
3.
Subjects must agree to use sun protective measures (such as a hat, sunglasses, protective 
clothing, sunscreen), limit prolonged exposure to natural sunlight, and avoid artificial 
sunlight (tanning beds or phototherapy) from baseline until the last dose of study drug.
5.
TREATMENT ALLOCATION AND BLINDING
Treatment Allocation/ Procedures for Randomization
Central randomization will be implemented in Study Part 2. Eligible subjects (confirmation by 
physician needed that the subject achieved a PASI score=0 at weeks 20 and 28) will be randomly
assigned to one of two guselkumab treatment groups (ratio 1:1) 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. 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.
Subjects will be equally stratified in study group 2a and 2b during randomization for i) disease 
GXUDWLRQ RI  RU ! years (note: disease duration will be calculated from date at which first 


44
Approved, Date: 14 June 2021
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Clinical Protocol CNTO1959PSO3012 Amendment 5
symptoms (plaque) were reported by subject to date of screening visit) and ii) for participation in 
substudy 1. Definitions when to stop/pause recruitment of subjects with longer disease duration 
will be provided in a separate document.
It is expected that about 280 of the subjects included in Study Part 1will be categorized as SRe and 
thus be eligible for central randomization in Study Part 2. However, this number is not fixed but 
can be slightly exceeded if potential SRe are still in Part 1. To limit the number of subjects in Study 
Part 2 recruitment might be stopped before the limit of 900-1000 subjects in Study Part 1 has been
reached but might also be extended if less than 280 subjects are likely to be defined as SRe.
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 and administration of study drug) 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 database lock (DBL) and 
unblinding. Under normal circumstances, the blind should not be broken for subjects, 
investigators, or site personnel until the end of the study and database lock.
In Study Part 3 starting at week 68 throughout week 220, subjects, investigators and site personnel
will remain blinded towards their injection interval (q8w or q16w) in Study Part 2. The sponsor 
will be unblinded after DBL at week 68 to conduct the analysis of the primary endpoint.
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. While the 
responsibility to break the treatment code in emergency situations resides solely with the 
investigator, 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 the IWRS, in the appropriate section of the case report form (CRF), 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.
In general, randomization codes will be disclosed fully only if the study is completed, and the 
clinical database is closed. However, since analyses are planned for each study part, the 
randomization codes and, if required, the translation of randomization codes into treatment groups 
will be disclosed to those authorized and only for those subjects included in the different analyses.


45
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6.
DOSAGE AND ADMINISTRATION
A guselkumab-prefilled syringe assembled with the UltraSafe Plus™ Passive Needle Guard (PFS-
U) device, designed to deliver a single, fixed dose of 100 mg and a matched PFS-U containing 
Placebo will be used. Products will be labeled in a blinded manner; it will not be possible to 
differentiate between active and Placebo-prefilled syringes.
For Study Part 1 all enrolled subjects will receive one injection of guselkumab according to the 
TES, ie at weeks 0, 4, 12, and 20.
Subjects with a PASI score=0 at weeks 20 and 28 are qualified for randomization in Study Part 2. 
In case of PASI score >0 at weeks 20 or/and 28, subjects will continue to get guselkumab 100 mg 
q8w with last administration in week 60.
Randomized subjects of Study Part 2 (study group 2a and 2b) will receive one injection of either 
guselkumab or matching Placebo solution for injection (ie, identical to guselkumab in color, smell, 
and shape) according to the following schemes:
x Study group 2a: guselkumab 100 mg q8w, ie at weeks 28/36/44/52/60
x Study group 2b: guselkumab 100 mg q16w, ie guselkumab at weeks 36 and 52; Placebo at 
weeks 28/44/60 (guselkumab and placebo will be provided blinded, IWRS will assure correct 
assignment).
Subjects of groups 2a and 2b with a PASI score <3 at week 68 are qualified for entering Study 
Part 3 and will be withdrawn from the study medication.
Subjects of groups 2a,2b, 3a and 3b losing control of disease, defined as PASI score >5 at any visit 
of Study Parts 2 or 3 (ie, until week 220), will enter the re-treatment arm with guselkumab 100 mg 
q8w for further 3 administrations (starting at that visit = re-treatment week 0, followed by 
administration at re-treatment-weeks 8 and 16). The final efficacy assessment for all subjects in 
the re-treatment arms will take place 24 weeks after loss of control and study termination will be 
28 weeks after loss of control (final study visit). Subjects with fluctuating disease (ie, PASI score 
3 to 5) or PASI >5 (subjects losing control of disease) at week 68 will also get the opportunity to 
enter the re-treatment-arm.
All study procedures should be completed prior to administering the study drug. Sub-cutaneous 
injections should be administered by qualified study site staff during the study visit, if possible. 
However, in cases where a site visit is not possible, subjects who have appropriate experience or 
have received required training may self-administer study drug at the times instructed by the 
investigator. Study site staff must ensure that those subjects have the appropriate experience or 
have received the required training to perform self-administration of SC injections. 
Self-administration at home is only allowed subsequent to performance of a phone or video visit. 
Application of study drug at home can also be performed by a Home Health Care service provider 
if agreed by the sponsor, investigator and subject.
During this virtual visit, site staff will perform safety evaluations according to protocol, ensure 
assessment of PRO instruments and efficacy assessments (video/photo assessment of applicable 
lesions) as far as possible, prior to (self-)administration of the investigational product.
Randomization to part 2a/b is only possible (in case of Super-Responder) if week 20 and week 28 
efficacy assessments have been done on-site, otherwise the subjects will enter part 2c.


46
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If laboratory tests are to be performed at this scheduled visit, the blood draw for safety monitoring 
(hematology and chemistry) can be postponed to the next visit or, if the investigator deems it 
medically necessary, performed in a local certified laboratory.
For women of childbearing potential, a negative pregnancy test must be available. The patient 
should confirm self-administration to the site in a timely manner and will be asked by the site 
personnel for administration-related and injection site reactions. Self-administration cannot take 
place on 2 consecutive visits.
Site personnel and subjects will remain blinded to the treatment assignments until the last subject
completes week 220 evaluations and the database has been locked.
During the safety follow-up period (week 68 through Week 72 for group 2 c, week R24 through 
week R28 of the re-treatment arm or in case of prematurely stop of study treatment 12 weeks after 
the last application of study drug), concomitant treatments for psoriasis may be administered at 
the investigator’s discretion as follows:
The Investigator may continue treatment with guselkumab or switch to another commercially 
available treatment. Due to the half-life of guselkumab, it is recommended not to start a new 
therapy other than commercially available guselkumab during safety follow-up period. If the 
investigator feels strongly that another therapy is needed, this should be discussed with the sponsor 
before initiation of the new therapy.
7.
TREATMENT COMPLIANCE
Each administration of study drug performed at a study visit will be recorded in the subject’s source 
documents, with the assistance of a staff member at the study site who will be supervising study 
drug administration at these visits. For any study drug administration performed by the subject 
outside of a study site, subjects will keep the syringe carton and return the empty carton to the 
study site at their next visit. The subject will record the corresponding date and time of the 
administration in the study drug application card. Study site personnel will utilize subject’s 
documentation to ensure compliance and record at-home study drug administrations in the eCRF.
Week 0 can be done once all screening activities are completed, results are available, and the 
subject is eligible, but latest 4 weeks after screening visit (+ 7 calendar days). From weeks 4 
through week 68 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. Study visits in Study Part 3 should occur within 
±14 days of the scheduled study visit. Visits during the re-treatment period (study groups 2d and 
3c) are also expected to occur within a range of ±7 days. Any out-of-range visit should be 
documented in the subject’s source notes and discussed with the sponsor.
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 eCRF and IWRS to 
ensure accuracy. Although it is understood that treatment may be interrupted for many reasons, 
compliance with the treatment schedule is strongly encouraged.


47
Approved, Date: 14 June 2021
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8.
CONCOMITANT THERAPY
Concomitant therapies will be recorded until week 220 for subjects participating in all three study 
parts. For subjects of the re-treatment arm concomitant therapies will be recorded until 12 weeks 
after the last dose of study drug. For subjects not participating in Study Part 3, concomitant 
therapies should be recorded beyond week 72 only in conjunction with related serious adverse 
events (SAEs) that meet the criteria outlined in Section 12.3.2. All therapies (prescription or over-
the-counter medications, including vaccines, vitamins, herbal supplements) different from study 
drug, as well as all shampoos, moisturizers or emollients used to treat psoriasis, must be recorded 
in the CRF. 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 68 – all subjects, whether SRe or not and re-treatment arms), discontinuation should be 
discussed with the Sponsor. If a prohibited therapy is initiated during weeks 68 to 220 (only SRe),
the subject should still complete the final visit at week 220, and the medication should be recorded 
as a concomitant medication.
For non-SRe: If a prohibited therapy is initiated after the final efficacy assessments at week 68 and 
until the end of the safety follow-up at week 72, the subject should still complete the final safety 
follow-up visit at week 72 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.
Concomitant Medications for Treatment of Psoriasis
Topical Therapy
Topical therapies that could affect psoriasis or the efficacy evaluation (eg, corticosteroids, tar, 
anthralin, calcipotriene, tazarotene, methotrexat [MTX], pimecrolimus, tacrolimus, and traditional 
Taiwanese, Korean, or Chinese medicines) are not permitted at any time during the study until 
week 220 and during re-treatment to not confound the efficacy data (incl. Study Part 3). The only 
allowable concomitant treatments for psoriasis throughout the study are shampoos (containing tar 
or salicylic acid only) and topical moisturizers. The subject should not use these topical agents 
(shampoos, moisturizers) on the day of a study visit. Non-medicated shampoos may be used on 
the day of the study visit.
Phototherapy or Systemic Therapy for Psoriasis
The use of phototherapy or systemic antipsoriatic medications is not permitted at any time during 
WKH VWXG\ 7KHVH PHGLFDWLRQV LQFOXGH WKRVH WDUJHWHG IRU UHGXFLQJ WXPRU QHFURVLV IDFWRU Į LQFOXGLQJ
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]), JAK-
inhibitors, alpha-4 integrin antagonists (including but not limited to natalizumab), apremilast, 
steroids, any conventional systemic therapy that could affect psoriasis or the efficacy evaluation 
(including but not limited to MTX, fumaric acid esters, cyclosporine, acitretin), herbal treatments, 
or traditional Taiwanese, Korean, or Chinese medicines, and any other biological agent or systemic
medication that could affect psoriasis or efficacy evaluation.


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8.2.
Concomitant Medications for Conditions other than Psoriasis
Every effort is to be made to keep subjects on stable concomitant medications if medically 
justified. If the medication is temporarily discontinued due to 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 medical records. 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, no longer than 2 weeks (cumulative) within six months. Longer use of 
corticosteroids should be discussed with the Sponsor and may require discontinuation of study 
drug. Inhaled, otitic, ocular, nasal, or other topical routes of mucosal delivery for corticosteroids 
are allowed throughout the study.
9.
STUDY EVALUATIONS
9.1.
Study Procedures
9.1.1.
Overview
The TES summarizes the frequency and timing of efficacy, immunogenicity, biomarker,
pharmacogenomic and safety measurements applicable to this study. All subjects will be asked to 
sign the consent forms (main study and optional substudies) before any study-related procedures 
are conducted.
All PRO assessments should be conducted/completed before any tests, procedures, or other 
consultations to prevent influencing subject perceptions (1st DLQI, 2nd PSSD, 3rd NAPPA-QoL, 
4th NAPPA-PBI). The other efficacy assessment (PASI, BSA and NAPPA-CLIN) should be 
completed after the PROs but before any study drug administrations. Further general instructions 
see Attachment 4. An exception to this order is the start of a re-treatment arm at a visit, which does 
not require all PRO’s needed at the visit week 0 of the re-treatment arm. In this case, PRO’s will 
be obtained immediately after efficacy assessments (which is the basis for re-treatment-decision) 
and prior to drug administration at that visit.
Urine, blood and biopsy collections should be kept as close to the specified time as possible. Actual 
dates of assessments will be recorded in the source documentation and CRF. A urine pregnancy 
test will be performed to confirm the absence of pregnancy at every study drug administration 
visit. Additional serum or urine pregnancy tests may be performed, as determined necessary by 
the investigator or required by local regulation, to establish the absence of pregnancy at any time 
during the subject's study participation.
The total blood volume for the study is approximately 230-330 mL (80-130 mL for safety, 30-
40 mL for pharmacokinetics, 6 mL for pharmacogenomics, and 125-135 mL for biomarkers).
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the 
samples. Details on required blood volume are provided below.


49
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Table 9.1-1: Required Blood Volume per Subject
average
incl. re-treatment arm
Safety
(including 
screening 
and 
posttreatment assessments)
Volume
per
Sample
(ml)
No. 
of
Samples
per
subject
Total
Volume of
Blood (mL)
Volume per 
Sample 
(ml)
No. 
of
Samples 
per subject
Total
Volume of 
Blood
(mL)
Hematology
2
7
14
2
10
20
Chemistry
6
7
42
6
10
60
Serology (HBV, HCV, HIV) 
6
1
6
6
1
6
HBV DNA testinga
3
1
3
3
1
3
TB testing
4
1
4
4
1
4
Pharmacokinetic/
Immunogenicity samples
7.5
4
30
7.5
5
37.5
Biomarkers (PBMCs)
16
5
80
16
5
80
Serum biomarkersf
8.5
5
42.5
8.5
6
51
Genetic (DNA) sampleb
6
1
6
6
1
6
SUM Safety
69
93
Approximate Totalc,d,e
221.5
Approximate Totalincl. Re-treatmentc, d, e
261.5
Calculated as number of samples multiplied by amount of blood per sample.
a. Performed only in subjects who test positive for core HBV antibody.
b. Blood samples will be collected only from subjects who have consented to provide optional DNA samples for research.
c. Repeat or unscheduled samples may be taken for safety reasons or technical issues with the samples.
d. Total blood increases by appx. 6 ml for subjects who consent to participate in the optional genetic substudy.
e. Total sum calculated for patients taking part in substudy 1 and 2.
f. For SRe, a maximum of 3 additional samples are planned between week 116 and 220.
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. Concomitant 
therapies will be recorded until week 220 for subjects participating in all three study parts. For 
subjects not participating in Study Part 3 concomitant therapies will be recorded beyond week 72 
(or 12 weeks after last administration of study drug in case of early discontinuation) only if they 
are in conjunction with SAEs that meet the criteria outlined in Section 12.3.2.
Throughout the study, it is important to monitor subjects for TB. Instructions for screening for TB 
are provided in Section 9.1.2.1; instructions for early detection of active TB are provided in 
Section 9.6.
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 to establish 
baseline characteristics for a subject's psoriasis. Subjects will undergo screening for TB (see 
Section 9.1.2.1), HBV (see Attachment 3) and antibodies to HCV and HIV. Each subject will be 
asked to sign the consent form(s) at screening before any study-related procedures are conducted.


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9.1.2.1.
TB screening
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 10), subjects must undergo 
testing for TB and their medical history assessment must include specific questions about a history 
of TB or known occupational or other personal exposure to individuals with active TB. Interferon-
gamma-release-assay (IGRA) TB-testing, i.e. QuantiFERON
®-TB Gold test (Manuel und Kumar 
2008) will generally be performed by the central laboratory. However, if available, test results 
from local laboratory can be accepted.
Investigators should screen for latent TB if they believe, based on their judgment, that the use of 
the test is clinically indicated in order to evaluate a subject who has high risk of having latent TB. 
If the QuantiFERON-TB Gold test is positive, the subject is considered to have latent TB infection 
for the purposes of eligibility for this study.
Subjects with a negative QuantiFERON-TB Gold test result are eligible for study participation. 
Subjects with a newly identified positive QuantiFERON-TB Gold 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 
subjects.
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.
9.1.2.2.
Screening Failure/Rescreening
If the subject has not met all inclusion criteria or met any exclusion criteria during the screening 
phase or is unable or unwilling to adhere to the prohibitions and restrictions of the study, the subject
is considered to be a screening failure and is not eligible for study participation at that time.
Exceptional and limited retesting of abnormal screening values that lead to exclusion are allowed 
only once. Eligibility may be reassessed using a single unscheduled visit during screening.
In general, if a subject is a screening failure but at some point in the future meets all of the 
eligibility criteria, the subject may be re-screened after a new informed consent has been obtained. 
Subjects who are re-screened will be assigned a new subject number and will restart a new 
screening phase. Re-screening will be permitted once.


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9.1.3.
Study Part 1: Open-label Treatment Phase
Study Part 1 will be a 28-week open-label, run-in period. All visit procedures will be performed 
as specified in the TES. All study procedures and evaluations are to be completed before 
administration of study drug. From weeks 0 to 28 it is expected that all visits will occur within a 
range of ±7 days.
All subjects who prematurely stop taking the study drug should complete the early termination 
visit (ETV) as listed in the TES. After ETV, safety follow-up should be conducted for 12 weeks 
after the last administration of study drug. For subjects who withdraw from study participation, 
every effort should be made to conduct final efficacy and safety evaluations as listed in the TES.
9.1.4.
Study Part 2: Double-blind Treatment Phase 
Subjects with a PASI score=0 at weeks 20 and 28 will be defined as SRe and are qualified for 
randomization in study group 2a or 2b. Following randomization via IWRS at week 28, eligible 
subjects will continue into the double-blind treatment period, with visits to be conducted every 
8 weeks. The final study agent injection will take place at week 60, final assessments will be made 
at week 68.
Subjects starting a prohibited psoriasis treatment do have to complete a safety follow up visit at 
week 72 visit or 12 weeks after last dose of guselkumab, whichever comes first. It is expected that 
all visits in the double-blind treatment phase will occur within a range of ±7 days. All study 
procedures and evaluations are to be conducted before administration of study drug. For further 
details on study agent administration, refer to Section 6.
Subjects not eligible for participation in the double-blind treatment period will continue to receive 
guselkumab 100 mg q8w until week 60 (last administration at week 60 visit) with final study 
assessments at week 68 and final safety follow-up visit at week 72.
All subjects who prematurely stop taking the study drug should complete the ETV and 12 weeks 
later the safety follow-up. For subjects who withdraw from study participation, every effort should 
be made to conduct final efficacy and safety evaluations.
9.1.5.
Study Part 3: Drug Withdrawal phase
Study Part 3 starts for subjects from group 2a and 2b after the assessments at week 68 which 
qualify the subject for this part. No study treatment is applied during the drug withdrawal phase. 
Topical therapies that could affect psoriasis, phototherapies or systemic antipsoriatic medications 
are not permitted at any time during the study until week 220 or week 248 (in case of re-treatment
starting at week 220). Subjects starting a prohibited psoriasis treatment will still have to complete 
the week 220 visit.
Visits are to be conducted every 12 weeks within ±14 calendar days of the anticipated visit date. 
In between the 12-weekly on-site visits, a telephone-visit 6 weeks (± 7 days) will be done after 
each on-site visit (ie, telephone visits at weeks 74, 86, 98, 110, 122, 134, 146, 158, 170, 182, 194, 
and 206) to assess whether the subject notices a worsening of his/her psoriasis. If so, the subject
must attend an on-site visit for efficacy assessment by the assessor as soon as possibly but not later 
than 2 weeks after the phone call. The week 220 visit should be conducted at least 160 weeks 
following the last study agent injection.


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9.1.6.
Re-treatment Phase
Subjects losing control of disease, defined as PASI score >5 at any visit during Study Parts 2 or 3 
(ie, until week 220), will enter the re-treatment arms (groups 2d or 3c) with three guselkumab 
100 mg administrations starting at that visit (= re-treatment week 0, followed by administration at 
re-treatment weeks 8 and 16).
If re-treatment is started at a visit, which would usually not require all PROs needed at the re-
treatment visit week 0, those PROs will be obtained immediately after efficacy assessments (basis 
for re-treatment-decision) and prior to drug administration at that visit.
The final efficacy assessment for all subjects in the re-treatment arms will take place 24 weeks 
after loss of disease control and study termination will be 28 weeks after loss of disease control 
(final study visit/safety follow-up). At visit week 24 of the re-treatment, the investigator may 
continue actual treatment with commercially available guselkumab (ie, not provided by the 
Sponsor) to maintain a q8w interval. Due to the half-life of guselkumab, it is recommended not to 
start a new therapy during safety follow-up period (ie, 12 weeks after last dose). If the investigator 
feels strongly that an additional therapy is needed, this should be discussed with the sponsor before 
initiation of the new therapy. 
Subjects with fluctuating disease (ie, PASI score 3 to 5) at the week 68 visit will also get the 
opportunity to enter the re-treatment-arm (3c). The last chance to start re-treatment will be the visit 
week 220.
9.2.
Efficacy Evaluations
Efficacy evaluations chosen for this study are consistent with those utilized to evaluate other 
therapies for psoriasis. Efficacy evaluations include:
x
Psoriasis Area and Severity Index (PASI) 
x
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA-CLIN)
x
Psoriasis-affected Body Surface Area (BSA) 
x
Dermatology Life Quality Index (DLQI) [PRO]
x
Psoriasis Symptom and Sign Diary (PSSD, 7-day version) [PRO]
x
Nail associated quality of life and patient- relevant treatment benefit (NAPPA-QoL/-PBI) 
[PRO]
x
Target Lesion Severity Score (TLSS; only for subjects participating in substudies 1 and 2).
9.2.1.
Efficacy Assessor Assessments
The efficacy assessor assessments (PASI, NAPPA-CLIN, BSA) will be performed at the site by 
an efficacy assessor trained by the Sponsor and at the appropriate visits as outlined by the TES. 
Efficacy assessments should preferably be done by a dermatologist but if a dermatologist is not 
available, a health care provider with at least 1 year of experience in performing the efficacy 
assessments (PASI, NAPPA-CLIN, BSA) may serve as efficacy assessor. Health care providers 
with less than 1 year of experience may serve as an efficacy assessor based upon the discretion 
and approval of the Sponsor.


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The Sponsor will provide PASI, NAPPA, BSA training prior to the screening of the first subject
at each site. If the efficacy assessor was trained by the Sponsor in a previous clinical study within 
the last 3 years and there is adequate documentation of this training (certification), that training 
will be considered adequate for this study. However, repeat training prior to start of the study is 
encouraged. Training documentation of each efficacy assessor should be maintained at the study 
site. All efficacy assessors at a site must be listed on the delegation log.
9.2.1.1.
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 (Feldman, et al. 1996). In the PASI system, the body is divided into four
regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is assessed 
separately for erythema, induration, and scaling, which are each rated on a scale from 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.
9.2.1.2.
Nail Assessment in Psoriasis and Psoriatic Arthritis 
The NAPPA is an instrument for assessing clinical and patient-reported outcomes in nail psoriasis
(Augustin, et al. 2014). It comprises three components: 
1.
NAPPA-QOL is a 20-item nail-specific quality of life (QoL) questionnaire covering the past 
week. Signs, stigma and everyday life are rated on a scale from 0 (no suffering) to 4 (high 
suffering). A global score is computed by averaging all items.
2.
NAPPA-PBI is a 24-item questionnaire to assess patient-defined needs before and patient-
rated benefits after treatment. The answers are given on a scale from 0 to 4, and a global score 
is calculated as follows: Each benefit item is multiplied with the respective importance item, 
and the product is divided by the sum of all importance items. The results are summed up over 
all items. The resulting global score ranges from 0 (no benefit) to 4 (highest possible benefit).
3.
NAPPA-CLIN is an instrument used by the physician to assess the least and the worst involved 
nail of both hands or both feet with scores ranging from 0 to 16.
9.2.1.3.
Psoriasis-affected Body Surface Area
The percentage of the psoriasis-affected body surface area (BSA %) is a system used for assessing 
the severity of psoriasis (Ramsay und Lawrence 1991). The plaque coverage is estimated using 
the rule of palm (1 palm of the hand = 1% BSA).
9.2.1.4.
Target Lesion Severity Score
The target lesion severity score (TLSS), also known as target plaque severity score (TPSS), 
documents the physician’s assessment of a subject’s target psoriasis lesion according to the 
following categories: induration, scaling, and erythema. Every effort should be made to ensure that 
the physician or designee who performed the TLSS evaluations for a subject at randomization 
performs the TLSS for that subject at all subsequent visits. A description of the TLSS is provided
in Attachment 1.


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9.2.2.
Patient-reported Outcomes
PROs will be assessed in the following order: 1st DLQI, 2nd 7-day version of PSSD, 3rd NAPPA-
QoL and 4th NAPPA-PBI), The questionnaires will be completed on paper sheets at the site by 
subjects at the appropriate visits as outlined by the TES. Data collected on the paper sheets will be 
handled as source data and will be transferred into the eCRF by the site staff.
9.2.2.1.
Dermatology Life Quality Index 
The DLQI is a dermatology specific QoL instrument designed to assess the impact of the disease 
on a patient’s QoL. It is a 10-item questionnaire that, in addition to evaluating overall QoL, can be 
used to assess six different aspects that may affect QoL: 1) symptoms and feelings, 2) daily 
activities, 3) leisure, 4) work or school performance, 5) personal relationships, and 6) treatment
(Finlay und Khan 1994). Each question is scored from 0 to 3, giving a possible score range from 
0 (no impact of skin disease on QoL) to 30 (maximum impact on QoL).
9.2.2.2.
Psoriasis Symptom and Sign Diary
The PSSD is a questionnaire designed to measure the severity of psoriasis symptoms and signs for 
the assessment of treatment benefit (Feldmann, et al. 2016). The PSSD is a patient self-
administered outcomes instrument that includes 11 items covering symptoms (itch, pain, stinging, 
burning and skin tightness) and patient observable signs (skin dryness, cracking, scaling, shedding 
or flaking, redness and bleeding) using 0 to 10 numerical rating scales for severity. Two subscores 
each ranging from 0 to 100 will be derived: the psoriasis symptom score and the psoriasis sign 
score. A higher score indicates more severe disease.
$ FKDQJH RI  SRLQWV LQ 366' V\PSWRP VFRUH RU VLJQ VFRUH DQG D -point change in individual 
PSSD item scale scores will be defined as clinically meaningful change (response). In this study, 
the 7-day-version of the PSSD will be used.
9.3.
Pharmacokinetics (PK)
Venous blood samples will be collected at the points in time shown in the TES for the 
determination of serum guselkumab concentrations. Serum collected for PK may additionally be 
used to evaluate safety or efficacy aspects that address concerns arising during or after the study
period. Genetic analyses will not be performed on these serum samples. Subject confidentiality 
will be maintained.
Each sample will be divided into 2 aliquots (1 aliquot for serum guselkumab concentration and 1 
aliquot as back-up sample). Samples must be collected before study drug administration. The exact 
dates and times of blood sampling must be recorded in the laboratory requisition form. The samples 
will be shipped to the central lab and analyzed (i) after the completion of Study Part 1 (after week 
28 visit) and (ii) after completion of the study including the re-treatment arm for analysis of the 
respective secondary endpoints. 
Subject confidentiality will be maintained. See the Laboratory Manual for further information 
regarding collection, handling, and shipment of biological samples. The sponsor, or its designee, 
will assay these samples using a validated, specific, and sensitive immunoassay method under 
conditions in which the subjects’ identity remains blinded.


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Note: One additional blood sample for PK assessments will be taken at the time when the subject
loses control of disease (PASI score >5 at any visit of Study Parts 2 or 3, RU 3$6,  DW ZHHN ).
However at R0, PK-samples will only be taken for Study Part 2d (ie, not for Study Part 3c).
9.4.
Biomarkers
The samples will be collected according to the points in time specified in the TES. Guidelines and 
specifications for sample collection and shipment information are provided in the Laboratory 
Manual.
Immunophenotyping of PBMCs
Whole blood samples will be collected from subjects who are enrolled by the sites selected for
substudy 1. Measurements include the quantity of different PBMCs. Immunophenotyping of 
PBMCs will be performed using flow cytometry by sites with expertise to conduct FACS-based 
cellular immunophenotypic characterization of freshly isolated blood cells. Subjects’ identity will 
remain blinded.
Immunophenotyping of skin biopsies
6 mm biopsies will be collected from subjects who are enrolled by the sites selected for 
substudy 1. Measurements include the quantity of Th17, Tc17 non-TRM T cells, TRM T cells,
Tregs and antigen presenting cells. Immunophenotyping of skin biopsies will be performed using 
flow cytometry by sites with expertise to conduct FACS-based cellular immunophenotypic 
characterization of freshly isolated biopsies. Subjects’ identity will remain blinded.
Gene expression analysis of skin biopsies
Skin biopsy samples will be collected according to the Time and Events Schedule from a subset 
of subjects who consent to participate in substudy 2. Each 6 mm biopsy will be split in two parts; 
one part will be stored for RNA gene expression analysis, while the other part will be frozen in 
OCT and stored for H&E, IHC and IF analyses. If two 3 mm biopsies have been taken instead of 
the 6 mm biopsy, one 3 mm biopsy will be stored in RNAlater for RNA preparation and gene 
expression analysis, while the other 3 mm biopsy will be frozen in OCT and stored for H&E, IHC 
and IF analyses.
The samples will be shipped to the central lab and analyzed later under conditions in which the 
subjects’ identity remains blinded.
Serum biomarkers
Serum samples of approximately 8.5 mL will be collected from all subjects to assess PD markers 
associated with the response to guselkumab as well as markers related to psoriasis (substudy 3). 
Measurements will include but are not limited to serum IL-17A, IL-17F, IL-22 levels and beta 
defensin. Detection and characterization of cytokines will be done using various immune assays.
9.5.
Pharmacogenomic (DNA) Evaluations
At week 0, a single whole blood sample of approximately 6 mL will be collected from a subset of 
subjects who consent to participate in substudy 4. The goal of the pharmacogenomic (DNA) 
analysis is to search for genetic factors that may influence molecular effects, clinical efficacy, or 
tolerability of guselkumab and to identify genetic factors associated with psoriasis. They will be 
performed using validated assay methods by or under the supervision of the Sponsor.


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DNA samples will be used for research related to guselkumab. They may also be used to develop 
tests/assays related to guselkumab. Pharmacogenomic research may consist of the analysis of one 
or more candidate genes or of the analysis of genetic markers throughout the genome in relation 
to guselkumab.
9.6.
Safety Evaluations
Safety and tolerability of guselkumab will be monitored until 12 weeks after last administration of 
study drug by collecting information on AEs, including injection site and allergic reactions, clinical 
laboratory tests (hematology, chemistry and pregnancy testing), physical examinations, vital signs, 
concomitant medication review, and early detection of tuberculosis (TB), as specified in the TES.
Subjects participating in Study Part 3 and not treated in the re-treatment arm will be monitored 
through week 220 by collecting information on AEs, including injection site and allergic reactions,
vital signs, weight, and concomitant medication review. Any clinically significant abnormalities 
persisting at the end of the study/early withdrawal will be followed by the investigator until 
resolution or until a clinically stable endpoint is reached.
In cases of self-administration of SC study intervention at home, subjects are requested to contact 
their treating physician as soon as possible to consider reporting of an adverse event.
Clinical laboratory safety monitoring may be performed at a certified local laboratory identified 
by the study site rather than at the central laboratory; for selected measures (eg, urine pregnancy), 
home testing may be employed.
The study will include the following safety evaluations:
Adverse Events
AEs will be reported by the subject for the duration of the study. AEs will be followed by the 
investigator as specified in Section 12.
Injection Site Reactions
An injection site reaction (ISR) 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 
ISR. If an ISR is observed, the subject should be treated at the investigator’s discretion. Any 
adverse reaction (eg, pain, erythema, induration) should be noted on the AE page of the eCRF.
Allergic Reactions
Subjects must be observed carefully for symptoms of an allergic reaction (e.g., rash, urticaria, 
itching, shortness of breath, or drop in blood pressure) for at least 30 minutes after the study drug 
injection. If an allergic reaction is observed, treatment should be administered according to 
standard practice. Any allergic reaction should be noted on the AE page of the eCRF.


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Clinical Laboratory Tests
Blood samples for hematology, serum chemistry and serology will be collected. The investigator 
must review the results, document this review, and record any clinically relevant changes occurring 
during the study in the AE section of the CRF. Clinically significant abnormal laboratory values 
should be followed as clinically appropriate or until they return to normal or are otherwise 
explained by the investigator. Laboratory reports must be filed with the source documents.
The following tests will be performed by the central laboratory:
x
Hematology Panel:
- hemoglobin
- white blood cell (WBC) count
- hematocrit
x
lymphocytes (%, absolute)*
- red blood cell (RBC) count
x
monocytes (%, absolute)*
- platelet count
x
neutrophils (%, absolute)*
x
eosinophils (%, absolute)*
x
basophils (%, absolute)*
x
Serum Chemistry Panel:
- sodium
- alkaline phosphatase (AP)
- potassium
- creatine phosphokinase (CPK)
- chloride
- lactic acid dehydrogenase (LDH)
- blood urea nitrogen (BUN)
- uric acid
- creatinine
- calcium
- glucose
- phosphate
- aspartate aminotransferase (AST)
- albumin
- alanine aminotransferase (ALT)
- total protein
- gamma-glutamyltransferase (GGT)
- cholesterol
- total bilirubin
- triglycerides
- magnesium
x
Serology: Samples for HIV antibody, hepatitis B (see Attachment 3) and hepatitis C virus antibodies 
will be obtained at screening.
x
Urine Pregnancy Testing for women of childbearing potential will be done at screening and at the 
times shown in the TES. 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.
Vital Signs
Blood pressure and heart rate measurements will be assessed as specified in the TES. 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.
Physical Examination 
Physical examinations will be performed by body systems, eg, eyes, ears/nose/throat, 
head/neck/thyroid, heart, lung, chest, abdomen etc., by the investigator or designated physician, 
nurse practitioner or physician assistant as specified in the TES. Total body skin examination will 
be performed to determine the presence of any suspected malignant skin lesions including basal 
cell carcinoma, squamous cell carcinoma, and melanoma. In addition, the study agent injection 
site is to be evaluated. Any new, clinically significant finding 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.


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Body height and weight
Body height and weight will be measured as specified in the TES. Subjects will be instructed to 
remove shoes and outdoor apparel and gear prior to these measurements.
Concomitant Medication Review
Concomitant medications will be reviewed and reported at each visit. A list of restricted and 
prohibited concomitant medications is provided in Section 8.
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. The following 
series of questions is suggested for use during the evaluation:
x
"Have you had a new cough of >14 days’ duration or a change in a chronic cough?”
x
“Have you had any of the following symptoms:
–
Persistent fever?
–
Unintentional weight loss?
–
Night sweats?”
x
“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.
Study drug administration should be interrupted during the investigation. A positive
QuantiFERON-TB Gold test result should be considered detection of latent TB. If the 
QuantiFERON-TB Gold test result is indeterminate, the test should be repeated. The 
QuantiFERON-TB Gold test will generally be performed by the central laboratory. However, if 
available, test results from local laboratory can be accepted.
If recommended, treatment for latent TB must be initiated prior to or simultaneously with the 
administration of further study agent. 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 TES.


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9.7.
Sample Collection and Handling
Actual dates and times of sample collection must be recorded in the CRF or laboratory requisition 
form. Refer to the TES 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 Study Part 1 if he or she has completed assessments 
at the week 28 visit. A subject will be considered to have completed Study Part 2 if he or she has 
completed the assessments of week 68. A subject will be considered to have completed Study Part 
3 if he or she has completed assessments at week 220 or re-treatment (week 24/28 SFU). Subjects
entering the re-treatment arms (2d or 3c) will be considered to have completed the re-treatment 
arm if he or she has completed assessments at week 24 visit after start of re-treatment.
10.2.
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 permanently discontinued if:
x
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.
x
The subject shows no response to study treatment at week 28, defined as no change or 
worsening of PASI score at week 28 in comparison to week 0.
x
The subject becomes pregnant.
x
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.
x
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.

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


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
A subject receiving treatment for latent TB discontinues this treatment prematurely or is 
noncompliant with the therapy.
x
A subject receiving treatment for latent TB discontinues this treatment prematurely or is 
noncompliant with the therapy. 
x
The subject initiates a protocol-prohibited medication, eg, for a worsening of his or her 
psoriasis (unless agreed to by the medical monitor).
x
The subject withdraws consent for administration of study drug.
x
The subject is unable to adhere to the study visit schedule or comply with protocol 
requirements.
x
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.
x
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.
x
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.
x
Discontinuation of study treatment for abnormal liver tests is required by the investigator 
when a subject meets one of the conditions outlined in Appendix 8A or in the presence of 
abnormal liver chemistries not meeting protocol-specified stopping rules if the investigator 
believes that it is in best interest of the subject.
Refer to Appendix 8B for follow-up assessments (and study treatment restart guidelines) 
following abnormal liver test results. Study Sponsor must provide written approval before 
study intervention is restarted.
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 a 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.
If a subject discontinues study treatment for any reason 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. 


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Withdrawal From the Study
A subject will be withdrawn from the study for any of the following reasons:
x
Lost to follow-up
x
Withdrawal of consent
x
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 at study start.
If a subject is lost to follow-up, every reasonable effort must be made by the study site personnel 
to contact the subject and determine the reason for discontinuation/withdrawal. The measures 
taken to follow up 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 CRF 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. If a subject
withdraws from the study before the end of week 68 early termination visit (ETV) assessments 
should be obtained. If the reason for withdrawal from the study is withdrawal of consent then no 
additional assessments are allowed.
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:
x
The collected samples will be retained and used in accordance with the subject's original 
separate informed consent for optional research samples.
x
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 substudy 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.


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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). In that
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). The SAP may be 
divided in three separate documents describing the analyses for the three study parts.
The statistical analyses in this study will be performed separately for each Study Part and will 
focus on the comparison of the two randomized treatment groups (ie, 2a: guselkumab 100 mg q8w 
vs. 2b: guselkumab 100 mg q16w) in Study Part 2. The analyses will be confirmatory for the 
primary endpoint, and exploratory for the major secondary endpoints and for all other secondary 
endpoints.
Descriptive statistics will include counts and proportions for categorical data, and mean, SD, 
median, interquartile range, and range for continuous data. Graphical data displays may also be 
used to summarize the data. The two-group large-sample normal approximation Wald Z-test with 
Mantel-Haenszel stratum weights for 'disease duration' will be used to compare the proportion of 
subjects responding to treatment. Continuous response parameters will be compared using an 
analysis of variance model with fixed effects for treatment group and disease duration and baseline 
value as a covariate. Time-to-event endpoints will be analyzed using Kaplan-Meier product limit 
methods to estimate the survival distributions and the median time-to-event. The confirmatory 
significance level for non-inferiority testing is fixed to a one-sided D=0.05. Besides the 
confirmatory testing of the primary endpoint all other inferential statistical testing (including 
calculation of confidence intervals) are to be interpreted in the exploratory sense only.
11.1.
Subject Information
Descriptive statistics by treatment group 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 randomized, double-blind, parallel-group, multicenter phase 3b trial is designed to 
demonstrate that guselkumab 100 mg q16w treatment is non-inferior to guselkumab 100 mg q8w 
treatment in SRe as assessed by the proportion of subjects with an absolute PASI score <3 at 
week 68. A non-inferiority margin of 10% was chosen based on a minimally clinically meaningful 
difference. This margin was also used in CNTO1959PSO3009 (ECLIPSE) study and is therefore 
considered a valid approach for evaluating non-inferiority of a new treatment.


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Clinical Protocol CNTO1959PSO3012 Amendment 5
The null hypothesis H0 and the alternative hypothesis HA are formulated as follows:
x
H0: PT - PS  -10% ('inferiority')
x
H1: PT - PS > -10% ('non-inferiority')
where PT and PS denote the proportions of subjects with an absolute PASI score <3 at week 68 in the guselkumab
100 mg q16w treatment arm (PT = proportion test treatment) and the guselkumab 100 mg q8w treatment arm 
(PS = proportion standard treatment).
Based on data from CNTO1959PSO3002 the proportion of subjects with an absolute PASI score 
<3 at week 68 is assumed to be 90% for guselkumab 100 mg q8w. The expected difference in 
proportions between the treatment groups (guselkumab 100 mg q16w minus guselkumab 100 mg 
q8w) is 0%.
According to current international guidance documents (CPMP, Points to consider on switching 
between superiority and non-inferiority 2001) the intent-to-treat analysis set and the per-protocol 
analysis set should have equal importance in a non-inferiority trial and their use should lead to 
similar conclusions for a robust interpretation.
Therefore, the sample size estimation using the power approach is performed for the per-protocol 
analysis set as described below. No formal adjustment of the significance level is necessary 
(CPMP, Points to Consider on Multiplicity Issues in Clinical Trials 2002).
When the sample size in each group is 112, a two-group large-sample normal approximation Wald 
Z-test of proportions with a one-sided 0.05 significance level will have 80% power to reject the 
null hypothesis that the guselkumab 100 mg q16w treatment is inferior to the guselkumab 100 mg 
q8w treatment (the difference in proportions, PT - PS  LV  -10%) in favor of the alternative 
hypothesis that the guselkumab 100 mg q16w treatment is non-inferior to the guselkumab 100 mg 
q8w treatment (the difference in proportions is > -10%), assuming that the expected difference in 
proportions is 0 and the proportion in the guselkumab 100 mg q8w treatment group is 90% 
(nQuery Advisor® 7.0). 
Considering routine clinical conditions it is assumed that a rate of about 20% randomized subjects
will not be evaluable for the per-protocol analysis in Study Part 2. Thus, 280 subjects (140 subjects
per treatment group) are planned to be randomized in a ratio of 1:1 to meet the required sample 
size of 224 subjects (112 subjects per treatment group) for the per-protocol analysis.
Based on data from CNTO1959PSO3001 and CNTO1959PSO3002, it is anticipated that 
approximately 35% of enrolled subjects in Study Part 1 will be eligible for randomization at 
week 28 in Study Part 2. Thus, a total of 800 subjects should be enrolled in Study Part 1 to ensure 
that at least 280 subjects are eligible for randomization in Study Part 2. Accounting for a 10% 
drop-out rate of subjects ineligible for randomization at week 28 because of study discontinuation 
prior to week 28, it is therefore planned to enroll a total of 888 subjects in Study Part 1.
Note: Screenings and enrollments will be adjusted if necessary (without protocol amendment) to 
achieve 280 SRe at week 28. Ongoing subjects in Study Part I will continue to Part II if eligible, 
irrespective of whether or not 280 SRe are already randomized. Only screenings will be closed.


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11.3.
Efficacy Analyses
Analysis Data Set
The efficacy analyses will be performed separately for each Study Part. For all efficacy analyses 
to compare guselkumab 100 mg q16w vs. guselkumab 100 mg q8w in Study Part 2, all randomized 
subjects at week 28 will be included. 
In Study Part 2 subjects will be analyzed according to the treatment group to which they were 
randomized regardless of the treatment they actually received (intent-to-treat analysis set). 
The per-protocol analysis set will consist of all subjects in the intent-to-treat analysis set 
terminating the study without any major deviation of the protocol and its procedures. Subjects with 
major protocol deviations will be excluded from the per-protocol analysis. 
The confirmatory analysis of the primary endpoint variable will be performed both for the intent-
to-treat analysis set and the per-protocol analysis set. 
In Study Part 1 and Study Part 3 all subjects treated with at least one dose of study drug will be 
included in the efficacy analyses. For all efficacy analyses in Study Part 1 and Study Part 3,
subjects will be analyzed according to the treatment they actually received. 
Primary Endpoint
The proportion of subjects with an absolute PASI score <3 at week 68 will be displayed in a 
frequency table providing the number and percentage of subjects. Graphical presentation will be 
presented by means of a bar chart. 
To test the non-inferiority of guselkumab 100 mg q16w to guselkumab 100 mg q8w with a non-
inferiority margin of 10% in Study Part 2, a one-sided (Į=0.05) two-group large-sample normal 
approximation Wald Z-test with Mantel-Haenszel stratum weights for 'disease duration' will be 
used. The Mantel-Haenszel estimate, the two-sided 90% Wald-type confidence limits, and the test 
for the difference of proportions will be computed by using Mantel-Haenszel stratum weights 
(Mantel und Haenszel 1959) and the Sato variance estimator (Sato 1989). Non-inferiority will be 
accomplished when the lower limit of the two-sided 90% confidence interval for the difference in 
response rates (guselkumab 100 mg q16w minus guselkumab 100 mg q8w) will be > -10% both 
for the intent-to-treat analysis and the per-protocol analysis. 
Non-responder imputation will be applied for subjects with missing data for the primary endpoint 
as described in Section 11.11.
Major Secondary Endpoints
The major secondary endpoints will comprise the endpoints as defined in Section 2.1.2. Statistical 
analyses will be descriptive and exploratory only.
The proportion of subjects responding to treatment will be displayed in frequency tables providing 
the number and percentage of subjects. Graphical presentation will be presented by means of bar 
charts. In Study Part 2 the two-group large-sample normal approximation Wald Z-test with 
Mantel-Haenszel stratum weights for 'disease duration' will be used to compare the proportion of 
subjects responding to treatment. The Mantel-Haenszel estimate, the two-sided Wald-type 90% 
confidence limits, and the test for the difference of proportions in Study Part 2 will be computed 
by using Mantel-Haenszel stratum weights (Mantel und Haenszel 1959) and the Sato variance 


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estimator (Sato 1989). Exploratory statistical analyses of response parameters in Study Part 1 and 
Study Part 3 will be performed analogously, as appropriate. 
Non-responder imputation will be applied for subjects with missing data for the major secondary 
endpoints as described in Section 11.11. Details will be provided in the SAP.
Other Secondary Endpoints
The other secondary endpoints will comprise the endpoints as defined in Section 2.1.2. Statistical 
analyses will be descriptive and exploratory only.
The proportion of subjects responding to treatment will be displayed in frequency tables providing 
the number and percentage of subjects. Graphical presentation will be presented by means of bar 
charts. For continuous response parameters absolute values and changes from baseline will be 
summarized by descriptive statistics and box and whisker plots. 
In Study Part 2 the two-group large-sample normal approximation Wald Z-test with Mantel-
Haenszel stratum weights for 'disease duration' will be used to compare the proportion of subjects
responding to treatment. The Mantel-Haenszel estimate, the two-sided 90% Wald-type confidence 
limits, and the test for the difference of proportions in Study Part 2 will be computed by using 
Mantel-Haenszel stratum weights (Mantel und Haenszel 1959) and the Sato variance estimator
(Sato 1989). Continuous response parameters in Study Part 2 will be compared using an analysis 
of variance model with fixed effects for treatment group and disease duration and baseline value 
as covariate. Time-to-event endpoints will be analyzed using Kaplan-Meier product limit methods 
to estimate the survival distributions and the median time-to-event. Exploratory statistical analyses 
of response parameters in Study Part 1 and Study Part 3 will be performed analogously, as 
appropriate. Details will be provided in the SAP.
Non-responder imputation (for binary endpoints) or Last Observation Carried Forward (LOCF) 
imputation (for continuous endpoints) will be applied for subjects with missing data for the other 
secondary endpoints as described in Section 11.11.
Criteria for Endpoints
Treatment failure: Subjects who discontinue study agent due to lack of efficacy, an AE, worsening 
of psoriasis, or who started a protocol-prohibited medication/therapy during the study period that 
could improve psoriasis are considered treatment failures. Treatment failure rules (TFR) will be 
applied after week 68 for a separate analysis. The treatment failure rules will be documented in 
detail in the SAP.
PASI 75 Responders:
SubjectV ZLWK  LPSURYHPHQW LQ 3$6, IURP EDVHOLQH DW ZHHN 
PASI 90 Responders:
SubjectV ZLWK  LPSURYHPHQW LQ 3$6, IURP EDVHOLQH DW ZHHN 
PASI 100 Responders
Subjects with 100% improvement in PASI from baseline at week 28
Maintenance of control 
of disease
Subjects with a PASI score <3
Fluctuating disease:
absolute PASI score 3 to 5
Loss of disease control
absolute PASI score >5


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11.4.
Pharmacokinetic Analyses
Serum guselkumab concentrations at specified visits will be summarized by efficacy response 
status.
Descriptive statistics, including arithmetic mean, SD, median, interquartile range, minimum, and 
maximum will be calculated at each sampling time. 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 dataset. The BQL concentrations will 
be treated as zero in the summary statistics.
If data permit, the relationships between serum guselkumab concentration and efficacy or serum 
biomarker level may be analyzed graphically. 
11.5.
Biomarker Analyses
Biomarker samples outlined in Section 9.4 will be used to define serum markers, skin gene 
expression and cellular profiles for correlation analyses to better understand:
1.) The mechanism of action and the molecular effects of guselkumab
2.) The pathogenesis of psoriasis including the differences between >2 years and 2 years disease 
duration 
3.) Inter-individual variability in clinical outcomes 
Furthermore, population subgroups may be identified who respond differently to guselkumab.
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.
11.6.
Pharmacogenomic Analyses
Pharmacogenomic analyses may include candidate gene analyses or genome-wide association 
analyses in relation to treatment response, maintenance of response, relapse, and non-response. 
These analyses are considered exploratory. Details of the analysis plan and summary of results 
from pharmacogenomics analyses will be reported separately.
11.7.
Safety Analyses
Safety data, including but not limited to, AEs, SAEs, infections, serious infections, changes in 
laboratory assessments, and changes in vital signs will be summarized. Treatment-emergent AEs
(TEAEs) will be summarized by treatment group and Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class (SOC) and preferred terms (PT).
Analysis Data Set
The safety analyses will be performed separately for each Study Part. For all safety analyses, all 
subjects treated with at least one dose of study drug will be included. For all the safety analyses, 
subjects will be analyzed according to the treatment they actually received.


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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. For each adverse 
event, the percentage of subjects who experience at least 1 occurrence of the given event will be 
summarized by treatment group.
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those 
subjects who die, who discontinue treatment due to an adverse event, or who experience a severe 
or a serious AE.
The following analyses will be used to assess the safety of subjects in the study: 
x
The incidence and type of AEs. 
x
The incidence and type of SAEs. 
x
The incidence and type of infections. 
x
The incidence and type of reasonably related AEs. 
x
The incidence and type of injection site reactions. 
x
The laboratory parameters and change from baseline in laboratory parameters (hematology 
and chemistry).
Clinical Laboratory Tests
Laboratory data will be summarized by type of laboratory test. 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 postbaseline abnormal laboratory results 
based on NCI-CTCAE grades will also be provided. Descriptive statistics will be calculated for 
each laboratory item at baseline and for observed values and changes from baseline at each 
scheduled point in time. Changes from baseline results will be presented in pre- versus 
posttreatment cross-tabulations (with classes for below, within, and above normal ranges) at 
selected points in time. Listings of subjects with any laboratory results outside the reference ranges 
or any markedly abnormal laboratory results will be provided. 
Vital Signs
Descriptive statistics of pulse/heart rate and blood pressure (systolic and diastolic) values and 
changes from baseline will be summarized at each scheduled time point. The percentage of 
subjects with values beyond clinically important limits (specified in the SAP) will be summarized.
Physical Examination
Physical examination findings will be summarized at each scheduled time point. Descriptive 
statistics will be calculated at baseline and for observed values and changes from baseline at each 
scheduled time point. Frequency tabulations of the abnormalities will be made.
11.8.
Other Analyses
Stratified Newcombe confidence limits for the common proportion difference with respect to the 
primary endpoint will also be provided by using the method of Yan and Su (Yan und Su 2010).
In addition, the primary endpoint will also be analyzed without adjustment for disease duration 
('unadjusted analysis'). The two-group large-sample normal approximation Z-test ('asymptotic 


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Wald test of noninferiority') along with the two-sided 90% Wald type and Newcombe confidence 
interval will be computed. 
For binary endpoints in Study Part 2 counts and percentage of subjects per treatment group along 
with odds ratio (OR), relative risk (RR) and risk difference (RD), two-sided 90% confidence 
intervals and p-values for treatment comparison based on Mantel-Haenszel weights adjusted for 
disease duration will be provided.
The change from baseline of continuous endpoints in Study Part 2 will be analyzed by an analysis 
of covariance model (ANCOVA) with the fixed effect factors for treatment group and disease 
duration and the baseline value as covariate. The Least-Squares means (LS means), the LS mean 
difference and the standardized mean difference (computed according to Hedges' g) with the two-
sided 90% CI will be provided from the ANCOVA model.
Statistical analyses for time to event endpoints in Study Part 2 will provide the median time-to-
even estimates per treatment group with two-sided 90% confidence intervals and the hazard ratio 
(including two-sided 90% confidence interval) calculated from Cox-regression with the factors 
treatment group and disease duration as covariate.
Exploration of possible heterogeneity of treatment effects across centers for the primary endpoint 
will be performed by descriptive frequency statistics including graphical display of the results of 
the individual centers, as appropriate. No pooling of centers will be performed.
11.9.
Statistical Analyses per Study Part
Statistical analyses will be performed for each Study Part.
The confirmatory analysis is planned to be performed at the end of Study Part 2, ie, after all 
subjects have completed their visit at week 68 (ie, 40 weeks after randomization) or discontinued 
earlier. This analysis will include the confirmatory analysis of the primary endpoint, and the 
exploratory analyses of the major secondary endpoints and all other predefined efficacy and safety 
analyses from week 28 until week 68.
The analyses of Study Part 1 and Study Part 3 will be exploratory. The exploratory analysis of 
Study Part 1 will occur after all subjects have completed their visit at week 28 (ie, 28 weeks after 
study inclusion) or discontinued earlier. This analysis will include the safety analysis and all 
efficacy measures after week 0 and will cover the time until the week 28 visit. The exploratory 
analyses of Study Part 3 will occur after all subjects have completed their visit at week 116 (ie, 
48 weeks after inclusion in Study Part 3 at week 68) or week 144 in case of subjects entering the 
re-treatment arm in week 116, at week 164 (ie, 96 weeks after inclusion in Study Part 3 at week 68) 
and at week 220 (ie, 152 weeks after inclusion in Study Part 3 at week 68), or week 248 in case of 
subjects entering the re-treatment arm in week 220 or discontinued earlier.
These analyses will include the safety evaluations and all efficacy measures after week 68, and 
will cover the time until week 116/164/220 and until week 144/192/248, respectively.


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11.10. Subgroup and Sensitivity Analyses
6XEJURXS DQDO\VHV DUH SODQQHG WR EH SHUIRUPHG DFFRUGLQJ WR GLVHDVH GXUDWLRQ  DQG ! years) 
and pre-treatment (systemic naïve/experienced, biologic naïve/experienced) for all endpoints.
Sensitivity analyses are planned to be performed with respect to the applied statistical procedure 
(see Section 11.9) and by applying different imputation rules for missing data (see Section 11.11).
Additional subgroup analyses, eg. age, gender, baseline PASI, and sensitivity analyses may be 
performed and will be specified in the SAP. Multiple logistic regression analysis may be used to 
investigate the relationship between potential prognostic or risk factors and a single binary 
outcome variable (eg, influence of age or PK-level on SRe in Study Part 1).
11.11. Handling of Missing Data
All available data will be included in the analyses and will be summarized as far as possible. If not 
otherwise specified, there will be no substitution of missing data, ie, missing data will not be 
replaced, missing data will be handled as ‘missing’ in the statistical evaluation (‘observed cases 
analysis’).
Non-responder imputation will be applied for subjects with missing data for the primary endpoint 
at week 68 as described below: 
Subjects who do not maintain control of disease DEVROXWH 3$6, VFRUH   RU subjects who 
discontinue study treatment during the study before week 68 will be considered non-responders 
for the primary endpoint at week 68. In addition, subjects who do not return for evaluation at 
week 68 will be considered non-responders at week 68.
Non-responder imputation for the other binary endpoints will be performed analogously. 
For continuous response parameters, the last available observation after baseline will be calculated 
and used for analysis in case of premature termination (Last Observation Carried Forward 
approach; LOCF). 
LOCF may also be used as sensitivity analysis for binary response parameters. Treatment failure 
rules (TFR) will be applied after week 68 for a separate analysis. Additional sensitivity analyses 
may be done by applying different imputation rules for missing data (eg, 'multiple imputation'). 
An 'observed cases analysis' for all binary and continuous endpoints without substitution of 
missing data may also be used. A more detailed description of the handling of missing data will 
be provided in the SAP.


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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
(SOPs) in conformity with regulatory requirements worldwide to ensure appropriate reporting of 
safety information; all clinical studies conducted by the Sponsor or its affiliates will be conducted 
in accordance with those procedures.
12.1.
Definitions
12.1.1.
Adverse Event Definitions and Classifications
Adverse Event
An adverse event (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 Council for
Harmonization- [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 for 
time of last AE recording).
Serious Adverse Event
A serious AE (SAE) based on ICH and EU Guidelines on Pharmacovigilance for Medicinal 
Products for Human Use is any untoward medical occurrence that at any dose:
x
Results in death
x
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.)
x
Requires inpatient hospitalization or prolongation of existing hospitalization
x
Results in persistent or significant disability/incapacity
x
Is a congenital anomaly/birth defect
x
Is a suspected transmission of any infectious agent via a medicinal product
x
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 any of the other SAE outcomes listed above. These should usually be 
considered serious.


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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 even if it is a component of the study endpoint 
(eg, all-cause mortality).
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 package insert/summary of product characteristics (SmPC
TREMFYA®).
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.
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.
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 de-challenge and re-challenge).
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).


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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:
x
Overdose of a Sponsor study drug
x
Suspected abuse/misuse of a Sponsor study drug
x
Accidental or occupational exposure to a Sponsor study drug
x
Any failure of expected pharmacologic action (ie, lack of effect) of a Sponsor study drug
x
Unexpected therapeutic or clinical benefit from use of a Sponsor study drug
x
Medication error involving a Sponsor product (with or without subject exposure to product)
x
Exposure to a Sponsor study drug from breastfeeding.
Special reporting situations should be recorded in the CRF. Any special reporting situation that 
meets the criteria of an SAE should be recorded on the SAE page of the CRF.
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. SAEs, 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.
All AEs, regardless of seriousness, severity, or presumed relationship to study drug, must be 
recorded using medical terminology in the source document and the CRF. Whenever possible, 
diagnoses should be given when signs and symptoms are due to a common etiology (eg, cough, 
runny nose, sneezing, sore throat, and head congestion should be reported as "upper respiratory 
infection"). Investigators must record in the CRF their opinion on 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). 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.
Subjects 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:
x
Study number


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x
Statement, in the local language(s), that the subject is participating in a clinical study
x
Investigator's name and 24-hour contact telephone number
x
Local Sponsor's name and 24-hour contact telephone number (for medical staff only)
x
Site number and subject number
x
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 signed 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).
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:
x
The event resolves
x
The event stabilizes
x
The event returns to baseline, if a baseline value/status is available
x
The event can be attributed to agents other than study drug or to factors unrelated to study 
conduct
x
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.
$Q\ SRVVLEOH +\¶V ODZ FDVH $67 RU $/7  [ 8/1 WRJHWKHU ZLWK ELOLUXELQ  ; 8/1 RU ,15
>1.5) is considered an important medical event and must be reported to the sponsor in an expedited 
manner using the Serious Adverse Event form, even before all other possible causes of liver injury 
have been excluded. The INR criterion is not applicable to participants receiving anticoagulants.
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:
x
Hospitalizations not intended to treat an acute illness or AE (eg, social reasons such as pending 
placement in long-term care facility)
x
Surgery or procedure planned before entry into the study (must be documented in the CRF). 
Note: Hospitalizations that were planned before the signing of the ICF, and where the 
underlying condition for which the hospitalization was planned has not worsened, will not be 
considered SAEs. Any AE that results in a prolongation of the originally planned 
hospitalization is to be reported as a new SAE.
The cause of death of a subject in a study within 12 weeks of the last dose of study drug, whether 
or not the event is expected or associated with the study drug, is considered an SAE.


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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 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.
12.4.
Events of Special Interest
Any newly identified malignancy or case of active TB occurring after the first administration of 
study agent in subjects participating in this clinical study must be reported by the investigator 
according to the procedures in Section 12.3. 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.
12.5.
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). A sample of the suspected 
product should be maintained for further investigation if requested by the Sponsor.


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13.2.
Contacting Sponsor Regarding Product Quality
Names (and corresponding telephone numbers) of the individuals who should be contacted 
regarding product quality issues are listed in the Contact Information page(s), provided as a 
separate document.
14.
STUDY DRUG INFORMATION
14.1.
Physical Description of Study Drug(s)
The guselkumab supplied for this study is 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) 
guselkumab in a 1 mL glass syringe with a 27-gauge, 1/2 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 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.
14.2.
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
Guselkumab and Placebo will be supplied to the study sites. All study drug must be stored at 
controlled temperatures ranging from 2°C to 8°C (36°F to 46°F) 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.
Prior to administration, the product should be inspected visually for particulate matter and 
discoloration. If discoloration (other than a slight yellow color), visible opaque particles, or other 
foreign particles are observed in the solution, the product should not be used. 
Study drug in PFS will be ready to use. Aseptic procedures must be used during the preparation 
and administration of the study material. Refer to the pharmacy manual/study site investigational 
product and procedures manual for additional guidance on study drug preparation, handling, and 
storage.


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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 drugs 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. Any study subject who will be self-administering study drug at home 
will receive detailed instructions on how to store study drug, disposal of used syringes, and 
handling of unused study material. Subjects will receive a sharps container to dispose of used 
syringes and will be instructed to return cartons to the study site. Subjects will record the time and 
date of study drug administration in the study drug application card.
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. Returned study drug must not be dispensed again, even to the 
same subject. Study drug may not be relabeled or reassigned for use by other subjects. The 
investigator agrees neither to dispense 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:
x
SmPC for guselkumab
x
Pharmacy manual/study site investigational product and procedures manual
x
Laboratory manual
x
PRO questionnaires 
x
IWRS Manual
x
eDC Manual
x
Sample ICF (including substudy ICFs and Photo-documentation ICF)
x
Sample genetic research for ICF, as applicable
x
Biopsy Manual (for biopsy substudy sites only)
x
Photo-documentation manual.


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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 (228 - 268 mL) is considered to be an acceptable amount of 
blood to be collected over this time period from the population in this study. As scheduled, the 
phlebotomy is highly unlikely to induce anemia or other blood volume-related complications.
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):
x
Final protocol and, if applicable, amendments
x
Sponsor-approved ICF (and any other written materials to be provided to the subjects)
x
Investigator's Brochure (or equivalent information) and amendments/addenda
x
Sponsor-approved subject recruiting materials
x
Information on compensation for study-related injuries or payment to subjects for 
participation in the study, if applicable
x
Investigator's curriculum vitae or equivalent information (unless not required, as documented
by the IEC/IRB)
x
Information regarding funding, name of the Sponsor, institutional affiliations, other potential 
conflicts of interest, and incentives for subjects
x
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 


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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:
x
Protocol amendments (excluding the ones that are purely administrative, with no 
consequences for subjects, data or study conduct)
x
Revision(s) to ICF and any other written materials to be provided to subjects
x
If applicable, new or revised subject recruiting materials approved by the Sponsor
x
Revisions to compensation for study-related injuries or payment to subjects for participation 
in the study, if applicable
x
New edition(s) of the Investigator's Brochure and amendments/addenda
x
Summaries of the status of the study at intervals stipulated in guidelines of the IEC/IRB (at 
least annually)
x
Reports of AEs that are serious, unlisted/unexpected, and associated with the study drug
x
New information that may adversely affect the safety of the subjects or the conduct of the 
study
x
Deviations from or changes to the protocol to eliminate immediate hazards to the subjects
x
Report of deaths of subjects under the investigator's care
x
Notification if a new investigator is responsible for the study at the site
x
Development Safety Update Report and Line Listings, where applicable
x
Any other requirements of the IEC/IRB.
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.
The reapproval should be documented in writing (excluding the ones that are purely 
administrative, with no consequences for subjects, data or trial conduct).
At the end of the study, the investigator (or Sponsor where required) will notify the IEC/IRB about 
the study completion.
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 ICFs (main and optional substudies) must be signed before 
performance of any study-related activity. The ICFs that 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.


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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, if needed.
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.
At some sites, 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 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.


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Exploratory DNA, PD, 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 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, to understand 
psoriasis, to understand differential drug responders, and to develop tests/assays related to 
guselkumab and 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).
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. Data recorded in the CRF and 
source documents will reflect any departure from the protocol, and 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.


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17.2.2.
Required Prestudy Documentation
The following documents must be provided to the Sponsor before shipment of study drug to a
study site:
x
Protocol and amendment(s), if any, signed and dated by the principal investigator
x
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 
protocol by title and number and must be signed (or sealed, where appropriate per local 
regulations) by the chairman or authorized designee.
x
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.
x
Regulatory authority approval or notification, if applicable
x
Signed and dated statement of investigator (eg, Form FDA 1572), if applicable
x
Documentation of investigator qualifications (eg, curriculum vitae)
x
Completed investigator financial disclosure form from the principal investigator, where 
required
x
Signed and dated clinical trial agreement, which includes the financial agreement
x
Any other documentation required by local regulations.
The following documents must be provided to the Sponsor before enrollment of the first subject:
x
Completed investigator financial disclosure forms from all subinvestigators
x
Documentation of subinvestigator qualifications (eg, curriculum vitae)
x
Name and address of any local laboratory conducting tests for the study, if applicable
x
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 participating subjects by an anonymized subject identification number and the age at initial 
informed consent.
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 other equivalent document).
The minimum source documentation requirements for Section 4.1 and Section 4.2 that specify a 
need for documented medical history are as follows:
x
Referral letter from treating physician or
x
Complete history of medical notes at the site
x
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 CRF entries, corrections, and alterations must be made by the investigator or authorized study-
site personnel. The investigator must verify that all data entries in the CRF are accurate and correct.
The study data will be transcribed by study-site personnel from the source documents onto an 
electronic CRF, if applicable. Study-specific data will be transmitted in a secure manner to the 
Sponsor.
Worksheets may be used for the capture of some data to facilitate completion of the CRF. Any 
such worksheets will become part of the subject's source documents. Data must be entered into 
CRF in English. The CRF 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 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 a CRF are needed after 
the initial entry into the CRF, this can be done in either of the following ways:
x
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).
x
Sponsor or Sponsor delegate can generate a query for resolution by the investigator and study-
site personnel.


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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 into the Sponsor's data base. 
Written instructions will be provided for collection, handling, storage, and shipment of samples.
Guidelines for CRF completion will be provided and reviewed with study-site personnel before 
the start of the study. The Sponsor will review CRF for accuracy and completeness during on-site 
monitoring visits and after transmission to the Sponsor; any discrepancies will be resolved with 
the investigator or designee, as appropriate. After upload of the data into the study database they 
will be verified for accuracy and consistency with the data sources. 
17.7.
Record Retention
In compliance with the ICH/GCP guidelines, the investigator/institution will maintain all CRF and 
all source documents that support the data collected from each 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 
administration in an ICH region and until there are no pending or contemplated marketing 
administrations in an ICH region or until at least 2 years have elapsed since the formal 
discontinuation of clinical development of the investigational product. These documents will be 
retained for a longer period if required by the applicable regulatory requirements or by an 
agreement with the Sponsor. It is the responsibility of the Sponsor to inform the 
investigator/institution as to when these documents no longer need to be retained.
If the responsible investigator retires, relocates, or for other reasons withdraws from the 
responsibility of keeping the study records, custody must be transferred to a person who will accept 
the responsibility. The Sponsor must be notified in writing of the name and address of the new 
custodian. Under no circumstance shall the investigator relocate or dispose of any study documents 
before having obtained written approval from the Sponsor.
If it becomes necessary for the Sponsor or the appropriate regulatory authority to review any 
documentation relating to this study, the investigator/institution must permit access to such reports.
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 CRF
with the source documents
(eg, hospital/clinic/physician’s office medical records). The nature and location of all source 
documents will be identified to ensure that all sources of original data required to complete the 
CRF are known to the Sponsor and study-site personnel and are accessible for verification by the 


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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 study progress 
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 visit for the last subject participating in the study. 
The final data from the study site will be sent to the Sponsor (or designee) after completion of the 
final subject visit 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 early closure of a study site by the Sponsor or investigator may include but are not
limited to:
x
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
x
Inadequate recruitment of subjects by the investigator
x
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 


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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 administration, formulas, manufacturing processes, basic scientific data, 
prior clinical data, formulation information) supplied by the Sponsor to the investigator and not 
previously published, and any data, including pharmacogenomic or exploratory biomarker
research data, generated as a result of this study, are considered confidential and remain the sole 
property of the Sponsor. The investigator agrees to maintain this information in confidence and 
use this information only to accomplish this study and will not use it for other purposes without 
the Sponsor's prior written consent.
The investigator understands that the information developed in the study will be used by the 
Sponsor in connection with the continued development of guselkumab, and thus may be disclosed 
as required to other clinical investigators or regulatory agencies. To permit the information derived 
from the clinical studies to be used, the investigator is obligated to provide the Sponsor with all 
data obtained in the study.
The results of the study will be reported in a Clinical Study Report generated by the Sponsor and 
will contain data from all study sites that participated in the study as per protocol. Recruitment
performance or specific expertise related to the nature and the key assessment parameters of the 
study will be used to determine a coordinating investigator for the study. Results of 
pharmacogenomic or exploratory biomarker analyses performed after the Clinical Study Report 
has been issued will be reported in a separate report and will not require a revision of the Clinical 
Study Report. Study 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 administration. 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 


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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, 18 months after study end date, or the 
Sponsor confirms there will be no multicenter study publication. Authorship of publications 
resulting from this study will be based on the guidelines on authorship, such as those described in 
the ICMJE Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly 
Work in Medical Journals, which state that the named authors must have made a significant 
contribution conception or  to the design of the work or the acquisition,  analysis or interpretation 
of the data, for the work; and drafted the work or revised it critically for important intellectual 
content; and given final approval of the version to be published; and agreed to be accountable for 
all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of 
the work are appropriately investigated and resolved.
Registration of Clinical Studies and Disclosure of Results
The Sponsor will register and disclose the existence and the results of clinical studies as required 
by law.


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Finlay, AY, und GK Khan. 1994. „Dermatology Life Quality Index (DLQI)- a simple practical 
measure for routine clinical use.“ Clin Exp Dermatol, 210-216.
Kollipara, R, C Downing, R Gordon, und et al. 2015. „Interleukin-23 in the pathogenesis and 
treatment of psoriasis.“ Skin Therapy Lett, 1-4.
Ltd, Janssen-Cilag. 2017. „SmPC Tremfya®.“ November.
Mantel, N, und W Haenszel. 1959. „Statistical Aspects of Analysis of Data from Retrospective 
Studies of Disease.“ J Natl Cancer Inst, 719-748.
Manuel, O, und D Kumar. 2008. „QuantiFERON-TB Gold assay for the diagnosis of latent 
tuberculosis infection.“ Expert Rev Mol Diagn, 247-256.
Ness-Schwickerath, K, C Jin, und C Morita. 2010. „Cytokine requirements for differentiation 
and expansion of IL-17A and IL-22 producing human V(gamma)2V(delta) 2 T cells.“ J
Immun, 7268-7280.
Papp, KA, A Blauvelt, AB Kimball, und et al. 2018. „Patient-reported symptoms and signs of 
moderate-to-severe psoriasis treated with guselkumab or adalimumab: results from the 
randomized VOYAGE 1 trial.“ J Eur Acad Dermatol Venereol, Epub ahead of print.
Ramsay, B, und CM Lawrence. 1991. „Measurement of involved surface area in patients with 
psoriasis.“ Br J Dermatol, 565-570.
Reich, K, AW Armstrong, P Foley, und et al. 2017. „Efficacy and safety of guselkumab, an anti-
interleukin-23 monoclonal antibody, compared with adalimumab for the treatment of 
patients with moderate to severe psoriasis with randomized withdrawal and retreatment: 
Results from...“ J Am Acad Dermatol, 418-431.


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Revicki, DA, MK Willian, A Menter, und et al. 2008. „Relationship between clinical response to 
therapy and health-related quality of life outcomes in patients with moderate to severe 
plaque psoriasis.“ Dermatology, 260-270.
Sato, T. 1989. „On the Variance Estimator of the Mantel-Haenszel Risk Difference.“ Biometrics,
1323-1324.
Sofen, H, S Smith, RT Matheson, und et al. 2014. „Guselkumab (an IL-23-specific mAb) 
demonstrates clinical and molecular response in patients with moderate-to-severe 
psoriasis.“ J Allergy Clin Immunol, 1032-1040.
Strober, B, Papp, KA, M Lebwohl, und et al. 2016. „Clinical meaningfulness of complete skin 
clearance in psoriasis.“ J Am Acad Dermatol, 77-82.
Takeshita, J, K Callis Duffin, DB Shin, und et al. 2014. „Patient-reported outcomes for psoriasis 
patients with clear versus almost clear skin in the clinical setting.“ J Am Acad Dermatol,
633-641.
Teunissen, M, M Munneke, J Bernink, und et al. 2014. „Enrichment of NCR+ ILC3 in lesional 
skin and blood of psoriasis patients.“ J Invest Dermatol, 2351-2360.
Villanova, F, B Flutter, I Tosi, und et al. 2014. „Characterization of innate lymphoid cells in 
human skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis.“ J Invest 
Dermatol, 984-991.
Viswanathan, HN, D Chau, CF Milmont, und et al. 2015. „Total skin clearance results in 
improvements in health-related quality of life and reduced symptom severity among 
patients with moderate to severe psoriasis.“ J Dermatol Treatment, 235-239.
Yan, X, und XG Su. 2010. „Stratified Wilson and Newcombe Confidence Intervals for Multiple 
Binomial Proportions.“ Statistics in Biopharmaceutical Reserach, 329-335.


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Attachment 1:
Assessment of Induration. Erythema and Scaling for Target Lesion Severity Score 
(TLSS) and Investigator’s Global Assessment (IGA)


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Attachment 2:
Psoriasis Area and Severity Index




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Attachment 4:
Instructions for the Completion of PRO Assessments


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Attachment 5:
Contraception 


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Attachment 6:
Guidance on Study Conduct during the COVID-19 Pandemic
BACKGROUND
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on the 
conduct of this clinical study due to, for example, self-isolation/quarantine by subjects and/or study-site 
personnel; travel restrictions and limited access to public places, including hospitals; and study site 
personnel being reassigned to critical tasks.
In alignment with recent health authority guidance, the sponsor is providing options for study-related 
subject management in the event of disruption to the conduct of the study. This guidance does not supersede 
any local or government guidelines or requirements or the clinical judgement of the investigator to protect 
the health and well-being of subjects and site staff. If at any time a subject’s safety is considered to be at 
unacceptable risk, study intervention will be discontinued, and study follow-up will be conducted.
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent possible 
remotely, virtually, or will be delayed until such time that on-site visits can be resumed. At each contact, 
subjects will be interviewed to collect safety data. Key efficacy endpoint assessments should be performed 
if required and as feasible. Subjects will also be questioned regarding general health status to fulfill any 
physical examination requirement.
Every effort should be made to adhere to protocol-specified assessments for subjects on study intervention, 
including follow up. Modifications to protocol-required assessments may be permitted after consultation 
between the subject and investigator, and with the agreement of the sponsor (see below).
The sponsor will continue to monitor the conduct and progress of the clinical study and any changes will 
be communicated to the sites and health authorities according to local guidance.
If a subject has tested positive for COVID 19, the investigator should contact the sponsor’s responsible 
medical officer or designee to discuss plans for study intervention and follow-up.
GUIDANCE SPECIFIC TO THIS PROTOCOL
Study Interventions and Assessments
Certain protocol-mandated visits to the study site may not be possible during the COVID-19 outbreak; 
therefore, temporary measures may be implemented if considered appropriate by the sponsor and 
investigator to maintain continuity of patient care and study integrity. Certain measures, such as those listed 
below, may be necessary and should be instituted in accordance with applicable (including local) laws, 
regulations, guidelines, and procedures.
Administration of Study Medication
In cases where a site visit is not possible under restrictions and limitations due to the COVID-19 pandemic, 
subjects may self-administer subcutaneous (SC) injections of study intervention outside a study site (eg, at 
home). Those subjects will receive instructions on compliance, storage, disposal of used syringes, handling 
of unused study material, and adverse event reporting. Self-administration on site under supervision of site 
personal is also allowed.
Notes on Shipment of Study Intervention to Subjects
If it is necessary to ship the study drug directly to study subjects, shipment by the study site itself is preferred 
under this exception due to the COVID-19 pandemic. Shipment should be made in a manner that allows 
tracking of both transport and delivery. The subject should acknowledge receipt of the shipment to the site 
(eg, by returning a dated and signed receipt form).


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In case adequate shipment by the study site is not possible (for example, owing to capacity limitations, 
logistics, or special transport conditions for the study drug), direct transport by the sponsor may be accepted 
in justified exceptional cases, provided that the sponsor appoints a suitably qualified service provider as
trustee. The sponsor must contractually oblige this service provider to maintain the pseudonymization and, 
if necessary, blinding of subjects to the sponsor using appropriate measures. Both the transport and 
handover conditions for study drug should be part of the contractual arrangements, so that pharmaceutical 
drug safety of study drug as well as protection of the privacy and personal data of subjects are adequately 
safeguarded. The study drug must be delivered directly to the subject or a person authorized by the subject 
and must not be given to neighbors or deposited at a storage location. Written confirmation of dose and 
dose regimens by the investigator should also be obtained prior to shipment.
The personnel of the service provider in charge of the transport should be trained and instructed accordingly. 
As personal data are transferred to the service provider, this requires a contract of assignment with the 
sponsor or legal representative.
For direct shipment of study drug to subjects, written instructions on storage and return of used and unused 
study drug should be provided to subjects. When shipped by study sites, the receipt, consumption and return 
of study drug supplies must be documented in a form that allows the study site to meet its documentation 
requirements (ie, drug accountability), as defined in ICH GCP 4.6.3.
Study Assessments and Analyses
Missed Assessments
Missed assessments/visits will be captured in the clinical trial management system for protocol deviations. 
Discontinuations of study drug and withdrawal from the study should be documented with the prefix 
“COVID-19-related” in the CRF.
Other relevant study data elements impacted by the COVID-19 pandemic should also be 
documented/labeled as “COVID-19-related” in CRFs and/or other study systems, as directed by sponsor 
guidance; these may include missed/delayed/modified study visits/assessments/dosing, and instances where 
temporary measures such as those above are implemented. 
Study Analyses
The Sponsor will evaluate the totality of impact of COVID-19 on collection of key study data and additional 
data analyses will be outlined in the statistical analysis plan(s).


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Attachment 7: Protocol Amendment History
This is the fourth global amendment. The summary of changes table for the current amendment is located after the 
Table of Contents (TOC). The summary of changes tables for the previous amendments are presented below:
Amendment 4 (15 June 2020)
Overall Rationale for the Amendment: To add an additional exclusion criterion for patients with 
confirmed or potential SARS-CoV-2 infection. Changes from COVID-19 related Amendment 3 were 
included in the full protocol.
Section Number
and Name
Description of Changes and Brief Rationale
Synopsis; 
6. Dosing and 
Administration
Description of Change: Added text to allow subcutaneous injections of study drug to 
be self-administered outside a study site, in cases where a study site visit is not possible, 
provided those subjects have appropriate experience or have received adequate training 
to perform self-administration of SC injections. 
Rationale: To provide flexibility of dose administration in cases where a study site visit 
is not possible.
5.2 Exclusion 
Criteria
Description of Change: Added exclusion criterion 40, to document exclusion of 
patients with confirmed or suspected SARS-CoV-2 infection or who have had close 
contact with a person with confirmed or suspected SARS-CoV-2 infection within 6 
weeks before baseline and to provide COVID-19-related guidance on study participation 
and exclusion.
Rationale: To exclude patients with confirmed or potential SARS-CoV-2 Infection.
7. Treatment 
Compliance; 
14.5. Drug 
Accountability
Description of Change: Clarified documentation requirements for self-administration 
of study drug. Added text on documentation requirements and on storage, disposal of 
used syringes, and handling of unused study material for subjects who will be self-
administering study drug at home.
Rationale: To provide details on handling of study materials and documentation for 
self-administration of study drug by subjects in cases where a study site visit is not 
possible.
9.6 Safety 
Evaluations
Description of Change: Clarified adverse event reporting procedure for subjects who 
will be self-administering study drug at home.
Rationale: To document adverse events for subjects in cases where a study site visit is 
not possible.
Attachment 6 -
Guidance on Study 
Conduct During 
the COVID-19
Pandemic
Description of Change: Added attachment as guidance on changes to study conduct 
and assessments due to restrictions and limitations during the COVID-19 pandemic.
Rationale: To provide guidance on study conduct and assessments during the
COVID-19 pandemic


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Amendment 3 (COVID-19 amendment) from 15 April 2020    
Overall Rationale for the Amendment: To allow for self-administration of subcutaneous study 
intervention outside a study site (eg, at home), in cases where a study site visit is not possible under 
restrictions and limitations during the COVID-19 pandemic. Guidance on other aspects of study conduct 
during the COVID-19 pandemic is also included.
Section Number
and Name
Description of Changes and Brief Rationale
Added Attachment 6-
Guidance on Study Conduct 
During the COVID-19 
Pandemic
Description of Change: Added attachment as guidance on changes to study 
conduct and assessments due to restrictions and limitations during the 
COVID-19 pandemic.
Rationale: To provide guidance on study conduct and assessments during the 
COVID-19 pandemic.
Amendment 2 from 29 May 2019
Overall Reason: The overall reason for the amendment is the extension of study sites from only 
Germany to Germany and France.
Applicable 
Section(s)
Description of Change(s)
Rationale: Extension of study sites to France.
Front page
Synopsis-
SUBJECT 
POPULATION
*Janssen-Cilag is a regional organization that operates through different
legal entities in various countries Germany.
…Subjects must have moderate-to-severe plaque-type psoriasis defined by
PASI >10 or affected body surface area (BSA) >10% and additionally a DLQI 
>10 according to German S3 guidelines….
Synopsis-
OVERVIEW of 
study design
3.1 Overview of 
study design
… subjects are therefore needed to be screened at up to 120 90 German 
study sites and 10 French study sites…
Rationale: Clarification of allowed psoriasis treatment during the safety follow-up period
Synopsis-Study Part 
2: Week 28 through 
Week 68
3.1 Overview of 
study design
… At visit week 68 (for group 2c), the investigator may continue 
treatment with commercially available guselkumab (ie. not provided by 
the sponsor) to maintain a q8 interval. Due to the half-life of 
guselkumab, it is recommended not to start a new therapy during safety 
follow-up period. If the investigator feels strongly that an additional 
therapy is needed, this should be discussed with the sponsor before 
initiation of the new therapy.


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Applicable 
Section(s)
Description of Change(s)
6. Dosage and 
Administration
During the safety follow-up period (Week 68 through Week 72 for 
group 2c, week R24 through week R28 of the re-treatment arm or in 
case of prematurely stop of study treatment 12 weeks after the last 
application of study drug), concomitant treatments for psoriasis may be 
administered at the investigator´s discretion as follows:
The Investigator may continue treatment with commercially available 
guselkumab (ie. not provided by the sponsor) to maintain a q8 interval. 
Due to the half-life of guselkumab, it is recommended not to start a new 
therapy during safety follow-up period. If the investigator feels strongly 
that an additional therapy is needed, this should be discussed with the 
sponsor before initiation of the new therapy.
Rationale: Two 3 mm biopsies may be taken instead of the 6 mm biopsy.
Synopsis-Study Part 
2: Week 28 through 
Week 68
3.1 Overview of 
study design
Time and event 
schedule- Biomarker
9.4 Biomarkers
Substudy 2 (Gene expression substudy): 
… Two 3 mm biopsies may be taken instead of the 6 mm biopsy if    
preferred by the investigator and consented by the patient. The splitting 
step is not applicable in that case. …
Footnote m: …A total of six 6 mm biopsy samples (or twelve 3 mm 
biopsy samples in sub 2 if appl., refer to Section 3.1). will be collected 
….
…. Each 6 mm biopsy will be split in two parts; one part will be stored for 
RNA gene expression analysis, while the other part will be frozen stored
for in OCT and stored for H&E, IHC and IF analyses. If two 3 mm 
biopsies have been taken instead of the 6 mm biopsy, one 3 mm biopsy 
will be stored in RNAlater for RNA preparation and gene expression 
analysis, while the other 3 mm biopsy will be frozen in OCT and stored 
for H&E, IHC and IF analyses. …
Rationale: A footnote is added to the Time and Event Schedule to improve clarity of the protocol.
Time and event 
schedule- safety 
assessments
Footnote added to chest radiograph: p: Only if no chest radiograph taken 
within the last 3 months before administration of first study drug is 
available.
Rationale: Fumaric acid esters are added to exclusion criterion 16.
4.2 Exclusion 
criteria
16. Has received any systemic immunosuppressant (eg, methotrexate, 
azathioprine, cyclosporine, 6-thioguanine, mercaptopurine, mycophenolate 
mofetil, tacrolimus, fumaric acid esters), …


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Applicable 
Section(s)
Description of Change(s)
Rationale: Definition added to be consistent with exclusion criterium 1
4.2 Exclusion 
criteria
Note
Prior to randomization at week 28 and again prior to entering Study Part 3 at 
week 68 exclusion criterion 1 (subject has a clinically active psoriasis 
arthritis which needs systemic therapy beyond NSAIDs) has to be re-
evaluated and subjects with diagnosed PsA who need systemic therapy 
beyond NSAIDs are to be excluded from further participation in the trial.
Amendment 1 06 December 2018
The overall reason for the amendment: The overall reason for the amendment is the request of the 
responsible Health Authority (HA) to add a discontinuation criterium for patients showing no response 
to study treatment by week 28.  
Applicable 
Section(s)
Description of Change(s)
Rationale: Addition of a discontinuation criterium for patients showing no response to study treatment 
by week 28 as requested by HA.
10.2.
Discontinuation of 
Study treatment
A subject´s study treatment must be permanently discontinued if: 
….
x The subject shows no response to study treatment at week 28, defined 
as no change or worsening of PASI score at week 28 in comparison 
to week 0.
…..
Rationale: Inconsistencies are corrected in the Time and Event Schedule to improve clarity of the 
protocol.
Time and event 
schedule
- Safety Assessments: Added missing X for Physical Examination at week 
28 for SRe
- Biomarkers: “optional” relocated from the header to substudy 1,2 and 4
- Week 72 (SFU): footnote added: *****: For all subjects (part 1 and 
part 2), who discontinue study treatment prematurely, every effort 
should be made to conduct the SFU visit 12 weeks after the last 
study drug administration.
- TES Re-Treatment: Skin biopsy and blood sample for PBMC for 
cellular substudy (1)k (optional)
- To occur within 4 3 weeks prior to week 0.


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Attachment 8: Liver Stopping Criteria and Follow-up Assessments
A: Liver chemistry stopping criteria and increased monitoring algorithm
Study intervention will be discontinued for a participant if liver chemistry stopping criteria are met.
Liver Chemistry Stopping Criteria and Increased Monitoring Algorithm
Liver Chemistry Increased Monitoring Algorithm with Continued Study Intervention for Participants with 
$/7 RU $67 [8/1 EXW [8/1
Abbreviations: ALT = alanine transaminase; AST = aspartate transaminase, INR = international normalized ratio; 
SAE = serious adverse event; ULN = upper limit of normal, Tbili = Total bilirubin.
Refer to Appendix 8 B: Liver Safety: Suggested Actions and Follow-up Assessments and Study 
Intervention Rechallenge Guidelines.


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B: Liver chemistry stopping criteria and follow-up assessments
Study intervention will be discontinued for a participant if liver chemistry stopping criteria are met.
Liver Chemistry Stopping Criteria and Follow-Up assessments
Liver Chemistry Stopping Criteria
ALT or AST-
absolute
ALT or AST t8xULN
ALT or AST-
Increase
ALT or AST t5xULN but <8xULN persists for t2 weeks
ALT or AST t3xULN but <5xULN persists for t4 weeks
Bilirubin1, 2
ALT or AST t3xULN and total bilirubin t2xULN (>35% direct bilirubin) 
INR2
ALT or AST t3xULN and international normalized ratio (INR) >1.5
Cannot Monitor
ALT or AST t5xULN but <8xULN and cannot be monitored weekly for t2 weeks
ALT or AST t3xULN but <5xULN and cannot be monitored weekly for t4 weeks
Symptomatic3
ALT or AST t3xULN associated with symptoms (new or worsening) believed to be related 
to liver injury or hypersensitivity
Suggested Actions, Monitoring, and Follow up Assessments
Actions
Follow Up Assessments
x
Immediately discontinue study intervention
x
Report the event to the sponsor within 24 hours
x
Complete the liver event reporting form and 
complete an SAE CRF if the event also met the 
criteria for an SAE2
x
Perform follow-up assessments as described in the 
Follow up Assessment column
x
Monitor the participant until liver chemistry test 
abnormalities resolve, stabilize, or return to baseline
MONITORING:
If ALT or AST t3xULN AND total bilirubin t2xULN 
or INR >1.5:
x
Repeat liver chemistry tests (include ALT, aspartate 
transaminase [AST], alkaline phosphatase, total 
bilirubin and INR) and perform liver event follow-up 
assessments within 24 hours
x
Monitor participant twice weekly until liver 
chemistry test abnormalities resolve, stabilize, or 
return to baseline
x
A specialist or hepatology consultation is 
recommended
If ALT or ASTt3xULN AND total bilirubin <2xULN 
and INR d1.5:
x
Repeat liver chemistry tests (include ALT, AST, 
alkaline phosphatase, total bilirubin and INR) and
perform liver chemistry follow-up assessments 
within 24 to 72 hours
x
Monitor participants weekly until liver chemistry 
abnormalities resolve, stabilize, or return to baseline
RESTART/RECHALLENGE
x
Do not restart/rechallenge participant with study 
intervention unless allowed per protocol and sponsor
approval is granted
x
Viral hepatitis serology4
x
Obtain blood sample for PK-analysis as quick as 
possible after the most recent dose4
x
Obtain serum creatine phosphokinase (CPK), 
lactate dehydrogenase (LDH), gamma-
glutamyltransferase [GGT], and glutamate 
dehydrogenase [GLDH], and serum albumin
x
Fractionate bilirubin if total bilirubin t2xULN
x
Obtain complete blood count with differential to 
assess eosinophilia
x
Record the appearance or worsening of clinical 
symptoms of liver injury, or hypersensitivity, on 
the liver event reporting form
x
Record use of concomitant medications 
(including acetaminophen, herbal remedies, 
recreational drugs, and other over-the-counter 
medications)
x
Record alcohol use on the liver event alcohol 
intake form
If ALT or AST t3xULN AND total bilirubin 
t2xULN or INR >1.5 obtain the following in 
addition to the assessments listed above:
x
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney microsomal 
antibodies, and quantitative total immunoglobulin 
G (IgG) or gamma globulins
x
Serum acetaminophen adduct assay, when 
available, to assess potential acetaminophen 
contribution to liver injury in participants with 
definite or likely acetaminophen use in the 
preceding week


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x
If restart/rechallenge not allowed per protocol or 
not granted, permanently discontinue study 
intervention and continue participant in the study for 
any protocol specified follow up assessments
x
Liver imaging (ultrasound, magnetic resonance, 
or computerized tomography) to evaluate liver 
disease; complete the liver imaging form
x
Liver biopsy may be considered and discussed 
with local specialist if available, for instance:

In patients when serology raises the possibility 
of autoimmune hepatitis (AIH)

In patients when suspected DILI progresses or 
fails to resolve on withdrawal of study 
intervention

In patients with acute or chronic atypical 
presentation
x
If liver biopsy conducted complete the liver 
biopsy form
1. Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study intervention if ALT or AST t3xULN and total bilirubin t2xULN. 
Additionally, if serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable 
urinary bilirubin on dipstick which is indicative of direct bilirubin elevations suggesting liver injury. 
2. All events of ALT or AST t3xULN and total bilirubin t2xULN (>35% direct bilirubin) or ALT or AST 
t3xULN and INR >1.5 may indicate severe liver injury (possible ‘Hy’s Law’) and must be reported to 
sponsor in an expedited manner and as an SAE if SAE criteria met (excluding studies of hepatic 
impairment or cirrhosis). The INR stated threshold value will not apply to participants receiving 
anticoagulants. 
3. New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or hypersensitivity (such as fever, rash or eosinophilia).
4. PK sample may not be required for participants known to be receiving placebo or non-comparator interventions. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study intervention prior 
to the PK blood sample draw on the CRF. If the date or time of the last dose is unclear, provide the participant’s 
best approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected 
in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are 
included in the pertinent Study Reference Manual.
Liver Chemistry Increased Monitoring Criteria with Continued Study Intervention
Liver Chemistry Increased Monitoring Criteria and Actions with Continued Study Intervention
Criteria
Actions
ALT or AST t5xULN and <8xULN and total 
bilirubin <2xULN or INR<1.5 without
symptoms believed to be related to liver 
injury or hypersensitivity, and who can be 
monitored weekly for 2 weeks
OR
ALT or ASTt3xULN and <5xULN and total 
bilirubin <2xULN or INR<1.5 without
symptoms believed to be related to liver 
injury or hypersensitivity, and who can be 
monitored weekly for 4 weeks
x
Notify the sponsor within 24 hours of learning of the 
abnormality to discuss participant safety
x
Participant must return weekly for repeat liver chemistry 
tests (ALT, AST, alkaline phosphatase, total bilirubin) until 
the abnormalities resolve, stabilize, or return to baseline
x
If at any time the participant meets liver chemistry stopping 
criteria proceed as described in the pertinent manual
x
If ALT or AST decreases from ALT or ASTt5xULN and
[8/1 WR [ULN but <5xULN, continue to monitor liver 
chemistries weekly
x
If, after 4 weeks of monitoring, ALT or AST<3xULN and 
total bilirubin <2xULN, monitor participants twice monthly 
until liver chemistry tests resolve, stabilize, or return to 
baseline
References:
James LP, Letzig L, Simpson PM, et al. Pharmacokinetics of Acetaminophen-Adduct in Adults with Acetaminophen 
Overdose and Acute Liver Failure. Drug Metab Dispos 2009; 37:1779-1784.
EASL Clinical Practice Guidelines: Drug-induced liver injury. Journal of Hepatology 2019; 70 (6):1222-1261.


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INVESTIGATOR AGREEMENT
I have read this protocol and agree that it contains all necessary details for carrying out this study. I will 
conduct the study as outlined herein and will complete the study within the time designated.
I will provide copies of the protocol and all pertinent information to all individuals responsible to me who 
assist in the conduct of this study. I will discuss this material with them to ensure that they are fully informed 
regarding the study drug, the conduct of the study, and the obligations of confidentiality. 
Coordinating Investigator (where required):
Name (typed or printed):
Institution and Address:
Signature:
Date:
(Day Month Year)
Principal (Site) Investigator:
Name (typed or printed):
Institution and Address:
Telephone Number:
Signature:
Date:
(Day Month Year)
Sponsor's Responsible Medical Officer:
Name (typed or printed):
Institution:
Janssen-Cilag GmbH, Neuss/ Germany
Signature:
Date:
(Day Month Year)
Note: If the address or telephone number of the investigator changes during the course of the study, written 
notification will be provided by the investigator to the Sponsor, and a protocol amendment will not be required.

PPD
PPD


CONFIDENTIAL
1
Status: Approved,  Date: 15 April 2020 
Janssen-Cilag GmbH* 
Clinical Protocol 
Appendix - Guidance on Study Conduct during the COVID-19 Pandemic 
Protocol Title 
A Phase 3b, Randomized, Double-blind, Parallel Group, Multicenter Study to Evaluate 
Further Therapeutic Strategies with Guselkumab in Patients with Moderate-to-Severe 
Plaque-Type Psoriasis 
GUIDE 
Protocol CNTO1959PSO3012; Phase 3b 
Amendment 3 
TREMFYA® (guselkumab) 
*Janssen-Cilag is a regional organization that operates through different legal entities in various countries.
The legal entity acting as the Sponsor for Janssen-Cilag studies may vary, such as, but not limited to
Janssen-Cilag International NV or Janssen Pharmaceuticals NV. The term “Sponsor” is used throughout
the protocol to represent these various legal entities. The Sponsor is identified on the Contact Information
page that accompanies the protocol.
EudraCT NUMBER: 
2018-001238-16 
Status: 
Approved 
Date: 
15 April 2020
Prepared by: Janssen-Cilag GmbH 
EDMS number: EDMS-ERI-165008226 
GCP Compliance:  This study will be conducted in compliance with Good Clinical Practice and applicable regulatory 
requirements. 
Confidentiality Statement 
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise. 
NCT03818035


TREMFYA® (guselkumab) 
 Clinical Protocol CNTO1959PSO3012 Amendment 3 
 
Appendix - Guidance on Study Conduct during the COVID-19 Pandemic 
 
CONFIDENTIAL 
2 
Approved, Date: 15 April 2020  
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
DOCUMENT HISTORY 
Document 
Date 
Amendment 3 (COVID-19 Attachment) 
15 April 2020 
Amendment 2 
29 May 2019 
Amendment 1 
06 December 2018 
Original Protocol 
05 July 2018 
Amendment 3, 15 April 2020 
Overall Rationale for the Amendment: To allow for self-administration of subcutaneous study drug 
outside a study site (eg, at home), in cases where a study site visit is not possible under restrictions and 
limitations during the COVID-19 pandemic. Guidance on other aspects of study conduct during the 
COVID-19 pandemic is also included. 
Section Number 
and Name 
 
Description of Changes and Brief Rationale 
Added Attachment 6- 
Guidance on Study Conduct 
During the COVID-19 
Pandemic 
Description of Change:  Added attachment as guidance on changes to study 
conduct and assessments due to restrictions and limitations during the 
COVID-19 pandemic. 
Rationale: To provide guidance on study conduct and assessments during the 
COVID-19 pandemic. 
 
 


TREMFYA® (guselkumab) 
 Clinical Protocol CNTO1959PSO3012 Amendment 3 
 
Appendix - Guidance on Study Conduct during the COVID-19 Pandemic 
 
CONFIDENTIAL 
3 
Approved, Date: 15 April 2020  
BACKGROUND 
It is recognized that the Coronavirus Disease 2019 (COVID-19) pandemic may have an impact on 
the conduct of this clinical study due to, for example, self-isolation/quarantine by subjects and/or 
study-site personnel; travel restrictions and limited access to public places, including hospitals; 
and study site personnel being reassigned to critical tasks. 
In alignment with recent health authority guidance, the sponsor is providing options for study-
related subject management in the event of disruption to the conduct of the study. This guidance 
does not supersede any local or government guidelines or requirements or the clinical judgement 
of the investigator to protect the health and well-being of subjects and site staff. If at any time a 
subject’s safety is considered to be at unacceptable risk, study drug will be discontinued, and study 
follow-up will be conducted. 
Scheduled visits that cannot be conducted in person at the study site will be performed to the extent 
possible remotely, virtually, or will be delayed until such time that on-site visits can be resumed. 
At each contact, subjects will be interviewed to collect safety data. Key efficacy endpoint 
assessments should be performed if required and as feasible. Subjects will also be questioned 
regarding general health status to fulfill any physical examination requirement. 
Every effort should be made to adhere to protocol-specified assessments for subjects on study 
drug, including follow up. Modifications to protocol-required assessments may be permitted after 
consultation between the subject and investigator, and with the agreement of the sponsor (see 
below). 
The sponsor will continue to monitor the conduct and progress of the clinical study and any 
changes will be communicated to the sites and health authorities according to local guidance. 
 
 


TREMFYA® (guselkumab) 
 Clinical Protocol CNTO1959PSO3012 Amendment 3 
 
Appendix - Guidance on Study Conduct during the COVID-19 Pandemic 
 
CONFIDENTIAL 
4 
Approved, Date: 15 April 2020  
GUIDANCE SPECIFIC TO THIS PROTOCOL 
If a subject has tested positive for COVID 19, the investigator should contact the sponsor’s 
responsible medical officer or designee to discuss plans for study drug and follow-up. 
Study Medications and Assessments 
Certain protocol-mandated visits to the study site may not be possible during the COVID-19 
outbreak; therefore, temporary measures may be implemented if considered appropriate by the 
sponsor and investigator to maintain continuity of patient care and study integrity. Certain 
measures, such as those listed below, may be necessary and should be instituted in accordance 
with applicable (including local) laws, regulations, guidelines, and procedures. 
Administration of Study Medication 
In cases where a site visit is not possible under restrictions and limitations due to the COVID-19 
pandemic, subjects may self-administer subcutaneous (SC) injections of study drug outside a study 
site (eg, at home). Those subjects will receive instructions on compliance, storage, disposal of used 
syringes, handling of unused study material, and adverse event reporting. The specific protocol 
changes are documented below: 
Dosage and Administration (Protocol Section 6.) 
Sub-cutaneous injections should be administered by qualified study site staff during the study visit, 
if possible. To limit contact with the site, personal self-administration on site is also allowed. 
However, in cases where a site visit is not possible, subjects who have appropriate experience or 
have received required training may self-administer study drug at the times instructed by the 
investigator. Study site staff must ensure that those subjects have the appropriate experience or 
have received the required training to perform self-administration of SC injections.  
Self-administration at home is only allowed subsequent to performance of a phone or video visit. 
Application of study drug at home can also be performed by a Home Health Care service provider 
if agreed by the sponsor, investigator and subject.  
During this virtual visit, site staff will perform safety evaluations according to protocol, ensure 
assessment of PRO instruments and efficacy assessments (video/photo assessment of applicable 
lesions) as far as possible. 
Randomization to part 2a/b is only possible (in case of Super-Responder) if week 20 and week 28 
efficacy assessments have been done on-site, otherwise the subjects will enter part 2c. 
If laboratory tests are to be performed at this scheduled visit, the blood draw for safety monitoring 
(hematology and chemistry) can be postponed to the next visit or, if the investigator deems it 
medically necessary, performed in a local certified laboratory.  
For women of childbearing potential, a negative pregnancy test must be available. The patient 
should confirm self-administration to the site in a timely manner and will be asked by the site 


TREMFYA® (guselkumab) 
 Clinical Protocol CNTO1959PSO3012 Amendment 3 
 
Appendix - Guidance on Study Conduct during the COVID-19 Pandemic 
 
CONFIDENTIAL 
5 
Approved, Date: 15 April 2020  
personnel for administration-related and injection site reactions. Self-administration cannot take 
place on 2 consecutive visits. 
Treatment Compliance and Drug Accountability (Protocol Sections 6.2.7 and 14.5.4) 
Each administration of study drug performed at a study visit will be recorded in the subject’s source 
documents, with the assistance of a staff member at the study site who will be supervising study 
drug administration at these visits. For any study drug administration performed by the subject 
outside of a study site, subjects will keep the syringe carton and return the empty carton to the 
study site at their next visit. The subject will record the corresponding date and time of the 
administration in the study drug application card. Study site personnel will utilize subject’s 
documentation to ensure compliance and record at-home study drug administrations in the eCRF. 
Any study subject who will be self-administering study drug at home will receive detailed 
instructions on how to store study drug, disposal of used syringes, and handling of unused study 
material. Subjects will receive a sharps container to dispose of used syringes and will be instructed 
to return cartons to the study site. Subjects will record the time and date of study drug 
administration in the study drug application card. 
Notes on Shipment of Study Medications to Subjects 
If it is necessary to ship the study drug directly to study subjects, shipment by the study site itself 
is preferred under this exception due to the COVID-19 pandemic. Shipment should be made in a 
manner that allows tracking of both transport and delivery. The subject should acknowledge 
receipt of the shipment to the site (eg, by returning a dated and signed receipt form). 
In case adequate shipment by the study site is not possible (for example, owing to capacity 
limitations, logistics, or special transport conditions for the study drug), direct transport by the 
sponsor may be accepted in justified exceptional cases, provided that the sponsor appoints a 
suitably qualified service provider as trustee. The sponsor must contractually oblige this service 
provider to maintain the pseudonymization and, if necessary, blinding of subjects to the sponsor 
using appropriate measures. Both the transport and handover conditions for study drug should be 
part of the contractual arrangements, so that pharmaceutical drug safety of study drug as well as 
protection of the privacy and personal data of subjects are adequately safeguarded. The study drug 
must be delivered directly to the subject or a person authorized by the subject, and must not be 
given to neighbors or deposited at a storage location. Written confirmation of dose and dose 
regimens by the investigator should also be obtained prior to shipment. 
The personnel of the service provider in charge of the transport should be trained and instructed 
accordingly. As personal data are transferred to the service provider, this requires a contract of 
assignment with the sponsor or legal representative. 
For direct shipment of study drug to subjects, written instructions on storage and return of used 
and unused study drug should be provided to subjects. When shipped by study sites, the receipt, 
consumption and return of study drug supplies must be documented in a form that allows the study 
site to meet its documentation requirements (ie, drug accountability), as defined in ICH GCP 4.6.3. 


TREMFYA® (guselkumab) 
 Clinical Protocol CNTO1959PSO3012 Amendment 3 
 
Appendix - Guidance on Study Conduct during the COVID-19 Pandemic 
 
CONFIDENTIAL 
6 
Approved, Date: 15 April 2020  
Study Assessments and Analyses 
Safety Assessments (Protocol Section 9.6) 
In cases of self-administration of SC study drug at home, subjects are requested to contact their 
treating physician as soon as possible to consider reporting of an adverse event. 
Clinical laboratory safety monitoring may be performed at a certified local laboratory identified 
by the study site rather than at the central laboratory; for selected measures (eg, urine pregnancy), 
home testing may be employed. 
Missed Assessments 
Missed assessments/visits will be captured in the clinical trial management system for protocol 
deviations. Discontinuations of study drug and withdrawal from the study should be documented 
with the prefix “COVID-19-related” in the CRF. 
Other relevant study data elements impacted by the COVID-19 pandemic should also be 
documented/labeled as “COVID-19-related” in CRFs and/or other study systems, as directed by 
sponsor guidance; these may include missed/delayed/modified study visits/assessments/dosing, 
and instances where temporary measures such as those above are implemented. 
Study Analyses 
The Sponsor will evaluate the totality of impact of COVID-19 on collection of key study data and 
additional data analyses will be outlined in the statistical analysis plan(s). 
 
 


TREMFYA® (guselkumab) 
 Clinical Protocol CNTO1959PSO3012 Amendment 3 
 
Appendix - Guidance on Study Conduct during the COVID-19 Pandemic 
 
CONFIDENTIAL 
7 
Approved, Date: 15 April 2020  
INVESTIGATOR AGREEMENT 
I have read this protocol and agree that it contains all necessary details for carrying out this study. 
I will conduct the study as outlined herein and will complete the study within the time designated. 
I will provide copies of the protocol and all pertinent information to all individuals responsible to 
me who assist in the conduct of this study. I will discuss this material with them to ensure that they 
are fully informed regarding the study interventions, the conduct of the study, and the obligations 
of confidentiality. 
Coordinating Investigator (where required): 
 
Name (typed or printed): 
 
Institution and Address: 
 
 
 
 
 
 
 
Signature: 
 
Date: 
 
 
 
 
(Day Month Year) 
 
Principal (Site) Investigator: 
 
Name (typed or printed): 
 
Institution and Address: 
 
 
 
 
 
 
 
Telephone Number: 
 
Signature: 
 
Date: 
 
 
 
 
(Day Month Year) 
 
Sponsor's Responsible Medical Officer: 
 
Name (typed or printed): 
  
Institution: 
Janssen-Cilag Germany 
Signature: 
Date: 
 
 
 
(Day Month Year) 
 
 
Note: If t
nges during the course of the study, 
written notification will be provided by the investigator to the sponsor, and a protocol amendment will not 
be required. 
(See signature stamp)
PPD
PPD

SAP_001.pdf: 
1 
Status: Final, Date: 06 July 2021 
Janssen Cilag GmbH 
Statistical Analysis Plan – Study Part 1 
Amendment 1 
A Phase 3b, Randomized, Double-blind, Parallel Group, Multicenter Study to Evaluate 
Further Therapeutic Strategies with Guselkumab in Patients with Moderate-to-Severe 
Plaque-Type Psoriasis 
GUIDE 
Protocol CNTO1959PSO3012; Phase 3b 
 TREMFYA® (guselkumab)  
Status: 
Final 
Date: 
06 July 2021 
Prepared by: 
Janssen-Cilag GmbH, Germany 
Document No.: EDMS-RIM-932103
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. 
NCT03818035


TREMFYA® (guselkumab)  
 
 
 
Statistical Analysis Plan CNTO1959PSO3012  
2 
Status: Final, Date: 06 July 2021 
TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................................... 2 
AMENDMENT HISTORY .............................................................................................................................. 4 
ABBREVIATIONS ........................................................................................................................................ 5 
1. 
INTRODUCTION.................................................................................................................................. 6 
1.1. 
Trial Objectives and Endpoints ........................................................................................................ 7 
1.1.1. 
Objectives ..................................................................................................................................... 7 
1.1.2. 
Endpoints ...................................................................................................................................... 8 
1.2. 
Trial Design ...................................................................................................................................... 9 
1.3. 
Statistical Hypotheses for Trial Objectives ..................................................................................... 12 
1.4. 
Sample Size Justification ............................................................................................................... 12 
1.5. 
Randomization and Blinding .......................................................................................................... 13 
2. 
GENERAL ANALYSIS DEFINITIONS FOR STUDY PART 1 .......................................................... 14 
2.1. 
Visit Windows ................................................................................................................................. 14 
2.2. 
Pooling Algorithm for Analysis Centers .......................................................................................... 15 
2.3. 
Analysis Sets .................................................................................................................................. 15 
2.3.1. 
All Enrolled Analysis Set ............................................................................................................. 15 
2.3.2. 
All Randomized Analysis Set ...................................................................................................... 15 
2.3.3. 
Efficacy Analysis Set(s) .............................................................................................................. 15 
2.3.3.1. 
Primary Efficacy Analysis Set .................................................................................................. 15 
2.3.3.2. 
Secondary Efficacy Analysis Set ............................................................................................. 15 
2.3.4. 
Safety Analysis Set ..................................................................................................................... 16 
2.3.5. 
Pharmacokinetics Analysis Set .................................................................................................. 16 
2.4. 
Definition of Subgroups .................................................................................................................. 17 
2.5. 
Study Day and Relative Day .......................................................................................................... 20 
2.6. 
Baseline and Endpoint ................................................................................................................... 20 
2.7. 
Imputation Rules for Missing AE Date/Time of Onset/Resolution ................................................. 20 
3. 
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW ....................................... 21 
4. 
SUBJECT INFORMATION ................................................................................................................ 21 
4.1. 
Demographics and Baseline Characteristics ................................................................................. 21 
4.2. 
Disposition Information................................................................................................................... 23 
4.3. 
Treatment Compliance ................................................................................................................... 23 
4.4. 
Extent of Exposure ......................................................................................................................... 23 
4.5. 
Protocol Deviations ........................................................................................................................ 23 
4.6. 
Prior and Concomitant Therapies .................................................................................................. 24 
5. 
EFFICACY ......................................................................................................................................... 26 
5.1. 
Analysis Specifications................................................................................................................... 26 
5.1.1. 
Level of Significance ................................................................................................................... 26 
5.1.2. 
Data Handling Rules ................................................................................................................... 26 
5.1.2.1. 
Treatment Failure Criteria ........................................................................................................ 26 
5.1.2.2. 
Treatment Failure Rules .......................................................................................................... 26 
5.1.2.3. 
Missing Data Imputation .......................................................................................................... 26 
5.2. 
Primary Efficacy Endpoint(s) .......................................................................................................... 27 
5.2.1. 
Definition ..................................................................................................................................... 27 
5.2.2. 
Estimand ..................................................................................................................................... 27 
5.2.3. 
Analysis Methods ........................................................................................................................ 27 
5.3. 
Major Secondary Endpoints ........................................................................................................... 27 
5.3.1. 
Definition ..................................................................................................................................... 27 
5.3.1.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 27 
5.3.2. 
Analysis Methods ........................................................................................................................ 28 


TREMFYA® (guselkumab) 
Statistical Analysis Plan CNTO1959PSO3012 
3 
Status: Final, Date: 06 July 2021 
5.3.2.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 28 
5.4. 
Other Secondary Endpoints ........................................................................................................... 28 
5.4.1. 
Definition ..................................................................................................................................... 29 
5.4.1.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 29 
5.4.1.2. 
Dermatology Life Quality Index (DLQI) ................................................................................... 29 
5.4.1.3. 
Body Surface Area (BSA%) ..................................................................................................... 29 
5.4.1.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) ............................................... 29 
5.4.1.5. 
Psoriasis Symptom and Sign Diary (PSSD) ............................................................................ 30 
5.4.2. 
Analysis Methods ........................................................................................................................ 31 
5.4.2.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 31 
5.4.2.2. 
Dermatology Life Quality Index (DLQI) ................................................................................... 31 
5.4.2.3. 
Body Surface Area (BSA%) ..................................................................................................... 32 
5.4.2.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) ............................................... 32 
5.4.2.5. 
Psoriasis Symptom and Sign Diary (PSSD) ............................................................................ 33 
5.5. 
Additional Endpoint(s) .................................................................................................................... 33 
5.5.1. 
Definition ..................................................................................................................................... 33 
5.5.2. 
Analysis Methods ........................................................................................................................ 33 
5.6. 
Additional Analyses ........................................................................................................................ 34 
6.
SAFETY ............................................................................................................................................. 35 
6.1. 
Adverse Events .............................................................................................................................. 35 
6.2. 
Clinical Laboratory Tests................................................................................................................ 36 
6.3. 
Vital Signs and Physical Examination Findings ............................................................................. 37 
6.4. 
Electrocardiogram .......................................................................................................................... 37 
6.5. 
Other Safety Parameters ............................................................................................................... 37 
7.
PHARMACOKINETICS/PHARMACODYNAMICS ........................................................................... 38 
7.1. 
Pharmacokinetics ........................................................................................................................... 38 
7.2. 
Immune Response ......................................................................................................................... 38 
7.3. 
Pharmacodynamics ........................................................................................................................ 38 
7.4. 
Pharmacokinetic/Pharmacodynamic Relationships ....................................................................... 38 
8.
BIOMARKERS................................................................................................................................... 38 
9.
HEALTH ECONOMICS ..................................................................................................................... 38 
REFERENCES ............................................................................................................................................ 39 
ATTACHMENTS ......................................................................................................................................... 40 


TREMFYA® (guselkumab) 
Statistical Analysis Plan CNTO1959PSO3012 
4 
Status: Final, Date: 06 July 2021 
AMENDMENT HISTORY 
This SAP was originally finalized early on 16-Jul-2020, leaving open some decisions to be taken at the 
Data Review Meeting. However, statistical issues were not discussed at the Data Review Meeting but at 
the Dry Run Meeting, which was held on 21-Jun-2021 (meeting minutes are available). All decisions taken 
in the Dry Run Meeting that require an SAP update are described in this SAP update in a fashion that the 
original text is still visible: in each respective section a new paragraph is added that introduces and explains 
the changes. This updated SAP is finalized and signed before database lock for Study Part 1. 
Table 1 – SAP Version History Summary 
SAP Version 
Version Date 
Change 
Rationale 
Final 
16 July 2020 
Not Applicable 
Initial release 
Amendment 1 
06 July 2021 
see text ‘update after dry run 
meeting’ in the respective SAP 
sections 
Release after dry-run meeting for 
Study Part 1 


TREMFYA® (guselkumab)  
 
 
 
Statistical Analysis Plan CNTO1959PSO3012  
5 
Status: Final, Date: 06 July 2021 
ABBREVIATIONS 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
ATC 
Anatomic therapeutic Class 
BMI 
Body mass index 
bpm 
beats per minute 
BSA 
Body surface area 
CI 
Confidence interval 
CLIN  
Clinical  
CSP 
Clinical Study Protocol 
DBL 
Database lock 
DLQI 
Dermatology Life Quality Index 
DMC 
Data Monitoring Committee 
eCRF 
electronic Case Report Form 
eg  
example given 
EP 
Endpoint 
FAE 
Fumaric acid ester 
FAS 
Full analysis set 
GCP 
Good Clinical Practice  
ICH 
International Council for Harmonization 
ie  
that is  
IQ 
Interquartile range 
ITT 
Intent-to-treat 
IWRS 
Interactive web response system 
LOCF 
Last observation carried forward 
LS 
Least squares 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
Methotrexate  
NAPPA 
Nail Assessment in Psoriasis and Psoriatic Arthritis 
nSR 
Non-Super-Responder 
OR 
Odds ratio 
PASI 
Psoriasis Area and Severity Index 
PBI  
Patient Benefit Index  
PK 
Pharmacokinetic(s) 
PP 
Per protocol 
PROs 
Patient reported outcomes 
PSSD 
Psoriasis Symptoms and Signs Diary 
PT 
Preferred terms 
PUVA 
Psoralene plus ultraviolet A radiation 
q8w/q16w  
every 8/16 weeks  
QoL 
Quality of life 
RD 
Risk difference 
RR 
Relative risk 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SOC 
System organ class 
SRe 
Super-Responder 
TEAE 
Treatment-emergent adverse event 
TES 
Time and Events Schedule  
ULN  
Upper limit normal  
UVB 
Ultra violet B radiation 
WHO 
World Health Organization 
WHO-DD 
World Health Organization Drug Dictionary 
 
 


TREMFYA® (guselkumab)  
 
 
 
Statistical Analysis Plan CNTO1959PSO3012  
6 
Status: Final, Date: 06 July 2021 
1. 
INTRODUCTION 
The statistical analysis plan (SAP) is a detailed technical extension to the Clinical Study Protocol 
(CSP) and follows the principles of the guideline ICH E9. 
Statistical analyses of Janssen-Cilag GmbH Clinical Study Protocol CNTO1959PSO3012 will be 
performed for each of the three Study Parts. 
The confirmatory analysis is planned to be performed at the end of Study Part 2, ie, after all 
subjects have completed their visit at week 68 (ie, 40 weeks after randomization) or discontinued 
earlier. This analysis will include the confirmatory analysis of the primary endpoint, and the 
exploratory analyses of the major secondary endpoints and all other predefined efficacy and safety 
analyses from week 28 until week 68. 
The analyses of Study Part 1 and Study Part 3 will be exploratory. The exploratory analysis of 
Study Part 1 will occur after all subjects have completed their visit at week 28 (ie, 28 weeks after 
study inclusion) or discontinued earlier. This analysis will include the safety analysis and all 
efficacy measures after week 0 and will cover the time until the week 28 visit. The exploratory 
analysis of Study Part 3 will occur after all subjects have completed their visit at week 116 (ie, 
48 weeks after inclusion in Study Part 3 at week 68) and week 144 visit in case of subjects entering 
the re-treatment arm in week 116 respectively or discontinued earlier. This analysis will include 
the safety analysis and all efficacy measures after week 68 and will cover the time until the 
week 116 visit (and week 144 visit respectively). 
Final decisions, about which patients will be included in the analyses of the Study Parts 1, 2, or 3, 
are made during the Data Review or Dry Run Meetings. 
This plan describes the statistical analyses planned to be performed for the analysis of Study Part 
1 (open-label treatment phase) and should be read in conjunction with the CSP and the electronic 
Case Report Form (eCRF). Statistical analyses of study data recorded after week 28 will be 
specified in separate SAPs. 
This SAP is the core document for all statistical programming planned to be performed for the 
analysis of Study Part 1 of study protocol no. CNTO1959PSO3012. 
 
 


TREMFYA® (guselkumab)  
 
 
 
Statistical Analysis Plan CNTO1959PSO3012  
7 
Status: Final, Date: 06 July 2021 
1.1. 
Trial Objectives and Endpoints 
1.1.1. 
Objectives 
Primary objective 
The primary objective of the study is to demonstrate that Super-Responders (SRe; defined as 
psoriasis subjects who receive on-label guselkumab treatment until week 20 and respond with a 
Psoriasis Area and Severity Index [PASI] score = 0 at weeks 20 and 28) maintain control of 
disease until week 68 with prolonged treatment intervals of 16 weeks (100 mg q16w). To be 
demonstrated in Study Part 2 
Secondary objectives 
Secondary objectives are to evaluate 
• whether subjects with short disease duration (≤2 years) show a more rapid and better 
guselkumab response compared to subjects with longer disease duration and whether 
subjects with shorter disease are more likely to maintain drug-free control of disease after 
guselkumab withdrawal. To be evaluated in Study Parts 1, 2 and 3.  
• whether different treatment intervals (weeks 28 to 60: guselkumab 100 mg q8w vs. 
guselkumab 100 mg q16w) affect the maintenance of drug-free control of disease after 
68 weeks of guselkumab treatment. To be evaluated in Study Part 3. 
• the safety and tolerability of guselkumab in subjects with moderate-to-severe plaque-type 
psoriasis. 
Note: Disease duration will be calculated from date at which first symptoms (plaque) were reported 
by subject to date of screening visit: 
o Disease duration (days)  =  Date of visit 1 - date of first symptoms +1. 
Exploratory objectives 
The exploratory objectives are to be explored in the mechanistic biomarker substudies. These 
objectives are not part of this SAP. 
 


TREMFYA® (guselkumab)  
 
 
 
Statistical Analysis Plan CNTO1959PSO3012  
8 
Status: Final, Date: 06 July 2021 
1.1.2. 
Endpoints 
For the endpoints, the following terms were defined: 
• Control of disease: PASI score <3 
• Fluctuating disease: PASI score 3 to 5 
• Loss of disease control: PASI score >5. 
Study groups are defined as follows: 
• 1: All participating subjects who are enrolled and are scheduled to receive guselkumab 
100 mg at weeks 0, 4, q8w until week 28 (Study Part 1) 
• 2a: SRe (PASI score = 0 at weeks 20 and 28) randomized to guselkumab 100 mg q8w at 
weeks 28 to 60 (Study Part 2) 
• 2b: SRe randomized to guselkumab 100 mg q16w at weeks 28 to 60 (Study Part 2) 
• 2c: non-SRe with a PASI score >0 at week 20 and/or 28 who will receive guselkumab 
100 mg q8w at weeks 28 to 60 (Study Part 2) 
• 2d: SRe with loss of disease control between week 28 and 68, who will enter the re-
treatment arm and receive guselkumab 100 mg at weeks 0, 8 and 16 calculated from the 
date of loss of disease control (Study Part 2) 
• 3a: SRe randomized to guselkumab 100 mg q8w in Study Part 2 with withdrawal of 
guselkumab at week 68 (Study Part 3) 
• 3b: SRe randomized to guselkumab 100 mg q16w in Study Part 2 with withdrawal of 
guselkumab at week 68 (Study Part 3) 
• 
3c: SRe with fluctuating disease at week 68 or loss of disease control at any other visit after 
week 68, who will enter the re-treatment arm and receive guselkumab 100 mg at weeks 0, 
8 and 16 calculated from the date of loss of disease control (Study Part 3). 
Primary endpoint 
The primary endpoint of the main study is the proportion of subjects in study groups 2a and 2b 
who achieve an absolute PASI score <3 at week 68. 
Major secondary endpoints 
Major secondary endpoints of this study are: 
• Time to improvement from baseline (week 0) in PASI (PASI 75/90/100 response and 
absolute PASI score = 0) for subjects with short (≤ 2 years) and longer (>2 years) disease 
duration per study group (1, 2a 2b, and 2c) 
• Proportion of subjects with short (≤2 years) and longer (>2 years) disease duration who 
achieve an absolute PASI score of 0, ≤1 and <3 at weeks 20, 28, 68 and 116 per study 
group (1, 2a, 2b, 2c, 3a and 3b)  
• 
Proportion of subjects who retain disease control (ie, absolute PASI score <3 at all visits) 
from week 68 through week 116 for subjects with short (≤ 2 years) and longer (>2 years) 
disease duration per study group (3a and 3b). 
 
 
 


TREMFYA® (guselkumab)  
 
 
 
Statistical Analysis Plan CNTO1959PSO3012  
9 
Status: Final, Date: 06 July 2021 
Other secondary endpoints of this study are: 
• Proportion of subjects who achieve a PASI 75/90/100 response at weeks 20, 28, 68 and 
116 per study group (1, 2a, 2b, 2c, 3a and 3b) 
• Time to loss of disease control (absolute PASI score >5 at any visit) after treatment 
withdrawal beyond week 68 per study group (3a and 3b) 
• Proportion of subjects with an absolute PASI score = 0 at all of the following visits: weeks 
12, 16, 20 and 28 (study group 1) 
• The change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at 
weeks 28 and 68 per study group (1, 2a, 2b, and 2c) 
• Proportion of subjects who achieve a DLQI score 0/1 and <5 at weeks 28 and 68 per study 
group (1, 2a, 2b, and 2c) 
• The change from baseline (week 0) in affected Body Surface Area (BSA) at weeks 12, 28, 
52, 68, 80, and 104 (all study groups) 
• The change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic 
Arthritis (NAPPA) score at weeks 28, 68 and 116 among subjects with nail psoriasis at 
baseline (week 0) (1, 2a, 2b, 2c, 3a and 3b). 
• The change from baseline (week 0) in the signs and symptoms aggregate scores of the 
Psoriasis Symptoms and Signs Diary (PSSD) at weeks 28, 68 and 116 (1, 2a, 2b, 2c, 3a 
and 3b) 
• The proportion of subjects who achieve a PSSD sign score = 0 at week 68 among subjects 
with a PSSD sign score ≥1 at week 28 per study group (2a, 2b and 2c). 
• The association between trough serum concentration and efficacy or serum biomarker level 
• The association between trough serum guselkumab levels at weeks 20, 28, 36 and 68 and 
achieving a PASI score <3 at week 68 per study group (2a and 2b) 
• Proportion of subjects who were re-treated due to loss of disease control (PASI >5) and 
regain control of disease (PASI <3) 24 weeks after start of re-treatment (study groups 2d 
and 3c) 
• 
Safety and tolerability with regard to adverse events (AEs) and abnormal laboratory results 
(all study groups). 
1.2. 
Trial Design 
The present trial is designed as a phase 3b, randomized, double-blind, parallel-group, multicenter, 
comparison study in subjects of at least 18 years of age with moderate to severe plaque-type 
psoriasis. The study will feature the following structure and design: 
Study Part 1: Screening through Week 28:  
This will be screening phase lasting up to four weeks (+ 7 calendar days) prior to first 
administration of guselkumab (week 0) followed by a 28-week run-in period with visits and 
administration of 100 mg guselkumab at weeks 4, 12, and 20. In case of a PASI score = 0 at 
weeks 20 and 28 subjects are qualified to be randomized either to study group 2a or 2b of Study 
Part 2. In case of PASI score >0 at weeks 20 and/or 28 the subjects will continue to receive 
guselkumab 100 mg q8w until week 60 (last administration at week 60 visit) with final study 
assessments at week 68 and final safety follow-up visit at week 72 (defined as study group 2c). 


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Study Part 2: Week 28 through Week 68:  
Subjects with a PASI score = 0 at weeks 20 and 28 will be defined as SRe and randomly assigned 
to the following two treatment groups: 2a) guselkumab 100 mg q8w or 2b) guselkumab 100 mg 
q16w. In addition, subjects with disease duration ≤2 years will be equally distributed to either 
group. Study visits of Study Part 2 will be conducted every 8 weeks. 
To blind the study, study treatment (guselkumab or Placebo) will be administered q8w starting at 
week 28 until the end of study therapy (last administration in week 60). The q16w group will 
receive Placebo at weeks 28, 44 and 60. Subjects losing control of disease, defined as PASI score 
>5 at any visit during Study Part 2 (ie, until week 60), will enter the Re-treatment arm (group 2d, 
see section Re-treatment below). 
The assessment for the primary endpoint (EP) will be at week 68 for both study groups (2a and 
2b).  
In case of PASI <3 at week 68 the subject will not receive any study medication and enter the drug 
withdrawal part (Study Part 3). In case of PASI ≥ 3 at visit week 68 the subject will enter the re-
treatment arm 3c (see section Re-treatment below). 
In case of PASI score >0 at weeks 20 and/or 28 the subjects will continue to receive guselkumab 
100 mg q8w until week 60 (last administration of study treatment) with final study assessments at 
week 68 and final safety follow-up visit at week 72 (defined as study group 2c). 
Study Part 3: Week 68 through Week 116:  
Subjects of group 2a and 2b with a PASI score <3 at week 68 will enter Study Part 3 and be 
withdrawn from the study medication and followed-up until week 116. Study visits of Study Part 
3 will be conducted every 12 weeks (ie, at weeks 80, 92, 104, and 116; ± 14 days). In between the 
12-weekly on-site visits, there will be a telephone-visit 6 weeks (± 7 days) after each visit (ie, 
telephone visits at weeks 74, 86, 98, and 110) to assess whether the subject notices a worsening of 
his/her psoriasis. If so, the subject must attend an on-site visit for efficacy assessment by the 
assessor as soon as possible but not later than 2 weeks after the phone call. 
 
 


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Re-treatment 
Subjects losing control of disease, defined as PASI score >5 at any visit during Study Part 2 or 3 
(ie, until week 116), will enter the re-treatment-arms (2d or 3c) with three guselkumab 100 mg 
administrations starting at that visit (= re-treatment-week 0, followed by administration at re-
treatment-weeks 8 and 16).  
If re-treatment is started at a visit which would usually not require all patient reported outcomes 
(PROs) needed at the first re-treatment visit, those PROs will be obtained immediately after 
efficacy assessments (basis for re-treatment-decision) and prior to drug administration at that visit. 
The final efficacy assessment for all subjects in the re-treatment-arms will take place 24 weeks 
after loss of control and study termination will be 28 weeks after loss of control (final study 
visit/safety follow-up). At visit week 24 of the re-treatment, the investigator may continue actual 
treatment with commercially available guselkumab (ie, not supplied by Sponsor) to maintain a 
q8w interval. Due to the half-life of guselkumab, it is recommended not to start a new therapy 
during safety follow-up period. If the investigator feels strongly that an additional therapy is 
needed, this should be discussed with the Sponsor before initiation of the new therapy.  
Subjects with fluctuating disease (ie, PASI score 3 to 5) at the week 68 visit will also get the 
opportunity to enter the re-treatment-arm (3c). The last chance to start re-treatment will be the visit 
week 116. 
A schematic diagram of the study design is provided below. 
 


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1.3. 
Statistical Hypotheses for Trial Objectives 
This randomized, double-blind, parallel-group, multicenter phase 3b trial is designed to 
demonstrate that guselkumab 100 mg q16w treatment is non-inferior to guselkumab 100 mg q8w 
treatment in SRe as assessed by the proportion of subjects with an absolute PASI score <3 at 
week 68. A non-inferiority margin of 10% was chosen based on a minimally clinically meaningful 
difference. This margin was also used in CNTO1959PSO3009 (ECLIPSE) study and is therefore 
considered a valid approach for evaluating non-inferiority of a new treatment. 
The null hypothesis H0 and the alternative hypothesis HA are formulated as follows: 
• H0: PT - PS  ≤ -10% ('inferiority') 
• H1: PT - PS  > -10% ('non-inferiority') 
where PT and PS denote the proportions of subjects with an absolute PASI score <3 at week 68 in 
the guselkumab 100 mg q16w treatment arm (PT = proportion test treatment) and the guselkumab 
100 mg q8w treatment arm (PS = proportion standard treatment). 
1.4. 
Sample Size Justification 
The sample size estimation using the power approach was performed for the per-protocol analysis 
set as described below. No formal adjustment of the significance level was necessary.  
When the sample size in each group is 112, a two-group large-sample normal approximation Wald 
Z-test of proportions with a one-sided 0.05 significance level will have 80% power to reject the 
null hypothesis that the guselkumab 100 mg q16w treatment is inferior to the guselkumab 100 mg 
q8w treatment (the difference in proportions, Pguselkumab 100mg q16w – P guselkumab 100mg q8w , is ≤ -10%) 
in favor of the alternative hypothesis that the guselkumab 100 mg q16w treatment is non-inferior 
to the guselkumab 100 mg q8w treatment (the difference in proportions is > -10%), assuming that 
the expected difference in proportions is 0 and the proportion in the guselkumab 100 mg q8w 
treatment group is 90% (nQuery Advisor® 7.0).  
Considering the frequency of drop-out rates and protocol violations from past trials, it is assumed 
that a rate of about 20% randomized subjects will not be evaluable for the per-protocol analysis in 
Study Part 2. Therefore, 280 subjects (140 subjects per treatment group) are planned to be 
randomized in a ratio of 1:1 to meet the required sample size of 224 subjects (112 subjects per 
treatment group) for the per-protocol analysis. 
Based on data from CNTO1959PSO3001 and CNTO1959PSO3002, it is anticipated that 
approximately 35% of enrolled subjects in Study Part 1 will be eligible for randomization at 
week 28 in Study Part 2. Thus, a total of 800 subjects should be enrolled in Study Part 1 to ensure 
that at least 280 subjects are eligible for randomization in Study Part 2. Accounting for a 10% 
drop-out rate of subjects ineligible for randomization at week 28 because of study discontinuation 
prior to week 28, it is therefore planned to enroll a total of 888 subjects in Study Part 1. 
Note: Screenings and enrollments will be adjusted if necessary (without protocol amendment), to 
achieve 280 SRe at week 28. Ongoing subjects in Study Part I will continue to Part 2 if eligible, 
irrespective of whether or not 280 SRe are already randomized. Only screenings will be closed. 


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1.5. 
Randomization and Blinding 
Treatment Allocation/ Procedures for Randomization 
Central randomization will be implemented in Study Part 2. Eligible subjects (confirmation by 
physician needed that the subject achieved a PASI score = 0 at weeks 20 and 28) will be randomly 
assigned to one of two guselkumab treatment groups (ratio 1:1) 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. The interactive web response 
system (IWRS) will assign a unique treatment code, which will dictate the treatment assignment 
and match a 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. 
Subjects will be equally stratified in study group 2a and 2b during randomization for i) disease 
duration of ≤2 or >2 years (note: disease duration will be calculated from date at which first 
symptoms (plaque) were reported by subject to date of screening visit) and ii) for participation in 
substudy 1. Definitions when to stop/pause recruitment of subjects with longer disease duration 
will be provided in a separate document. 
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 and administration of study drug) 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 database lock (DBL) and 
unblinding. 
Under normal circumstances, the blind should not be broken for subjects, investigators, or site 
personnel until the end of the study and database lock. 
In Study Part 3 (drug withdrawal) starting at week 68 throughout week 116, subjects, investigators 
and site personnel will remain blinded towards their injection interval (q8w or q16w) in Study Part 
2. The sponsor will be unblinded after DBL at week 68 to conduct the analysis of the primary 
endpoint. 
 


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2. 
GENERAL ANALYSIS DEFINITIONS FOR STUDY PART 1 
The following general analysis definitions refer only to Study Part 1. 
2.1. 
Visit Windows 
As subjects do not always adhere to the protocol visit schedule, the following rules are applied to 
assign actual visits to analysis visits. Listed below are the visit windows and the target days for 
each visit. The reference day is Study Day 1 (for definition see section 2.5). If a subject has 2 or 
more actual visits in one visit window, the visit closest to the target day will be used as the protocol 
visit for that visit window. The other additional visit(s) will not be used in the summaries or 
analyses, but they can be used for determination of clinically important endpoints. If 2 actual visits 
are equidistant from the target day within a visit window, the later visit will be used. 
All assignments will be made in chronological order. Once a visit date is assigned to a visit 
window, it will no longer be used for a later time point except for the endpoint. Listed below (Table 
1) are the visit windows and the target days for each visit defined in the protocol. 
Table 1 – Visit Windows 
Parameter 
Analysis 
Period 
Scheduled Visit  
Time Interval 
(label on output) 
Time Interval 
(Day)* 
Target Time 
Point (Day) 
All 
1 
Scr 
Screening 
-35 to -1 
 
 
1 
W0 
Baseline 
-14 to 6 
1 
 
1 
W4 
Week 4 
15 to 43 
29 
 
1 
W12 
Week 12 
71 to 99 
85 
 
1 
W20 
Week 20 
127 to 155 
141 
 
1 
W28 
Week 28 
183 to 211 
197 
*Relative to Study Day 1 
If there are visits outside of the defined windows, final decisions on the allocation of the actual 
visit to an earlier or later planned visit or if the data will not be included in the analysis will be 
made during the Data Review Meeting. Since at Week 16 neither IP is administrated nor decisive 
assessments are conducted, deviations from the visit window will not constitute a major protocol 
deviation. 
Update after the Dry Run Meeting: A visit window for week 16 is introduced to allocate PASI 
values at study days 100 to 126 to an analysis window. Also, the week 28 window was expanded. 
All values made at visits outside of defined windows will not be taken into account for by-visit 
analyses. 
Table 1 – Visit Windows 
Parameter 
Analysis 
Period 
Scheduled Visit  
Time Interval 
(label on output) 
Time Interval 
(Day)* 
Target Time 
Point (Day) 
All 
1 
Scr 
Screening 
-35 to -1 
 
 
1 
W0 
Baseline 
-14 to 6 
1 
 
1 
W4 
Week 4 
15 to 43 
29 
 
1 
W12 
Week 12 
71 to 99 
85 
 
1 
W16 
Week 16 
100 to 126 
113 
 
1 
W20 
Week 20 
127 to 155 
141 
 
1 
W28 
Week 28 
183 or higher 
197 
*Relative to Study Day 1 


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2.2. 
Pooling Algorithm for Analysis Centers 
No pooling of centers will be performed. 
2.3. 
Analysis Sets 
In Study Part 1 all subjects treated with at least one dose of study agent will be included in the 
efficacy and safety analyses.  
2.3.1. 
All Enrolled Analysis Set 
The all enrolled analysis set includes all subjects who were enrolled and were scheduled to receive 
study agent. 
2.3.2. 
All Randomized Analysis Set 
Not applicable for Study Part 1 analysis.  
2.3.3. 
Efficacy Analysis Set(s) 
In Study Part 1 all subjects treated with at least one dose of study agent will be included in the 
efficacy analyses (intent-to-treat (ITT) analysis set).  
The per-protocol (PP) analysis set will consist of all subjects in the ITT analysis set completing or 
terminating the Study Part 1 without any major deviation of the protocol and its procedures until 
the week 28 visit. Subjects with major protocol deviations (if not administrative) will be excluded 
from the per-protocol analysis. 
Note: At the Data Review Meeting for Study Part 1 it will be decided whether a per-protocol 
analysis will be performed for Study Part 1. 
Update after the Dry Run Meeting: It was decided not to perform a PP analysis for Study Part 1. 
The change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic Arthritis 
(NAPPA) score at week 28 will be evaluated among subjects with nail psoriasis at baseline (week 
0). Nail psoriasis at baseline (week 0). will be defined as follows:  
• eCRF question 'Was Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
performed?' is answered with 'Yes'. 
o  if 'Yes', patient has nail psoriasis, if NAPPA-CLIN > 1 at BL 
2.3.3.1. 
Primary Efficacy Analysis Set 
The ITT analysis set will be used as the primary efficacy analysis set. 
2.3.3.2. 
Secondary Efficacy Analysis Set 
The PP analysis will be used as the secondary efficacy analysis set, if applicable. 


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2.3.4. 
Safety Analysis Set 
For all safety analyses, all subjects treated with at least one dose of study agent will be included 
(intent-to-treat (ITT) analysis set).  
2.3.5. 
Pharmacokinetics Analysis Set 
The PK analysis and the definition of the PK analysis set will be provided in a separate SAP. 
 
 


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2.4. 
Definition of Subgroups 
In general, summary tabulation for Study Part 1 data will be provided by disease duration (≤2 and 
>2 years) and overall.  
Subgroup analyses are planned to be performed for demographics and selected baseline 
characteristics for the following subgroups. 
• Country  
o Germany 
o France 
• Response Status (defined at week 20/28) 
o Super-Responder (SR) 
o Non-Super-Responder (nSR) 
Summary tabulation for these subgroup analyses will provide subgroup results by disease duration 
and overall where the subgroup factor is nested within the main group factor 'disease duration', ie., 
the following display will be used for the subgroup factor 'country' and analogously for the 
subgroup factor 'response status':  
PSO duration <= 2 years, 
N = xxx 
PSO duration > 2 years,  
N = xxx 
Total,  
N = xxx 
Germany,  
N = xxx 
France,  
N = xxx 
Germany,  
N = xxx 
France,  
N = xxx 
Germany,  
N = xxx 
France,  
N = xxx 
Selected baseline characteristics planned to be used for the subgroup analyses will include the 
following variables: 
• Age at Diagnosis 
• BSA (affected by psoriasis) 
• DLQI 
• PSSD 
• NAPPA-CLIN (hands and feet) 
• PASI 
• Prior Psoriasis Therapies 
• Last Psoriasis Therapy  
• Prior Non-Psoriasis Medication 
• Concomitant Non-Psoriasis Medication 
 


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Subgroup analyses are also planned to be performed for the proportion of Super-Responders and for 
the major secondary endpoints for the following subgroups.   
• Gender 
o male 
o female 
• Age at baseline in years 
o < 45 
o ≥ 45 to 65 
o > 65 
• BMI 
o normal ≤ 25  
o overweight > 25 – 30  
o obese > 30 
• Weight in kg 
o  ≤ 90 
o  > 90 
• Disease duration in years 
o > 2 to 10 
o > 10 
• PASI at baseline 
o < 20 
o ≥ 20 
• PSO-pretreatment (for hierarchical categorization see Section 4.6): 
o Topical therapy  
o Phototherapy 
o Non-biologic systemic therapy 
o Biologic therapy 
 


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• PSO-pretreatment with biologics: 
o 1 biologic 
o 2 biologics or more biologics 
• PSO-pretreatment: IL-17 inhibitors (Ixekizumab, Secukinumab or Brodalumab) 
o ever used 
o never used 
Results of the major secondary endpoints 'time to improvement from baseline (week 0) in PASI 
(PASI 75/90/100 response and absolute PASI score = 0)' will also be displayed for the subgroup 
'Response Status' as defined above. 
Additionally to the primary and the major secondary endpoints, DLQI will also be analyzed by 
response status. 
Summary tabulation for these subgroup analyses will provide subgroup results for the total sample 
within each subgroup category but NOT by disease duration, ie., the following display will be used 
for the subgroup factor 'gender' and analogously for the other subgroup factors  
Male, 
N = xxx 
Female,  
N = xxx 
 
Subgroup analyses for the proportion of Super-Responders and for the major secondary endpoints 
will be performed for the ITT analysis set using non-responder imputation (for binary endpoints) 
or Last Observation Carried Forward (LOCF) imputation (for continuous endpoints). An 'observed 
cases analysis' without imputation of missing data will also be done. Subgroup analysis may also 
be performed for the PP analysis set, if decided at the Data Review Meeting for Study Part 1. 
No exploratory inferential statistical methods will be used to compare the results between subgroup 
categories within each subgroup, eg, no p-values will be calculated to compare the results between 
the subgroups 'male' and 'female'. 
Note: At the Data Review Meeting for Study Part 1 it will be decided which subgroup analyses 
will actually be performed for Study Part 1. 
Update after the Dry Run Meeting: For the analysis of baseline parameters, the following 
subgroups will not be evaluated: 
• Country (Germany, France). 
For the analysis of efficacy parameters, the following subgroups will not be evaluated: 
• Gender (male, female) 


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• PASI at baseline (< 20, ≥ 20) 
• PSO-pretreatment: IL-17 inhibitors (ever used, never used). 
For the analysis of efficacy parameters, the subgroups by PSO-pretreatment with biologics will be 
set up as: 
o 0 biologics 
o 1 biologic 
o 2 or more biologics 
 
2.5. 
Study Day and Relative Day 
Study Day 1 or Day 1 refers to the start of the first study agent administration. All efficacy and 
safety assessments at all visits will be assigned a day relative to this date. 
Study day or relative day for a visit is defined as: 
• 
Visit date - (date of Study Day 1) +1, if visit date is ≥ date of Day 1 
• 
Visit date - Date of Day 1, if visit date < date of Day 1 
There is no 'Day 0'. 
2.6. 
Baseline and Endpoint 
Baseline is defined as the last observation (ie, value, measurement) prior to the start of the first 
study agent administration at baseline (week 0). 
Endpoint is defined as the last available postbaseline result within the analysis period until week 
28. Unscheduled visit results are included in this definition and will be considered as the endpoint 
value if the unscheduled visit result is the last postbaseline result available within the analysis 
period. 
2.7. 
Imputation Rules for Missing AE Date/Time of Onset/Resolution 
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 
− 
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 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 


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• 
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 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 day of the date of death, if the 
death occurred in that month. 
• 
If the resolution date of an adverse event is missing both day and month, it will be set to the 
earliest of December 31 of the year or the day and month of the date of death, if the death 
occurred in that year. 
• 
Completely missing resolution dates will not be imputed. 
 
3. 
INTERIM ANALYSIS AND DATA MONITORING COMMITTEE REVIEW 
Statistical analyses will be performed separately for each of the three Study Parts. No formal 
confirmatory interim analysis is planned for this study. 
A data monitoring committee has NOT been employed for review of efficacy and/or safety data. 
4. 
SUBJECT INFORMATION 
If not otherwise specified, the ITT analysis set will be used for all tabulations of subject 
information data. Summary tabulation will be provided by disease duration (≤2 and >2 years) and 
overall.  
The number of subjects in each analysis set will be summarized and listed. In addition, the 
distribution of subjects by country, and site ID will be presented. 
Update after the Dry Run Meeting: The distribution table by site ID will be skipped. 
4.1. 
Demographics and Baseline Characteristics 
Subjects' demographic data (eg, age, weight, BMI, height, sex, child bearing potential, and race) 
and baseline disease characteristics (eg, age at diagnosis, BSA [%], baseline DLQI, PSSD, 
NAPPA-CIN (if applicable), PASI score, psoriasis arthritis, and nail assessment) will be 
summarized. Subgroup analyses of subjects' demographic data and selected baseline disease 
characteristics will be performed for the subgroups 'country' (Germany/France) and 'response 


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status' (super-responder/non-super-responder). Tabulation of demographic data by 'response 
status' will be repeated for the subgroup 'country´. In addition, summaries of subjects' medical 
history and current diagnoses will be provided.  
Table 2 presents a list of the demographic variables that will be summarized.   
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)  
 
BMI  
Height (cm) 
Categorical Variables 
 
Age ([< 45, >= 45 to 65, > 65 years)]) 
Frequency distribution with the 
number and percentage of subjects 
in each category. 
Sex (male, female) 
Child bearing potential (of child bearing potential, permanently sterilized, 
postmenopausal)  
BMI (normal ≤ 25, overweight > 25 – 30, Obese > 30) 
Racea (White, Asian, Black, Multiple, Other, Unknown) 
aIf multiple race categories are indicated, the Race is recorded as 'Multiple' 
Update after the Dry Run Meeting: For age and BMI, cumulative distribution curves by disease 
duration and overall will be done. In addition, a summary table will tabulate the disease duration 
in years and months. Here, one year is set to 365 days, and one month is set to 30.5 days. A 
frequency table for disease duration will provide counts and percentages for the following 
categories: 
• 
≤ 6 months 
• 
> 6 to ≤ 12 months 
• 
> 12 to ≤ 18 months 
• 
> 18 to ≤ 24 months 
• 
> 2 years to ≤ 5 years 
• 
> 5 to ≤ 8 years 
• 
> 8 to ≤ 12 years 
• 
> 12 to ≤ 15 years 
• 
More than 15 years. 
 
 


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4.2. 
Disposition Information 
Screened subjects and reason for screen failures will be summarized. 
The number of subjects in the following disposition categories will be summarized throughout the 
study for Study Part 1: 
• 
Subjects receiving study agent 
• 
Subjects completing Study Part 1 
• 
Subjects who discontinued study agent 
• 
Reasons for discontinuation of study agent 
• 
Subjects who terminated study prematurely 
• 
Reasons for termination of study 
Pertinent disposition information results will also be displayed by country and center. 
Listings of subjects will be provided for the following categories: 
• 
Subjects who discontinued study agent 
• 
Subjects who terminated study prematurely 
4.3. 
Treatment Compliance 
Study agent compliance will be summarized descriptively. Study agent compliance will be 
calculated as follows: 
Study agent compliance (%) = 100 x number of actual administrations / number of planned 
administrations) 
Study agent compliance will also be assessed by protocol deviations related to study drug 
administration (ie, incorrect and missed administrations). 
4.4. 
Extent of Exposure 
The number and percentage of subjects who receive study agent will be summarized. Descriptive 
statistics will be presented for number of study agent administrations. 
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 study. Subjects 
with major protocol deviations will be identified prior to database lock and the subjects with major 
protocol deviations will be summarized by category. 
• 
Developed withdrawal criteria but not withdrawn 
• 
Entered but did not satisfy criteria 
• 
Received a disallowed concomitant treatment 


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• 
Received wrong treatment or incorrect dose 
• 
Other: to be defined in the major protocol deviation criteria document 
The study selection criteria will also be grouped into the following 5 categories: psoriasis disease 
criteria, medication criteria, laboratory criteria, medical history criteria, and other and will be 
summarized. 
4.6. 
Prior and Concomitant Therapies 
Subjects’ prior psoriasis therapy history with topical therapy, phototherapy (PUVA, UVB), non-
biologic systemic therapies (MTX, Cyclosporine, FAE, Acitretin, Apremilast, Tofacitinib, oral 
steroids, and other, if applicable), and biologic medications (Infliximab, Etanercept, Adalimumab, 
Efalizumab, Ustekinumab, Secukinumab, Ixekizumab, Brodalumab, Certolizumab, and other, if 
applicable) will be summarized. The allocation of medications to the four categories of therapy 
was approved at the Dry Run Meeting. 
Subjects' last psoriasis therapy prior to participation in this study will be analyzed analogously. 
Subgroup analyses will be performed for the subgroups 'country' (Germany/France) and 'response 
status' (super-responder/non-super-responder). In addition, reasons for which subjects 
discontinued previous systemic therapies including PUVA, Methotrexate, FAE, Cyclosporine, 
Adalimumab, Ustekinumab, Secukinumab, Ixekinumab, Certolizumab (contraindication, 
inadequate response, intolerance [ie, AEs], or other) will be summarized. 
For analysis of psoriasis therapies by therapy regimen as described above, the patients will be 
counted in only one therapy regimen according to the following hierarchical derivation procedure. 
 
Therapy regimen 
Derivation 
Topical therapy 
All patients receiving at least one prior psoriasis medication of the 
type 'Topical' as defined above who did not receive a medication of 
another type. 
Phototherapy 
All patients receiving at least one prior psoriasis medication of the 
type 'Phototherapy' as defined above who did not receive a 
medication of another type except 'Topical' 
Non-biologic 
systemic 
therapy 
All patients receiving at least one prior psoriasis medication of the 
subtype 'Non-biologic systemic' as defined above who did not 
receive a medication of another type except 'Topical' or 
'Phototherapy'. 
Biologic therapy 
All patients receiving at least one prior psoriasis medication of the 
subtype 'Biologics' as defined above who did not receive a 
medication of another type except 'Topical' (type), 'Phototherapy' 
(type), or 'Non-biologic systemic' (subtype). 
 
 


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In addition, the number of subjects who received concomitant treatment with a moisturizer for 
psoriasis will be summarized. 
Prior and concomitant non-psoriasis therapies will be summarized descriptively. Subgroup 
analyses will be performed for the subgroups 'country' (Germany/France) and 'response status' 
(super-responder/non-super-responder).  
Prior and Concomitant therapies (psoriasis and non-psoriasis) will be coded using the World 
Health Organization Drug Dictionary (WHO-DD). Prior therapies are defined as any therapy used 
before the day of first dose (partial or complete) of study agent. Concomitant therapies are defined 
as any therapy used on or after the same day as the first dose of study agent, including those that 
started before and continue on after the first dose of study agent. In the statistical analysis only 
therapies will be counted as ‘concomitant' for Study Part 1, which started before the date of 
randomization (start of Study Part 2). 
Summaries of concomitant therapies will be presented by Anatomic Therapeutic Class (ATC) level 
2 term and Preferred Name. The proportion of subjects who receive each concomitant therapy will 
be summarized as well as the proportion of subjects who receive at least 1 concomitant therapy. 
Prior therapies (incl. psoriasis therapies) will be summarized by ATC level 2 term and Preferred 
Name. 
Update after the Dry Run Meeting: The frequency table of subjects’ prior psoriasis therapy history 
will be repeated by displaying preferred names by category used for hierarchization. This will be 
done by disease duration and by response status.  
 


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5. 
EFFICACY 
If not otherwise specified, the ITT analysis set will be used for all tabulations of efficacy data from 
Study Part 1. Summary tabulation will be provided by disease duration (≤2 and >2 years) and 
overall.  
The analyses of Study Part 1 will be exploratory. The exploratory analysis of Study Part 1 will 
occur after all subjects have completed their visit at week 28 (ie, 28 weeks after study inclusion) 
or discontinued earlier. This analysis will include all efficacy measures after week 0 and will cover 
the time until the week 28 visit.  
For all continuous efficacy variables, descriptive statistics will include the N, mean, standard 
deviation, median, IQ range, minimum, and maximum. Categorical variables will be summarized 
using frequency counts and percentages. Graphical data displays will also be used to summarize 
the data. 
5.1. 
Analysis Specifications 
5.1.1. 
Level of Significance 
Not applicable for Study Part 1 analysis.  
5.1.2. 
Data Handling Rules 
5.1.2.1. 
Treatment Failure Criteria 
Subjects who discontinue study agent due to lack of efficacy, an AE, worsening of psoriasis, or 
who started a protocol-prohibited medication/therapy during the study period that could improve 
psoriasis are considered treatment failures. The protocol-prohibited medications/therapies are 
listed in section 8.1 of the CSP. 
5.1.2.2. 
Treatment Failure Rules 
No treatment failure rules will be applied in Study Part 1 analysis. 
5.1.2.3. 
Missing Data Imputation 
Non-responder imputation (for binary endpoints) or Last Observation Carried Forward (LOCF) 
imputation (for continuous endpoints) will be applied for subjects with missing data for the major 
and secondary endpoints in Study Part 1. Time-to-event analyses of binary endpoints will be 
performed on the observed cases only (ie, missing data will not be replaced for time-to-event 
analyses). 
An 'observed cases analysis' for all binary and continuous endpoints in Study Part 1 without 
imputation of missing data will also be done. 
 


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5.2. 
Primary Efficacy Endpoint(s) 
5.2.1. 
Definition 
Not applicable for Study Part 1 analysis. 
5.2.2. 
Estimand 
Not applicable for Study Part 1 analysis. 
5.2.3. 
Analysis Methods 
Not applicable for Study Part 1 analysis. 
5.3. 
Major Secondary Endpoints 
Major secondary endpoints of this study in Study Part 1 are: 
• Time to improvement from baseline (week 0) in PASI (PASI 75/90/100 response and 
absolute PASI score = 0) for subjects with short (≤ 2 years) and longer (>2 years) disease 
duration 
• 
Proportion of subjects with short (≤2 years) and longer (>2 years) disease duration who 
achieve an absolute PASI score of 0, ≤1 and <3 at weeks 20, 28.  
5.3.1. 
Definition 
5.3.1.1. 
Psoriasis Area and Severity Index (PASI) 
The Psoriasis Area and Severity Index (PASI) is an instrument 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 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 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 a PASI score of 0 will be considered PASI 100 responders. 
Time to improvement in PASI 
The time to improvement in PASI is defined as time from baseline (week 0) to first onset of 
response. In the absence of documented improvement, the time to improvement will be censored 
at the date of week 28 or the date of discontinuation in case of early treatment discontinuation. 
Update after the Dry Run Meeting: The time to improvement in PASI will be computed as: 


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• 
Date of improvement - Date of Study Day 1, if the subject shows improvement, 
• 
Date of week 28 or date of discontinuation - Date of Study Day 1, if the subject shows no 
improvement. 
 
5.3.2. 
Analysis Methods 
5.3.2.1. 
Psoriasis Area and Severity Index (PASI) 
Time-to-event endpoints will be analyzed using the Kaplan-Meier product limit method and Cox 
proportional hazards model. Summary tables will provide counts and percentages for subjects with 
short (≤ 2 years) and longer (>2 years) disease duration, the median time-to-event with 95% 
confidence intervals (CI), and the hazard ratio (including 95% CI and the p-value calculated from 
Cox-regression with the factor 'disease duration'). The survival curves will also be displayed 
graphically. Time-to-event analyses of binary endpoints will be performed on the observed cases 
only (ie, no missing data imputation for time-to-event analyses). 
A Chi-square test will be used to test the difference between subjects with short (≤2 years) and 
longer (>2 years) disease duration for binary endpoints. A 95% confidence interval for the 
difference will be calculated based on Wald statistic. For binary endpoints counts and percentages 
for subjects with short (≤ 2 years) and longer (>2 years) disease duration, along with odds ratio 
(OR), relative risk (RR) and risk difference (RD), 95% confidence intervals (95% CIs) and p-
values for the factor effect 'disease duration' using the Chi-square test will be provided. 
Subgroup analyses will be performed as specified in section 2.4. 
Update after the Dry Run Meeting: The time to PASI response will be evaluated only for all 
subjects and by disease duration, but not for other subgroups. Instead, the number of PASI 
responders by visit will be shown by disease duration and the following subgroups: 
• 
Response status (Super-Responder, Non-Super-Responder) 
• 
PSO-pretreatment with biologics (ever used, never used) 
• 
PSO-pretreatment with biologics (0, 1, 2 or more). 
The survival curves will also be displayed by response status (Super-Responder, Non-Super-
Responder) and by PSO-pretreatment with biologics (never used, ever used; 0, 1, 2 or more). 
5.4. 
Other Secondary Endpoints 
Other secondary endpoints of this study in Study Part 1 are: 
• Proportion of subjects who achieve a PASI 75/90/100 response at weeks 20, 28 
• Proportion of subjects with an absolute PASI score = 0 at all of the following visits: weeks 
12, 16, 20 and 28 
• The change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at 
week 28  


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• Proportion of subjects who achieve a DLQI score 0/1 and <5 at week 28 
• The change from baseline (week 0) in affected Body Surface Area (BSA) at weeks 12 and 
28 
• The change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic 
Arthritis (NAPPA) score at week 28 among subjects with nail psoriasis at baseline (week 
0) 
• The change from baseline (week 0) in the signs and symptoms aggregate scores of the 
Psoriasis Symptoms and Signs Diary (PSSD) at week 28 
5.4.1. 
Definition 
5.4.1.1. 
Psoriasis Area and Severity Index (PASI) 
Refer to section 5.3.1.1. 
5.4.1.2. 
Dermatology Life Quality Index (DLQI) 
The Dermatology Life Quality Index (DLQI) is a dermatology-specific quality of life instrument 
designed to assess the impact of the disease on a subject’s quality of life. It is a 10-item 
questionnaire that, in addition to evaluating overall quality of life, can be used to assess 6 different 
aspects that may affect quality of life: 1) symptoms and feelings, 2) daily activities, 3) leisure, 4) 
work or school performance, 5) personal relationships, and 6) treatment. 
The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and 
a minimum of 0. A higher score indicates more severe disease. A score of ≤1 indicates no effect 
at all of disease on subject’s health related quality of life. 
For a partially answered questionnaire (eg, not all 10 answers in the DLQI questionnaire were 
available) the following rules will be applied: 
1. If one question is left unanswered this will be scored 0 and the scores will be summed and 
expressed as usual out of a maximum of 30. 
2. If two or more questions are left unanswered the questionnaire will not be scored. 
3. If question 7 is answered 'yes' this will be scored 3. If question 7 is answered 'no' or 'not 
relevant' but then either 'a lot' or 'a little' is ticked this will be scored 2 or 1. If it is answered 
'no', but the second half is left incomplete, the score will remain 0. 
Update after the Dry Run Meeting: The answer "Not relevant" will be scored 0, as intended by the 
score developers. 
5.4.1.3. 
Body Surface Area (BSA%) 
One physical measure to define disease severity is to determine how much of the Body Surface 
Area (BSA) is affected by psoriasis. Involved BSA is calculated by using the palm of the subject’s 
hand as equivalent to 1% of the BSA (rule of palm). 
5.4.1.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
The NAPPA is an instrument for assessing clinical and patient-reported outcomes in nail psoriasis 
(Augustin, et al. 2014). It comprises three components:  


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1. NAPPA-QOL is a 20-item nail-specific quality of life (QoL) questionnaire covering the 
past week. Signs, stigma and everyday life are rated on a scale from 0 (no suffering) to 4 
(high suffering). The NAPP-QOL global score is computed by averaging all items. In case 
more than 25% of the items are missing (5 or more items missing), the score is not 
computed for the respective patient.  
2. NAPPA-PBI is a 24-item questionnaire to assess patient-defined needs before and patient-
rated benefits after treatment. The answers are given on a scale from 0 to 4. The weighted 
NAPPA-PBI global score is computed as follows: For score calculation, both "does not 
apply" and "question unanswered" will be treated as missing values. The global score will 
be calculated using all items pairs (importance + benefit) for which the patient has given a 
response other than "does not apply". Each benefit item is multiplied with the respective 
importance item, and the product is divided by the sum of all importance items. The results 
are summed up over all items. The resulting global score ranges from 0 (no benefit) to 4 
(highest possible benefit). Only if more than 25% of items pairs are unanswered (=5 or 
more item pairs with missing values), no global score will be calculated. 
3. NAPPA-CLIN has been developed from the NAPSI score, a nail psoriasis-specific score, 
which in its original version comprises the assessment of matrix and nail bed involvement 
in every finger and toe by 8 criteria for each nail. The NAPPA-CLIN is a simplified version 
of the NAPSI which only assesses the least and the worst involved nail of both hands, or 
both feet, respectively. Score (matrix or bed for hands or feed)) is 0 if the findings are not 
present, 1 if they are present in 1 quadrant of the nail, 2 if present in 2 quadrants of a nail, 
3 if present in 3 quadrants of a nail, and 4 if present in 4 quadrants of a nail:  
- thus, each nail has a matrix score (0-4) and a nail bed score (0-4), and the total nail 
score is the sum of those 2 individual scores (0-8) for hands or feet; 
- sum of the total score of all involved nails is the total NAPPA-CLIN score for that 
patient at that time for hands or feet. 
- thus, the NAPPA-CLIN scores for hands or feet range from 0 to 16 empirically. 
- if a matrix score or a nail bed score is missing, the NAPPA-CLIN score is also missing.  
Update after the Dry Run Meeting: 
For NAPPA-QOL, the last sentence is changed to: In case more than 25% of the items are missing 
(6 or more items missing), the score is not computed for the respective patient. 
For NAPPA-PBI, the last sentence is changed to: Only if more than 25% of items pairs are 
unanswered (=7 or more item pairs with missing values), no global score will be calculated. 
5.4.1.5. 
Psoriasis Symptom and Sign Diary (PSSD) 
The Psoriasis Symptom and Sign Diary (PSSD) is a patient-reported outcome (PRO) questionnaire 
designed to measure the severity of psoriasis symptoms and signs for the assessment of treatment 
benefit. The PSSD includes 11 items covering symptoms (itch, pain, stinging, burning and skin 
tightness) and subject observable signs (skin dryness, cracking, scaling, shedding or flaking, 
redness and bleeding) using 0 (=absent) to 10 (=worst imaginable) numerical rating scales for 
severity. Two subscores will be derived: the psoriasis symptom score and the psoriasis sign score. 


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A higher score indicates more severe disease. Additionally, the single items itch, pain, and scaling 
and also the other single items will be evaluated. The subjects will complete the 7-day recall 
version of the PSSD as indicated in the TES.  
The calculations of PSSD symptom, and sign scores are listed below. 
Symptom Score (0-100) 
a) Symptom score includes itch (Q1), pain (Q11), stinging (Q10), burning (Q9) and skin 
tightness (Q4). 
b) Averaging items on the symptom scores when at least 3 items (≥50% of 5 items) on this 
scale are answered. Then, the average value is converted into 0-100 scoring such that 
Symptom score = average value x 10 with 0 representing the least severe and 100 the most 
severe. Otherwise the symptom score will be set to missing. 
Sign Score (0-100) 
a) Sign score includes skin dryness (Q2), cracking (Q3), scaling (Q5), shedding or flaking 
(Q6), redness (Q7) and bleeding (Q8). 
b) Averaging items on the sign scores when at least 3 items (≥50% of 6 items) on this scale 
are answered. Then, the average value is converted into 0-100 scoring such that Sign score 
= average value x 10 with 0 representing the least severe and 100 the most severe. 
Otherwise the sign score will be set to missing. 
5.4.2. 
Analysis Methods 
5.4.2.1. 
Psoriasis Area and Severity Index (PASI) 
• Proportion of subjects who achieve a PASI 75/90/100 response at weeks 20, 28 
• Proportion of subjects with an absolute PASI score = 0 at all of the following visits: weeks 
12, 16, 20 and 28 
The proportion of subjects will be displayed in a frequency table providing the number and 
percentage of subjects. Graphical presentation will be presented by means of a bar chart. 
A Chi-square test will be used to test the difference of proportions between subjects with short (≤2 
years) and longer (>2 years) disease duration. A 95% confidence interval for the difference will 
be calculated based on Wald statistic. 
5.4.2.2. 
Dermatology Life Quality Index (DLQI) 
• The change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at 
week 28  
• Proportion of subjects who achieve a DLQI score 0/1 and <5 at week 28 
The change from baseline in DLQI will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the week 28 value and the change from baseline value 
will be displayed. 
The proportion of subjects achieving a DLQI score of 0 or 1 and <5 at week 28 will be displayed 
in a frequency table providing the number and percentage of subjects. Graphical presentation will 
be presented by means of a bar chart. In addition, cross-tabulations will be provided between the 


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proportion of subjects who achieve a DLQI score 0/1 and <5 at week 28 and the proportion of 
subjects who achieve a PASI 75/90/100 response at weeks 28. 
An analysis of covariance (ANCOVA) model will be used to test the difference in change from 
baseline between subjects with short (≤2 years) and longer (>2 years) disease duration ; the change 
from baseline being the dependent variable, and disease duration, and baseline value of endpoint 
as independent variables. A 95% confidence interval for the difference in Least Squares (LS)means 
and p-value will be calculated based on contrast test statistics. A Chi-square test will be used to 
test the difference of proportions between subjects with short (≤2 years) and longer (>2 years) 
disease duration. A 95% confidence interval for the difference will be calculated based on Wald 
statistic. 
Update after the Dry Run Meeting: No cross-tabulations between PASI and DLQI will be done. 
Also, the box plots will not be presented. 
5.4.2.3. 
Body Surface Area (BSA%) 
• The change from baseline (week 0) in affected Body Surface Area (BSA) at weeks 12 and 
28 
The change from baseline in BSA will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the week 12/28 value and the change from baseline 
value will be displayed. 
An ANCOVA model will be used to test the difference in change from baseline between subjects 
with short (≤2 years) and longer (>2 years) disease duration; the change from baseline being the 
dependent variable, and disease duration, and baseline value of endpoint as independent variables.   
A 95% confidence interval for the difference in LSmeans and p-value will be calculated based on 
contrast test statistics. 
Update after the Dry Run Meeting: The box plots will not be presented. 
5.4.2.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
• The change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic 
Arthritis (NAPPA) scores at week 28 among subjects with nail psoriasis at baseline (week 
0) 
The change from baseline in the global scores of NAPPA-QOL, NAPPA-PBI, and NAPPA-CLIN 
will be summarized by descriptive statistics using appropriate tabulation and box plots. The 
baseline value, the week 28 value and the change from the baseline value will be displayed. 
According to the definition of the global score of NAPPA-PBI the week 28 value is already the 
change from baseline value. 
An ANCOVA model will be used to test the difference in change from baseline between subjects 
with short (≤2 years) and longer (>2 years) disease duration; the change from baseline being the 
dependent variable, and disease duration, and baseline value of endpoint as independent variables.   
A 95% confidence interval for the difference in LSmeans and p-value will be calculated based on 
contrast test statistics. For the global score of NAPPA-PBI a corresponding ANOVA model 
without baseline value as covariate will be used. 


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Update after the Dry Run Meeting: The box plots will not be presented. 
5.4.2.5. 
Psoriasis Symptom and Sign Diary (PSSD) 
• The change from baseline (week 0) in the signs and symptoms aggregate scores of the 
Psoriasis Symptoms and Signs Diary (PSSD) at week 28 
The change from baseline will be summarized by descriptive statistics using appropriate tabulation 
and box plots. The baseline value, the week 28 value and the change from the baseline value will 
be displayed. 
An ANCOVA model will be used to test the difference in change from baseline between subjects 
with short (≤2 years) and longer (>2 years) disease duration; the change from baseline being the 
dependent variable, and disease duration, and baseline value of endpoint as independent variables.   
A 95% confidence interval for the difference in LSmeans and p-value will be calculated based on 
contrast test statistics. 
Update after the Dry Run Meeting: The box plots will not be presented. 
5.5. 
Additional Endpoint(s) 
5.5.1. 
Definition 
Additional endpoints of this study in Study Part 1 are: 
• Proportion of Super-Responders (SRe; defined as psoriasis subjects who receive on-label 
guselkumab treatment until week 20 and respond with a Psoriasis Area and Severity Index 
[PASI] score = 0 at weeks 20 and 28) 
Update after the Dry Run Meeting: The definition for super-response only includes PASI values 
at weeks 20 and 28 and is independent from the number of injections given. So even with less than 
4 injections, a subject may be a Super-Responder. 
5.5.2. 
Analysis Methods 
The proportion of Super-Responders will be displayed in a frequency table providing the number 
and percentage of subjects. Graphical presentation will be presented by means of a bar chart. 
A Chi-square test will be used to test the difference of proportions between subjects with short (≤2 
years) and longer (>2 years) disease duration. A 95% confidence interval for the difference will 
be calculated based on Wald statistic. 
Subgroup analyses will be performed as specified in section 2.4. 
Univariate and multivariate logistic regression analyses may also be used to investigate the 
relationship between potential prognostic or risk factors (ie, factors defined as subgroups in section 
2.4) and the single binary outcome variable SRe. 


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Update after the Dry Run Meeting: The impact of confounders on super-response will be 
investigated in the following univariate logistic regression models: 
• Disease duration (categorical: disease duration ≤2 years, >2 years) 
• Age at baseline (continuous, and categorical: <45, 45-65, >65 years) 
• Age at PSO onset (continuous) 
• BMI at baseline (continuous and categorical: ≤25, >25 to 30, >30 kg/m²) 
• PSO pretreatment with biologics (categorical; ever used, never used) 
• PASI at baseline (continuous) 
• BSA affected at baseline (continuous) 
• Body weight at baseline (continuous) 
• Gender (categoric: Male, Female) 
• DLQI at baseline (continuous). 
 
5.6. 
Additional Analyses 
In addition to the efficacy analyses of the study endpoints described above continuous and binary 
endpoints related to PASI, DLQI, PSSD, affected BSA, NAPPA, and PSSD at all scheduled study 
visits during the active treatment period until Week 28 will be summarized descriptively (observed 
cases analysis for continuous endpoints; observed cases analysis and non-responder imputation for 
binary endpoints). 
 
 
 
 
 


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6. 
SAFETY 
All safety analyses in Study Part 1 will be based on the ITT analysis set. Data from the safety 
follow-up will not be included in Study Part 1 analysis; last visit to be included for Study Part 1 
analysis is week 28 or early termination visit in case of discontinuation in Study Part 1. Safety 
data, including but not limited to, AEs, SAEs, infections, serious infections, changes in laboratory 
assessments, and changes in vital signs will be summarized by disease duration (≤2 and >2 years) 
and overall. Treatment-emergent AEs (TEAEs) will be summarized by treatment group and 
Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) and preferred 
terms (PT). 
For all continuous safety variables, descriptive statistics will include the N, mean, standard 
deviation, median, IQ range, minimum, and maximum. Categorical variables will be summarized 
using frequency counts and percentages. 
6.1. 
Adverse Events 
The verbatim terms used in the eCRF by investigators to identify adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after 
the initial administration of study agent until the day of week 28 visit (or early termination visit, if 
applicable.) in Study Part 1 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 treatment adverse event, the number and percentage of subjects who experience at least 
1 occurrence of the given event will be summarized by treatment group. Summary tabulation will 
also provide the number of events, if applicable. 
Summary tables will be provided for: 
• 
AEs 
• 
Serious AEs (SAEs) 
• 
AEs leading to discontinuation of study agent 
• 
AEs by severity 
• 
AEs by relationship to study agent 
• 
Infections 
• 
Serious Infections 
• 
Injection site reactions 
In addition to the summary tables, listings will be provided for subjects who: 
• 
Had (S)AEs 


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• 
Had AEs leading to discontinuation of study agent 
Deaths will be displayed by actual treatment received. Frequencies for the following parameters 
will be included in the summary table: 
• 
Number of subjects who died 
• 
Cause of death 
• 
Relationship to study agent (yes/no) (yes includes the following eCRF items: possible, 
probable, very likely) 
A listing of subjects who died will be provided. 
6.2. 
Clinical Laboratory Tests 
All clinical laboratory tests will be displayed for the subjects included in the ITT analysis set. 
Descriptive statistics will be presented for all chemistry and hematology laboratory tests at 
scheduled time points. 
Change from baseline (week 0) to postbaseline time points (week 12, week 20) will be summarized 
for chemistry and hematology tests. Box plots of change from baseline to postbaseline time points 
will be provided.  
Number and percentage of subjects with postbaseline clinically important laboratory values and/or 
markedly abnormal postbaseline values will be presented over time. 
The clinically important laboratory findings to be reported are described below: 
• 
[AST (U/L): 2x ULN] 
• 
[ALT (U/L): 2x ULN] 
• 
[Alkaline phosphatase (U/L): 2x ULN] 
Markedly abnormal laboratory findings to be reported are described below: 
• 
[AST (U/L): 3x ULN] 
• 
[ALT (U/L): 5x ULN] 
 A listing of clinically important laboratory values will be provided. 
Shift tables will be provided summarizing the shift in laboratory values from baseline to post-
baseline time points with respect to abnormality criteria (low, normal, high). 
Update after the Dry Run Meeting: Lab values given as borderline value only (eg <8 or >200) will 
be evaluated by ignoring the sign. Also, the box plots will not be presented.  
 


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6.3. 
Vital Signs and Physical Examination Findings 
Continuous vital sign parameters including weight, pulse, blood pressure (systolic and diastolic), 
will be summarized at each assessment time point. Change from baseline will be summarized for 
the open-label treatment period until week 28. Descriptive statistics (mean, standard deviation, 
median, IQ range, minimum and maximum) will be presented. A listing of subjects with treatment-
emergent clinically important vital signs will be presented, along with a listing of all vital sign 
measurements. 
Incidence of treatment-emergent clinically important vital signs while on treatment, as defined in 
Table 3, will be summarized for subjects who had a baseline assessment and at least 1 postbaseline 
assessment for that vital sign. 
Table 3: [Clinically Important/Markedly Abnormal] Vital Signs 
Vital Sign 
Criteria 
Pulse 
>120 bpm and with >30 bpm increase from baseline 
 
<50 bpm and with >20 bpm decrease from baseline 
Systolic blood pressure 
>180 mm Hg and with >40 mm Hg increase from baseline 
 
<90 mm Hg and with >30 mm Hg decrease from baseline 
Diastolic blood pressure 
>105 mm Hg and with >30 mm Hg increase from baseline 
 
<50 mm Hg and with >20 mm Hg decrease from baseline 
 
Abnormal findings in physical examination (additional to psoriasis findings) at screening, baseline 
visit (week 0), week 20 and week 28 will be tabulated by the body systems given in the eCRF. 
Details on abnormal findings in verbatim terms will be displayed in individual data listings. 
6.4. 
Electrocardiogram 
Not applicable 
6.5. 
Other Safety Parameters 
Tuberculosis Evaluation 
Categorical data on tuberculosis evaluation at each scheduled visit will be displayed in a frequency 
table providing the number and percentage of subjects per category. 
Urine Pregnancy Test 
Categorical data on urine pregnancy tests at each scheduled visit will be displayed in a frequency 
table providing the number and percentage of subjects per category. 
 
 


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7. 
PHARMACOKINETICS/PHARMACODYNAMICS 
7.1. 
Pharmacokinetics 
Not applicable for Study Part 1 analysis. 
7.2. 
Immune Response 
Not applicable for Study Part 1 analysis. 
7.3. 
Pharmacodynamics 
Not applicable for Study Part 1 analysis. 
7.4. 
Pharmacokinetic/Pharmacodynamic Relationships 
Not applicable for Study Part 1 analysis. 
8. 
BIOMARKERS 
Not applicable for Study Part 1 analysis. 
9. 
HEALTH ECONOMICS 
Not applicable for Study Part 1 analysis. 
 


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REFERENCES 
 
None  
 
 


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Status: Final, Date: 06 July 2021 
 
ATTACHMENTS 
 
None 
 


CONFIDENTIAL – FOIA Exemptions Apply in U.S. 
1 
Status: Final,  Date: 15 Dec 2021 
Janssen Cilag GmbH 
Statistical Analysis Plan – Study Part 2 
A Phase 3b, Randomized, Double-blind, Parallel Group, Multicenter Study to Evaluate 
Further Therapeutic Strategies with Guselkumab in Patients with Moderate-to-Severe 
Plaque-Type Psoriasis 
GUIDE 
Protocol CNTO1959PSO3012; Phase 3b 
 TREMFYA® (guselkumab)  
Status: 
Final 
Date: 
15 Dec 2021 
Prepared by: 
Janssen-Cilag GmbH, Germany  
Document No.: EDMS-RIM-612870 
Compliance:  The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement 
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise. 
NCT03818035


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Status: Final,  Date: 15 Dec 2021 
 
TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................................... 2 
VERSION HISTORY ..................................................................................................................................... 4 
1. 
INTRODUCTION.................................................................................................................................. 5 
1.1. 
Objectives and Endpoints ................................................................................................................ 6 
1.1.1. 
Objectives ..................................................................................................................................... 6 
1.1.2. 
Endpoints ...................................................................................................................................... 7 
1.2. 
Study Design .................................................................................................................................... 8 
2. 
STATISTICAL HYPOTHESES .......................................................................................................... 11 
3. 
SAMPLE SIZE DETERMINATION .................................................................................................... 11 
4. 
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS OF STUDY PART 2 .................................... 12 
4.1. 
All Enrolled Analysis Set ................................................................................................................ 12 
4.2. 
Efficacy Analysis Set(s).................................................................................................................. 12 
4.2.1. 
Intent-to-Treat Analysis Set (ITT) ............................................................................................... 12 
4.2.2. 
Per-protocol Analysis Set (PP) ................................................................................................... 12 
4.2.3. 
Nail Psoriasis Analysis Set ......................................................................................................... 12 
4.2.4. 
Safety Analysis Set ..................................................................................................................... 13 
4.2.5. 
Pharmacokinetics Analysis Set .................................................................................................. 13 
5. 
STATISTICAL ANALYSES FOR STUDY PART 2 ........................................................................... 13 
5.1. 
General Considerations ................................................................................................................. 13 
5.1.1. 
Visit Windows ............................................................................................................................. 14 
5.1.2. 
Pooling Algorithm for Analysis Centers ...................................................................................... 14 
5.1.3. 
Study Day and Relative Day ....................................................................................................... 15 
5.1.4. 
Baseline and Endpoint ................................................................................................................ 15 
5.1.5. 
Imputation Rules for Missing AE Date/Time of Onset/Resolution .............................................. 15 
5.1.6. 
Treatment Failure Criteria ........................................................................................................... 16 
5.1.7. 
Treatment Failure Rules ............................................................................................................. 16 
5.1.8. 
Missing Data Imputation ............................................................................................................. 16 
5.2. 
Participant Dispositions .................................................................................................................. 17 
5.3. 
Primary Endpoint(s) Analysis ......................................................................................................... 18 
5.3.1. 
Definition of Endpoint(s) ............................................................................................................. 18 
5.3.2. 
Estimand ..................................................................................................................................... 18 
5.3.3. 
Analysis Methods ........................................................................................................................ 20 
5.4. 
Major Secondary Endpoint(s) Analysis .......................................................................................... 21 
5.4.1. 
Definition of Endpoint(s) ............................................................................................................. 21 
5.4.1.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 21 
5.4.2. 
Estimand(s) ................................................................................................................................. 21 
5.4.3. 
Analysis Methods ........................................................................................................................ 22 
5.5. 
Other Secondary Endpoint(s) ........................................................................................................ 22 
5.5.1. 
Definition of Endpoint(s) ............................................................................................................. 23 
5.5.1.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 23 
5.5.1.2. 
Dermatology Life Quality Index (DLQI) ................................................................................... 23 
5.5.1.3. 
Body Surface Area (BSA%) ..................................................................................................... 23 
5.5.1.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) ............................................... 23 
5.5.1.5. 
Psoriasis Symptom and Sign Diary (PSSD) ............................................................................ 24 
5.5.2. 
Estimand(s) ................................................................................................................................. 25 
5.5.3. 
Analysis Methods ........................................................................................................................ 25 
5.5.3.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 25 
5.5.3.2. 
Dermatology Life Quality Index (DLQI) ................................................................................... 25 


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5.5.3.3. 
Body Surface Area (BSA%) ..................................................................................................... 26 
5.5.3.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) ............................................... 26 
5.5.3.5. 
Psoriasis Symptom and Sign Diary (PSSD) ............................................................................ 27 
5.6. 
Additional Analyses ........................................................................................................................ 27 
5.7. 
Safety Analyses ............................................................................................................................. 28 
5.7.1. 
Extent of Exposure ..................................................................................................................... 28 
5.7.2. 
Adverse Events ........................................................................................................................... 28 
5.7.3. 
Additional Safety Assessments .................................................................................................. 29 
5.7.3.1. 
Clinical Laboratory Tests ......................................................................................................... 29 
5.7.3.2. 
Vital Signs and Physical Examination Findings....................................................................... 30 
5.7.3.3. 
Electrocardiogram ................................................................................................................... 30 
5.7.3.4. 
Other Safety Parameters ......................................................................................................... 30 
5.8. 
Other Analyses ............................................................................................................................... 31 
5.8.1. 
Pharmacokinetics ....................................................................................................................... 31 
5.8.2. 
Immunogenicity ........................................................................................................................... 31 
5.8.3. 
Pharmacodynamics .................................................................................................................... 31 
5.8.4. 
Pharmacokinetic/Pharmacodynamic Relationships ................................................................... 31 
5.8.5. 
Biomarkers .................................................................................................................................. 31 
5.8.6. 
Health Economics ....................................................................................................................... 31 
5.8.7. 
Other Variables and/or Parameters ............................................................................................ 31 
5.8.8. 
Definition of Subgroups .............................................................................................................. 32 
5.9. 
Interim Analyses ............................................................................................................................. 33 
5.9.1. 
Data Monitoring Committee (DMC) or Other Review Board ...................................................... 33 
6. 
SUPPORTING DOCUMENTATION .................................................................................................. 34 
6.1. 
Appendix 1 List of Abbreviations .................................................................................................... 34 
6.2. 
Appendix 2 Changes to Protocol-Planned Analyses ..................................................................... 35 
6.3. 
Appendix 3 Demographics and Baseline Characteristics .............................................................. 36 
6.4. 
Appendix 4 Protocol Deviations ..................................................................................................... 37 
6.5. 
Appendix 5 Prior and Concomitant Medications ............................................................................ 38 
6.6. 
Appendix 6 Medical History ........................................................................................................... 39 
6.7. 
Appendix 7 Intervention Compliance ............................................................................................. 39 
6.8. 
Appendix 8 Adverse Events of Special Interest ............................................................................. 39 
6.9. 
Appendix 9 Medications of Special Interest ................................................................................... 39 
6.10. 
Appendix 10 Laboratory Toxicity Grading ...................................................................................... 39 
7. 
REFERENCES................................................................................................................................... 40 
 
 
 
 


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VERSION HISTORY 
 
Table 1 – SAP Version History Summary 
SAP Version 
Approval Date 
Change 
Rationale 
1 
15 Dec 2021 
Not Applicable 
Initial release 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1. 
INTRODUCTION 
The statistical analysis plan (SAP) is a detailed technical extension to the Clinical Study Protocol 
(CSP) and follows the principles of the guideline ICH E9. 
Statistical analyses of Janssen-Cilag GmbH Clinical Study Protocol CNTO1959PSO3012 will be 
performed for each of the three Study Parts. 
The confirmatory analysis is planned to be performed at the end of Study Part 2, ie, after all 
subjects have completed their visit at week 68 (ie, 40 weeks after randomization) or discontinued 
earlier. This analysis will include the confirmatory analysis of the primary endpoint, and the 
exploratory analyses of the major secondary endpoints and all other predefined efficacy and safety 
analyses from week 28 until week 68. 
The analyses of Study Part 1 and Study Part 3 will be exploratory. The exploratory analysis of 
Study Part 1 will occur after all subjects have completed their visit at week 28 (ie, 28 weeks after 
study inclusion) or discontinued earlier. This analysis will include the safety analysis and all 
efficacy measures after week 0 and will cover the time until the week 28 visit. The exploratory 
analyses of Study Part 3 will occur after all subjects have completed their visit at week 116 (ie, 48 
weeks after inclusion in Study Part 3 at week 68) or week 144 in case of subjects entering the re-
treatment arm in week 116, or at week 164 (ie, 96 weeks after inclusion in Study Part 3 at week 
68) or at week 220 (ie, 152 weeks after inclusion in Study Part 3 at week 68), or week 248 in case 
of subjects entering the re-treatment arm in week 220 or discontinued earlier. These analyses will 
include the safety evaluations and all efficacy measures after week 68, and will cover the time 
until week 116/164/220 and until week 144/192/248, respectively. 
Final decisions, about which patients will be included in the analyses of the Study Parts 1, 2, or 3, 
are made during the Data Review or Dry Run Meetings. 
This plan describes the statistical analyses planned to be performed for the analysis of Study Part 
2 (randomized, double blind treatment phase) and should be read in conjunction with the CSP and 
the electronic Case Report Form (eCRF). Statistical analyses of study data recorded before week 
28 and after week 68 are specified in separate SAPs, if not otherwise specified.  
This SAP is the core document for all statistical programming planned to be performed for the 
analysis of Study Part 2 of study protocol no. CNTO1959PSO3012. The statistical analyses will 
focus on the comparison of the two randomized, double blind treatment groups (ie, group 2a: 
guselkumab 100 mg q8w vs. group 2b: guselkumab 100 mg q16w) in Study Part 2. If not otherwise 
specified, descriptive statistical analyses of study group 2c (non-SRe with a PASI score >0 at week 
20 and/or 28 who will receive guselkumab 100 mg q8w at weeks 28 to 60 in Study Part 2) will be 
performed likewise. 
Note: Subjects losing control of disease, defined as PASI score >5 at any visit during Study Part 2 
or 3 (ie, until week 116), will enter the re-treatment-arms (2d or 3c) with three guselkumab 100 mg 
administrations starting at that visit (= re-treatment-week 0, followed by administration at re-
treatment-weeks 8 and 16). Statistical analyses of re-treatment study data will be specified in a 
separate SAP. 
 
 


TREMFYA®  (guselkumab)  
 
 
 
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Status: Final,  Date: 15 Dec 2021 
1.1. 
Objectives and Endpoints 
1.1.1. 
Objectives 
Primary objective 
The primary objective of the study is to demonstrate that Super-Responders (SRe; defined as 
psoriasis subjects who receive on-label guselkumab treatment until week 20 and respond with a 
Psoriasis Area and Severity Index [PASI] score = 0 at weeks 20 and 28) maintain control of 
disease until week 68 with prolonged treatment intervals of 16 weeks (100 mg q16w). To be 
demonstrated in Study Part 2. 
Secondary objectives 
Secondary objectives are to evaluate 
• whether subjects with short disease duration (≤2 years) show a more rapid and better 
guselkumab response compared to subjects with longer disease duration and whether 
subjects with shorter disease are more likely to maintain drug-free control of disease after 
guselkumab withdrawal. To be evaluated in Study Parts 1, 2 and 3.  
• whether SRe with short disease duration and PASI=0 at week 116 (ie, remission for one 
year after withdrawal) will show sustained remission (ie, PASI=0) over two additional 
years compared to subjects with longer disease duration. To be evaluated in Study Part 3. 
• whether SRe with short disease duration and PASI>0 to ≤5 at week 116 (ie, partial relapse 
for one year after withdrawal) will show continued loss of response or stabilization of 
disease worsening over two additional years compared to subjects with longer disease 
duration. To be evaluated in Study Part 3. 
• whether different treatment intervals (weeks 28 to 60: guselkumab 100 mg q8w vs. 
guselkumab 100 mg q16w) affect the maintenance of drug-free control of disease after 
68 weeks of guselkumab treatment. To be evaluated in Study Part 3. 
• the safety and tolerability of guselkumab in subjects with moderate-to-severe plaque-type 
psoriasis. 
Note: Disease duration will be calculated from date at which first symptoms (plaque) were reported 
by subject to date of screening visit: 
o Disease duration (days)  =  Date of visit 1 - date of first symptoms +1. 
Exploratory objectives 
The exploratory objectives are to be explored in the mechanistic biomarker substudies. These 
objectives are out of scope of this SAP. 
 
 


TREMFYA®  (guselkumab)  
 
 
 
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1.1.2. 
Endpoints 
For the endpoints, the following terms were defined: 
• Control of disease: PASI score <3 
• Fluctuating disease: PASI score 3 to 5 
• Loss of disease control: PASI score >5. 
Study groups are defined as follows: 
• 1: All participating subjects who are enrolled and are scheduled to receive guselkumab 
100 mg at weeks 0, 4, q8w until week 28 (Study Part 1) 
• 2a: SRe (PASI score = 0 at weeks 20 and 28) randomized to guselkumab 100 mg q8w at 
weeks 28 to 60 (Study Part 2) 
• 2b: SRe randomized to guselkumab 100 mg q16w at weeks 28 to 60 (Study Part 2) 
• 2c: non-SRe with a PASI score >0 at week 20 and/or 28 who will receive guselkumab 
100 mg q8w at weeks 28 to 60 (Study Part 2) 
• 2d: SRe with loss of disease control between week 28 and 68, who will enter the re-
treatment arm and receive guselkumab 100 mg at weeks 0, 8 and 16 calculated from the 
date of loss of disease control (Study Part 2) 
• 3a: SRe randomized to guselkumab 100 mg q8w in Study Part 2 with withdrawal of 
guselkumab at week 68 (Study Part 3) 
• 3b: SRe randomized to guselkumab 100 mg q16w in Study Part 2 with withdrawal of 
guselkumab at week 68 (Study Part 3) 
• 
3c: SRe with fluctuating disease at week 68 or loss of disease control at any other visit after 
week 68, who will enter the re-treatment arm and receive guselkumab 100 mg at weeks 0, 
8 and 16 calculated from the date of loss of disease control (Study Part 3). 
Primary endpoint 
The primary endpoint of the main study is the proportion of subjects in study groups 2a and 2b 
who achieve an absolute PASI score <3 at week 68. 
Major secondary endpoints 
Major secondary endpoints of this study are: 
• Time to improvement from baseline (week 0) in PASI (PASI 75/90/100 response and 
absolute PASI score=0) for subjects with short (≤ 2 years) and longer (>2 years) disease 
duration per study group (1, 2a, 2b, and 2c) 
• Proportion of subjects with short (≤2 years) and longer (>2 years) disease duration who 
achieve an absolute PASI score of 0, ≤1 and <3 at weeks 20, 28, 68, 116, 164, and 220 per 
study group (1, 2a, 2b, 2c, 3a, and 3b) 
• 
Proportion of subjects who retain disease control (ie, absolute PASI score <3 at all visits) 
from week 68 through week 116, from week 68 through week 164, and from week 68 
through week 220 for subjects with short (≤ 2 years) and longer (>2 years) disease duration 
per study group (3a and 3b). 
 


TREMFYA®  (guselkumab)  
 
 
 
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Other secondary endpoints of this study are: 
• Proportion of subjects who achieve a PASI 75/90/100 response at weeks 20, 28, 68, 116, 
164, and 220 per study group (1, 2a, 2b, 2c, 3a, and 3b) 
• Time to loss of disease control (absolute PASI score >5 at any visit) after treatment 
withdrawal beyond week 68 per study group (3a and 3b) 
• Proportion of subjects with an absolute PASI score=0 at all of the following visits: weeks 
12, 16, 20, and 28 (study group 1) 
• Change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at 
weeks 28, 68, 116, 164, and 220 per study group (1, 2a, 2b, 2c, 3a, 3b, and 3c) 
• Proportion of subjects who achieve a DLQI score 0/1 and <5 at weeks 28, 68, 116, 164, 
and 220 per study group (1, 2a, 2b, 2c, 3a, 3b, and 3c) 
• Change from baseline (week 0) in affected Body Surface Area (BSA) at weeks 12, 28, 52, 
68, 80, 104, 116, 140, 164, 188, 212, and 220 (all study groups) 
• Change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic Arthritis 
(NAPPA) score at weeks 28, 68, 116, 164, and 220 among subjects with nail psoriasis at 
baseline (week 0; 1, 2a, 2b, 2c, 3a, and 3b). 
• Change from baseline (week 0) in the signs and symptoms aggregate scores of the Psoriasis 
Symptoms and Signs Diary (PSSD) at weeks 28, 68, 116, 164, and 220 (1, 2a, 2b, 2c, 3a 
and 3b) 
• Proportion of subjects who achieve a PSSD sign score=0 at week 68 among subjects with 
a PSSD sign score ≥1 at week 28 per study group (2a, 2b, and 2c). 
• Association between trough serum guselkumab concentration and efficacy or serum 
biomarker level 
• Association between trough serum guselkumab levels at weeks 20, 28, 36, and 68 and 
achieving a PASI score <3 at week 68 per study group (2a and 2b) 
• Proportion of subjects who were re-treated due to loss of disease control (PASI >5) and 
regain control of disease (PASI <3) 24 weeks after start of re-treatment (study groups 2d 
and 3c) 
• Safety and tolerability with regard to adverse events (AEs) and abnormal laboratory results 
(all study groups). 
1.2. 
Study Design 
The present trial is designed as a phase 3b, randomized, double-blind, parallel-group, multicenter, 
comparison study in subjects of at least 18 years of age with moderate to severe plaque-type 
psoriasis. The study will feature the following structure and design: 
Study Part 1: Screening through Week 28:  
This will be screening phase lasting up to four weeks (+ 7 calendar days) prior to first 
administration of guselkumab (week 0) followed by a 28-week run-in period with visits and 
administration of 100 mg guselkumab at weeks 4, 12, and 20. In case of a PASI score = 0 at 
weeks 20 and 28 subjects are qualified to be randomized either to study group 2a or 2b of Study 
Part 2. In case of PASI score >0 at weeks 20 and/or 28 the subjects will continue to receive 


TREMFYA®  (guselkumab)  
 
 
 
Statistical Analysis Plan CNTO1959PSO3012  
 
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Status: Final,  Date: 15 Dec 2021 
guselkumab 100 mg q8w until week 60 (last administration at week 60 visit) with final study 
assessments at week 68 and final safety follow-up visit at week 72 (defined as study group 2c). 
Study Part 2: Week 28 through Week 68:  
Subjects with a PASI score = 0 at weeks 20 and 28 will be defined as SRe and randomly assigned 
to the following two treatment groups: 2a) guselkumab 100 mg q8w or 2b) guselkumab 100 mg 
q16w. In addition, subjects with disease duration ≤2 years will be equally distributed to either 
group. Study visits of Study Part 2 will be conducted every 8 weeks. 
To blind the study, study treatment (guselkumab or Placebo) will be administered q8w starting at 
week 28 until the end of study therapy (last administration in week 60). The q16w group will 
receive Placebo at weeks 28, 44 and 60. Subjects losing control of disease, defined as PASI score 
>5 at any visit during Study Part 2 (ie, until week 60), will enter the Re-treatment arm (group 2d, 
see section Re-treatment below). 
The assessment for the primary endpoint (EP) will be at week 68 for both study groups (2a and 
2b).  
In case of PASI <3 at week 68 the subject will not receive any study medication and enter the drug 
withdrawal part (Study Part 3). In case of PASI ≥ 3 at visit week 68 the subject will enter the re-
treatment arm 3c (see section Re-treatment below). 
In case of PASI score >0 at weeks 20 and/or 28 the subjects will continue to receive guselkumab 
100 mg q8w until week 60 (last administration of study treatment) with final study assessments at 
week 68 and final safety follow-up visit at week 72 (defined as study group 2c). 
Study Part 3: Week 68 through Week 220:  
Subjects of group 2a and 2b with a PASI score <3 at week 68 will enter Study Part 3 and be 
withdrawn from the study medication and followed-up until week 220. Study visits of Study Part 
3 will be conducted every 12 weeks (ie, at weeks 80, 92, 104, 116, 128, 140, 152, 164, 176, 188, 
200, and 212; ± 14 days). In between the 12-weekly on-site visits, a telephone-visit 6 weeks (± 
7 days) will be done after each on-site visit (ie, telephone visits at weeks 74, 86, 98, 110, 122, 134, 
146, 158, 170, 182, 194, and 206) to assess whether the subject notices a worsening of his/her 
psoriasis. If so, the subject must attend an on-site visit for efficacy assessment by the assessor as 
soon as possible but not later than 2 weeks after the phone call. For patients not starting re-
treatment, the final visit will take place at week 220. 
 
 


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Re-treatment 
Subjects losing control of disease, defined as PASI score >5 at any visit during Study Part 2 or 3 
(ie, until week 220), will enter the re-treatment-arms (2d or 3c) with three guselkumab 100 mg 
administrations starting at that visit (= re-treatment-week 0, followed by administration at re-
treatment-weeks 8 and 16). 
If re-treatment is started at a visit which would usually not require all PROs needed at the first re-
treatment visit, those PROs will be obtained immediately after efficacy assessments (basis for re-
treatment-decision) and prior to drug administration at that visit. 
The final efficacy assessment for all subjects in the re-treatment-arms will take place 24 weeks 
after loss of control and study termination will be 28 weeks after loss of control (final study 
visit/safety follow-up). At visit week 24 of the re-treatment, the investigator may continue actual 
treatment with commercially available guselkumab (ie, not supplied by Sponsor) to maintain a 
q8w interval. Due to the half-life of guselkumab, it is recommended not to start a new therapy 
during safety follow-up period (ie, 12 weeks after last dose). If the investigator feels strongly that 
an additional therapy is needed, this should be discussed with the Sponsor before initiation of the 
new therapy. 
Subjects with fluctuating disease (ie, PASI score 3 to 5) at the week 68 visit will also get the 
opportunity to enter the re-treatment-arm (3c). 
The last chance to start re-treatment will be the visit week 220 (ie, final efficacy assessment at 
week 244 with final study visit/safety follow-up at week 248). 
A schematic diagram of the study design is provided below. 
 


TREMFYA®  (guselkumab)  
 
 
 
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2. 
STATISTICAL HYPOTHESES 
This randomized, double-blind, parallel-group, multicenter phase 3b trial is designed to 
demonstrate that guselkumab 100 mg q16w treatment is non-inferior to guselkumab 100 mg q8w 
treatment in SRe as assessed by the proportion of subjects with an absolute PASI score <3 at 
week 68. A non-inferiority margin of 10% was chosen based on a minimally clinically meaningful 
difference. This margin was also used in CNTO1959PSO3009 (ECLIPSE) study and is therefore 
considered a valid approach for evaluating non-inferiority of a new treatment. 
The null hypothesis H0 and the alternative hypothesis HA are formulated as follows: 
• H0: PT - PS  ≤ -10% ('inferiority') 
• H1: PT - PS  > -10% ('non-inferiority') 
where PT and PS denote the proportions of subjects with an absolute PASI score <3 at week 68 in 
the guselkumab 100 mg q16w treatment arm (PT = proportion test treatment) and the guselkumab 
100 mg q8w treatment arm (PS = proportion standard treatment). 
3. 
SAMPLE SIZE DETERMINATION 
The sample size estimation using the power approach was performed for the per-protocol analysis 
set as described below. No formal adjustment of the significance level was necessary.  
When the sample size in each group is 112, a two-group large-sample normal approximation Wald 
Z-test of proportions with a one-sided 0.05 significance level will have 80% power to reject the 
null hypothesis that the guselkumab 100 mg q16w treatment is inferior to the guselkumab 100 mg 
q8w treatment (the difference in proportions, Pguselkumab 100mg q16w – P guselkumab 100mg q8w , is ≤ -10%) 
in favor of the alternative hypothesis that the guselkumab 100 mg q16w treatment is non-inferior 
to the guselkumab 100 mg q8w treatment (the difference in proportions is > -10%), assuming that 
the expected difference in proportions is 0 and the proportion in the guselkumab 100 mg q8w 
treatment group is 90% (nQuery Advisor® 7.0).  
Considering the frequency of drop-out rates and protocol violations from past trials, it is assumed 
that a rate of about 20% randomized subjects will not be evaluable for the per-protocol analysis in 
Study Part 2. Therefore, 280 subjects (140 subjects per treatment group) are planned to be 
randomized in a ratio of 1:1 to meet the required sample size of 224 subjects (112 subjects per 
treatment group) for the per-protocol analysis. 
Based on data from CNTO1959PSO3001 and CNTO1959PSO3002, it is anticipated that 
approximately 35% of enrolled subjects in Study Part 1 will be eligible for randomization at 
week 28 in Study Part 2. Thus, a total of 800 subjects should be enrolled in Study Part 1 to ensure 
that at least 280 subjects are eligible for randomization in Study Part 2. Accounting for a 10% 
drop-out rate of subjects ineligible for randomization at week 28 because of study discontinuation 
prior to week 28, it is therefore planned to enroll a total of 888 subjects in Study Part 1. 
Note: Screenings and enrollments will be adjusted if necessary (without protocol amendment), to 
achieve 280 SRe at week 28. Ongoing subjects in Study Part I will continue to Part 2 if eligible, 
irrespective of whether or not 280 SRe are already randomized. Only screenings will be closed. 


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4. 
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS OF STUDY PART 2 
In Study Part 2 the following analysis sets will be defined for the efficacy and safety analyses.  
4.1. 
All Enrolled Analysis Set 
Not applicable for Study Part 2 (only applicable for Study Part 1). However, for Study Part 2 the 
number of 'Subjects starting Study Part 2' will be reported and used for display of summary tables, 
if applicable. 
Note: The all enrolled analysis set in Study Part 1 includes all subjects who were enrolled and were 
scheduled to receive study agent. 
4.2. 
Efficacy Analysis Set(s) 
The confirmatory efficacy analysis of the primary endpoint variable and the exploratory analyses 
of the secondary endpoint variables will be performed both for the intent-to-treat analysis set (ITT) 
and the per-protocol analysis set (PP). 
4.2.1. 
Intent-to-Treat Analysis Set (ITT) 
For all efficacy analyses to compare guselkumab 100 mg q16 (group 2b) vs. guselkumab 100 mg 
q8w (group 2a) in Study Part 2, all randomized subjects at week 28 will be included in the intent-
to-treat analysis set (ITT). Subjects will be analyzed according to the treatment group to which 
they were randomized regardless of the treatment they actually received. 
For all efficacy analyses of study group 2c (non-SRe with a PASI score >0 at week 20 and/or 28 
who will receive guselkumab 100 mg q8w at weeks 28 to 60 in Study Part 2) all subjects treated 
with at least one dose of study agent during Study Part 2 will be included in the intent-to-treat 
analysis set (ITT). 
Note: In the current SAP template the term 'full analysis set' is used. In this SAP the term 'intent -
to-treat analysis set' is used instead to match the Clinical Study Protocol. In terms of content, there 
is no difference between the two names. 
4.2.2. 
Per-protocol Analysis Set (PP) 
The per-protocol analysis set (PP) will consist of all subjects in the intent-to-treat analysis set (ITT) 
completing or terminating the Study Part 2 without any major deviation of the protocol and its 
procedures until the week 68 visit. Subjects with major protocol deviations (except those not 
effecting the primary endpoint) will be excluded from the per-protocol analysis. 
4.2.3. 
Nail Psoriasis Analysis Set 
The change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic Arthritis 
(NAPPA) score at week 28, 52, and 68 will be evaluated among subjects with nail psoriasis at 
baseline (week 0). Nail psoriasis at baseline (week 0) will be defined as follows:  
• eCRF question 'Was Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
performed?' is answered with 'Yes'. 
o  if 'Yes', patient has nail psoriasis, if NAPPA-CLIN ≥ 1 at baseline (week 0) 


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These analyses will be performed both for the intent-to-treat analysis set (ITT) and the per-protocol 
analysis set (PP). 
4.2.4. 
Safety Analysis Set 
For all safety analyses, all subjects treated with at least one dose of study agent during Study Part 
2 will be included. For all the safety analyses, subjects will be analyzed according to the treatment 
they actually received. 
4.2.5. 
Pharmacokinetics Analysis Set 
The PK analysis and the definition of the PK analysis set is out of scope for this SAP.  
5. 
STATISTICAL ANALYSES FOR STUDY PART 2 
Description of planned statistical analyses in Study Part 2 will focus on the comparison of the two 
randomized treatment groups (ie, group 2a: guselkumab 100 mg q8w vs. group 2b: guselkumab 
100 mg q16w) in Study Part 2. If not otherwise specified, descriptive statistical analyses of study 
group 2c (non-SRe with a PASI score >0 at week 20 and/or 28 who will receive guselkumab 
100 mg q8w at weeks 28 to 60 in Study Part 2) will be performed likewise. Inferential statistics 
(ie, p-values, confidence intervals, etc.) will be provided only for the week 68 data of endpoints in 
Study Part 2. 
Note: Statistical analysis of Study Part 2 will also include analyses of study data recorded before 
week 28. Data of Study Part 1 will be summarized by descriptive statistics only. No exploratory 
inferential statistics (ie, p-values, confidence intervals, etc.) will be provided for the data of Study 
Part 1. 
5.1. 
General Considerations 
The following general analysis definitions refer only to Study Part 2.  
The primary analysis of Study Part 2 will be confirmatory. The confirmatory significance level for 
non-inferiority testing is fixed to a one-sided α = 0.05. Besides the confirmatory testing of the 
primary endpoint all other inferential statistical testing (including calculation of confidence 
intervals) are to be interpreted in the exploratory sense only. 
Descriptive statistics will include counts and proportions for categorical data, and, mean, SD, 
median, interquartile range, and range for continuous data. Graphical data displays will also be 
used to summarize the data. The two-group large-sample normal approximation Wald Z-test with 
Mantel-Haenszel stratum weights for 'disease duration' will be used to compare the proportion of 
subjects responding to treatment. Continuous response parameters will be compared using a 
univariate analysis of variance model with fixed effects for treatment group and disease duration 
and baseline value as a covariate. In addition, a multivariate linear mixed model for repeated 
measures (MMRM) will be used to test the difference in change from baseline between treatment 
groups; the repeated measures of change from baseline being the dependent variables, treatment, 
disease duration, and baseline value of endpoint as independent variables. Time-to-event endpoints 


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will be analyzed using Kaplan-Meier product limit methods to estimate the survival distributions 
and the median time-to-event. 
In general, summary tables will be displayed by treatment group (for SRe and non-SRe) as the 
main classification variable and for the total of the sample (SRe only; not for efficacy analyses) in 
the respective analysis set, if not otherwise specified; ie, results will be provided for group 2a, 
group 2b, total of group 2a and group 2b (not for efficacy analyses), and group 2c. Additional 
classification variables are explicitly mentioned in the following text. Individual subject data 
listings will be presented parameter wise and will be sorted by treatment group, study site, subject's 
identification number and study visit, if applicable. A more detailed description of the planned 
statistical analyses are provided in the sections below. 
5.1.1. 
Visit Windows 
As subjects do not always adhere to the protocol visit schedule, the following rules are applied to 
assign actual visits to analysis visits. Listed below are the visit windows and the target days for 
each visit. The reference day is Study Day 1 (for definition see section 5.1.3). If a subject has 2 or 
more actual visits in one visit window, the visit closest to the target day will be used as the protocol 
visit for that visit window. The other additional visit(s) will not be used in the summaries or 
analyses, but they can be used for determination of clinically important endpoints. If 2 actual visits 
are equidistant from the target day within a visit window, the later visit will be used. 
All assignments will be made in chronological order. Once a visit date is assigned to a visit 
window, it will no longer be used for a later time point except for the endpoint. Listed below (Table 
1) are the visit windows and the target days for each visit defined in the protocol. 
Table 1 – Visit Windows 
Parameter 
Analysis 
Period 
Scheduled Visit  
Time Interval 
(label on output) 
Time Interval 
(Day)* 
Target Time 
Point (Day) 
All 
1 
Scr 
Screening 
-35 to -1 
 
 
1 
W0 
Baseline 
-14 to 6 
1 
 
1 
W4 
Week 4 
15 to 43 
29 
 
1 
W12 
Week 12 
71 to 99 
85 
 
1 
W16 
Week 16 
100 to 126 
113 
 
1 
W20 
Week 20 
127 to 155 
141 
 
1 
W28 
Week 28 
183 to 211 
197 
 
2 
W36 
Week 36 
239 to 267 
253 
 
2 
W44 
Week 44 
295 to 323 
309 
 
2 
W52 
Week 52 
351 to 379 
365 
 
2 
W60 
Week 60 
407 to 435 
421 
 
2 
W68  
Week 68 
463 to 491 
477 
*Relative to [Study Day 1] 
If there are visits outside of the defined windows, final decisions on the allocation of the actual 
visit to an earlier or later planned visit or if the data will not be included in the analysis will be 
made during the Data Review or Dry Run Meeting.  
5.1.2. 
Pooling Algorithm for Analysis Centers 
No pooling of centers will be performed. 


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5.1.3. 
Study Day and Relative Day 
Study Day 1 or Day 1 refers to the start of the first study agent administration within Study Part 1. 
All efficacy and safety assessments at all visits will be assigned a day relative to this date. 
Study day or relative day for a visit is defined as: 
• 
Visit date - (date of Study Day 1) +1, if visit date is ≥ date of Day 1 
• 
Visit date - Date of Day 1, if visit date < date of Day 1 
There is no 'Day 0'. 
5.1.4. 
Baseline and Endpoint 
Baseline for Study Part 2 is defined as the last observation (ie, value, measurement) prior to the 
start of the first study agent administration at baseline (week 0) in Study Part 1. 
Endpoint for Study Part 2 is defined as the last available postbaseline result within the analysis 
period from week 28 until week 68. Unscheduled visit results are included in this definition and 
will be considered as the endpoint value if the unscheduled visit result is the last postbaseline result 
available within the analysis period from week 28 until week 68. 
5.1.5. 
Imputation Rules for Missing AE Date/Time of Onset/Resolution 
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 
− 
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 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 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: 


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• 
If the resolution date of an adverse event is missing day only, it will be set to the earliest of 
the last day of the month of occurrence of resolution or the day of the date of death, if the 
death occurred in that month. 
• 
If the resolution date of an adverse event is missing both day and month, it will be set to the 
earliest of December 31 of the year or the day and month of the date of death, if the death 
occurred in that year. 
• 
Completely missing resolution dates will not be imputed. 
5.1.6. 
Treatment Failure Criteria 
No treatment failure criteria are defined for Study Part 2 analysis. 
5.1.7. 
Treatment Failure Rules 
NA 
5.1.8. 
Missing Data Imputation 
Data of study endpoints from subjects who started a protocol-prohibited medication/therapy during 
the study period that could improve psoriasis will be set to 'missing' from that point onward. The 
protocol-prohibited medications/therapies are listed in section 8.1 of the CSP. For the statistical 
analysis of Study Part 2 protocol prohibited medication/therapy will be identified in the SDTM 
DV domain as DVDECOD='RECEIVED DISALLOWED CONCOMITANT TREATMENT'. 
After the rule for handling of protocol-prohibited medication/therapy is applied, missing data will 
be handled as follows. 
• 
Non-responder imputation for binary efficacy endpoints will be applied for subjects with 
missing data in Study Part 2.  
• 
Last Observation Carried Forward (LOCF) imputation for continuous efficacy endpoints will 
be applied for subjects with missing data in Study Part 2.  
• This approach implies that a separate "endpoint" visit will be calculated that gets the 
imputed value, thus leaving the observed value as it is, if data are summarized 
descriptively only. 
• 
Time-to-event analyses of binary endpoints will be performed after the rule for handling of 
protocol-prohibited medication/therapy is applied (missing data will not be replaced for time-
to-event analyses).  
• 
In addition, the following alternative approaches will be applied (supplementary analyses): 
• 
Multiple imputation will be used for calculation of response rates regarding PASI < 3 (ie, 
the primary endpoint), PASI <= 1 and PASI = 0.  
• 
Multiple imputation methods generate multiple copies of the original dataset by 
replacing missing values using an appropriate stochastic model, analyze them as 
complete sets and finally combine the different parameter estimates across the datasets 
to produce a unique point estimate and standard error taking into account the 
uncertainty of the imputation process. 


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• 
Derived variables will not be imputed but will be derived from imputed values (eg, if 
the PASI score <3 at week 68 is missing, the PASI score at week 68 will be imputed 
to calculate whether the patient achieves an absolute PASI score <3 at week 68). 
• 
Multiple imputation will only be done for the two randomized treatment groups. For 
the multiple imputation, the SAS procedures MI and MIANALYZE will be used. The 
exact multiple imputation procedure is data-dependent (method, missing data pattern, 
etc.) and will be determined prior to unblinding. The number of imputations will be set 
to 100. The Fully Conditional Specification (FCS) regression method will be used to 
impute values for continuous data with an arbitrary missing data pattern. The FCS 
method is more flexible in that it allows for classification variables as covariates in the 
imputed model. Covariates that are considered for inclusion in the multiple imputation 
model for better prediction of the missing values are: treatment group, disease duration, 
and non-missing values of the analysis variables at all scheduled times within the 
analysis period from week 28 until week 68. 
• 
For continuous endpoints the missing data issues will be handled implicitly through using 
the mixed model repeated measures (MMRM) approach which does not employ formal 
imputation. The use of MMRM is based on the assumption of missing at random (MAR) 
and the assumption that dropouts would behave similarly to other patients in the same 
treatment group, and possibly with similar covariate values, had they not dropped out. 
An 'observed cases analysis' for all binary and continuous endpoints in Study Part 2 without any 
imputation of missing data (ie, also not set to missing once protocol-prohibited medication/therapy 
is started) will also be done. These analyses will provide only descriptive statistical results and 
will also include by-visit data of Study Part 1 (see section 5.6). 
5.2. 
Participant Dispositions 
The number of subjects in the following disposition categories will be summarized throughout the 
study for Study Part 2 by treatment groups (ie, groups 2a, 2b, 2c) and overall total of group 2a and 
group 2b: 
• 
Subjects randomized (only for SRe) 
• 
Subjects who received study agent within Study Part 2 
• 
Subjects who completed Study Part 2 
• 
Subjects who discontinued study agent within Study Part 2 
• 
Reasons for discontinuation of study agent within Study Part 2 
• 
Subjects who terminated study prematurely within Study Part 2 
• 
Reasons for termination of study within Study Part 2. 
 
 


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5.3. 
Primary Endpoint(s) Analysis 
The confirmatory analysis of the primary endpoint variable will be performed both for the intent-
to-treat analysis set and the per-protocol analysis set.  
5.3.1. 
Definition of Endpoint(s) 
The primary endpoint is the proportion of subjects in study groups 2a and 2b who achieve an 
absolute PASI score <3 at week 68. 
5.3.2. 
Estimand 
Primary Trial Objective: The primary objective of the study is to demonstrate that Super-
Responders (SRe; defined as psoriasis subjects who receive on-label guselkumab treatment until 
week 20 and respond with a Psoriasis Area and Severity Index [PASI] score = 0 at weeks 20 and 
28) maintain control of disease until week 68 with prolonged treatment intervals of 16 weeks 
(100 mg q16w). To be demonstrated in Study Part 2 
Estimand Scientific Question of Interest: Is guselkumab 100 mg q16w treatment non-inferior to 
guselkumab 100 mg q8w treatment in SRe as assessed by the proportion of subjects with an 
absolute PASI score <3 at week 68 and a non-inferiority margin of 10%? 
Study intervention: 
• 
Study group 2a: guselkumab 100 mg q8w, ie at weeks 28/36/44/52/60 
• 
Study group 2b: guselkumab 100 mg q16w, ie guselkumab at weeks 36 and 52; Placebo at 
weeks 28/44/60 (guselkumab and placebo will be provided blinded, IWRS will assure correct 
assignment). 
Population: Subjects of at least 18 years of age with moderate to severe plaque-type psoriasis. 
Subjects with a PASI score = 0 at weeks 20 and 28 will be defined as SRe and randomly assigned 
at week 28 to the following two treatment groups: 2a) guselkumab 100 mg q8w or 2b) guselkumab 
100 mg q16w. The confirmatory analysis of the primary endpoint variable will be performed for 
both the intent-to-treat analysis set and the per-protocol analysis set. 
Variable: Responder binary variable, where a responder is defined as a subject in study groups 2a 
and 2b achieving an absolute PASI score <3 at week 68 who does not: 
• discontinue study agent due to lack of efficacy, an AE, worsening of psoriasis, or  
• started a protocol-prohibited medication/therapy during the study period that could 
improve psoriasis are considered non-responders. 
Summary measure (Population-level summary): proportion (percentage) of subjects; after the 
rule for handling of protocol-prohibited medication/therapy is applied, non-responder imputation 
will be applied for subjects with missing data. 
 
 


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Intercurrent events and their corresponding strategies: 
Intercurrent events 
Strategy for addressing intercurrent events 
• 
Discontinuation of study 
agent due to lack of efficacy, 
an AE, worsening of psoriasis 
Composite Strategy: A participant with this 
intercurrent event is considered as a non-responder 
after this event, the occurrence of this intercurrent 
event being captured in the variable definition. 
• 
Start of  protocol-prohibited 
medication/therapy during the 
study period that could 
improve psoriasis. 
Composite Strategy: Same as above 
Sensitivity and Supplementary Analysis for Estimands 
The following sensitivity analyses will be performed (after the rule for handling of protocol-
prohibited medication/therapy and non-responder imputation are applied). 
• Stratified Newcombe confidence limits for the common proportion difference with respect 
to the primary endpoint will also be provided by using the method of Yan and Su (Yan und 
Su 2010). 
• The primary endpoint will also be analyzed without adjustment for disease duration 
('unstratified analysis'). The two-group large-sample normal approximation Z-test will be 
used along with  
• the two-sided 90% Wald type confidence interval, and 
• the two-sided 90% Newcombe confidence interval.  
The sensitivity analyses described above will also be performed using multiple imputation after 
the rule for handling of protocol-prohibited medication/therapy is applied. Details on handling of 
missing data are described in section 5.1.8. 
No supplementary analyses to target alternative estimands will be performed. 
 
 


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5.3.3. 
Analysis Methods 
The proportion of subjects with an absolute PASI score <3 at week 68 will be displayed in a 
frequency table providing the number and percentage of subjects per treatment group along with 
odds ratio (OR), relative risk (RR) and risk difference (RD), and two-sided Wald-type confidence 
intervals (90% CIs) stratified by 'disease duration'. For single proportions within each treatment 
group unstratified two-sided 90% CIs according to Clopper-Pearson will be calculated. Graphical 
presentation will be presented by means of a bar chart. 
To test the non-inferiority of guselkumab 100 mg q16w to guselkumab 100 mg q8w with a non-
inferiority margin of 10% in Study Part 2, a one-sided (α = 0.05) two-group large-sample normal 
approximation Wald Z-test with Mantel-Haenszel stratum weights for 'disease duration' will be 
used ('stratified analysis' of non-inferiority). The Mantel-Haenszel estimate, the two-sided 90% 
Wald-type confidence limits, and the test for the difference of proportions will be computed by 
using Mantel-Haenszel stratum weights (Mantel & Haenszel, 1959) and the Sato variance 
estimator (Sato 1989). Non-inferiority will be accomplished when the lower limit of the two-sided 
90% confidence interval for the difference in response rates (guselkumab 100 mg q16w minus 
guselkumab 100 mg q8w) will be > -10% both for the intent-to-treat analysis and the per-protocol 
analysis. 
Stratified Newcombe confidence limits for the common proportion difference with respect to the 
primary endpoint will also be provided by using the method of Yan and Su (Yan und Su 2010) as 
specified in section 5.3.2. 
In addition, the primary endpoint will also be analyzed without adjustment for disease duration 
('unstratified analysis' of non-inferiority). The two-group large-sample normal approximation Z-
test along with the two-sided 90% Wald type and Newcombe confidence interval will be computed 
as specified in section 5.3.2.  
Subgroup analyses will be performed unstratified for the subgroups as specified in section 5.8.8. 
 
 


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5.4. 
Major Secondary Endpoint(s) Analysis 
Statistical analyses will be descriptive and exploratory only, and will be performed both for the 
intent-to-treat analysis set and the per-protocol analysis set.  
Major secondary endpoints of this study in Study Part 2 are: 
• Time to improvement from baseline (week 0) in PASI (PASI 75/90/100 response and 
absolute PASI score = 0) for subjects with short (≤ 2 years) and longer (>2 years) disease 
duration (group 2c only) 
• Proportion of subjects who achieve an absolute PASI score of 0, ≤1 and <3 at week 68. 
5.4.1. 
Definition of Endpoint(s) 
5.4.1.1. 
Psoriasis Area and Severity Index (PASI) 
The Psoriasis Area and Severity Index (PASI) is an instrument 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 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 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 a PASI score of 0 will be considered PASI 100 responders. 
Time to improvement in PASI (group 2c only) 
The time to improvement in PASI is defined as time from baseline (week 0) to first onset of 
response. In the absence of documented improvement, the time to improvement will be censored 
at the date of week 68 or the date of discontinuation in case of early treatment discontinuation. 
The time to improvement in PASI will be computed as: 
• 
Date of improvement - Date of Study Day 1, if the subject shows improvement, 
• 
Date of week 68 or date of discontinuation - Date of Study Day 1, if the subject shows no 
improvement. 
5.4.2. 
Estimand(s) 
NA 


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5.4.3. 
Analysis Methods 
Time-to-event endpoints will be analyzed using the Kaplan-Meier product limit method and Cox 
proportional hazards model. Summary tables will provide counts and percentages, the median 
time-to-event with 90% confidence intervals (CI), and the hazard ratio (including 90% CI and the 
p-value calculated from Cox-regression with the factors 'treatment group' and 'disease duration'). 
The survival curves will also be displayed graphically. Time-to-event analyses of binary endpoints 
will be performed on the observed cases only after the rule for handling of protocol-prohibited 
medication/therapy is applied. (ie, missing data will not be replaced for time-to-event analyses). 
The proportion of subjects responding to treatment will be displayed in frequency tables providing 
the number and percentage of subjects per treatment group along with odds ratio (OR), relative 
risk (RR) and risk difference (RD), and two-sided Wald-type 90% confidence intervals (90% CIs) 
stratified by 'disease duration'. For single proportions within each treatment group unstratified two-
sided 90% CIs according to Clopper-Pearson will be calculated. Graphical presentation will be 
presented by means of bar charts. The two-group large-sample normal approximation Wald Z-test 
with Mantel-Haenszel stratum weights for 'disease duration' will be used to compare the proportion 
of subjects responding to treatment. The Mantel-Haenszel estimate, the two-sided Wald-type 90% 
confidence limits, and the test for the difference of proportions will be computed by using Mantel-
Haenszel stratum weights (Mantel & Haenszel, 1959) and the Sato variance estimator (Sato 1989). 
Details on handling of missing data are described in section 5.1.8. Subgroup analyses will be 
performed unstratified for the subgroups as specified in section 5.8.8. 
5.5. 
Other Secondary Endpoint(s) 
Statistical analyses will be descriptive and exploratory only, and will be performed both for the 
intent-to-treat analysis set and the per-protocol analysis set. Details on handling of missing data 
are described in section 5.1.8. 
Other secondary endpoints of this study in Study Part 2 are: 
• 
Proportion of subjects who achieve a PASI 75/90/100 response at week 68 
• 
The change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at 
week  68 
• 
Proportion of subjects who achieve a DLQI score 0/1 and <5 at week 68 
• 
The change from baseline (week 0) in affected Body Surface Area (BSA) at weeks 52, and 68 
• 
The change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic Arthritis 
(NAPPA) score at week  68 among subjects with nail psoriasis at baseline (week 0). 
• 
The change from baseline (week 0) in the signs and symptoms aggregate scores of the 
Psoriasis Symptoms and Signs Diary (PSSD) at week  68 
• 
The proportion of subjects who achieve a PSSD sign score = 0 at week 68 among subjects 
with a PSSD sign score ≥1 at week 28 


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5.5.1. 
Definition of Endpoint(s) 
5.5.1.1. 
Psoriasis Area and Severity Index (PASI) 
Refer to section 5.4.1.1. 
5.5.1.2. 
Dermatology Life Quality Index (DLQI) 
The Dermatology Life Quality Index (DLQI) is a dermatology-specific quality of life instrument 
designed to assess the impact of the disease on a subject’s quality of life. It is a 10-item 
questionnaire that, in addition to evaluating overall quality of life, can be used to assess 6 different 
aspects that may affect quality of life: 1) symptoms and feelings, 2) daily activities, 3) leisure, 4) 
work or school performance, 5) personal relationships, and 6) treatment. 
The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and 
a minimum of 0. A higher score indicates more severe disease. A score of ≤1 indicates no effect 
at all of disease on subject’s health related quality of life. 
For a partially answered questionnaire (eg, not all 10 answers in the DLQI questionnaire were 
available) the following rules will be applied: 
1. If one question is left unanswered this will be scored 0 and the scores will be summed and 
expressed as usual out of a maximum of 30. 
2. If two or more questions are left unanswered the questionnaire will not be scored. 
3. If question 7 is answered 'yes' this will be scored 3. If question 7 is answered 'no' or 'not 
relevant' but then either 'a lot' or 'a little' is ticked this will be scored 2 or 1. If it is answered 
'no', but the second half is left incomplete, the score will remain 0. 
Note: The answer "Not relevant" will be scored 0, as intended by the score developers. 
5.5.1.3. 
Body Surface Area (BSA%) 
One physical measure to define disease severity is to determine how much of the Body Surface 
Area (BSA) is affected by psoriasis. Involved BSA is calculated by using the palm of the subject’s 
hand as equivalent to 1% of the BSA (rule of palm). 
5.5.1.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
The NAPPA is an instrument for assessing clinical and patient-reported outcomes in nail psoriasis 
(Augustin, et al. 2014). It comprises three components:  
1. NAPPA-QOL is a 20-item nail-specific quality of life (QoL) questionnaire covering the 
past week. Signs, stigma and everyday life are rated on a scale from 0 (no suffering) to 4 
(high suffering). The NAPPA-QOL global score is computed by averaging all items. In 
case more than 25% of the items are missing (6 or more items missing), the score is not 
computed for the respective patient. 
2. NAPPA-PBI is a 24-item questionnaire to assess patient-defined needs before and patient-
rated benefits after treatment. The answers are given on a scale from 0 to 4. The weighted 
NAPPA-PBI global score is computed as follows: For score calculation, both "does not 
apply" and "question unanswered" will be treated as missing values. The global score will 
be calculated using all items pairs (importance + benefit) for which the patient has given a 


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response other than "does not apply". Each benefit item is multiplied with the respective 
importance item, and the product is divided by the sum of all importance items. The results 
are summed up over all items. The resulting global score ranges from 0 (no benefit) to 4 
(highest possible benefit). Only if more than 25% of items pairs are unanswered (=7 or 
more item pairs with missing values), no global score will be calculated. 
3. NAPPA-CLIN has been developed from the Nail Psoriasis Severity Index (NAPSI) score, 
a nail psoriasis-specific score, which in its original version comprises the assessment of 
matrix and nail bed involvement in every finger and toe by 8 criteria for each nail. The 
NAPPA-CLIN is a simplified version of the NAPSI which only assesses the least and the 
worst involved nail of both hands, or both feet, respectively. Score (matrix or bed for hands 
or feed)) is 0 if the findings are not present, 1 if they are present in 1 quadrant of the nail, 
2 if present in 2 quadrants of a nail, 3 if present in 3 quadrants of a nail, and 4 if present in 
4 quadrants of a nail:  
- thus, each nail has a matrix score (0-4) and a nail bed score (0-4), and the total nail 
score is the sum of those 2 individual scores (0-8) for hands or feet; 
- sum of the total score of all involved nails is the total NAPPA-CLIN score for that 
patient at that time for hands or feet. 
- thus, the NAPPA-CLIN scores for hands or feet range from 0 to 16 empirically. 
- if a matrix score or a nail bed score is missing, the NAPPA-CLIN score is also missing.  
5.5.1.5. 
Psoriasis Symptom and Sign Diary (PSSD) 
The Psoriasis Symptom and Sign Diary (PSSD) is a patient-reported outcome (PRO) questionnaire 
designed to measure the severity of psoriasis symptoms and signs for the assessment of treatment 
benefit. The PSSD includes 11 items covering symptoms (itch, pain, stinging, burning and skin 
tightness) and subject observable signs (skin dryness, cracking, scaling, shedding or flaking, 
redness and bleeding) using 0 (=absent) to 10 (=worst imaginable) numerical rating scales for 
severity. Two subscores will be derived: the psoriasis symptom score and the psoriasis sign score. 
A higher score indicates more severe disease. Additionally, the single items itch, pain, and scaling 
and also the other single items will be evaluated. The subjects will complete the 7-day recall 
version of the PSSD as indicated in the TES.  
The calculations of PSSD symptom, and sign scores are listed below. 
Symptom Score (0-100) 
a) Symptom score includes itch (Q1), pain (Q11), stinging (Q10), burning (Q9) and skin 
tightness (Q4). 
b) Averaging items on the symptom scores when at least 3 items (≥50% of 5 items) on this 
scale are answered. Then, the average value is converted into 0-100 scoring such that 
Symptom score = average value x 10 with 0 representing the least severe and 100 the most 
severe. Otherwise the symptom score will be set to missing. 
Sign Score (0-100) 
a) Sign score includes skin dryness (Q2), cracking (Q3), scaling (Q5), shedding or flaking 


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(Q6), redness (Q7) and bleeding (Q8). 
b) Averaging items on the sign scores when at least 3 items (≥50% of 6 items) on this scale 
are answered. Then, the average value is converted into 0-100 scoring such that Sign score 
= average value x 10 with 0 representing the least severe and 100 the most severe. 
Otherwise the sign score will be set to missing. 
5.5.2. 
Estimand(s) 
 NA 
5.5.3. 
Analysis Methods 
5.5.3.1. 
Psoriasis Area and Severity Index (PASI) 
• Proportion of subjects who achieve a PASI 75/90/100 response at week 68 
The proportion of subjects responding to treatment will be displayed in frequency tables providing 
the number and percentage of subjects per treatment group along with odds ratio (OR), relative 
risk (RR) and risk difference (RD), and two-sided Wald-type 90% confidence intervals (90% CIs) 
stratified by 'disease duration'. For single proportions within each treatment group unstratified two-
sided 90% CIs according to Clopper-Pearson will be calculated. Graphical presentation will be 
presented by means of bar charts. 
The two-group large-sample normal approximation Wald Z-test with Mantel-Haenszel stratum 
weights for 'disease duration' will be used to compare the proportion of subjects responding to 
treatment. The Mantel-Haenszel estimate, the two-sided Wald-type 90% confidence limits, and 
the test for the difference of proportions will be computed by using Mantel-Haenszel stratum 
weights (Mantel & Haenszel, 1959) and the Sato variance estimator (Sato 1989). 
5.5.3.2. 
Dermatology Life Quality Index (DLQI) 
• The change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at 
week  68 
• Proportion of subjects who achieve a DLQI score 0/1 and <5 at week 68 
The change from baseline in DLQI will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the week 28 and week 68 values and the respective 
changes from baseline value will be displayed. 
A univariate analysis of covariance (ANCOVA) model will be used to test the difference in change 
from baseline between treatment groups; the change from baseline being the dependent variable, 
treatment, disease duration, and baseline value of endpoint as independent variables. A 90% 
confidence interval for the difference in Least Squares (LS)means and p-value will be calculated 
based on contrast test statistics. The LS means, the LS mean difference and the standardized mean 
difference (computed according to Hedges' g) with the 90% CI and two-sided p-value will be 
provided from the ANCOVA model. 
In addition, a multivariate linear mixed model for repeated measures (MMRM) will be used to test 
the difference in change from baseline between treatment groups; the repeated measures of change 
from baseline at week s 28, 52,  and 68 being the dependent variables, treatment, disease duration, 


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and baseline value of endpoint as independent variables. Inferential results will be provided 
likewise as for the univariate model.  
The proportion of subjects responding to treatment will be displayed in a frequency table providing 
the number and percentage of subjects per treatment group along with odds ratio (OR), relative 
risk (RR) and risk difference (RD), and two-sided Wald-type 90% confidence intervals (90% CIs) 
stratified by 'disease duration'. For single proportions within each treatment group unstratified two-
sided 90% CIs according to Clopper-Pearson will be calculated. Graphical presentation will be 
presented by means of bar charts. 
The two-group large-sample normal approximation Wald Z-test with Mantel-Haenszel stratum 
weights for 'disease duration' will be used to compare the proportion of subjects responding to 
treatment. The Mantel-Haenszel estimate, the two-sided Wald-type 90% confidence limits, and 
the test for the difference of proportions will be computed by using Mantel-Haenszel stratum 
weights (Mantel & Haenszel, 1959) and the Sato variance estimator (Sato 1989). 
5.5.3.3. 
Body Surface Area (BSA%) 
• The change from baseline (week 0) in affected Body Surface Area (BSA) at week 68 
The change from baseline in BSA will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the weeks 12, 28, and 68 values and the respective 
changes from baseline value will be displayed. 
A univariate analysis of covariance (ANCOVA) model will be used to test the difference in change 
from baseline between treatment groups; the change from baseline being the dependent variable, 
treatment, disease duration, and baseline value of endpoint as independent variables. A 90% 
confidence interval for the difference in Least Squares (LS)means and p-value will be calculated 
based on contrast test statistics. The LS means, the LS mean difference and the standardized mean 
difference (computed according to Hedges' g) with the 90% CI and two-sided p-value will be 
provided from the ANCOVA model. 
In addition, a multivariate linear mixed model for repeated measures (MMRM) will be used to test 
the difference in change from baseline between treatment groups; the repeated measures of change 
from baseline at week s 28, 52,  and 68 being the dependent variables, treatment, disease duration, 
and baseline value of endpoint as independent variables. Inferential results will be provided 
likewise as for the univariate model. 
5.5.3.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
• The change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic 
Arthritis (NAPPA) scores at week  68 among subjects with nail psoriasis at baseline (week 
0) 
The change from baseline in the global scores of NAPPA-QOL, NAPPA-PBI, and NAPPA-CLIN 
will be summarized by descriptive statistics using appropriate tabulation and box plots. The 
baseline value, the week 28 and 68 values and the respective changes from the baseline value will 
be displayed. According to the definition of the global score of NAPPA-PBI the week 28 and 68 
value are already the change from baseline value. 


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No inferential statistical analyses will be performed for global scores of NAPPA-QOL, NAPPA-
PBI, and NAPPA-CLIN. 
5.5.3.5. 
Psoriasis Symptom and Sign Diary (PSSD) 
• The change from baseline (week 0) in the signs and symptoms aggregate scores of the 
Psoriasis Symptoms and Signs Diary (PSSD) at week 68 
• 
Proportion of subjects who achieve a PSSD sign score=0 at week 68 among subjects with 
a PSSD sign score ≥1 at week 28 per study group 
The change from baseline will be summarized by descriptive statistics using appropriate tabulation 
and box plots. The baseline value, the week 28 and 68 values and the respective changes from the 
baseline value will be displayed. 
A univariate analysis of covariance (ANCOVA) model will be used to test the difference in change 
from baseline between treatment groups; the change from baseline being the dependent variable, 
treatment, disease duration, and baseline value of endpoint as independent variables. A 90% 
confidence interval for the difference in Least Squares (LS)means and p-value will be calculated 
based on contrast test statistics. The LS means, the LS mean difference and the standardized mean 
difference (computed according to Hedges' g) with the 90% CI and two-sided p-value will be 
provided from the ANCOVA model. 
In addition, a multivariate linear mixed model for repeated measures (MMRM) will be used to test 
the difference in change from baseline between treatment groups; the repeated measures of change 
from baseline at week s 28, 52,  and 68 being the dependent variables, treatment, disease duration, 
and baseline value of endpoint as independent variables. Inferential results will be provided 
likewise as for the univariate model. 
The proportion of subjects responding to treatment will be displayed in a frequency table providing 
the number and percentage of subjects per treatment group along with odds ratio (OR), relative 
risk (RR) and risk difference (RD), and two-sided Wald-type 90% confidence intervals (90% CIs) 
stratified by 'disease duration'. For single proportions within each treatment group unstratified two-
sided 90% CIs according to Clopper-Pearson will be calculated. Graphical presentation will be 
presented by means of bar charts. 
The two-group large-sample normal approximation Wald Z-test with Mantel-Haenszel stratum 
weights for 'disease duration' will be used to compare the proportion of subjects responding to 
treatment. The Mantel-Haenszel estimate, the two-sided Wald-type 90% confidence limits, and 
the test for the difference of proportions will be computed by using Mantel-Haenszel stratum 
weights (Mantel & Haenszel, 1959) and the Sato variance estimator (Sato 1989). 
5.6. 
Additional Analyses 
In addition to the efficacy analyses of the study endpoints described above, continuous and binary 
endpoints related to PASI, DLQI, PSSD, affected BSA, NAPPA, and PSSD at all scheduled study 
visits during the active treatment periods in Study Parts 1 and 2 (Week 0 until Week 68) will be 
summarized descriptively (observed cases analysis for continuous endpoints; observed cases 


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analysis and non-responder imputation (after the rule for handling of protocol-prohibited 
medication/therapy is applied) for binary endpoints ). 
5.7. 
Safety Analyses 
All safety analyses in Study Part 2 will be based on the safety analysis set based on actual treatment 
received. Data from the safety follow-up will not be included in Study Part 2 analysis; last visit to 
be included for Study Part 2 analysis is week 68 or early termination visit in case of discontinuation 
in Study Part 2. Safety data, including but not limited to, AEs, SAEs, infections, serious infections, 
changes in laboratory assessments, and changes in vital signs will be summarized by treatment 
group and overall. Treatment-emergent AEs (TEAEs) will be summarized by treatment group and 
Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) and preferred 
terms (PT). 
For all continuous safety variables, descriptive statistics will include the N, mean, standard 
deviation, median, IQ range, minimum, and maximum. Categorical variables will be summarized 
using frequency counts and percentages. 
5.7.1. 
Extent of Exposure 
The number and percentage of subjects who receive study agent will be summarized. Descriptive 
statistics will be presented for number of study agent administrations. 
5.7.2. 
Adverse Events 
The verbatim terms used in the eCRF by investigators to identify adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring at or after 
the day of week 28 until the day of week 68 visit (or early termination visit, if applicable.) in Study 
Part 2 is considered to be treatment emergent. If the event occurs on the day of week 28, 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 in Study Part 2 based on partial onset date or resolution date. All reported treatment-
emergent adverse events will be included in the analysis.  For each treatment adverse event, the 
number and percentage of subjects who experience at least 1 occurrence of the given event will be 
summarized by treatment group. Summary tabulation will also provide the number of events, if 
applicable. 
Summary tables will be provided for: 
• 
AEs 
• 
Serious AEs (SAEs) 
• 
AEs leading to discontinuation of study agent 
• 
AEs by severity 
• 
AEs by relationship to study agent 
• 
Infections 


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• 
Serious Infections 
• 
Injection site reactions 
In addition to the summary tables, listings will be provided for subjects who: 
• 
Had (S)AEs 
• 
Had AEs leading to discontinuation of study agent 
Deaths will be displayed by actual treatment received. Frequencies for the following parameters 
will be included in the summary table: 
• 
Number of subjects who died 
• 
Cause of death 
• 
Relationship to study agent (yes/no) (yes includes the following eCRF items: possible, 
probable, very likely) 
A listing of subjects who died will be provided. 
5.7.3. 
Additional Safety Assessments 
5.7.3.1. 
Clinical Laboratory Tests 
All clinical laboratory tests will be displayed for the subjects included in the safety analysis set. 
Descriptive statistics will be presented for all chemistry and hematology laboratory tests at 
scheduled time points (weeks 0, 12, 20, 28, 36, 52, and 68) in Study Parts 1 and 2. 
Change from baseline (week 0) to postbaseline time points (weeks 12, 20, 28, 36, 52, and 68) in 
Study Parts 1 and 2 will be summarized for chemistry and hematology tests. 
Number and percentage of subjects with postbaseline clinically important laboratory values and/or 
markedly abnormal postbaseline values will be presented over time. 
The clinically important laboratory findings to be reported are described below: 
• 
[AST (U/L): 2x ULN] 
• 
[ALT (U/L): 2x ULN] 
• 
[Alkaline phosphatase (U/L): 2x ULN] 
Markedly abnormal laboratory findings to be reported are described below: 
• 
[AST (U/L): 3x ULN] 
• 
[ALT (U/L): 5x ULN] 
 A listing of clinically important laboratory values will be provided. 


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Shift tables will be provided summarizing the shift in laboratory values from baseline to post-
baseline time points (weeks 36, 52, and 68) in Study Part 2 with respect to abnormality criteria 
(low, normal, high). 
Lab values given as borderline value only (eg <8 or >200) will be evaluated by ignoring the sign.  
5.7.3.2. 
Vital Signs and Physical Examination Findings 
Continuous vital sign parameters including weight, pulse, blood pressure (systolic and diastolic), 
will be summarized at each assessment time point (weeks 0, 4, 12, 16, 20, 28, 36, 44, 52, 60, and 
68). Change from baseline (week 0) will be summarized for the randomized treatment period from 
week 28 until week 68. Descriptive statistics (mean, standard deviation, median, IQ range, 
minimum and maximum) will be presented. A listing of subjects with treatment-emergent 
clinically important vital signs will be presented, along with a listing of all vital sign 
measurements. 
Incidence of treatment-emergent clinically important vital signs while on treatment, as defined in 
Table 3, will be summarized for subjects who had a baseline assessment and at least 1 postbaseline 
assessment for that vital sign. 
Table 3: [Clinically Important/Markedly Abnormal] Vital Signs 
Vital Sign 
Criteria 
Pulse 
>120 bpm and with >30 bpm increase from baseline 
 
<50 bpm and with >20 bpm decrease from baseline 
Systolic blood pressure 
>180 mm Hg and with >40 mm Hg increase from baseline 
 
<90 mm Hg and with >30 mm Hg decrease from baseline 
Diastolic blood pressure 
>105 mm Hg and with >30 mm Hg increase from baseline 
 
<50 mm Hg and with >20 mm Hg decrease from baseline 
Abnormal findings in physical examination (additional to psoriasis findings) at baseline visit 
(week 0), week 28, 60, and week 68 will be tabulated by the body systems given in the eCRF. 
Details on abnormal findings in verbatim terms will be displayed in individual data listings. 
5.7.3.3. 
Electrocardiogram 
Not applicable for Study Part 2 analysis. 
5.7.3.4. 
Other Safety Parameters 
Tuberculosis Evaluation 
Categorical data on tuberculosis evaluation at each scheduled visit from week 28 until week 68 
will be displayed in a frequency table providing the number and percentage of subjects per 
category. 
 
 


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Urine Pregnancy Test 
Categorical data on urine pregnancy tests at each scheduled visit from week 28 until week 68 will 
be displayed in a frequency table providing the number and percentage of subjects per category. 
5.8. 
Other Analyses 
5.8.1. 
Pharmacokinetics 
The PK analysis is out of scope for this SAP. 
5.8.2. 
Immunogenicity 
Not applicable for Study Part 2 analysis. 
5.8.3. 
Pharmacodynamics 
Not applicable for Study Part 2 analysis. 
5.8.4. 
Pharmacokinetic/Pharmacodynamic Relationships 
Not applicable for Study Part 2 analysis. 
5.8.5. 
Biomarkers 
Not applicable for Study Part 2 analysis. 
5.8.6. 
Health Economics 
Not applicable for Study Part 2 analysis. 
5.8.7. 
Other Variables and/or Parameters 
Not applicable for Study Part 2 analysis. 
 


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5.8.8. 
Definition of Subgroups 
Subgroup analyses are planned to be performed for the primary endpoint and for the major 
secondary endpoints for the following subgroups in study groups 2a, 2b, and 2c. All subgroup 
analysis will be performed unstratified, ie, without use of 'disease duration' as stratification factor 
in the exploratory inferential statistical analysis. 
• Disease duration 
o ≤ 2 years 
o > 2 years 
• Age at baseline in years 
o < 45 
o ≥ 45 to 65 
o > 65 
• BMI 
o normal ≤ 25  
o overweight > 25 – 30  
o obese > 30 
• Weight in kg 
o  ≤ 90 
o  > 90 
• Disease duration in years 
o > 2 to 10 
o > 10 
• PSO-pretreatment (for hierarchical categorization see section 6.5): 
o Topical therapy  
o Phototherapy 
o Non-biologic systemic therapy 
o Biologic therapy 
• PSO-pretreatment with biologics: 
o 0 biologics 
o 1 biologic 
o 2 or more biologics 
 
 


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Subgroup analyses for the primary endpoint and for the major secondary endpoints will be 
performed on either ITT or PP analysis set (not for both sets) after the rule for handling of protocol-
prohibited medication/therapy is applied using non-responder imputation for binary endpoints and 
observed cases analyses for time-to-event endpoints. The decision which analysis set should be 
used for the subgroup analyses will be taken at the Data Review Meeting for Study Part 2. 
Note: At the Data Review Meeting and/or Dry Run Meeting for Study Part 2 it will be decided 
which subgroup analyses will actually be performed for Study Part 2. 
5.9. 
Interim Analyses 
Statistical analyses will be performed separately for each of the three Study Parts. No formal 
confirmatory interim analysis is planned for this study.  
A data monitoring committee has NOT been employed for review of efficacy and/or safety data. 
5.9.1. 
Data Monitoring Committee (DMC) or Other Review Board 
A data monitoring committee has NOT been employed for review of efficacy and/or safety data. 
 
 
 


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6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1 List of Abbreviations 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
ATC 
Anatomic therapeutic Class 
BMI 
Body mass index 
bpm 
beats per minute 
BSA 
Body surface area 
CI 
Confidence interval 
CLIN  
Clinical  
CSP 
Clinical Study Protocol 
DLQI 
Dermatology Life Quality Index 
DMC 
Data Monitoring Committee 
eCRF 
electronic Case Report Form 
eg  
example given 
EP 
Endpoint 
FAE 
Fumaric acid ester 
FOIA 
Freedom of Information Act 
FCS 
Fully Conditional Specification 
GCP 
Good Clinical Practice  
ICH 
International Council for Harmonization 
ie  
that is  
IQ 
Interquartile range 
ITT 
Intent-to-treat 
IWRS 
Interactive web response system 
LOCF 
Last observation carried forward 
LS 
Least squares 
MAR 
Missing at random 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mmHg 
Millimeter of mercury 
MMRM 
Multivariate linear mixed model for repeated measures 
MTX 
Methotrexate  
NAPPA 
Nail Assessment in Psoriasis and Psoriatic Arthritis 
NAPSI 
Nail Psoriasis Severity Index 
OR 
Odds ratio 
PASI 
Psoriasis Area and Severity Index 
PBI  
Patient Benefit Index  
PK 
Pharmacokinetic(s) 
PP 
Per protocol 
PROs 
Patient reported outcomes 
PSO 
Psoriasis 
PSSD 
Psoriasis Symptoms and Signs Diary 
PT 
Preferred terms 
PUVA 
Psoralene plus ultraviolet A radiation 
q8w/q16w  
every 8/16 weeks  
QoL 
Quality of life 
RD 
Risk difference 
RR 
Relative risk 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SD 
Standard deviation 
SDTM 
Standard Data Tabulation Model 
SOC 
System organ class 


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SRe 
Super-Responder 
TEAE 
Treatment-emergent adverse event 
TES 
Time and Events Schedule  
ULN  
Upper limit normal  
UVB 
Ultra violet B radiation 
vs. 
versus 
WHO-DD 
World Health Organization Drug Dictionary 
6.2. 
Appendix 2 Changes to Protocol-Planned Analyses 
No important changes from the planned analyses specified in the protocol were performed.  
 
 


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6.3. 
Appendix 3 Demographics and Baseline Characteristics 
Subjects' demographic data (eg, age, weight, BMI, height, sex, child bearing potential, and race) 
and baseline disease characteristics (eg, age at diagnosis, BSA [%], baseline DLQI, PSSD, 
NAPPA-CIN (if applicable), PASI score, psoriasis arthritis, and nail assessment) will be 
summarized. In addition, summaries of subjects' medical history and current diagnoses will be 
provided (see section 6.6).  
Table 2 presents a list of the demographic variables that will be summarized.   
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)  
 
BMI  
Height (cm) 
Categorical Variables 
 
Age ([< 45, >= 45 to 65, > 65 years)]) 
Frequency distribution with the 
number and percentage of subjects 
in each category. 
Sex (male, female) 
Child bearing potential (of child bearing potential, permanently sterilized, 
postmenopausal)  
BMI (normal ≤ 25, overweight > 25 – 30, Obese > 30) 
Racea (White, Asian, Black, Multiple, Other, Unknown) 
aIf multiple race categories are indicated, the Race is recorded as 'Multiple' 
 
 
 
 
 


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6.4. 
Appendix 4 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 study. Subjects 
with major protocol deviations will be identified prior to database lock and the subjects with major 
protocol deviations will be summarized by category. 
• 
Developed withdrawal criteria but not withdrawn 
• 
Entered but did not satisfy criteria 
• 
Received a disallowed concomitant treatment 
• 
Received wrong treatment or incorrect dose 
• 
Other: to be defined in the major protocol deviation criteria document 
The study selection criteria will also be grouped into the following 5 categories: psoriasis disease 
criteria, medication criteria, laboratory criteria, medical history criteria, and other and will be 
summarized. 
 
 
 


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6.5. 
Appendix 5 Prior and Concomitant Medications 
Subjects’ prior psoriasis therapy history with topical therapy, phototherapy (PUVA, UVB), non-
biologic systemic therapies (MTX, Cyclosporine, FAE, Acitretin, Apremilast, Tofacitinib, oral 
steroids, and other, if applicable), and biologic medications (Infliximab, Etanercept, Adalimumab, 
Efalizumab, Ustekinumab, Secukinumab, Ixekizumab, Brodalumab, Certolizumab, and other, if 
applicable) will be summarized. The allocation of medications to the four categories of therapy 
will be approved at the Data Review Meeting and/or Dry Run Meeting. 
Subjects' last psoriasis therapy prior to participation in this study will be analyzed analogously. In 
addition, reasons for which subjects discontinued previous systemic therapies including PUVA, 
Methotrexate, FAE, Cyclosporine, Adalimumab, Ustekinumab, Secukinumab, Ixekinumab, 
Certolizumab (contraindication, inadequate response, intolerance [ie, AEs], or other) will be 
summarized. 
For analysis of psoriasis therapies by therapy regimen as described above, the patients will be 
counted in only one therapy regimen according to the following hierarchical derivation procedure. 
 
Therapy regimen 
Derivation 
Topical therapy 
All patients receiving at least one prior psoriasis medication of the 
type 'Topical' as defined above who did not receive a medication of 
another type. 
Phototherapy 
All patients receiving at least one prior psoriasis medication of the 
type 'Phototherapy' as defined above who did not receive a 
medication of another type except 'Topical' 
Non-biologic 
systemic 
therapy 
All patients receiving at least one prior psoriasis medication of the 
subtype 'Non-biologic systemic' as defined above who did not 
receive a medication of another type except 'Topical' or 
'Phototherapy'. 
Biologic therapy 
All patients receiving at least one prior psoriasis medication of the 
subtype 'Biologics' as defined above who did not receive a 
medication of another type except 'Topical' (type), 'Phototherapy' 
(type), or 'Non-biologic systemic' (subtype). 
 
In addition, the number of subjects who received concomitant treatment with a moisturizer for 
psoriasis will be summarized. 
Prior and concomitant non-psoriasis therapies will be summarized descriptively.  
Prior and Concomitant therapies (psoriasis and non-psoriasis) will be coded using the World 
Health Organization Drug Dictionary (WHO-DD). Prior therapies are defined as any therapy used 
before the day of first dose (partial or complete) of study agent at week 0. Concomitant therapies 
are defined as any therapy used on or after the same day as the first dose of study agent, including 


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those that started before and continue on after the first dose of study agent. In the statistical analysis 
only therapies will be counted as ‘concomitant' for Study Part 2 analysis, which started before or 
at the date of week 68 (start of Study Part 3). 
Summaries of concomitant therapies will be presented by Anatomic Therapeutic Class (ATC) level 
2 term and Preferred Name. The proportion of subjects who receive each concomitant therapy will 
be summarized as well as the proportion of subjects who receive at least 1 concomitant therapy. 
Prior therapies (incl. psoriasis therapies) will be summarized by ATC level 2 term and Preferred 
Name. 
The frequency table of subjects’ prior psoriasis therapy history will be repeated by displaying 
preferred names by category used for hierarchization. 
 
6.6. 
Appendix 6 Medical History 
Categorical family history data will be summarized by means of a frequency table. The number 
and percentage of subjects with findings regarding the medical history terms of interest will be 
displayed in MedDRA system organ class (SOC) and preferred terms (PT). Summary tabulation 
will also consider whether the disease is ongoing or not at screening visit. 
6.7. 
Appendix 7 Intervention Compliance 
Study agent compliance will be summarized descriptively. Study agent compliance will be 
calculated as follows: 
Study agent compliance (%) = 100 x number of actual administrations / number of planned 
administrations) 
Study agent compliance will also be assessed by protocol deviations related to study drug 
administration (ie, incorrect and missed administrations). 
6.8. 
Appendix 8 Adverse Events of Special Interest 
Not applicable for Study Part 2 analysis. 
 
6.9. 
Appendix 9 Medications of Special Interest 
Not applicable for Study Part 2 analysis. 
6.10. 
Appendix 10 Laboratory Toxicity Grading 
Not applicable for Study Part 2 analysis. 
 
 


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7. 
REFERENCES 
Protocol CNTO1959PSO3012; Phase 3b,  AMENDMENT 5, Janssen-Cilag GmbH,  Approved 14 
June 2021 
Mantel, N, & W Haenszel. 1959. „Statistical Aspects of Analysis of Data from Retrospective 
Studies of Disease.“ J Natl Cancer Inst, 719-748. 
Sato, T. 1989. „On the Variance Estimator of the Mantel-Haenszel Risk Difference.“ Biometrics, 
1323-1324. 
Yan, X, & XG Su. 2010. „Stratified Wilson and Newcombe Confidence Intervals for Multiple 
Binomial Proportions.“ Statistics in Biopharmaceutical Research, 329-335. 
 


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Janssen Cilag GmbH 
Statistical Analysis Plan – Study Part 3 
A Phase 3b, Randomized, Double-blind, Parallel Group, Multicenter Study to Evaluate 
Further Therapeutic Strategies with Guselkumab in Patients with Moderate-to-Severe 
Plaque-Type Psoriasis 
GUIDE 
Protocol CNTO1959PSO3012; Phase 3b 
 TREMFYA® (guselkumab)  
Status: 
Final 
Date: 
14 Feb 2023 
Prepared by: 
Janssen-Cilag GmbH, Germany 
Document No.: EDMS-EDMS-RIM-852786 
Compliance:  The study described in this report was performed according to the principles of Good Clinical Practice (GCP). 
Confidentiality Statement 
The information provided herein contains Company trade secrets, commercial or financial information that the Company 
customarily holds close and treats as confidential.  The information is being provided under the assurance that the recipient 
will maintain the confidentiality of the information under applicable statutes, regulations, rules, protective orders or 
otherwise. 
NCT03818035


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TABLE OF CONTENTS 
TABLE OF CONTENTS ............................................................................................................................... 2 
VERSION HISTORY ..................................................................................................................................... 4 
1. 
INTRODUCTION.................................................................................................................................. 5 
1.1. 
Objectives and Endpoints ................................................................................................................ 6 
1.1.1. 
Objectives ..................................................................................................................................... 6 
1.1.2. 
Endpoints ...................................................................................................................................... 7 
1.2. 
Study Design .................................................................................................................................... 8 
2. 
STATISTICAL HYPOTHESES .......................................................................................................... 11 
3. 
SAMPLE SIZE DETERMINATION .................................................................................................... 11 
4. 
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS OF STUDY PART 3 .................................... 12 
4.1. 
All Enrolled Analysis Set ................................................................................................................ 12 
4.2. 
Efficacy Analysis Set(s).................................................................................................................. 12 
4.2.1. 
Intent-to-Treat Analysis Set (ITT) ............................................................................................... 12 
4.2.2. 
Per-protocol Analysis Set (PP) ................................................................................................... 12 
4.2.3. 
Nail Psoriasis Analysis Set ......................................................................................................... 12 
4.2.4. 
Safety Analysis Set ..................................................................................................................... 13 
4.2.5. 
Pharmacokinetics Analysis Set .................................................................................................. 13 
5. 
STATISTICAL ANALYSES FOR STUDY PART 3 ........................................................................... 13 
5.1. 
General Considerations ................................................................................................................. 13 
5.1.1. 
Visit Windows ............................................................................................................................. 14 
5.1.2. 
Pooling Algorithm for Analysis Centers ...................................................................................... 15 
5.1.3. 
Study Day and Relative Day ....................................................................................................... 15 
5.1.4. 
Baseline and Endpoint ................................................................................................................ 15 
5.1.5. 
Imputation Rules for Missing AE Date/Time of Onset/Resolution .............................................. 15 
5.1.6. 
Treatment Failure Criteria ........................................................................................................... 16 
5.1.7. 
Treatment Failure Rules ............................................................................................................. 16 
5.1.8. 
Missing Data Imputation ............................................................................................................. 16 
5.2. 
Participant Dispositions .................................................................................................................. 17 
5.3. 
Primary Endpoint(s) Analysis ......................................................................................................... 17 
5.3.1. 
Definition of Endpoint(s) ............................................................................................................. 17 
5.3.2. 
Estimand ..................................................................................................................................... 17 
5.3.3. 
Analysis Methods ........................................................................................................................ 17 
5.4. 
Major Secondary Endpoint(s) Analysis .......................................................................................... 17 
5.4.1. 
Definition of Endpoint(s) ............................................................................................................. 18 
5.4.1.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 18 
5.4.2. 
Estimand(s) ................................................................................................................................. 18 
5.4.3. 
Analysis Methods ........................................................................................................................ 18 
5.5. 
Other Secondary Endpoint(s) ........................................................................................................ 19 
5.5.1. 
Definition of Endpoint(s) ............................................................................................................. 19 
5.5.1.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 19 
5.5.1.2. 
Dermatology Life Quality Index (DLQI) ................................................................................... 20 
5.5.1.3. 
Body Surface Area (BSA%) ..................................................................................................... 20 
5.5.1.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) ............................................... 20 
5.5.1.5. 
Psoriasis Symptom and Sign Diary (PSSD) ............................................................................ 21 
5.5.2. 
Estimand(s) ................................................................................................................................. 22 
5.5.3. 
Analysis Methods ........................................................................................................................ 22 
5.5.3.1. 
Psoriasis Area and Severity Index (PASI) ............................................................................... 22 
5.5.3.2. 
Dermatology Life Quality Index (DLQI) ................................................................................... 22 


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5.5.3.3. 
Body Surface Area (BSA%) ..................................................................................................... 23 
5.5.3.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) ............................................... 24 
5.5.3.5. 
Psoriasis Symptom and Sign Diary (PSSD) ............................................................................ 24 
5.6. 
Additional Analyses ........................................................................................................................ 24 
5.7. 
Safety Analyses ............................................................................................................................. 26 
5.7.1. 
Extent of Exposure ..................................................................................................................... 26 
5.7.2. 
Adverse Events ........................................................................................................................... 27 
5.7.3. 
Additional Safety Assessments .................................................................................................. 27 
5.7.3.1. 
Clinical Laboratory Tests ......................................................................................................... 27 
5.7.3.2. 
Vital Signs and Physical Examination Findings....................................................................... 28 
5.7.3.3. 
Electrocardiogram ................................................................................................................... 28 
5.7.3.4. 
Other Safety Parameters ......................................................................................................... 28 
5.8. 
Other Analyses ............................................................................................................................... 28 
5.8.1. 
Pharmacokinetics ....................................................................................................................... 28 
5.8.2. 
Immunogenicity ........................................................................................................................... 29 
5.8.3. 
Pharmacodynamics .................................................................................................................... 29 
5.8.4. 
Pharmacokinetic/Pharmacodynamic Relationships ................................................................... 29 
5.8.5. 
Biomarkers .................................................................................................................................. 29 
5.8.6. 
Health Economics ....................................................................................................................... 29 
5.8.7. 
Other Variables and/or Parameters ............................................................................................ 29 
5.8.8. 
Definition of Subgroups .............................................................................................................. 29 
5.9. 
Interim Analyses ............................................................................................................................. 31 
5.9.1. 
Data Monitoring Committee (DMC) or Other Review Board ...................................................... 31 
6. 
SUPPORTING DOCUMENTATION .................................................................................................. 32 
6.1. 
Appendix 1  List of Abbreviations ................................................................................................... 32 
6.2. 
Appendix 2  Changes to Protocol-Planned Analyses .................................................................... 33 
6.3. 
Appendix 3  Demographics and Baseline Characteristics ............................................................. 33 
6.4. 
Appendix 4  Protocol Deviations .................................................................................................... 33 
6.5. 
Appendix 5  Prior and Concomitant Medications ........................................................................... 34 
6.6. 
Appendix 6  Medical History .......................................................................................................... 35 
6.7. 
Appendix 7  Intervention Compliance ............................................................................................ 35 
6.8. 
Appendix 8  Adverse Events of Special Interest ............................................................................ 35 
6.9. 
Appendix 9  Medications of Special Interest .................................................................................. 35 
6.10. 
Appendix 10  Laboratory Toxicity Grading ..................................................................................... 35 
7. 
REFERENCES................................................................................................................................... 36 
 
 
 
 


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VERSION HISTORY 
 
Table 1 – SAP Version History Summary 
SAP Version 
Approval Date 
Change 
Rationale 
1.0 
20 Oct 2022 
Not applicable 
Initial release 
2.0 
14 Feb 2023 
See text “Update after the Dry 
Run Meeting” in the respective 
SAP sections 
Release after Dry Run Meeting 
for the Week 116 analysis of 
Study Part 3 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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1. 
INTRODUCTION 
The statistical analysis plan (SAP) is a detailed technical extension to the Clinical Study Protocol 
(CSP) and follows the principles of the guideline ICH E9. 
Statistical analyses of Janssen-Cilag GmbH CSP CNTO1959PSO3012 are performed for each of 
the three Study Parts (of which Parts 1 and 2 are already completed: 
• The exploratory analysis of Study Part 1 (“Open-label treatment phase”) occurred after all 
subjects had completed their visit at week 28 (ie, 28 weeks after study inclusion) or 
discontinued earlier. This analysis included the safety analysis and all efficacy measures 
until the week 28 visit. 
• The confirmatory analysis of this study was performed at the end of Study Part 2 (“Double-
blind treatment phase”), ie, after all subjects had completed their visit at week 68 (ie, 
40 weeks after randomization) or discontinued earlier. This analysis included the 
confirmatory analysis of the primary endpoint, and the exploratory analyses of the major 
secondary endpoints and all other predefined efficacy and safety analyses from week 28 
until week 68). 
The analyses of Study Part 3 (“Drug withdrawal phase”) will be exploratory and will occur after 
all subjects have completed, if not gone into re-treatment before, their visit at week 116 (ie, 
48 weeks after inclusion in Study Part 3 at week 68), at week 164 (ie, 96 weeks after inclusion in 
Study Part 3 at week 68), and at week 220 (ie, 152 weeks after inclusion in Study Part 3 at week 
68). Only subjects who started Study Part 3 in study groups 3a or 3b will be included in the 
analyses. These analyses will include the safety evaluations and all efficacy measures after week 
68 and will cover the time until week 116/164/220, respectively. Thus, the statistical analysis for 
Study Part 3 will consist of two interim analyses and one final analysis. All three analyses are 
described in the current SAP. 
Final decisions about which subjects are to be included in the analyses of the Study Parts 1, 2, or 
3, are made during the Data Review or Dry Run Meetings. 
This current SAP describes the statistical analyses planned to be performed for Study Part 3 and 
should be read in conjunction with the CSP and the electronic Case Report Form (eCRF). 
Statistical analyses of study data recorded before week 68 have been specified in separate SAPs, 
if not otherwise specified. 
This plan is the core document for all statistical programming planned for the analyses of Study 
Part 3 of study protocol no. CNTO1959PSO3012. The statistical analyses will focus on the 
comparison of the two groups which were randomized for double-blind treatment in Study Part 2, 
ie, group 3a (guselkumab 100 mg q8w in Study Part 2 but no treatment in Study Part 3) vs. group 
3b (guselkumab 100 mg q16w in Study Part 2 but no treatment in Study Part 3). 
Note: Subjects losing control of disease, defined as PASI score >5 at any visit during Study Part 2 
(ie, until week 68) or Study Part 3 (ie, until weeks 116, 164, or 220), and subjects with fluctuating 
disease (PASI score 3 to 5) at week 68 will enter the re-treatment-arms (2d or 3c) with three 
guselkumab 100 mg administrations starting at that visit (= re-treatment week 0, followed by 
administration at re-treatment weeks 8 and 16). Statistical analyses of re-treatment study data will 
be specified in a separate SAP. Evaluating the endpoint related to the re-treatment phase in a 
separate analysis allows an earlier analysis of the endpoints measured in study groups 3a and 3b. 
 
 


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1.1. 
Objectives and Endpoints 
1.1.1. 
Objectives 
Primary objective 
The primary objective of the study is to demonstrate that Super-Responders (SRe; defined as 
psoriasis subjects who receive on-label guselkumab treatment until week 20 and respond with a 
Psoriasis Area and Severity Index [PASI] score = 0 at weeks 20 and 28) maintain control of 
disease until week 68 with prolonged treatment intervals of 16 weeks (100 mg q16w). To be 
demonstrated in Study Part 2. 
Secondary objectives 
Secondary objectives are to evaluate 
• whether subjects with short disease duration (≤2 years) show a more rapid and better 
guselkumab response compared to subjects with longer disease duration and whether 
subjects with shorter disease are more likely to maintain drug-free control of disease after 
guselkumab withdrawal. To be evaluated in Study Parts 1, 2 and 3. 
• whether SRe with short disease duration and PASI=0 at week 116 (ie, remission for one 
year after withdrawal) will show sustained remission (ie, PASI=0) over two additional 
years compared to subjects with longer disease duration. To be evaluated in Study Part 3. 
• whether SRe with short disease duration and PASI>0 to ≤5 at week 116 (ie, partial relapse 
for one year after withdrawal) will show continued loss of response or stabilization of 
disease worsening over two additional years compared to subjects with longer disease 
duration. To be evaluated in Study Part 3. 
• whether different treatment intervals (weeks 28 to 60: guselkumab 100 mg q8w vs. 
guselkumab 100 mg q16w) affect the maintenance of drug-free control of disease after 
68 weeks of guselkumab treatment. To be evaluated in Study Part 3. 
• the safety and tolerability of guselkumab in subjects with moderate-to-severe plaque-type 
psoriasis. 
Note: Disease duration will be calculated from date at which first symptoms (plaque) were reported 
by subject to date of screening visit: 
o Disease duration (days)  =  Date of visit 1 – date of first symptoms +1. 
Exploratory objectives 
The exploratory objectives are to be explored in the mechanistic biomarker substudies. These 
objectives are out of scope of this SAP. 
 
 


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1.1.2. 
Endpoints 
For the endpoints, the following terms were defined: 
• Control of disease: PASI score <3 
• Fluctuating disease: PASI score 3 to 5 
• Loss of disease control: PASI score >5. 
Study groups are defined as follows: 
• 1: All participating subjects who are enrolled and are scheduled to receive guselkumab 
100 mg at weeks 0, 4, q8w until week 28 (Study Part 1) 
• 2a: SRe (PASI score = 0 at weeks 20 and 28) randomized to guselkumab 100 mg q8w at 
weeks 28 to 60 (Study Part 2) 
• 2b: SRe randomized to guselkumab 100 mg q16w at weeks 28 to 60 (Study Part 2) 
• 2c: non-SRe with a PASI score >0 at week 20 and/or 28 who will receive guselkumab 
100 mg q8w at weeks 28 to 60 (Study Part 2) 
• 2d: SRe with loss of disease control between week 28 and 68, who will enter the re-
treatment arm and receive guselkumab 100 mg at weeks 0, 8 and 16 calculated from the 
date of loss of disease control (Study Part 2) 
• 3a: SRe randomized to guselkumab 100 mg q8w in Study Part 2 with withdrawal of 
guselkumab at week 68 (Study Part 3) 
• 3b: SRe randomized to guselkumab 100 mg q16w in Study Part 2 with withdrawal of 
guselkumab at week 68 (Study Part 3) 
• 
3c: SRe with fluctuating disease at week 68 or loss of disease control at any other visit after 
week 68, who will enter the re-treatment arm and receive guselkumab 100 mg at weeks 0, 
8 and 16 calculated from the date of loss of disease control (Study Part 3). 
Primary endpoint 
The primary endpoint of the main study is the proportion of subjects in study groups 2a and 2b 
who achieve an absolute PASI score <3 at week 68. 
Major secondary endpoints 
Major secondary endpoints of this study are: 
• Time to improvement from baseline (week 0) in PASI (PASI 75/90/100 response and 
absolute PASI score=0) for subjects with short (≤ 2 years) and longer (>2 years) disease 
duration per study group (1, 2a, 2b, and 2c) 
• Proportion of subjects with short (≤2 years) and longer (>2 years) disease duration who 
achieve an absolute PASI score of 0, ≤1 and <3 at weeks 20, 28, 68, 116, 164, and 220 per 
study group (1, 2a, 2b, 2c, 3a, and 3b) 
• 
Proportion of subjects who retain disease control (ie, absolute PASI score <3 at all visits) 
from week 68 through week 116, from week 68 through week 164, and from week 68 
through week 220 for subjects with short (≤ 2 years) and longer (>2 years) disease duration 
per study group (3a and 3b). 


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Other secondary endpoints of this study are: 
• Proportion of subjects who achieve a PASI 75/90/100 response at weeks 20, 28, 68, 116, 
164, and 220 per study group (1, 2a, 2b, 2c, 3a, and 3b) 
• Time to loss of disease control (absolute PASI score >5 at any visit) after treatment 
withdrawal beyond week 68 per study group (3a and 3b) 
• Proportion of subjects with an absolute PASI score=0 at all of the following visits: weeks 
12, 16, 20, and 28 (study group 1) 
• Change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at 
weeks 28, 68, 116, 164, and 220 per study group (1, 2a, 2b, 2c, 3a, 3b, and 3c) 
• Proportion of subjects who achieve a DLQI score 0/1 and <5 at weeks 28, 68, 116, 164, 
and 220 per study group (1, 2a, 2b, 2c, 3a, 3b, and 3c) 
• Change from baseline (week 0) in affected Body Surface Area (BSA) at weeks 12, 28, 52, 
68, 80, 104, 116, 140, 164, 188, 212, and 220 (all study groups) 
• Change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic Arthritis 
(NAPPA) score at weeks 28, 68, 116, 164, and 220 among subjects with nail psoriasis at 
baseline (week 0; 1, 2a, 2b, 2c, 3a, and 3b). 
• Change from baseline (week 0) in the signs and symptoms aggregate scores of the Psoriasis 
Symptoms and Signs Diary (PSSD) at weeks 28, 68, 116, 164, and 220 (1, 2a, 2b, 2c, 3a 
and 3b) 
• Proportion of subjects who achieve a PSSD sign score=0 at week 68 among subjects with 
a PSSD sign score ≥1 at week 28 per study group (2a, 2b, and 2c). 
• Association between trough serum guselkumab concentration and efficacy or serum 
biomarker level 
• Association between trough serum guselkumab levels at weeks 20, 28, 36, and 68 and 
achieving a PASI score <3 at week 68 per study group (2a and 2b) 
• Proportion of subjects who were re-treated due to loss of disease control (PASI >5) and 
regain control of disease (PASI <3) 24 weeks after start of re-treatment (study groups 2d 
and 3c) 
• Safety and tolerability with regard to adverse events (AEs) and abnormal laboratory results 
(all study groups). 
1.2. 
Study Design 
The present trial is designed as a phase 3b, randomized, double-blind, parallel-group, multicenter, 
comparison study in subjects of at least 18 years of age with moderate to severe plaque-type 
psoriasis. The study features the following structure and design: 
Study Part 1: Screening through Week 28:  
Part 1 consists of a screening phase lasting up to four weeks (+ 7 calendar days) prior to first 
administration of guselkumab (week 0), followed by a 28-week run-in period with visits and 
administration of 100 mg guselkumab at weeks 4, 12, and 20. In case of a PASI score = 0 at 
weeks 20 and 28, subjects are qualified to be randomized either to study group 2a or 2b of Study 
Part 2. In case of PASI score >0 at weeks 20 and/or 28, the subjects continue to receive guselkumab 


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100 mg q8w until week 60 (last administration at week 60 visit) with final study assessments at 
week 68 and final safety follow-up visit at week 72 (defined as study group 2c). 
Study Part 2: Week 28 through Week 68:  
Subjects with a PASI score = 0 at weeks 20 and 28 are defined as SRe and randomly assigned to 
the following two treatment groups: 2a) guselkumab 100 mg q8w or 2b) guselkumab 100 mg 
q16w. In addition, subjects with disease duration ≤2 years are equally distributed to either group 
by stratified randomization. Study visits of Study Part 2 are conducted every 8 weeks. 
To blind the study, study treatment (guselkumab or Placebo) is administered q8w starting at 
week 28 until the end of study therapy (last administration in week 60). The q16w group receives 
Placebo at weeks 28, 44 and 60. Subjects losing control of disease, defined as PASI score >5 at 
any visit during Study Part 2 (ie, until week 60), enter the Re-treatment arm (group 2d, see section 
Re-treatment below). 
The assessment for the primary endpoint is made at week 68 for both study groups (2a and 2b). 
In case of PASI <3 at week 68, the subject does not receive any study medication and enters the 
drug withdrawal part (Study Part 3). In case of PASI ≥ 3 at visit week 68 the subject enters the re-
treatment arm 3c (see section Re-treatment below). 
In case of PASI score >0 at weeks 20 and/or 28 the subjects continue to receive guselkumab 
100 mg q8w until week 60 (last administration of study treatment) with final study assessments at 
week 68 and final safety follow-up visit at week 72 (defined as study group 2c). 
Study Part 3: Week 68 through Week 220:  
Subjects of group 2a and 2b with a PASI score <3 at week 68 enter Study Part 3 (in study groups 
3a and 3b, respectively); they are withdrawn from the study medication and followed-up until 
week 220. Study visits of Study Part 3 are conducted every 12 weeks (ie, at weeks 80, 92, 104, 
116, 128, 140, 152, 164, 176, 188, 200, and 212; ± 14 days). In between the 12-weekly on-site 
visits, a telephone-visit 6 weeks (± 7 days) is done after each on-site visit (ie, telephone visits at 
weeks 74, 86, 98, 110, 122, 134, 146, 158, 170, 182, 194, and 206) to assess whether the subject 
notices a worsening of his/her psoriasis. If so, the subject must attend an on-site visit for efficacy 
assessment by the assessor as soon as possible but not later than 2 weeks after the phone call. For 
patients not starting re-treatment, the final visit takes place at week 220. 
Re-treatment 
Subjects losing control of disease, defined as PASI score >5 at any visit during Study Part 2 or 3 
(ie, until week 220), enter the re-treatment-arms (2d or 3c) with three guselkumab 100 mg 
administrations starting at that visit (= re-treatment-week 0, followed by administration at re-
treatment-weeks 8 and 16). 
If re-treatment is started at a visit which would usually not require all patient-reported outcomes 
needed at the first re-treatment visit, those patient-reported outcomes are obtained immediately 
after efficacy assessments (basis for re-treatment-decision) and prior to drug administration at that 
visit. 
The final efficacy assessment for all subjects in the re-treatment arms takes place 24 weeks after 
loss of control, and study termination is 28 weeks after loss of control (final study visit/safety 
follow-up). At visit week 24 of the re-treatment, the investigator may continue actual treatment 


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with commercially available guselkumab (ie, not supplied by Sponsor) to maintain a q8w interval. 
Due to the half-life of guselkumab, it is recommended not to start a new therapy during safety 
follow-up period (ie, 12 weeks after last dose). If the investigator feels strongly that an additional 
therapy is needed, this should be discussed with the Sponsor before initiation of the new therapy. 
Subjects with fluctuating disease (ie, PASI score 3 to 5) at the week 68 visit also get the 
opportunity to enter the re-treatment-arm (3c). 
The last chance to start re-treatment is the visit week 220 (ie, final efficacy assessment at week 244 
with final study visit/safety follow-up at week 248). 
A schematic diagram of the study design is provided below. 
 
 
 
 


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2. 
STATISTICAL HYPOTHESES 
This randomized, double-blind, parallel-group, multicenter phase 3b trial is designed to 
demonstrate that guselkumab 100 mg q16w treatment is non-inferior to guselkumab 100 mg q8w 
treatment in SRe as assessed by the proportion of subjects with an absolute PASI score <3 at 
week 68. A non-inferiority margin of 10% was chosen based on a minimally clinically meaningful 
difference. This margin was also used in CNTO1959PSO3009 (ECLIPSE) study and is therefore 
considered a valid approach for evaluating non-inferiority of a new treatment. 
The null hypothesis H0 and the alternative hypothesis HA (to be demonstrated in Study Part 2) are 
formulated as follows: 
• H0: PT – PS  ≤ -10% ('inferiority') 
• H1: PT – PS  > -10% ('non-inferiority'), 
where PT and PS denote the proportions of subjects with an absolute PASI score <3 at week 68 in 
the guselkumab 100 mg q16w treatment arm (PT = proportion test treatment) and the guselkumab 
100 mg q8w treatment arm (PS = proportion standard treatment). 
3. 
SAMPLE SIZE DETERMINATION 
The sample size estimation using the power approach was performed for the per-protocol analysis 
set as described below. No formal adjustment of the significance level was necessary. 
When the sample size in each group is 112, a two-group large-sample normal approximation Wald 
Z-test of proportions with a one-sided 0.05 significance level will have 80% power to reject the 
null hypothesis that the guselkumab 100 mg q16w treatment is inferior to the guselkumab 100 mg 
q8w treatment (the difference in proportions, Pguselkumab 100mg q16w – Pguselkumab 100mg q8w , is ≤ -10%) 
in favor of the alternative hypothesis that the guselkumab 100 mg q16w treatment is non-inferior 
to the guselkumab 100 mg q8w treatment (the difference in proportions is > -10%), assuming that 
the expected difference in proportions is 0 and the proportion in the guselkumab 100 mg q8w 
treatment group is 90% (nQuery Advisor® 7.0). 
Considering the frequency of drop-out rates and protocol violations from past trials, it is assumed 
that a rate of about 20% randomized subjects will not be evaluable for the per-protocol analysis in 
Study Part 2. Therefore, 280 subjects (140 subjects per treatment group) are planned to be 
randomized in a ratio of 1:1 to meet the required sample size of 224 subjects (112 subjects per 
treatment group) for the per-protocol analysis. 
Based on data from CNTO1959PSO3001 and CNTO1959PSO3002, it is anticipated that 
approximately 35% of enrolled subjects in Study Part 1 will be eligible for randomization at 
week 28 in Study Part 2. Thus, a total of 800 subjects should be enrolled in Study Part 1 to ensure 
that at least 280 subjects are eligible for randomization in Study Part 2. Accounting for a 10% 
drop-out rate of subjects ineligible for randomization at week 28 because of study discontinuation 
prior to week 28, it is therefore planned to enroll a total of 888 subjects in Study Part 1. 
Note: Screenings and enrollments will be adjusted if necessary (without protocol amendment), to 
achieve 280 SRe at week 28. Ongoing subjects in Study Part I will continue to Part 2 if eligible, 
irrespective of whether or not 280 SRe are already randomized. Only screenings will be closed. 
 
 


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4. 
POPULATIONS (ANALYSIS SETS) FOR ANALYSIS OF STUDY PART 3 
In Study Part 3 the following analysis sets will be defined for the efficacy and safety analyses. 
4.1. 
All Enrolled Analysis Set 
Not applicable for Study Part 3 (only applicable for Study Part 1). However, for Study Part 3 the 
number of 'Subjects starting Study Part 3 in groups 3a or 3b' will be reported and used for display 
of summary tables, if applicable. 
Note: The All enrolled analysis set in Study Part 1 included all subjects who were enrolled and 
were scheduled to receive study agent. 
4.2. 
Efficacy Analysis Set(s) 
The exploratory efficacy analysis of the secondary endpoint variables will be performed for the 
Intent-to-treat analysis set (ITT). If decided at the Dry Run Meeting, also the Per-protocol analysis 
set (PP) will be evaluated. 
Update after the Dry Run Meeting: The PP analysis will not be performed. 
4.2.1. 
Intent-to-Treat Analysis Set (ITT) 
For all efficacy analyses to compare study groups 3a and 3b in Study Part 3, all subjects entering 
Study Part 3 (either group 3a or 3b) will be included in the Intent-to-treat analysis set (ITT). 
Note1: Subjects entering study group 3c, ie, the re-treatment arm, will be evaluated separately. 
Analysis is not covered by the present SAP. 
Note 2: In the current SAP template the term 'full analysis set' is used. In this SAP the term 'intent-
to-treat analysis set' is used instead to match the Clinical Study Protocol. In terms of content, there 
is no difference between the two names. 
4.2.2. 
Per-protocol Analysis Set (PP) 
The Per-protocol analysis set (PP) will consist of all subjects in the Intent-to-treat analysis set 
(ITT) without any major deviation of the protocol and its procedures until the week 116/164/220 
visit. Subjects with major protocol deviations (except those not effecting the secondary endpoints) 
will be excluded from the per-protocol analysis. 
4.2.3. 
Nail Psoriasis Analysis Set 
The change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic Arthritis 
(NAPPA) score at the respective scheduled week will be evaluated among subjects with nail 
psoriasis at baseline (week 0). Nail psoriasis at baseline (week 0) will be defined as follows: 
• eCRF question 'Was Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
performed?' is answered with 'Yes' 
o  if 'Yes', patient has nail psoriasis if NAPPA-CLIN ≥ 1 at baseline (week 0). 
These analyses will be performed for the Intent-to-treat analysis set (ITT) and, if requested, the 
Per-protocol analysis set (PP). 


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4.2.4. 
Safety Analysis Set 
For all safety analyses, all subjects who entered groups 3a or 3b of Study Part 3 will be included 
in the Safety analysis set; hence the Safety analysis set is identical to the ITT analysis set. 
Note: For study groups 3a and 3b there is no administration of study agent in Study Part 3; if 
treatment was started in Study Part 3 the subject is evaluated in study group 3c for the analysis of 
re-treatment phase which is not covered by this SAP. 
4.2.5. 
Pharmacokinetics Analysis Set 
The PK analysis and the definition of the PK analysis set is out of scope for this SAP. 
5. 
STATISTICAL ANALYSES FOR STUDY PART 3 
Description of planned statistical analyses in Study Part 3 will focus on the comparison of the two 
study groups 3a and 3b which are without administration of study agent in Study Part 3 (ie, group 
3a: randomized to guselkumab 100 mg q8w in Study Part 2 vs. group 3b: randomized to 
guselkumab 100 mg q16w in Study Part 2). Inferential statistics (ie, exploratory p-values, 
confidence intervals, etc.) will be provided only for the week 116/164/220 data of endpoints in 
Study Part 3. 
Note 1: Statistical analysis of Study Part 3 will also include analyses of study data recorded before 
week 68. Data of Study Parts 1 and 2 will be summarized by descriptive statistics only. No 
exploratory inferential statistics (ie, p-values, confidence intervals, etc.) will be provided for the 
data of Study Parts 1 and 2. 
Note 2: Subjects of group 3a and 3b who start re-treatment with guselkumab within Study Part 3 
(up to week 116) will be evaluated only up to the study visit R0 at which PASI >5 is shown. If 
PASI was ≥3 already at week 68 the subject will not be evaluated for Study Part 3 in the scope of 
this SAP; a separate SAP will describe the analysis of the re-treatment phase. 
5.1. 
General Considerations 
The following general analysis definitions refer only to Study Part 3. 
The statistical analysis of Study Part 3 will be exploratory. All inferential statistical testing 
(including calculation of confidence intervals) is to be interpreted in the exploratory sense only. 
Descriptive statistics will include counts and proportions for categorical data, and mean, SD, 
median, interquartile range, and range, for continuous data. Graphical data displays will also be 
used to summarize the data. 
The two-group large-sample normal approximation Wald Z-test with Mantel-Haenszel stratum 
weights for 'disease duration' will be used to compare the proportion of subjects still maintain 
control of disease. Continuous response parameters will be compared using a univariate analysis 
of covariance model with fixed effects for study group, and disease duration and baseline value as 
covariates. Time-to-event endpoints will be analyzed using Kaplan-Meier product limit methods 
to estimate the survival distributions and the median time-to-event. 
In general, summary tables will be displayed by study group as the main classification variable 
and for the total of the sample (not for efficacy analyses) in the respective analysis set; ie, results 
will be provided for group 3a, group 3b, and total of group 3a and group 3b (not for efficacy 
analyses). Additional classification variables are explicitly mentioned in the following text. 


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Individual subject data listings will be presented parameter-wise and will be sorted by study group, 
study site, subject's identification number and study visit, if applicable. A more detailed description 
of the planned statistical analyses is provided in the sections below. 
5.1.1. 
Visit Windows 
As subjects do not always adhere to the protocol visit schedule, the following rules are applied to 
assign actual visits to analysis visits. Listed below are the visit windows and the target days for 
each visit. The reference day is Study Day 1 (for definition see section 5.1.3). If a subject has two 
or more actual visits in one visit window, the visit closest to the target day will be used as the 
protocol visit for that visit window. The other additional visit(s) will not be used in the summaries 
or analyses, but they can be used for determination of clinically important endpoints. If two actual 
visits are equidistant from the target day within a visit window, the later visit will be used. 
All assignments will be made in chronological order. Once a visit date is assigned to a visit 
window, it will no longer be used for a later time point except for the endpoint. Listed below (Table 
2) are the visit windows and the target days for each visit defined in the protocol. 
Table 2 – Visit Windows 
Parameter 
Analysis 
Period 
Scheduled 
Visit  
Time Interval 
(label on output) 
Time Interval 
(Day)* 
Target Time 
Point (Day) 
All 
1 
Scr 
Screening 
-35 to -1 
 
 
1 
W0 
Baseline 
-14 to 6 
1 
 
1 
W4 
Week 4 
15 to 43 
29 
 
1 
W12 
Week 12 
71 to 99 
85 
 
1 
W16 
Week 16 
100 to 126 
113 
 
1 
W20 
Week 20 
127 to 155 
141 
 
1 
W28 
Week 28 
183 to 211 
197 
 
2 
W36 
Week 36 
239 to 267 
253 
 
2 
W44 
Week 44 
295 to 323 
309 
 
2 
W52 
Week 52 
351 to 379 
365 
 
2 
W60 
Week 60 
407 to 435 
421 
 
2 
W68 
Week 68 
463 to 491 
477 
 
3 
W80 
Week 80 
533 to 589 
561 
 
3 
W92 
Week 92 
617 to 673 
645 
 
3 
W104 
Week 104 
701 to 757 
729 
 
3 
W116 # 
Week 116 
785 to 841 
813 
 
3 
W128 
Week 128 
869 to 925 
897 
 
3 
W140 
Week 140 
953 to 1009 
981 
 
3 
W152 
Week 152 
1037 to 1093 
1065 
 
3 
W164 # 
Week 164 
1121 to 1177 
1149 
 
3 
W176 
Week 176 
1205 to 1261 
1233 
 
3 
W188 
Week 188 
1289 to 1345 
1317 
 
3 
W200 
Week 200 
1373 to 1429 
1401 
 
3 
W212 
Week 212 
1457 to 1513 
1485 
 
3 
W220 # 
Week 220 
1513 to 1569 
1541 
*  Relative to Study Day 1 
#  W116, W164 and W220 are the final visits for the interim or final analyses of Study Part 3 – for these 
no upper border of the visit window will be applied (ie, all W116/W164/W220 visits later than the upper 
border will be used for analysis of the respective evaluation). 


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Telephone visits scheduled at weeks 74, 86, 98, 110, 122, 134, 146, 158, 170, 182, 194, and 206, 
will not be re-assigned, as no endpoint data are assessed at these visits. 
If there are site visits outside of the defined windows above, final decisions on the allocation of 
the actual visit to an earlier or later planned visit or whether the data will not be included in the 
analysis will be made during the Data Review or Dry Run Meeting. 
Update after the Dry Run Meeting: The windows for the week 28, week 68, week 116 and week 
164 visits were expanded. All values obtained at visits outside of defined windows will not be 
taken into account for by-visit analyses. The new visit windows are as follows: 
Table 2 – Visit Windows 
Parameter 
Analysis 
Period 
Scheduled 
Visit  
Time Interval 
(label on output) 
Time Interval 
(Day)* 
Target Time 
Point (Day) 
 
1 
W28 
Week 28 
183 to 238 
197 
 
2 
W68 
Week 68 
463 to 532 
477 
 
3 
W116 # 
Week 116 
758 to 968 
813 
 
3 
W164 # 
Week 164 
1094 to 1204 
1149 
*  Relative to Study Day 1 
#  W116, W164 and W220 are the final visits for the interim or final analyses of Study Part 3 – for these 
no upper border of the visit window will be applied (ie, all W116/W164/W220 visits later than the upper 
border will be used for analysis of the respective evaluation). 
5.1.2. 
Pooling Algorithm for Analysis Centers 
No pooling of centers will be performed. 
5.1.3. 
Study Day and Relative Day 
Study Day 1 or Day 1 refers to the start of the first study agent administration within Study Part 1. 
All efficacy and safety assessments at all visits will be assigned a day relative to this date. 
Study day or relative day for a visit is defined as: 
• 
Visit date – (date of Study Day 1) +1,  if visit date is ≥ date of Day 1 
• 
Visit date – Date of Day 1,  if visit date < date of Day 1. 
There is no 'Day 0'. 
5.1.4. 
Baseline and Endpoint 
Baseline for Study Part 3 is defined as the last observation (ie, value, measurement) prior to the 
start of the first study agent administration at baseline (week 0) in Study Part 1. 
Endpoint for Study Part 3 is defined as the last available post-baseline result within the analysis 
period from week 68 until week 116/164/220. Results obtained at unscheduled visits are included 
in this definition and will be considered as the endpoint value if the unscheduled visit result is the 
last post-baseline result available within the analysis period from week 68 until week 116/164/220. 
5.1.5. 
Imputation Rules for Missing AE Date/Time of Onset/Resolution 
Partial onset dates of adverse events (AEs) will be imputed as follows: 
• 
If the onset date of an AE is missing day only, it will be set to: 


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− 
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 
− 
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 
− 
Day of study agent start or day of AE resolution date, whichever is 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 AE 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 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 day of the date of death, if the 
death occurred in that month. 
• 
If the resolution date of an adverse event is missing both day and month, it will be set to the 
earliest of December 31 of the year or the day and month of the date of death, if the death 
occurred in that year. 
• 
Completely missing resolution dates will not be imputed. 
5.1.6. 
Treatment Failure Criteria 
No treatment failure criteria are defined for Study Part 3 analysis. 
5.1.7. 
Treatment Failure Rules 
NA 
5.1.8. 
Missing Data Imputation 
Data of study endpoints from subjects who started a protocol-prohibited medication/therapy during 
the study period that could improve psoriasis will be set to 'missing' from that point onward. The 
protocol-prohibited medications/therapies are listed in section 8.1 of the CSP. For the statistical 
analysis of Study Part 3, protocol prohibited medication/therapy will be identified in the SDTM 
DV domain as DVDECOD='RECEIVED DISALLOWED CONCOMITANT TREATMENT'. 
After the rule for handling of protocol-prohibited medication/therapy is applied, missing data will 
be handled as follows: 
• 
Non-responder imputation for binary efficacy endpoints will be applied for subjects with 
missing data at any study visit. 


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• 
Last Observation Carried Forward (LOCF) imputation for continuous efficacy endpoints will 
be applied for subjects with missing data in Study Part 3. 
• This approach implies that a separate "endpoint" visit will be calculated that gets the 
imputed value, thus leaving the observed value as it is, if data are summarized 
descriptively only. 
• Update after the Dry Run Meeting: The earliest visit used for LOCF approach is the week 
68 visit; no data from Parts 1 and 2 will be used as LOCF value for the week 116 visit. 
• 
Time-to-event analyses of binary endpoints will be performed after the rule for handling of 
protocol-prohibited medication/therapy is applied (missing data will not be replaced for time-
to-event analyses). 
An 'observed cases analysis' for all binary and continuous endpoints in Study Part 3 without any 
imputation of missing data (ie, also not set to missing once protocol-prohibited medication/therapy 
is started) will also be done. These analyses will provide only descriptive statistical results and 
will also include by-visit data of Study Parts 1 and 2 (see section 5.6). 
5.2. 
Participant Dispositions 
The number of subjects in the following disposition categories will be summarized throughout the 
study for Study Part 3 by study groups (ie, groups 3a, 3b) and the total of group 3a and 3b: 
• 
Subjects who entered groups 3a or 3b of Study Part 3 # 
• 
Subjects of groups 3a and 3b who completed Study Part 3 until the week 116/164/220 visit 
• 
Subjects of groups 3a and 3b who discontinued Study Part 3 prematurely until the week 
116/164/220 visit, respectively 
• 
Reasons for termination of study within Study Part 3 (subjects of groups 3a and 3b). 
# without those subjects who started re-treatment already at the week 68 visit 
5.3. 
Primary Endpoint(s) Analysis 
Not applicable for the Study Part 3 analysis. 
5.3.1. 
Definition of Endpoint(s) 
Not applicable for the Study Part 3 analysis. 
5.3.2. 
Estimand 
Not applicable for the Study Part 3 analysis. 
5.3.3. 
Analysis Methods 
Not applicable for the Study Part 3 analysis. 
5.4. 
Major Secondary Endpoint(s) Analysis 
Statistical analyses will be descriptive and exploratory only. They will be performed for the Intent-
to-treat analysis set and, if requested, the Per-protocol analysis set. 
Major secondary endpoints of this study in Study Part 3 are: 


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• Proportion of subjects with short (≤2 years) and longer (>2 years) disease duration who 
achieve an absolute PASI score of 0, ≤1 and <3 at weeks 116, 164, and 220, per study 
group 
• Proportion of subjects who retain disease control (ie, absolute PASI score <3 at all visits) 
from week 68 through week 116, from week 68 through week 164, and from week 68 
through week 220, for subjects with short (≤ 2 years) and longer (>2 years) disease duration 
per study group. 
5.4.1. 
Definition of Endpoint(s) 
5.4.1.1. 
Psoriasis Area and Severity Index (PASI) 
The Psoriasis Area and Severity Index (PASI) is an instrument 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 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. 
5.4.2. 
Estimand(s) 
NA 
5.4.3. 
Analysis Methods 
• Proportion of subjects who achieve an absolute PASI score of 0, ≤1 and <3 at weeks 116, 
164, and 220 
• Proportion of subjects who retain disease control from week 68 through week 116, from 
week 68 through week 164, and from week 68 through week 220 
The proportion of subjects responding to treatment or maintaining disease control will be displayed 
in frequency tables providing the number and percentage of subjects per study group (NRI and OC 
analysis) along with odds ratio (OR), relative risk (RR) and risk difference (RD), and two-sided 
Wald-type 95% confidence intervals (95% CIs) stratified by 'disease duration' (NRI analysis only). 
For single proportions within each study group, unstratified two-sided 95% CIs according to 
Clopper-Pearson will be calculated. Graphical presentation will be presented by means of bar 
charts. 
The two-group large-sample normal approximation Wald Z-test with Mantel-Haenszel stratum 
weights for 'disease duration' will be used to compare the respective proportion of subjects among 
the study groups. The Mantel-Haenszel estimate, the two-sided Wald-type 95% confidence limits, 
and the test for the difference of proportions will be computed by using Mantel-Haenszel stratum 
weights (Mantel & Haenszel, 1959) and the Sato variance estimator (Sato 1989). 
The respective proportion of subjects will also be given by disease duration category (assessed at 
baseline, ie, ≤2 years, >2 years) and overall, providing exploratory p-values (unadjusted Chi² test) 
for the difference between disease duration categories. 
Details on handling of missing data are described in section 5.1.8. Subgroup analyses will be 
performed unstratified for the subgroups as specified in section 5.8.8. 
Update after the Dry Run Meeting: Statistical testing will also be performed for the OC analysis. 


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Results will also be given for the entire population. In addition, in a modified OC analysis all 
subjects fulfilling the criteria for re-treatment within the week 116 visit window (ie, PASI>5) will 
be disregarded. 
5.5. 
Other Secondary Endpoint(s) 
Statistical analyses will be descriptive and exploratory only. They will be performed for the Intent-
to-treat analysis set and, if requested, the Per-protocol analysis set. Details on handling of missing 
data are described in section 5.1.8. 
Other secondary endpoints of this study to be evaluated in Study Part 3 are: 
• 
Proportion of subjects who achieve a PASI 75/90/100 response at weeks 116, 164, and 220, 
per study group 
• 
Time to loss of disease control (absolute PASI score >5 at any visit) after treatment withdrawal 
beyond week 68 per study group 
• 
Change from baseline (week 0) in Dermatology Life Quality Index (DLQI) score at weeks 
116, 164, and 220, per study group 
• 
Proportion of subjects who achieve a DLQI score 0/1 and <5 at weeks 116, 164, and 220, per 
study group 
• 
Change from baseline (week 0) in affected Body Surface Area (BSA) at weeks 80, 104, 116, 
140, 164, 188, 212, and 220 
• 
Change from baseline (week 0) in the Nail Assessment in Psoriasis and Psoriatic Arthritis 
(NAPPA) score at weeks 116, 164, and 220, among subjects with nail psoriasis at baseline 
(week 0) 
• 
Change from baseline (week 0) in the signs and symptoms aggregate scores of the Psoriasis 
Symptoms and Signs Diary (PSSD) at weeks 116, 164, and 220. 
5.5.1. 
Definition of Endpoint(s) 
5.5.1.1. 
Psoriasis Area and Severity Index (PASI) 
Efficacy endpoints related to the PASI score are defined below: 
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 a PASI score of 0 will be considered PASI 100 responders. 
Time to loss of disease control 
The time to loss of disease control is defined as time from the week 68 visit (start of withdrawal 
phase) to first date PASI is >5 within Study Part 3. In the absence of documented disease control, 
the time to loss of disease control will be censored at the date of the last PASI assessment until the 
week 116/164/220 visit. The time to loss of disease control will be computed as: 


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• 
Date of PASI >5 – Date of week 68, if the subject loses disease control, 
• 
Date of last PASI assessment – Date of week 68, if the subject maintains disease control. 
• 
In case the subject missed the week 68 visit, the start date of the withdrawal phase will be 
estimated as 8 weeks (56 days) after the week 60 visit. 
5.5.1.2. 
Dermatology Life Quality Index (DLQI) 
The Dermatology Life Quality Index (DLQI) is a dermatology-specific quality of life instrument 
designed to assess the impact of the disease on a subject’s quality of life. It is a 10-item 
questionnaire that, in addition to evaluating overall quality of life, can be used to assess 6 different 
aspects that may affect quality of life: 1) symptoms and feelings, 2) daily activities, 3) leisure, 4) 
work or school performance, 5) personal relationships, and 6) treatment. 
The DLQI is calculated by summing the score of each question resulting in a maximum of 30 and 
a minimum of 0. A higher score indicates more severe disease. A score of ≤1 indicates no effect 
at all of disease on subject’s health related quality of life. 
For a partially answered questionnaire (eg, not all 10 answers in the DLQI questionnaire are 
available) the following rules will be applied: 
1. If one question is left unanswered this will be scored 0 and the scores will be summed and 
expressed as usual out of a maximum of 30. 
2. If two or more questions are left unanswered the questionnaire will not be scored. 
3. If question 7 is answered 'yes' this will be scored 3. If question 7 is answered 'no' or 'not 
relevant' but then either 'a lot' or 'a little' is ticked this will be scored 2 or 1. If it is answered 
'no', but the second half is left incomplete, the score will remain 0. 
Note: The answer "Not relevant" will be scored 0, as intended by the score developers. 
5.5.1.3. 
Body Surface Area (BSA%) 
One physical measure to define disease severity is to determine how much of the Body Surface 
Area (BSA) is affected by psoriasis. Involved BSA is calculated by using the palm of the subject’s 
hand as equivalent to 1% of the BSA (rule of palm). 
5.5.1.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
The NAPPA is an instrument for assessing clinical and patient-reported outcomes in nail psoriasis 
(Augustin, et al. 2014). It comprises three components:  
1. NAPPA-QOL is a 20-item nail-specific quality of life (QoL) questionnaire covering the 
past week. Signs, stigma and everyday life are rated on a scale from 0 (no suffering) to 4 
(high suffering). The NAPPA-QOL global score is computed by averaging all items. In 
case more than 25% of the items are missing (6 or more items missing), the score is not 
computed for the respective patient. 
2. NAPPA-PBI is a 24-item questionnaire to assess patient-defined needs before and patient-
rated benefits after treatment. The answers are given on a scale from 0 to 4. The weighted 
NAPPA-PBI global score is computed as follows: For score calculation, both "does not 
apply" and "question unanswered" will be treated as missing values. The global score will 
be calculated using all items pairs (importance + benefit) for which the patient has given a 
response other than "does not apply". Each benefit item is multiplied with the respective 


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importance item, and the product is divided by the sum of all importance items. The results 
are summed up over all items. The resulting global score ranges from 0 (no benefit) to 4 
(highest possible benefit). Only if more than 25% of items pairs are unanswered (=7 or 
more item pairs with missing values), no global score will be calculated. 
3. NAPPA-CLIN has been developed from the Nail Psoriasis Severity Index (NAPSI) score, 
a nail psoriasis-specific score, which in its original version comprises the assessment of 
matrix and nail bed involvement in every finger and toe by 8 criteria for each nail. The 
NAPPA-CLIN is a simplified version of the NAPSI which only assesses the least and the 
worst involved nail of both hands, or both feet, respectively. Score (matrix or bed for hands 
or feet)) is 0 if the findings are not present, 1 if they are present in 1 quadrant of the nail, 2 
if present in 2 quadrants of a nail, 3 if present in 3 quadrants of a nail, and 4 if present in 4 
quadrants of a nail:  
- thus, each nail has a matrix score (0-4) and a nail bed score (0-4), and the total nail 
score is the sum of those 2 individual scores (0-8) for hands or feet; 
- sum of the total score of all involved nails is the total NAPPA-CLIN score for that 
patient at that time for hands or feet; 
- thus, the NAPPA-CLIN scores for hands or feet range from 0 to 16 empirically; 
- if a matrix score or a nail bed score is missing, the NAPPA-CLIN score is also missing. 
5.5.1.5. 
Psoriasis Symptom and Sign Diary (PSSD) 
The Psoriasis Symptom and Sign Diary (PSSD) is a patient-reported outcome (PRO) questionnaire 
designed to measure the severity of psoriasis symptoms and signs for the assessment of treatment 
benefit. The PSSD includes 11 items covering symptoms (itch, pain, stinging, burning and skin 
tightness) and subject observable signs (skin dryness, cracking, scaling, shedding or flaking, 
redness and bleeding) using 0 (=absent) to 10 (=worst imaginable) numerical rating scales for 
severity. Two subscores will be derived: the psoriasis symptom score and the psoriasis sign score. 
A higher score indicates more severe disease. Additionally, the single items itch, pain, and scaling 
and also the other single items will be evaluated. The subjects will complete the 7-day recall 
version of the PSSD as indicated in the Time and Events Schedule. 
The calculations of PSSD symptom, and sign scores are listed below. 
Symptom Score (0-100) 
a) Symptom score includes itch (Q1), pain (Q11), stinging (Q10), burning (Q9) and skin 
tightness (Q4). 
b) Averaging items on the symptom scores when at least 3 items (≥50% of 5 items) on this 
scale are answered. Then, the average value is converted into 0-100 scoring such that 
Symptom score = average value x 10 with 0 representing the least severe and 100 the most 
severe. Otherwise, the symptom score will be set to missing. 
Sign Score (0-100) 
a) Sign score includes skin dryness (Q2), cracking (Q3), scaling (Q5), shedding or flaking 
(Q6), redness (Q7) and bleeding (Q8). 
b) Averaging items on the sign scores when at least 3 items (≥50% of 6 items) on this scale 
are answered. Then, the average value is converted into 0-100 scoring such that Sign score 


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= average value x 10 with 0 representing the least severe and 100 the most severe. 
Otherwise, the sign score will be set to missing. 
5.5.2. 
Estimand(s) 
NA 
5.5.3. 
Analysis Methods 
5.5.3.1. 
Psoriasis Area and Severity Index (PASI) 
• Proportion of subjects who achieve a PASI 75/90/100 response at weeks 116, 164, and 220 
The proportion of subjects still meeting the response criteria will be displayed in frequency tables 
providing the number and percentage of subjects per study group (NRI and OC analysis) along 
with odds ratio (OR), relative risk (RR) and risk difference (RD), and two-sided Wald-type 95% 
confidence intervals (95% CIs) stratified by 'disease duration' (NRI analysis only). For single 
proportions within each study group, unstratified two-sided 95% CIs according to Clopper-Pearson 
will be calculated. Graphical presentation will be presented by means of bar charts. 
The two-group large-sample normal approximation Wald Z-test with Mantel-Haenszel stratum 
weights for 'disease duration' will be used to compare the proportion of responding subjects among 
the study groups. The Mantel-Haenszel estimate, the two-sided Wald-type 95% confidence limits, 
and the test for the difference of proportions will be computed by using Mantel-Haenszel stratum 
weights (Mantel & Haenszel, 1959) and the Sato variance estimator (Sato 1989). 
Update after the Dry Run Meeting: Statistical testing will also be performed for the OC analysis. 
Results will also be given for the entire population. In addition, in a modified OC analysis all 
subjects fulfilling the criteria for re-treatment within the week 116 visit window (ie, PASI>5) will 
be disregarded. 
• Time to loss of disease control after treatment withdrawal beyond week 68 
Time-to-event endpoints will be analyzed using the Kaplan-Meier product limit method and Cox 
proportional hazards model. Summary tables will provide counts and percentages by study group, 
the median time-to-event with 95% confidence intervals (CI), and the hazard ratio (including 95% 
CI and the p-value calculated from Cox-regression with the factors 'study group' and 'disease 
duration'). The survival curves will also be displayed graphically. Time-to-event analyses of binary 
endpoints will be performed on the observed cases only after the rule for handling of protocol-
prohibited medication/therapy is applied. (ie, missing data will not be replaced for time-to-event 
analyses). 
Time to loss of disease control will also be evaluated by disease duration category (assessed at 
baseline, ie, ≤2 years, >2 years) and overall, providing exploratory p-values (unadjusted log-rank 
test) for the difference between disease duration categories. 
5.5.3.2. 
Dermatology Life Quality Index (DLQI) 
• Change from baseline (week 0) in DLQI score at weeks 116, 164, and 220 
The change from baseline in DLQI will be summarized by descriptive statistics using appropriate 
tabulation. The baseline value, the week 116/164/220 value, and the respective change from 
baseline value, will be displayed. 


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A univariate analysis of covariance (ANCOVA) model will be used to test the difference in change 
from baseline between study groups; the change from baseline being the dependent variable, and 
former treatment, disease duration, and baseline value of endpoint, as independent variables. A 
95% confidence interval for the difference in Least Squares (LS) means and p-value will be 
calculated based on contrast test statistics. The LS means, the LS mean difference and the 
standardized mean difference (computed according to Hedges' g), together with the 95% CI and 
two-sided p-value, will be provided from the ANCOVA model. 
• Proportion of subjects who achieve a DLQI score 0/1 and <5 at weeks 116, 164, and 220 
The proportion of subjects meeting the response criteria will be displayed in a frequency table 
providing the number and percentage of subjects per study group (NRI and OC analysis) along 
with odds ratio (OR), relative risk (RR) and risk difference (RD), and two-sided Wald-type 95% 
confidence intervals (95% CIs) stratified by 'disease duration' (NRI analysis only). For single 
proportions within each study group, unstratified two-sided 95% CIs according to Clopper-Pearson 
will be calculated. Graphical presentation will be presented by means of bar charts. 
The two-group large-sample normal approximation Wald Z-test with Mantel-Haenszel stratum 
weights for 'disease duration' will be used to compare the proportion of responding subjects among 
the study groups. The Mantel-Haenszel estimate, the two-sided Wald-type 95% confidence limits, 
and the test for the difference of proportions will be computed by using Mantel-Haenszel stratum 
weights (Mantel & Haenszel, 1959) and the Sato variance estimator (Sato 1989). 
The respective proportion of subjects will also be given by disease duration category (assessed at 
baseline, ie, ≤2 years, >2 years) and overall, providing exploratory p-values (unadjusted Chi² test) 
for the difference between disease duration categories. 
Update after the Dry Run Meeting: Statistical testing will also be performed for the OC analysis. 
Results will also be given for the entire population. In addition, in a modified OC analysis all 
subjects fulfilling the criteria for re-treatment within the week 116 visit window (ie, PASI>5) will 
be disregarded. Moreover, the statistical comparison of disease duration categories will be repeated 
for OC. 
5.5.3.3. 
Body Surface Area (BSA%) 
• Change from baseline (week 0) in affected BSA at weeks 80, 104, 116, 140, 164, 188, 212, 
and 220 
The change from baseline in BSA affected by psoriasis will be summarized by descriptive statistics 
using appropriate tabulation. The baseline value, the values for the respective weeks, and the 
respective changes from baseline, will be displayed. 
A univariate analysis of covariance (ANCOVA) model will be used to test the difference in change 
from baseline between study groups; the change from baseline being the dependent variable, and 
former treatment, disease duration, and baseline value of endpoint, as independent variables. A 
95% confidence interval for the difference in Least Squares (LS) means and p-value will be 
calculated based on contrast test statistics. The LS means, the LS mean difference and the 
standardized mean difference (computed according to Hedges' g), together with the 95% CI and 
two-sided p-value, will be provided from the ANCOVA model. 


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5.5.3.4. 
Nail Assessment in Psoriasis and Psoriatic Arthritis (NAPPA) 
• Change from baseline (week 0) in the NAPPA score at weeks 116, 164, and 220, among 
subjects with nail psoriasis at baseline (week 0) 
The change from baseline in the global scores of NAPPA-QOL, NAPPA-PBI, and NAPPA-CLIN 
will be summarized by descriptive statistics using appropriate tabulation. The baseline value, the 
value for the endpoint week of the respective analysis, and the respective change from the baseline 
value, will be displayed. According to the definition of the global score of NAPPA-PBI, the post-
baseline values are already the changes from baseline (there is no baseline value). 
No inferential statistical analyses will be performed for global scores of NAPPA-QOL, NAPPA-
PBI, and NAPPA-CLIN. 
5.5.3.5. 
Psoriasis Symptom and Sign Diary (PSSD) 
• Change from baseline (week 0) in the PSSD Signs and Symptoms aggregate scores at 
weeks 116, 164, and 220 
The change from baseline in the respective PSSD score will be summarized by descriptive 
statistics using appropriate tabulation. The baseline value, the value for the endpoint week of the 
respective analysis, and the respective change from the baseline value, will be displayed. 
A univariate analysis of covariance (ANCOVA) model will be used to test the difference in change 
from baseline between study groups; the change from baseline being the dependent variable, and 
former treatment, disease duration, and baseline value of endpoint, as independent variables. A 
95% confidence interval for the difference in Least Squares (LS) means and p-value will be 
calculated based on contrast test statistics. The LS means, the LS mean difference and the 
standardized mean difference (computed according to Hedges' g), together with the 95% CI and 
two-sided p-value, will be provided from the ANCOVA model. 
5.6. 
Additional Analyses 
In addition to the efficacy analyses of the study endpoints described above, continuous and binary 
endpoints related to PASI, DLQI, PSSD, affected BSA, NAPPA, and PSSD, at all scheduled study 
visits during Study Parts 1, 2 and 3 (Week 0 until Week 116/164/220) will be summarized 
descriptively (observed cases analysis for continuous endpoints; observed cases analysis and non-
responder imputation (after the rule for handling of protocol-prohibited medication/therapy is 
applied) for binary endpoints). For binary endpoints and the PASI score by visit, data will be 
presented for the overall population as well. 
New analyses that were not pre-planned in the CSP are introduced as follows: 
• Proportion of subjects with short (≤2 years) and longer (>2 years) disease duration who 
achieve an absolute PASI score of ≤5 at weeks 116, 164, and 220, per study group 
The proportion of subjects responding to treatment will be displayed in frequency tables providing 
the number and percentage of subjects per study group (NRI and OC analysis) along with odds 
ratio (OR), relative risk (RR) and risk difference (RD), and two-sided Wald-type 95% confidence 
intervals (95% CIs) stratified by 'disease duration' (NRI analysis only). For single proportions 
within each study group, unstratified two-sided 95% CIs according to Clopper-Pearson will be 
calculated. Graphical presentation will be presented by means of bar charts. 


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The two-group large-sample normal approximation Wald Z-test with Mantel-Haenszel stratum 
weights for 'disease duration' will be used to compare the proportion of subjects with PASI ≤5 
among the study groups. The Mantel-Haenszel estimate, the two-sided Wald-type 95% confidence 
limits, and the test for the difference of proportions will be computed by using Mantel-Haenszel 
stratum weights (Mantel & Haenszel, 1959) and the Sato variance estimator (Sato 1989). 
The proportion of subjects who achieve an absolute PASI score of ≤5 will also be given by disease 
duration category (assessed at baseline, ie, ≤2 years, >2 years) and overall, providing exploratory 
p-values (unadjusted Chi² test) for the difference between disease duration categories. 
Update after the Dry Run Meeting: Statistical testing will also be performed for the OC analysis. 
Results will also be given for the entire population. In addition, in a modified OC analysis all 
subjects fulfilling the criteria for re-treatment within the week 116 visit window (ie, PASI>5) will 
be disregarded. 
• Proportion of subjects with PASI ≤5 over time 
For each scheduled study visit during Study Parts 1, 2 and 3, the proportion of subjects meeting 
the response criterion will be displayed in a frequency table providing the number and percentage 
of subjects, per study group and disease duration category (≤2 years, >2 years), and overall. No 
inferential statistics will be provided. 
• PASI values over time in subjects with PASI >0 and ≤5 at week 116 
For each scheduled study visit during Study Parts 1, 2 and 3, summary statistics for observed 
values will be provided, restricted to only those subjects who show PASI >0 and ≤5 at week 116. 
Results will be given per study group and disease duration category (≤2 years, >2 years), and 
overall. No inferential statistics will be provided. 
• PASI values over time in subjects with PASI ≥0 and ≤5 at week 116 
For each scheduled study visit during Study Parts 1, 2 and 3, summary statistics for observed 
values will be provided, restricted to only those subjects who show PASI ≥0 and ≤5 at week 116. 
Results will be given per study group and disease duration category (≤2 years, >2 years), and 
overall. No inferential statistics will be provided. 
• Time to end of the treatment-free period 
The time to end of the treatment-free period is defined as time from the visit guselkumab was 
injected the last time in Study Part 2 to the date of the R0 visit at which re-treatment started, 
irrespective of PASI assessments. For subjects without re-treatment until the week 116/164/220 
visit, the time to end of the treatment-free period will be censored at the date of the week 
116/164/220 visit or the date of study termination, whatever comes first. The time to end of the 
treatment-free period will be computed as: 
• 
Date of R0 visit – Date of last guselkumab injection in Study Part 2, if the subject started re-
treatment, 
• 
First date of (week 116/164/220 visit or study termination) – Date of last guselkumab injection 
in Study Part 2, if the subject did not start re-treatment. 
The time to end of the treatment-free period will be analyzed using the Kaplan-Meier product limit 
method and Cox proportional hazards model. Summary tables will provide counts and percentages 
by study group and total, the median time-to-event with 95% confidence intervals (CI), and the 
hazard ratio (including 95% CI and the p-value calculated from Cox-regression with the factors 


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'study group' and 'disease duration'). The survival curves will also be displayed graphically. Time-
to-event analyses of binary endpoints will be performed on the observed cases only after the rule 
for handling of protocol-prohibited medication/therapy is applied. (ie, missing data will not be 
replaced for time-to-event analyses). 
Time to end of the treatment-free period will also be evaluated by disease duration category 
(assessed at baseline, ie, ≤2 years, >2 years) and overall, providing exploratory p-values 
(unadjusted log-rank test) for the difference between disease duration categories. 
• Proportion of subjects with DLQI values falling in quality-of-life categories 
DLQI values, if available within a visit window and if not after start of a prohibited medication, 
will be assigned to one of the categories presented in the following table: 
Table 3 – DLQI Categories 
DLQI Score 
Meaning of Category 
0 to 1 
Psoriasis has no effect on quality of life 
2 to 5 
Psoriasis has a mild effect on quality of life 
6 to 10 
Psoriasis has a moderate effect on quality of life 
11 to 20 
Psoriasis has a severe effect on quality of life 
21 to 30 
Psoriasis has a very severe effect on quality of life 
For selected study visit during Study Parts 1 (baseline, week 28), 2 (weeks 52 and 68) and 3 (weeks 
80, 92, 104, 116, 140, 164, and 220), the proportion of subjects in each category will be displayed 
in a frequency table providing the number and percentage of subjects, per study group and disease 
duration category (≤2 years, >2 years), and overall. No inferential statistics will be provided. 
Update after the Dry Run Meeting: Percentages will be based on the available number of subjects 
with non-missing data per visit. 
5.7. 
Safety Analyses 
All safety analyses in Study Part 3 will be based on the Safety analysis set. Data from the safety 
follow-up at week 72 (study groups 2c and 3c) will not be included in the Study Part 3 analyses; 
last visit to be included for the Study Part 3 analyses is week 116/164/220 or R0 visit in case re-
treatment was started. Safety data, including but not limited to, adverse events (AEs), serious AEs, 
infections, serious infections, and changes in vital signs, will be summarized by study group and 
overall. AEs will be summarized by Medical Dictionary for Regulatory Activities (MedDRA) 
system organ class (SOC) and Preferred Terms (PT) for each study group and overall. 
For all continuous safety variables, descriptive statistics will include the N, mean, standard 
deviation, median, quartiles, minimum, and maximum. Categorical variables will be summarized 
using frequency counts and percentages. 
5.7.1. 
Extent of Exposure 
The number and percentage of subjects who received study agent during Study Parts 1 and 2 will 
be summarized. Descriptive statistics will be presented for the number of study agent 
administrations. 


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5.7.2. 
Adverse Events 
The verbatim terms used in the eCRF by investigators to describe adverse events will be coded 
using the Medical Dictionary for Regulatory Activities (MedDRA). Any AE occurring after the 
day of the week 68 visit until the day of the week 116/164/220 visit (or the R0 visit, if applicable) 
in Study Part 3 will be included in the analysis. If the onset date is recorded partially only or is 
completely missing, then the event will be considered for analysis unless it is known to be prior to 
the week 68 visit based on partial onset date or resolution date. In case a subject missed the week 
68 visit, the date of the week 68 visit will be estimated as 8 weeks (56 days) after the week 60 
visit. 
For each adverse event, the number and percentage of subjects who experience at least one 
occurrence of the given event will be summarized by study group and overall. Summary tabulation 
will also provide the number of events, if applicable. 
Summary tables will be provided for: 
• 
AEs 
• 
Serious AEs (SAEs) 
• 
AEs by severity 
• 
AEs by relationship to study agent 
• 
Infections 
• 
Serious infections 
• 
Injection site reactions. 
In addition to the summary tables, listings will be provided for subjects who: 
• 
Had (S)AEs. 
Deaths will be displayed study group. Frequencies for the following parameters will be included 
in the summary table: 
• 
Number of subjects who died 
• 
Cause of death 
• 
Relationship to study agent (yes/no) (yes includes the following eCRF items: possible, 
probable, very likely). 
A listing of subjects who died will also be provided. 
Update after the Dry Run Meeting: Any AE occurring after the day of the week 68 visit until the 
day of the week 116/164/220 visit (or the day before the R0 visit, if applicable, ie, the day of the 
R0 visit is excluded) in Study Part 3 will be included in the analysis. 
5.7.3. 
Additional Safety Assessments 
5.7.3.1. 
Clinical Laboratory Tests 
Laboratory assessments were not done in Study Part 3 (except for single cases in an unscheduled 
visit), these were only planned for the re-treatment phase (study group 3c, see separate SAP). 
Therefore, no analysis of laboratory parameters will be done for study groups 3a and 3b. 


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5.7.3.2. 
Vital Signs and Physical Examination Findings 
Continuous vital sign parameters including weight, pulse, and blood pressure (systolic and 
diastolic), will be summarized at each assessment time point throughout Study Parts 1, 2, and 3. 
Changes from baseline (week 0) will be summarized for all post-baseline visits from week 4 until 
week 116/164/220. Descriptive statistics (mean, standard deviation, median, quartiles, minimum 
and maximum) will be presented. A listing of subjects with treatment-emergent clinically 
important vital signs will be presented, along with a listing of all vital sign measurements. 
Incidence of treatment-emergent clinically important vital signs while on treatment, as defined in 
Table 4, will be summarized for subjects who had a baseline assessment and at least 1 post-baseline 
assessment for that vital sign. 
Table 4 – Clinically Important / Markedly Abnormal Vital Signs 
Vital Sign 
Criteria 
Pulse 
>120 bpm and with >30 bpm increase from baseline 
<50 bpm and with >20 bpm decrease from baseline 
Systolic blood pressure 
>180 mmHg and with >40 mmHg increase from baseline 
<90 mmHg and with >30 mmHg decrease from baseline 
Diastolic blood pressure 
>105 mmHg and with >30 mmHg increase from baseline 
<50 mmHg and with >20 mmHg decrease from baseline 
Physical examinations were not done in Study Part 3, these were only planned for the re-treatment 
phase (study group 3c, see separate SAP). Therefore, no analysis of physical examinations will be 
done for study groups 3a and 3b. 
5.7.3.3. 
Electrocardiogram 
Not applicable for this study. 
5.7.3.4. 
Other Safety Parameters 
Tuberculosis Evaluation 
Tuberculosis evaluations were not done in Study Part 3, these were only planned for the re-
treatment phase (study group 3c, see separate SAP). Therefore, no analysis of tuberculosis 
evaluations will be done for study groups 3a and 3b. 
Urine Pregnancy Test 
Urine pregnancy tests were not done in Study Part 3, these were only planned for the re-treatment 
phase (study group 3c, see separate SAP). Therefore, no analysis of urine pregnancy tests will be 
done for study groups 3a and 3b. 
5.8. 
Other Analyses 
5.8.1. 
Pharmacokinetics 
Not applicable for Study Part 3 analysis. 


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5.8.2. 
Immunogenicity 
Not applicable for Study Part 3 analysis. 
5.8.3. 
Pharmacodynamics 
Not applicable for Study Part 3 analysis. 
5.8.4. 
Pharmacokinetic/Pharmacodynamic Relationships 
Not applicable for Study Part 3 analysis. 
5.8.5. 
Biomarkers 
Not applicable for Study Part 3 analysis. 
5.8.6. 
Health Economics 
Not applicable for Study Part 3 analysis. 
5.8.7. 
Other Variables and/or Parameters 
Not applicable for Study Part 3 analysis. 
5.8.8. 
Definition of Subgroups 
Subgroup analyses are planned to be performed for the major secondary endpoints in study groups 
3a and 3b as well as for other endpoints: 
• Proportion of subjects who achieve an absolute PASI score of 0, ≤1 and <3 at week 
116/164/220 
• Proportion of subjects who retain disease control (PASI <3) from week 68 on 
• PASI values over time 
• Time to end of the treatment-free period 
• Proportion of subjects who achieve a DLQI score 0/1 or <5 over time. 
All subgroup analysis will be performed unstratified, ie, without use of 'disease duration' as 
stratification factor in the exploratory inferential statistical analysis. The following subgroups will 
be defined: 
• Disease duration at baseline 
o ≤ 2 years 
o > 2 years 
• Age at baseline 
o < 45 years 
o ≥ 45 to 65 years 
o > 65 years 
• BMI at baseline 
o normal (≤ 25 kg/m²) 
o overweight (> 25 – 30 kg/m²) 
o obese (> 30 kg/m²) 


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• Body weight at baseline 
o ≤ 90 kg 
o > 90 kg 
• PSO-pretreatment (for hierarchical categorization see section 6.5) 
o No prior therapy 
o Topical therapy 
o Phototherapy 
o Non-biologic systemic therapy 
o Biologic therapy 
• PSO-pretreatment with biologics 
o Biologic naïve (including subjects without PSO-pretreatment) 
o 1 or more biologics. 
Based on the week 68 visit (nominal, not necessarily within the visit window), the following 
subgroups will be defined, if PASI was assessed: 
• PASI score at week 68 
o PASI =0 at week 68 
o PASI >0 at week 68. 
For these subgroups the following endpoints will be analyzed: 
• Proportion of subjects who achieve an absolute PASI score of 0, ≤1 and <3 at week 
116/164/220 
• Proportion of subjects who achieve an absolute PASI score <3 and ≤5 by visit 
• PASI values over time 
• Time to end of the treatment-free period 
• Proportion of subjects who achieve a DLQI score 0/1 and <5 over time 
• Proportion of subjects with DLQI values falling in quality-of-life categories. 
Subgroup analyses will be performed on both, the ITT and the PP analysis set (if evaluated), after 
the rule for handling of protocol-prohibited medication/therapy has been applied using non-
responder imputation for binary endpoints (for the proportion of subjects with DLQI values falling 
in quality-of-life categories: observed cases analysis) and observed cases analyses for time-to-
event endpoints. The decision whether the PP should be used for the subgroup analyses will be 
taken at the Data Review Meeting for Study Part 3. 
Note: At the Data Review Meeting and/or Dry Run Meeting for Study Part 3 it will be decided 
which subgroup analyses will actually be performed for Study Part 3. 
Update after the Dry Run Meeting: No PP analysis will be performed. All subgroups defined in 
the final SAP (version 1.0) will be kept for analysis, and none will be added. In new tables, for 
each subgroup category the subgroups will be compared by statistical testing for the total of 
subjects (not separately for group 3a and 3b); the only exception where this will not be done are 
the subgroups created based on the prior psoriasis therapy regimen. New figures to display 
subgroups will be generated for the time to end of the treatment-free period. 


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5.9. 
Interim Analyses 
No formal confirmatory interim analysis is planned for this study. Statistical analyses are 
performed separately for each of the three Study Parts. The statistical analysis of Study Parts 1 and 
2 did not represent an interim analysis of the study, they rather evaluated disjoint study phases. 
Study Part 3 was prolonged by a CSP amendment. In order to obtain early results for the Drug 
withdrawal phase, the data of Study Part 3 will be analyzed after all subjects still in study had their 
week 116, 164, or 220 visit (or discontinued before). The week 116 and week 164 analysis are 
regarded as explorative interim analyses for Study Part 3. 
5.9.1. 
Data Monitoring Committee (DMC) or Other Review Board 
A data monitoring committee has not been employed for review of efficacy and/or safety data. 
 
 
 


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6. 
SUPPORTING DOCUMENTATION 
6.1. 
Appendix 1  List of Abbreviations 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
ANCOVA 
Analysis of covariance 
AST 
Aspartate aminotransferase 
ATC 
Anatomic therapeutic class 
BMI 
Body mass index 
bpm 
beats per minute 
BSA 
Body surface area 
CI 
Confidence interval 
CLIN 
Clinical 
CSP 
Clinical Study Protocol 
DLQI 
Dermatology Life Quality Index 
DMC 
Data Monitoring Committee 
eCRF 
electronic Case Report Form 
eg 
example given 
FAE 
Fumaric acid ester 
FOIA 
Freedom of Information Act 
GCP 
Good Clinical Practice  
ICH 
International Council for Harmonization 
ie 
that is 
ITT 
Intent-to-treat 
LOCF 
Last observation carried forward 
LS 
Least squares 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
mmHg 
Millimeter of mercury 
MTX 
Methotrexate 
NAPPA 
Nail Assessment in Psoriasis and Psoriatic Arthritis 
NAPSI 
Nail Psoriasis Severity Index 
OR 
Odds ratio 
PASI 
Psoriasis Area and Severity Index 
PBI 
Patient Benefit Index 
PK 
Pharmacokinetic(s) 
PP 
Per protocol 
PSO 
Psoriasis 
PSSD 
Psoriasis Symptoms and Signs Diary 
PUVA 
Psoralene plus ultraviolet A radiation 
q8w/q16w  
every 8/16 weeks  
QoL 
Quality of life 
RD 
Risk difference 
RR 
Relative risk 
SAE 
Serious adverse event 
SAP 
Statistical Analysis Plan 
SAS 
Statistical Analysis System 
SD 
Standard deviation 
SDTM 
Standard Data Tabulation Model 
SOC 
System organ class 
SRe 
Super-Responder 
ULN 
Upper limit of normal range 
UVB 
Ultraviolet B radiation 
vs. 
versus 
WHO-DD 
World Health Organization Drug Dictionary 


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6.2. 
Appendix 2  Changes to Protocol-Planned Analyses 
No important changes from the planned analyses specified in the protocol and its amendments 
were applied. 
However, the time point of analyses is changed slightly. While the CSP states that “interim 
analyses are planned after all subjects have completed their visit at week 116 (or at week 144 in 
case of subjects entering the re-treatment arm in week 116) and at week 164 (or at week 192 in 
case of subjects entering re-treatment arm in week 164). The final analysis will be performed after 
all subjects have completed their visit at week 220 (or at week 248 in case of subjects entering the 
re-treatment arm in week 220)”, it was decided to split the analyses of group 3a/3b subjects and 
the analyses of group 3c subjects (re-treatment phase). By this, the results for the week 
116/164/220 analyses of study groups 3a and 3b will be available as soon as possible. A separate 
SAP will be written for the analysis of the re-treatment phase that will include – beneath the group 
3c – also the analysis of study group 2d (subjects who entered the re-treatment phase already in 
study part 2). 
In addition, some new analyses have been added to the evaluation; see section 5.6 for details. 
6.3. 
Appendix 3  Demographics and Baseline Characteristics 
Subjects' demographic data (eg, age, weight, BMI, height, sex, childbearing potential, and race) 
and baseline disease characteristics (eg, age at diagnosis, BSA [%], baseline DLQI, PSSD, 
NAPPA-CIN (if applicable), PASI score, psoriasis arthritis, and nail assessment) will be 
summarized. In addition, summaries of subjects' medical history and current diagnoses will be 
provided (see section 6.6). 
Table 5 presents a list of the demographic variables that will be summarized. 
Table 5 – Demographic Variables 
Continuous Variables 
Summary Type 
Age (years) 
Descriptive statistics (N, mean, 
standard deviation [SD], 
median, quartiles, and range 
[minimum and maximum]). 
Weight (kg) 
Height (cm) 
BMI (kg/m²) 
Categorical Variables 
 
Age (< 45, >= 45 to 65, > 65 years) 
Frequency distribution with the 
number and percentage of 
subjects in each category. 
Sex (male, female) 
Childbearing potential (of childbearing potential, permanently 
sterilized, postmenopausal) 
BMI (normal ≤ 25, overweight > 25 – 30, obese > 30 kg/m²) 
Racea (White, Asian, Black, Multiple, Other, Unknown) 
a If multiple race categories are indicated, the Race is recorded as 'Multiple' 
6.4. 
Appendix 4  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 study. Subjects 


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with major protocol deviations will be identified prior to database lock and the subjects with major 
protocol deviations will be summarized by category. 
• 
Developed withdrawal criteria but not withdrawn 
• 
Entered but did not satisfy criteria 
• 
Received a disallowed concomitant treatment 
• 
Received wrong treatment or incorrect dose 
• 
Other: to be defined in the Major Protocol Deviation Criteria document. 
The study selection criteria will also be grouped into the following 5 categories (psoriasis disease 
criteria, medication criteria, laboratory criteria, medical history criteria, and other), and will be 
summarized in a frequency table. 
6.5. 
Appendix 5  Prior and Concomitant Medications 
Subjects’ prior psoriasis therapy history with topical therapy, phototherapy (PUVA, UVB), non-
biologic systemic therapies (MTX, Cyclosporine, FAE, Acitretin, Apremilast, Tofacitinib, oral 
steroids, and other, if applicable), and biologic medications (Infliximab, Etanercept, Adalimumab, 
Efalizumab, Ustekinumab, Secukinumab, Ixekizumab, Brodalumab, Certolizumab, and other, if 
applicable) will be summarized. The allocation of medications to the four categories of therapy 
will be approved at the Data Review Meeting and/or Dry Run Meeting. 
Subjects' last psoriasis therapy prior to participation in this study will be analyzed analogously. In 
addition, reasons for which subjects discontinued previous systemic therapies including PUVA, 
Methotrexate, FAE, Cyclosporine, Adalimumab, Ustekinumab, Secukinumab, Ixekinumab, 
Certolizumab (contraindication, inadequate response, intolerance [ie, AEs], or other) will be 
summarized. 
For analysis of psoriasis therapies by therapy regimen as described above, the patients will be 
counted in only one therapy regimen according to the following hierarchical derivation procedure: 
Table 6 – Hierarchic Prior Psoriasis Therapy Regimen 
Therapy regimen 
Derivation 
Topical therapy 
All patients receiving at least one prior psoriasis medication of the 
type 'Topical' as defined above who did not receive a medication 
of another type. 
Phototherapy 
All patients receiving at least one prior psoriasis medication of the 
type 'Phototherapy' as defined above who did not receive a 
medication of another type except 'Topical' 
Non-biologic systemic 
therapy 
All patients receiving at least one prior psoriasis medication of the 
subtype 'Non-biologic systemic' as defined above who did not 
receive a medication of another type except 'Topical' or 
'Phototherapy'. 
Biologic therapy 
All patients receiving at least one prior psoriasis medication of the 
subtype 'Biologics' as defined above who did not receive a 
medication of another type except 'Topical' (type), 'Phototherapy' 
(type), or 'Non-biologic systemic' (subtype). 


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In addition, the number of subjects who received concomitant treatment with a moisturizer for 
psoriasis will be summarized. 
Prior and concomitant non-psoriasis therapies will be summarized descriptively. 
Prior and Concomitant therapies (psoriasis and non-psoriasis) will be coded using the World 
Health Organization Drug Dictionary (WHO-DD). Prior therapies are defined as any therapy used 
before the day of first dose (partial or complete) of study agent at week 0. Concomitant therapies 
are defined as any therapy used on or after the same day as the first dose of study agent, including 
those that started before and continue on after the first dose of study agent. In the statistical analysis 
only therapies will be counted as ‘concomitant' for Study Part 3 analysis, which started before or 
at the date of the week 116/164/220 visit (stop of the respective Study Part 3 analysis window). 
Summaries of concomitant therapies will be presented by Anatomic Therapeutic Class (ATC) level 
2 term and Preferred Name. The proportion of subjects who receive each concomitant therapy will 
be summarized as well as the proportion of subjects who receive at least one concomitant therapy. 
Prior therapies (incl. psoriasis therapies) will also be summarized by ATC level 2 term and 
Preferred Name. 
The frequency table of subjects’ prior psoriasis therapy history will be repeated by displaying 
Preferred Names by category used for hierarchization. 
6.6. 
Appendix 6  Medical History 
Categorical family history data will be summarized by means of a frequency table. The number 
and percentage of subjects with findings regarding the medical history terms of interest will be 
displayed in MedDRA system organ class (SOC) and Preferred Terms (PT). Summary tabulation 
will also consider whether the disease is ongoing or not at screening visit. 
6.7. 
Appendix 7  Intervention Compliance 
Study agent compliance within Study Part 2 will be summarized descriptively. Study agent 
compliance will be calculated as follows: 
Study agent compliance (%) = 100 x number of actual administrations / number of planned 
administrations). 
Study agent compliance during Study Parts 1 and 2 will also be assessed by protocol deviations 
related to study drug administration (ie, incorrect and missed administrations), if rated relevant for 
Study Part 3. 
6.8. 
Appendix 8  Adverse Events of Special Interest 
Not applicable for Study Part 3 analysis. 
6.9. 
Appendix 9  Medications of Special Interest 
Not applicable for Study Part 3 analysis. 
6.10. 
Appendix 10  Laboratory Toxicity Grading 
Not applicable for Study Part 3 analysis. 
 
 


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7. 
REFERENCES 
Protocol CNTO1959PSO3012; Phase 3b,  AMENDMENT 5, Janssen-Cilag GmbH,  Approved 14 
June 2021 
Mantel, N, & W Haenszel. 1959. „Statistical Aspects of Analysis of Data from Retrospective 
Studies of Disease.“ J Natl Cancer Inst, 719-748. 
Sato, T. 1989. „On the Variance Estimator of the Mantel-Haenszel Risk Difference.“ Biometrics, 
1323-1324.