Clinical trial NCT02951533
Conditions: Psoriasis
Sponsor: Janssen-Cilag G.m.b.H
Start date: 2016-12-12; Completion date: 2019-02-06
Enrollment: 119 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of the study is to compare the efficacy of Guselkumab with commercially available active comparator Fumaderm initial/Fumaderm tablets for the treatment of adult participants with moderate to severe plaque-type psoriasis who have not yet received any systemic therapy.

Detailed description:

Arms: arm 1: Participants will receive Guselkumab 100 milligram (mg) administered as 100 milligram per milliliter (mg/mL) solution subcutaneously (SC) by single-use prefilled syringe (PFS) at weeks 0, 4, 12 and 20. arm 2: Participants will receive Fumaderm initial/Fumaderm tablets by self administration at week 0. The individual FAE dose representing the optimal efficacy/tolerability ratio needs to be determined for each participant according to local prescription information. To this aim, FAE doses will be slowly increased beginning with increasing doses of Fumderm initial (containing 30 mg dimethylfumarate) over the first 3 weeks. Thereafter, participants will be switched to Fumaderm tablets (containing 120 mg dimethylfumarate) starting with 1 tablet per day. Fumaderm dose may be increased to a maximum of 3\*2 tablets per day. The decision to maintain, increase or decrease the FAE dose depends on efficacy, safety and tolerability.
Interventions: intervention 1: Guselkumab intervention 2: Fumaric Acid Esters
Intervention descriptions: intervention 1: Participants will receive 100 mg of Guselkumab as 100 mg/mL solution subcutaneously. intervention 2: Participants will receive Fumaderm initial/ Fumaderm tablets through self-administration.

Protocol documents:
Prot_002.pdf: 
1 
Approved, Date: 22 January 2018 Approved, Date: 22 January 2018  
 
Janssen-Cilag GmbH*, Germany 
 
Clinical Protocol 
 
Multicenter, randomized, open-label, efficacy assessor-blinded, active comparator-
controlled phase 3b study to compare the efficacy of guselkumab to fumaric acid esters 
(Fumaderm® initial/ Fumaderm®) for adult patients with moderate to severe plaque 
psoriasis who are candidates for and naive to systemic treatment 
 
POLARIS 
 
Protocol CNTO1959PSO3008; Phase 3b 
AMENDMENT INT-2 
 
CNTO1959 (guselkumab)    
 
*Janssen-Cilag is a regional organization that operates through different legal entities in Germany. 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: 2016-002135-15 
 
Status: 
ApprovedApproved3.0 
Date: 
22 January 201822 January 2018 
Prepared by: Janssen-Cilag GmbH, Germany  
EDMS number: EDMS-ERI-126661962 
 
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. 
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TABLE OF CONTENTS 
 
Page 
TABLE OF CONTENTS ................................................................................................................. 2 
LIST OF ATTACHMENTS............................................................................................................. 4 
PROTOCOL AMENDMENTS ........................................................................................................ 6 
SYNOPSIS ..................................................................................................................................... 20 
ABBREVIATIONS ........................................................................................................................ 36 
1. 
INTRODUCTION ................................................................................................................. 37 
1.1. 
Background ......................................................................................................................... 37 
1.2. 
Comparator ......................................................................................................................... 40 
1.3. 
Overall Rationale for the Study ............................................................................................ 40 
2. 
OBJECTIVES AND HYPOTHESES .................................................................................... 41 
2.1. 
Objectives ........................................................................................................................... 41 
2.2. 
Hypotheses ......................................................................................................................... 41 
3. 
STUDY DESIGN AND RATIONALE ................................................................................... 42 
3.1. 
Overview of Study Design ................................................................................................... 42 
3.2. 
Study Design Rationale ........................................................................................................ 45 
4. 
SUBJECT POPULATION .................................................................................................... 46 
4.1. 
Inclusion Criteria ................................................................................................................. 46 
4.2. 
Exclusion Criteria ................................................................................................................ 49 
4.3. 
Prohibitions and Restrictions ................................................................................................ 51 
4.4. 
Treatment Assignment Criteria for Study Part II (Week 24 through Week 56) ......................... 52 
4.4.1. 
Study Part IIb: Treatment Switch Safety Criteria ................................................................ 52 
4.5. 
Eligibility Criteria for Study Part III: Week 64 until loss of response or Week 100 ................... 53 
5. 
TREATMENT ALLOCATION AND BLINDING ................................................................ 53 
6. 
DOSAGE AND ADMINISTRATION ................................................................................... 53 
6.1. 
Study Drug Dosage .............................................................................................................. 54 
6.1.1. 
Study Part I and Study Part IIa: Active Comparative Treatment ........................................... 54 
6.1.2. 
Study Part IIb: Continuation/Switch of Study Treatment (Week 32 through Week 56) .......... 54 
6.1.3. 
Safety Follow-up Phase: Psoriasis Treatment ..................................................................... 55 
6.1.4. 
Study Part III, Follow-up Extension Phase: Guselkumab Withdrawal, No Study 
Treatment (Week 64 through Week 100) ............................................................................ 55 
6.2. 
Study Drug Administration .................................................................................................. 55 
6.2.1. 
Guselkumab ..................................................................................................................... 55 
6.2.2. 
Fumaric Acid Esters ......................................................................................................... 55 
7. 
TREATMENT COMPLIANCE ............................................................................................ 57 
8. 
PRESTUDY AND CONCOMITANT THERAPY ................................................................. 58 
8.1. 
Concomitant Medications for Treatment of Psoriasis ............................................................. 58 
8.1.1. 
Treatment Phase ............................................................................................................... 58 
8.1.2. 
Safety Follow-Up Phase .................................................................................................... 58 
8.1.3. 
Follow-up Extension Phase ............................................................................................... 59 
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8.2. 
Concomitant Medications for Conditions Other than Psoriasis ................................................ 59 
9. 
STUDY EVALUATIONS ...................................................................................................... 59 
9.1. 
Study Procedures ................................................................................................................. 59 
9.1.1. 
Overview ......................................................................................................................... 59 
9.1.2. 
Screening Phase ............................................................................................................... 60 
9.1.3. 
Screening Failure/Re-screening ......................................................................................... 61 
9.1.4. 
Open-Label Assessor-blinded Treatment Phase .................................................................. 61 
9.1.5. 
Safety Follow-up Phase .................................................................................................... 62 
9.1.6. 
Follow-up Extension Phase after Guselkumab Withdrawal .................................................. 62 
9.2. 
Efficacy .............................................................................................................................. 62 
9.2.1. 
Evaluations ...................................................................................................................... 62 
9.2.2. 
Endpoints......................................................................................................................... 62 
9.2.3. 
Blinded Efficacy Assessment ............................................................................................ 63 
9.2.3.1. 
Involved Body Surface Area (BSA%) ............................................................................. 64 
9.2.3.2. 
Investigator’s Global Assessment (IGA) ......................................................................... 64 
9.2.3.3. 
Scalp Specific Investigator Global Assessment (ss-IGA) .................................................. 64 
9.2.3.4. 
Psoriasis Area and Severity Index (PASI)........................................................................ 64 
9.2.4. 
Patient-reported outcomes (PROs) ..................................................................................... 65 
9.2.4.1. 
Dermatology Life Quality Index ..................................................................................... 65 
9.2.4.2. 
Psoriasis Symptom and Sign Diary ................................................................................. 65 
9.2.4.3. 
Short Form Health Survey (SF-36) ................................................................................. 65 
9.3. 
Safety Evaluations ............................................................................................................... 66 
9.4. 
Sample Collection and Handling ........................................................................................... 68 
10. 
SUBJECT COMPLETION/DISCONTINUATION OF STUDY TREATMENT/ 
WITHDRAWAL FROM THE STUDY ................................................................................. 68 
10.1. 
Completion ......................................................................................................................... 68 
10.2. 
Discontinuation of Study Treatment/Withdrawal from the Study ............................................ 68 
11. 
STATISTICAL METHODS .................................................................................................. 71 
11.1. 
Subject Information ............................................................................................................. 71 
11.2. 
Sample Size Determination .................................................................................................. 71 
11.3. 
Efficacy Analyses ................................................................................................................ 72 
11.4. 
Criteria for Endpoints .......................................................................................................... 74 
11.5. 
Safety Analyses ................................................................................................................... 74 
11.6. 
Interim and Final Analyses ................................................................................................... 75 
12. 
ADVERSE EVENT/ADVERSE DRUG REACTION REPORTING ..................................... 76 
12.1. 
Definitions .......................................................................................................................... 76 
12.1.1. 
Adverse Event/Adverse Drug Reaction Definitions and Classifications ................................ 76 
12.1.2. 
Attribution Definitions ...................................................................................................... 77 
12.1.3. 
Severity Criteria ............................................................................................................... 77 
12.2. 
Special Reporting Situations ................................................................................................. 78 
12.3. 
Procedures .......................................................................................................................... 78 
12.3.1. 
All Adverse Events/Adverse Drug Reactions ...................................................................... 78 
12.3.2. 
Serious Adverse Events/Serious Adverse Drug Reactions ................................................... 79 
12.3.3. 
Pregnancy ........................................................................................................................ 79 
12.3.4. 
Events of Special Interest .................................................................................................. 80 
12.4. 
Contacting Sponsor Regarding Safety ................................................................................... 80 
 
 
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13. 
PRODUCT QUALITY COMPLAINT HANDLING ............................................................. 80 
13.1. 
Procedures .......................................................................................................................... 80 
13.2. 
Contacting Sponsor Regarding Product Quality ..................................................................... 80 
14. 
STUDY DRUG INFORMATION .......................................................................................... 80 
14.1. 
Physical Description of Study Drug(s) .................................................................................. 80 
14.2. 
Packaging ........................................................................................................................... 81 
14.3. 
Labeling ............................................................................................................................. 81 
14.4. 
Preparation, Handling, and Storage ....................................................................................... 81 
14.5. 
Drug Accountability ............................................................................................................ 82 
15. 
STUDY-SPECIFIC MATERIALS ........................................................................................ 82 
16. 
ETHICAL ASPECTS ............................................................................................................ 83 
16.1. 
Study-Specific Design Considerations................................................................................... 83 
16.2. 
Regulatory Ethics Compliance.............................................................................................. 83 
16.2.1. 
Investigator Responsibilities .............................................................................................. 83 
16.2.2. 
Independent Ethics Committee or Institutional Review Board ............................................. 83 
16.2.3. 
Informed Consent ............................................................................................................. 84 
16.2.4. 
Privacy of Personal Data ................................................................................................... 85 
17. 
ADMINISTRATIVE REQUIREMENTS .............................................................................. 85 
17.1. 
Protocol Amendments .......................................................................................................... 85 
17.2. 
Regulatory Documentation ................................................................................................... 86 
17.2.1. 
Regulatory Approval/Notification ...................................................................................... 86 
17.2.2. 
Required Pre-study Documentation ................................................................................... 86 
17.3. 
Subject Identification, Enrollment, and Screening Logs .......................................................... 87 
17.4. 
Source Documentation ......................................................................................................... 87 
17.5. 
Case Report Form Completion ............................................................................................. 88 
17.6. 
Data Quality Assurance/Quality Control ............................................................................... 88 
17.7. 
Record Retention ................................................................................................................. 88 
17.8. 
Monitoring .......................................................................................................................... 89 
17.9. 
Study Completion/Termination ............................................................................................. 89 
17.9.1. 
Study Completion/End of Study ........................................................................................ 89 
17.9.2. 
Study Termination ............................................................................................................ 89 
17.10.  On-Site Audits .................................................................................................................... 90 
17.11.  Use of Information and Publication ....................................................................................... 90 
REFERENCES .............................................................................................................................. 92 
ATTACHMENTS .......................................................................................................................... 93 
INVESTIGATOR AGREEMENT ................................................................................................. 98 
 
LIST OF ATTACHMENTS 
Attachment 1: Investigator´s Global Assessment (IGA) ............................................................................ 93 
Attachment 2: Psoriasis Area and Severity Index (PASI) .......................................................................... 94 
Attachment 3: QuantiFERON TB Gold Plus Test ...................................................................................... 95 
Attachment 4: Hepatitis B Virus (HBV) Screening with HBV DNA ......................................................... 94 
Attachment 5: Scalp-specific IGA (ss-IGA) ............................................................................................... 95 
 
 
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LIST OF TABLES 
Table 1: Time and Events Schedule: From Screening through Week 24 (Study Part I) ............................. 27 
Table 2: Time and Events Schedule: From Week 24 through Week 64 (Study Part II) ............................. 31 
Table 3: Time and Events Schedule: Follow-Up Extension Week 64 through Week 100 (Study 
Part III) ..................................................................................................................................... 34 
Table 4: Uptitration of Fumaderm® initial .................................................................................................. 56 
Table 5: Uptitration of Fumaderm® ............................................................................................................ 56 
Table 6: Volume of Blood to be Collected from Each Subject ................................................................... 60 
 
LIST OF FIGURES 
Figure 1: Schematic Overview of the Study ............................................................................................... 44 
 
 
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PROTOCOL AMENDMENTS 
Protocol Version  
Issue Date 
Original Protocol 
3. August 2016 
Amendment INT-1 
Amendment INT-2 
25. April 2017 
22. January 2018 
AMENDMENT INT-2  
This amendment is considered substantial based on the criteria set forth in Article 10(a) of Directive 
2001/20/EC of the European Parliament and the Council of the European Union.  
Rationale 
Amendment INT-2 is implemented to investigate maintenance of response after guselkumab withdrawal in 
a 36-week study extension in subjects who responded well (PASI 90 response) to guselkumab. 
Implementation 
Amendment INT-2 will be implemented at study sites with subjects under guselkumab treatment. 
Study Design Overview 
With protocol Amendment INT-2, the study will be split into three parts (Study Part I, II and III): 
 Study Part I (Core Study, Active Comparative Treatment)— Week 0 through Week 24 
No change in treatment plan. 
 Study Part II (Extension, Continuation/Switch of Study Treatment)—Week 24 through Week 56 
No change in treatment plan but adaption of a secondary endpoint. 
 Safety Follow-up Phase—Week 56 through Week 64 
No change. Wording adapted for clarity reasons. 
Note: Subjects who start a new systemic psoriasis treatment including commercially available 
guselkumab therapy or received another protocol-prohibited medication/therapy during safety follow-
up phase are not eligible to enter Study Part III.  
 Study Part III (Follow-up Extension, Guselkumab Withdrawal, No Study Treatment)—Week 64 
through Week 100 
Subjects who received guselkumab in Study Part II (subjects who started with guselkumab from Week 
0 and subjects who switched from fumaric acid esters to guselkumab treatment in Week 32), had no 
psoriatic arthritis diagnosed at baseline and achieved a PASI 90 response at end of Study Part II (Week 
56) may enter follow-up extension at Week 64. To be eligible for follow-up extension (Study Part III) 
subjects must not have started a new psoriasis treatment including commercial guselkumab therapy, or 
started any other prohibited treatment/therapy. In Study Part III, subjects are withdrawn from study 
treatment and will be followed until loss of response (defined as an increase in absolute PASI >5), but 
until Week 100 at the latest, which is almost 1 year after the last guselkumab treatment at visit Week 
52.  
All other subjects may not enter Study Part III and complete the study at Week 64. 
Statistical Analysis 
Confirmatory analysis of the primary endpoint and secondary analysis for Study Part I and II data remain 
unchanged. However, one secondary endpoint for Study Part II has been adapted to capture the proportion 
of patients with PASI 75, 90 or 100 responses throughout the study period baseline to Week 56 for all 
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patients enrolled. Previously this parameter was to be analyzed for subjects of the FAE group who were 
PASI 75 non-responders at Week 32 and switched to guselkumab, only. The final exploratory statistical 
analysis of Study Part III will be performed after the last subject has lost response, discontinued study 
participation or has completed the visit at Week 100. New secondary endpoints for exploratory analysis of 
study results are defined as follows. 
- Proportion of subjects with a PASI 75/90/100 response compared to baseline and DLQI score 0 or 1 
at Week 56 
- Maintenance of PASI 90 response after guselkumab withdrawal  
- Time to loss of response after guselkumab withdrawal 
All significant changes to the protocol are summarized in the following table. Deleted sections are crossed 
out. Amended sections are presented in bold script and underlined. Additionally, minor changes to the 
language of the protocol and minor editorial changes are implemented with this amendment to improve 
clarity. Changes of minor significance are not listed below. 
Applicable Section(s) 
Description of Change(s) 
Synopsis and  
Section 2.1, Objectives 
The secondary objectives of the study are 
 
in Study Parts I and II: to compare improvement of health-related quality of life 
(QOL) and other patient-reported outcomes (PRO) when systemic treatment-
naïve subjects with moderate to severe plaque-type psoriasis are treated with 
guselkumab compared to FAE. 
 
in Study Part II: to compare sustainability of response to treatment when systemic 
treatment-naïve subjects with moderate to severe plaque-type psoriasis are treated 
with guselkumab compared to FAE. 
 
in Study Part III (guselkumab withdrawal): to investigate the maintenance 
of response in subjects withdrawn from study treatment, and to explore 
prediction parameters of disease modification. 
Rationale: Implementation of Study Part III objectives.
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Applicable Section(s) 
Description of Change(s) 
Synopsis and 
Section 3.1, overview 
of study design 
This study will have a 3-week screening phase, a 56-week treatment phase and a safety 
follow-up phase until Week 64, followed by a follow-up extension phase after 
withdrawal of guselkumab until loss of response or until Week 100 at the latest (as 
shown in Figure 1). The maximum duration of a subject’s participation in this study will be 
67 103 weeks. With protocol Amendments INT-1 and INT-2, the study will be split into 
two three parts (Study Part I, and II and III): 
… 
Efficacy of treatment will be assessed before any tests, procedures or other evaluations, 
first by the subject him/herself (1st DLQI, 2nd PSSD 7-day version, and 3rd SF-36), and 
subsequently, in Study Part I and II, by a blinded efficacy assessor (BSA%, IGA, ss-IGA, 
and PASI). Preferably the same efficacy assessor continues evaluation of the disease in 
Study Part II, but efficacy assessments are no longer blinded. 
… 
Study Part II (Extension, Continuation/Switch of Study Treatment)—Week 24 through 
Week 56 
…  
Study Part III (Follow-up extension, guselkumab withdrawal, no study treatment)—
Week 64 through Week 100 
Subjects who received guselkumab in Study Part II (subjects who started guselkumab 
treatment at Week 0 or switched from FAE to guselkumab treatment in Week 32), 
had no psoriatic arthritis diagnosed at baseline and achieved a PASI 90 response at 
end of Study Part II (Week 56) may enter follow-up extension at Week 64. To be 
eligible for follow-up extension subjects must have signed ICF for Study Part III 
before or at Week 64, must not have started a new psoriasis treatment (including 
commercially available guselkumab therapy) or started any other protocol-prohibited 
medication/therapy. In Study Part III, subjects are withdrawn from guselkumab 
treatment and will be followed until loss of response (defined as an increase in absolute 
PASI >5), but until Week 100 at the latest, which is almost 1 year after the last 
guselkumab treatment at visit Week 52.  
All other subjects may not enter Study Part III and terminate study at Week 64. 
Efficacy assessments will be performed first by the subject him/herself, and 
subsequently by an efficacy assessor. Preferably, in Study Part III the same efficacy 
assessor as in Study Parts I and II continues evaluation of the disease, but efficacy 
assessments are no longer blinded. 
The maximum duration of a subject’s participation will be 103 weeks including a 3-
week screening phase. 
Safety Follow-up Phase 
 
Safety FUP (Part I) – Week 24 through Week 32 
For subjects who complete study treatment at Week 24 a final safety follow-up 
visit is completed at Week 32.  
 
Safety Follow-up (Part II) – Week 56 through Week 64 
All ongoing subjects complete the safety follow-up until Week 64. For subjects 
who complete study treatment at Week 56 a final safety follow-up visit is 
completed at Week 64. For subjects entering Study Part III the safety follow-
up visit will be conducted and subjects will continue as described below. 
Safety Follow-up after discontinuation/withdrawal – 12 weeks after last 
treatment  
 
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Applicable Section(s) 
Description of Change(s) 
Synopsis and 
Section 3.1, overview 
of study design 
(continued) 
For subjects who discontinue study treatment or withdraw from study 
participation, final study assessments are obtained and a final safety follow-up 
visit is completed 12 weeks after last treatment.  
… 
The overall duration of the study is expected to be approximately 21 30 months (start in 
December 2016, stop in July 2019October 2018). The estimated frequency and timing of 
the study visits are summarized in the ‘Time and Events Schedule’ (TES). 
Section 3.1 only 
 
Efficacy of treatment will be assessed before any tests, procedures or other evaluations, 
first by the subject him/herself (1st DLQI, 2nd PSSD 7-day version, and 3rd SF-36), and 
subsequently, in Study Part I and II, by a blinded efficacy assessor (BSA%, IGA, ss-IGA, 
and PASI). Preferably, the same efficacy assessor continues evaluation of the disease 
in Study Part III, but efficacy assessments are no longer blinded. 
… 
The confirmatory analysis will be conducted after the primary endpoint at Week 24 is 
reached including subjects who have completed the Week 24 visit and subjects who have 
terminated the study prematurely (Section 11.3). The finalsecond and third statistical 
analyseis will be performed after Week 64 and after Week 100 (see Section 11). 
Synopsis and 
Section 3.1, overview 
of study design  
A subject will be considered to have completed Study Part I or Study Part II if he or 
she has completed assessments at Week 24 and Week 56, respectively. A subject will 
be considered to have completed Study Part III if he or she has completed assessments 
at Week 100 or completed final assessments after loss of response.  
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 transferred to the sponsor (or designee) 
after completion of the final subject visit at that study site, in the time specified in the 
Clinical Trial Agreement. The overall duration of the study is expected to be approximately 
21 30 months (start in December 2016, stop in July 2019October 2018). The estimated 
frequency and timing of the study visits are summarized in the ‘Time and Events Schedule’ 
(TES). 
Note: Figure 1 has been adapted to new study design! 
Rationale: Description of new study design, safety follow-up changed for clarity reasons and adjustment of study 
duration. 
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Applicable Section(s) 
Description of Change(s) 
Synopsis and 
Section 6, Dosage and 
administration 
Study Part IIb, continuation/switch of study treatmentactive treatment: Week 32 through 
Week 56 
… 
Subjects who complete Study Part II enter the safety follow-up phase after completion of 
all Study Part II assessments at Week 56. For these subjects, the safety follow-up phase 
spans Week 56 to Week 64. All subjects, regardless whether they continue with Study 
Part III or not, complete the safety follow-up visit at Week 64. For all subjects who do 
not enter Study Part III, study participation ends with athe safety FUP visit at Week 64. 
Subjects who discontinue study treatment or withdraw from study participation, 
safety follow-up visit is completed 12 weeks after last treatment.  
 
During the safety follow-up phase treatments for psoriasis may be administered at the 
investigator’s discretion as follows: 
 
Group I (Gus): If commercially available, investigator may continue actual 
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 additional therapy 
is needed, this should be discussed with the sponsor before initiation of the new 
therapy.  
Note: Subjects who start a new psoriasis treatment, including commercially available 
guselkumab, during safety follow-up phase are not eligible to enter Study Part III.  
 
Group II (FAE): Investigator may either continue the actual FAE treatment with 
commercially available drug or switch to another commercially available 
treatment.   
Study Part III, follow-up extension phase, guselkumab withdrawal, no study 
treatment: Week 64 through Week 100 
Subjects in the guselkumab group who are eligible to enter Study Part III are 
withdrawn from study treatment and followed until loss of response or until Week 
100 at the latest. Eligible subjects in the guselkumab group may enter Study Part III 
after end of safety FUP. All subjects complete the safety FUP visit and eligible subjects 
continue with efficacy assessments at visit Week 64. Subjects may start a commercially 
available topical psoriasis treatment at Week 64 or later at the investigator’s 
discretion, except topical corticosteroids class IV (alone or in combination) and 
phototherapy. 
Section 6, section 
headings 
6.1.2. 
Study Part IIb: Continuation/Switch of Study Treatment (Week 32 through 
Week 56) 
6.1.4. 
Study Part III, Follow-up Extension Phase: Guselkumab Withdrawal, No 
Study Treatment (Week 64 through Week 100) 
Rationale: Implementation of Study Part III; additional editorial changes.
Synopsis, Statistical 
methods  
They will be exploratory for all other secondary endpoints including Study Part II and Part 
III endpoints. 
Rationale: Implementation of Part III statistical analysis.
 
 
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Applicable Section(s) 
Description of Change(s) 
Synopsis and Section 
9.2.2, Statistical 
methods and Endpoints 
- Proportion of subjects of the FAE group who were PASI 75 non-responders at 
Week 32 and switched to guselkumab with a  
- PASI 75 response (compared to Week 0baseline) at Week 56 
- PASI 90 response (compared to Week 0baseline) at Week 56 
- PASI 100 response (compared to Week 0baseline) at Week 56 
- DLQI score 0 or 1 at Week 56 
- Proportion of subjects with a  
- PASI 75 response (compared to baseline) at Week 32 
- PASI 90 response (compared to baseline) at Week 32 
- PASI 100 response (compared to baseline) at Week 32 
- DLQI score 0 or 1 at Week 32 
- Maintenance of response after guselkumab withdrawal. Proportion of 
subjects of the guselkumab group (GUS-GUS and FAE-GUS) with a   
- PASI 90 response at Week 56 who maintain response until Week 100 
- Time to loss of response from Week 56 after guselkumab withdrawal until 
Week 100 
Synopsis and Section 
11.3, Efficacy analyses 
For all efficacy analyses in the follow-up extension phase (Study Part III; Week 
100 analysis), all subjects who entered Study Part III and received guselkumab 
from Week 0 and subjects who received FAE from Week 0 to Week 32 and 
switched to guselkumab will be analyzed. 
Synopsis, DBL  
Data base locks (DBL) will be after the Week 24/64/100 visit data are ready for 
statistical analysis (ie, clean data). All analyses including all primary and secondary 
analyses as well as additional analyses as described in detail in the SAPs will be 
performed after the respective DBLs.
Rationale: Adjustment of statistical analysis to changed study design; adaption of secondary endpoint for analysis of 
Study Part II to capture proportion of subjects with PASI 75/90/100 response in all patients from baseline to Week 
56; minor editorial changes. Statistical analyses will be performed after completion of each study part. 
Time and events 
schedule 
Table 2, footnote h3: Safety Follow-up/Final Study Visit Study Part II (≤Week 64): For 
subjects who complete Study Part II or discontinue study treatment or withdraw from 
study participation in Study Part II. Safety FUP Part II visit is completed at Week 64 or 12 
weeks after last treatment (whatever comes first). 
Table 3: Time and Events Schedule: Follow-Up Extension Week 64 through Week 100 
(Study Part III) 
(new table describing schedule of Study Part II: please refer to table) 
Rationale: Adjustment of time and events schedule to changed study design.
Section 1.1, 
Background 
As of 30 June 201731 August 2016, 15 18 clinical studies of guselkumab have been 
completed or are ongoing. Seven Ten clinical studies have been completed and eight studies 
are ongoing. 
Rationale: Adjustment to current development; three more studies have been completed since implementation of 
Amendment INT-1. 
Section 1.3., Overall 
Rationale of the Study 
Finally, a withdrawal element has been incorporated into the study design (Study Part 
III) to assess the maintenance of response in subjects who discontinue guselkumab. 
Maintenance of response after drug withdrawal is indicative of disease modification. 
Rationale: Overall rationale for Study Part III.
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
12 
Approved, Date: 22 January 2018 Approved22 January 2018 
Applicable Section(s) 
Description of Change(s) 
Section 3.2, Study 
design rationale 
(continued) 
To help improve objectivity and decrease bias, given the open-label design, during Study 
Part I and II efficacy assessments will be performed by a blinded assessor, meaning the 
assessor of dermatological evaluation will not know the treatment group the subject to be 
evaluated belongs to. 
… 
Part II of this study (Week 24 to 56) is designed to exploratorily assess the sustainability 
of treatment efficacy (guselkumab and FAE). 
… 
Part III of this study (Week 64 to 100) is designed to assess the maintenance of 
response after guselkumab withdrawal in subjects who responded well (PASI 90 
response) to guselkumab. Maintenance of response after drug withdrawal is indicative 
of disease modification. 
Rationale: Specification and description of rationale of new study design.
Section 4.3, 
Prohibitions and 
restrictions 
2. Agree to follow the contraceptive requirements as noted in the inclusion criteria. 
Women participating in Study Part III, who are of childbearing potential (e.g. 
not premenarchal, not postmenopausal and not permanently sterile) and use a 
highly effective method of contraception, have to agree to remain on a highly 
effective method of contraception throughout the study. 
… 
4. Avoid donating blood for at least 90 days after last study treatment completion (ie, 
final safety follow-up visit) of the study. Subjects entering Study Part III should 
avoid donating blood until end of study (Final Study Visit),. 
Rationale: Implementation of Part III restrictions regarding contraceptive requirements and caution against blood 
donation. 
Section 4.5, Patient 
eligibility 
4.5. 
Eligibility Criteria for Study Part III: Week 64 until loss of response 
or Week 100 
Subjects treated with guselkumab in Study Part II (subjects who started guselkumab 
treatment at Week 0 or switched from FAE to guselkumab treatment in Week 32) 
may enter Study Part III at Week 64 when he/she: 
 
Signed ICF of Study Part III before or at Week 64  
 
Achieved a PASI 90 response at the end of Study Part II (Week 56) 
 
Had no diagnosis of psoriatic arthritis (PsA) at baseline 
 
Did not start a new psoriasis treatment before Week 64, including 
commercially available guselkumab 
 
Did not start any other protocol-prohibited medication/therapy 
 
Is a woman and used a highly effective method of contraception during Study 
Part I and II and agrees to remain on a highly effective method of 
contraception throughout the study. 
Rationale: Definition of eligibility criteria for Study Part III.
Section 5, Treatment 
allocation and blinding 
Blinding 
As this is an open study, blinding procedures for the treatment are not applicable. However, 
a blinded efficacy evaluator will assess effectiveness of treatment as described in Section 
9.2.3. During Study Part III, subjects who received guselkumab during Study Parts I 
or II only are eligible for Study Part III. During Study Part III subjects are no longer 
on study treatment, thus, efficacy assessments during Study Part III are no longer 
blinded. 
Rationale: Description of Study Part III procedures.
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
13 
Approved, Date: 22 January 2018 Approved22 January 2018 
Applicable Section(s) 
Description of Change(s) 
Section 7, Treatment 
compliance 
During Study Part III visits should occur within ±14 days of the scheduled visit. 
Rationale: Sentence added to implement Part III visits.
Section 8, Prestudy and 
Concomitant therapy 
… 
For subjects entering Study Part III, psoriasis therapy/medication will be recorded 
until end of study. In case any protocol-prohibited therapy is applied (for psoriasis or 
any other indication), the subject is withdrawn from study participation. Prohibited 
therapy is recorded as well as any newly planned psoriasis therapy, if already known 
at the end of the study.  
8.1.1. Treatment Phase 
… 
Topical therapies that could affect psoriasis (eg, corticosteroids, tar, anthralin, 
calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, methoxsalen, 
pimecrolimus, tacrolimus, and traditional Taiwanese, Korean, or Chinese 
medicines) are not permitted until Week 56, for subjects entering Study Part III 
until Week 64 (see Section 8.1.2. and 8.1.3).  
…. 
The use of phototherapy or systemic anti-psoriatic medications is not permitted 
until the Week 56 visit, for subjects entering Study Part III until end of study 
(see Section 8.1.2 and 8.1.3). 
… 
8.1.2 
Safety Follow-Up Phase 
See section 6.1.3 for instructions regarding treatment of psoriasis during the follow-up 
phase. Furthermore, for subjects to be eligible for Study Part III all psoriasis 
treatments/therapies, including commercially available guselkumab and topical 
treatments that could affect psoriasis (see Section 8.1.1), are prohibited. 
8.1.3 
Follow-up Extension Phase 
During Study Part III use of commercially available topical psoriasis treatment is 
allowed at the investigator’s discretion. However, topical corticosteroids class IV 
(alone or in combination) and phototherapy are prohibited until end of study (Week 
100). Systemic psoriasis therapies, including commercially available guselkumab, are 
prohibited during Study Part III. Patients starting any protocol-prohibited therapy 
will be withdrawn. 
Rationale: Implementation of Study Part III documentation.
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
14 
Approved, Date: 22 January 2018 Approved22 January 2018 
Applicable Section(s) 
Description of Change(s) 
Section 9.1.1, Study 
procedures, overview 
The Time and Events Schedules (TES), positioned after the SYNPOSIS, (Table 1 [Part 
I], Table 2 [Part II] and Table 3 [Part III]) summarizes the frequency and timing of 
efficacy, immunogenicity, and safety measurements applicable to performed during this 
study. 
All subjects will be asked to sign the consent form(s) (ICF I, II and III) before any 
study-related procedures of the respective study part (I, II, III) are conducted.  
Note: At the time amendment INT-1 has been implemented all subjects were enrolled 
and had signed the ICF established at study initiation (identical to ICF I). All subjects 
on study treatment were asked to acknowledge and sign ICF II for Study Part II 
(study extension). ICF II had to be signed by Week 24 at the latest by all subjects 
continuing with Study Part II.  
All subjects that might be eligible to enter Study Part III will be asked to acknowledge 
and sign ICF III (follow-up extension) by Week 64 at the latest. 
Adverse events and concomitant medication recording will start after ICF I has been 
signed and will continue until the last study-related procedure of Study Part I and II, 
respectively, has been completed. During Study Part III, adverse drug reactions and 
deaths will be recorded until end of study. Concomitant therapies will be recorded 
beyond Week 64 if they are in conjunction with serious adverse events that meet the 
criteria outlined in Section 12.3.2. In addition, any psoriasis treatment will be 
recorded throughout Study Part III. 
Rationale: Implementation of Study Part III procedures.
Section 9.1.2, Study 
procedures, screening 
phase 
The subjects will be asked to sign the consent form at the screening visit before any study 
related procedures are conducted (ICF I). Note: At the time this amendment is implemented 
all subjects will have been enrolled and will have signed the ICF established at study 
initiation (identical to ICF I). All subjects on study treatment will be asked to consent ICF 
II for Study Part II (study extension). ICF II has to be signed by Week 24 at the latest by 
all patients continuing to Study Part II. FAdverse events and concomitant medication 
recording will start after signing the informed consent and will continue until the last study-
related procedure has been completed. Concomitant therapies will be recorded beyond 
Week 64 if they are in conjunction with serious adverse events that meet the criteria 
outlined in Section 12.3.2. 
Rationale: Editorial change, paragraph has been shifted to Section 9.1.1.
Sections 9.1.5 and 
9.1.6, Study 
procedures, safety 
follow-up and follow-
up extension 
Subjects will be instructed that study drug will not be made available to them after they 
have completed/ discontinued the drug and that they should return to their physician to 
determine standard of care if not entering Study Part III.  
9.1.6. 
Follow-up Extension Phase after Guselkumab Withdrawal  
No study treatment is applied during the follow-up extension phase. During Study 
Part III, subjects may start a commercially available topical psoriasis treatment at 
Week 64 or later at the investigator’s discretion, except topical corticosteroids class 
IV (alone or in combination) and phototherapy. Subjects will be followed for safety 
information (ie, vital signs, physical examination, ADRs and death; no laboratory 
assessments) and unblinded efficacy assessments as specified in the TES until loss of 
response or until Week 100 at the latest. Subjects starting a systemic psoriasis 
treatment including commercially available guselkumab or other prohibited 
medication/therapy will be withdrawn. For subjects who withdraw from study 
participation, every effort should be made to conduct final efficacy and safety 
evaluations as listed in the TES (FSV Part III, see Section 10.2). 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
15 
Approved, Date: 22 January 2018 Approved22 January 2018 
Applicable Section(s) 
Description of Change(s) 
Rationale: Implementation of Study Part III procedures.
Section 9.2, Efficacy, 
Evaluations 
Efficacy evaluations chosen for this study are consistent with those used to evaluate other 
therapies for psoriasis. Efficacy evaluations will be first done by subjects (PROs) and then 
by the blinded efficacy assessor (Study Parts I and II; during Part III the assessor is no 
longer blinded). 
Rationale: Specification of procedures. 
Section 9.2.3, Blinded 
efficacy assessment 
An independent, blinded efficacy assessor, approved by the Sponsor, will be designated at 
each study site to perform all efficacy assessments (BSA%, IGA, ss-IGA, and PASI) 
starting with baseline visit until end of treatment phase (ie, Week 56). As only subjects 
treated with guselkumab may enter the follow-up extension phase, efficacy 
assessments are not blinded during Study Part III. It is recommended to have the 
efficacy assessments at screening be done by the same blinded assessor as the following 
assessments, including assessments during the follow-up extension phase. 
Rationale: Specification of procedures. 
Section 9.3, Safety 
evaluations 
Safety will be monitored through Week 64until end of study. 
… 
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, 
surrogate, or the subject's legally acceptable representative) for the duration of the study 
until end of Study Part II (ie, Week 64). During Study Part III (after Week 64) only 
adverse drug reactions and deaths will be recorded. Adverse events/adverse drug 
reactions will be followed by the investigator as specified in Section 12. 
Rationale: Implementation of Study Part III procedures.
Section 9.3, Safety 
evaluations 
Urine pregnancy testing is required for all women of childbearing potential at all study 
visits until end of Study Part II. 
… 
Blood samples for serum chemistry and hematology, and a random urine sample for 
urinalysis will be collected at visits specified in the TES. 
Rationale: Specification of procedures. 
Section 10.1, 
Completion 
A subject will be considered to have completed Study Part III when he or she has 
completed last assessments after loss of response, withdrawal from study participation 
or at Week 100 at the latest. 
Rationale: Implementation of Study Part III.
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
16 
Approved, Date: 22 January 2018 Approved22 January 2018 
Applicable Section(s) 
Description of Change(s) 
Section 10.2, 
Discontinuation, 
withdrawal 
However, regular safety follow-up ends for all subjects not entering Study Part III at 
Week 64. 
… 
A subject will be withdrawn from the study for any of the following reasons: 
 
Lost to follow-up 
 
Withdrawal of consent 
 
Death 
 
Start of a protocol-prohibited medication/therapy during Study Part III  
… 
A subject’s study participation from Study Part III must be discontinued if a protocol-
prohibited medication/therapy (for his/her psoriasis or another indication) is started 
before completion of the final study visit after loss of response or at Week 100.  
… 
Similarly, for subjects who are not eligible for Study Part III, the Study Part II safety 
follow-up visit (Week 64) should be performed, as indicated in the TES. For subjects 
not completing Study Part III, every effort should be made to conduct a final study 
visit (FSV Part III) as indicated in the TES. 
Rationale: Implementation of Study Part III procedures.
Section 11, Statistical 
analysis 
The SAP will be divided in threetwo separate documents describing analyses for the 
threetwo study parts. 
… 
The analyses will be confirmatory for the primary endpoint and the major secondary 
endpoints, and exploratory for all other secondary endpoints including Study Part II and 
Part III analyses. 
Section 11.3 
Analysis data set 
For all efficacy analyses in the follow-up extension phase (Study Part III, Week 100 
analysis), all subjects who entered Study Part III and received guselkumab from Week 
0 and subjects who received FAE from Week 0 to Week 32 and switched to 
guselkumab will be analyzed. 
… 
The final second statistical analysis will be performed after all subjects have completed the 
Week 64 visit or have terminated the study prematurely. 
… 
The third statistical analysis will be performed after all subjects have completed the 
Week 100 visit or have terminated the study prematurely or lost their response. Third 
data base lock (DBL) will be after the Final Study Visit/Week 100 visit data are ready 
for statistical analysis (ie, clean data). All analyses will be performed after DBL and 
will be described in detail in the SAP for Week 100 analysis. Following the rationale 
for Study Part III, the Week 100 analysis will focus on PASI 90 responders at Week 
56 taking into account baseline disease characteristics and study treatment to explore 
prediction parameters of disease modification. 
Rationale: Implementation of Study Part III procedures.
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
17 
Approved, Date: 22 January 2018 Approved22 January 2018 
Applicable Section(s) 
Description of Change(s) 
Other secondary 
endpoints 
 
The other secondary endpoints will comprise the endpoints as defined in Section 9.2.2. For 
the other secondary analyses including Study Part II and Part III analyses, the chi-square 
test will be used to compare the proportion of subjects responding to treatment. 
… 
Time-to-event endpoints will be analyzed using Kaplan-Meier product limit methods 
to estimate the survival distributions and the median time-to-event. 
Rationale: Implementation of Study Part III procedures.
Section 11.3, Primary 
endpoint 
Graphical presentation will be presented by means of a bar chart. Subjects who meet 
treatment failure criteria (eg, subjects who discontinue study treatment or who started a 
protocol-prohibited medication/therapy during the study, (Section 11.4, Section 8.1) before 
Week 24 will be considered non-responders for the primary endpoint at Week 24. 
Rationale: Treatment failure criteria as previously specified in the Protocol were not used in Week 24 analysis. 
Analysis has been detailed in the corresponding SAP.
Section 11.3, Subgroup 
analysis 
Subgroup analyses will be performed to evaluate consistency of the primary endpoint and 
selected major secondary endpoints over demographics (including baseline weight) and 
baseline disease characteristics. 
Rationale: Week 24 analyses were performed as specified in the corresponding SAP.
Section 11.3, Missing 
Data 
Subjects who discontinue study treatment meet treatment failure criteria before Week 24 
will be considered as non-responders at Week 24. In addition, subjects or who do not return 
for evaluation at Week 24 or 56 will be considered non-responders at Week 24 or 56, 
respectively. 
Rationale: Treatment failure criteria as previously specified in the Protocol were not used in Week 24 analysis. 
Analysis has been detailed in the corresponding SAP.
Section 11.4, Criteria 
for endpoints 
Treatment Failure: Subjects who discontinue study treatment due to lack of efficacy or an 
AE of worsening of psoriasis, or who started a protocol-prohibited medication/therapy 
during the study that could improve psoriasis are considered treatment failures. The 
treatment failure rules will be documented in detail in the SAP. 
Rationale: Treatment failure criteria as previously specified in the Protocol were not used in Week 24 analysis. 
Analysis has been detailed in the corresponding SAP.
Section 11.4, Criteria 
for endpoints 
Loss of Response, Study Part III: Increase in absolute PASI >5  
Rationale: Implementation of Study Part III criteria.
Section 11.5 
Safety analysis 
Safety data, including but not limited to, AEs, SAEs, ADRs, SADRs, infections, serious 
infections, mortality, changes in laboratory assessments, and changes in vital signs will be 
summarized. Treatment-emergent AEs will be summarized by treatment group and Medical 
Dictionary for Regulatory Activities (MedDRA) system organ class and preferred terms. 
Analysis Data Set 
The final safety Safety analyseis covering the time until the Week 64 and until Week 100 
safety visits will be performed separately with the final Week 64 and Week 100 analyseis. 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
18 
Approved, Date: 22 January 2018 Approved22 January 2018 
Applicable Section(s) 
Description of Change(s) 
Adverse 
Events/Adverse Drug 
Reactions 
Adverse Events/Adverse Drug Reactions 
The verbatim terms used in the eCRF by investigators to identify adverse events (AEs) or 
adverse drug reactions (ADRs) will be coded using the Medical Dictionary for Regulatory 
Activities (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 AE, the percentage of subjects who experience at least 1 occurrence 
of the given event will be summarized by treatment group. (S)ADRs documented during 
Study Part III will be treated correspondingly. 
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for 
those subjects who die, who discontinue treatment due to an AE, or who experience a severe 
or a serious adverse event (SAE) or serious adverse drug reaction (SADR). The incidence 
of injection site reactions, SAEs, SADRs and premature discontinuations due to AEs/ADRs 
will be summarized separately. 
Rationale: Implementation of Study Part III.
Section 11.6, Interim 
and final analyses 
11.6. 
Interim and Final Analyses 
… 
The final second exploratory analysis will occur after all subjects have completed their visit 
at 64 weeks after randomization or discontinued earlier. This analysis will include the final 
safety analysis and all efficacy measures after Week 24 and will cover the time until the 
Week 64 safety visit. 
The third and final exploratory analysis will occur after all subjects have completed 
their visit at 100 weeks after randomization or discontinued earlier. This analysis will 
include the safety analysis and all efficacy measures after Week 64 and will cover the 
time until the Week 100 safety visit. 
Rationale: Implementation of Study Part III procedures.
Section 12, Adverse 
events/adverse drug 
reactions 
adverse event/adverse drug reaction 
(various passages in the text as applicable) 
Adverse Drug Reaction 
An ADR is defined as all untoward and unintended responses to an investigational 
medicinal product (IMP) related to any dose administered. ‘Response to a medicinal 
product’ means that a causal relationship between a medicinal product and an 
adverse event is possible, probable, or very likely. Thus, an ADR is characterized by 
the fact that a causal relationship between the medicinal product and the occurrence 
of the event is suspected. All adverse events judged by either the investigator or the 
sponsor as having a reasonable causal relationship to a medicinal product qualify as 
ADRs. 
Rationale: ADRs/SADRs will be reported during Study Part III: definition added and text adjusted accordingly 
where applicable. 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
19 
Approved, Date: 22 January 2018 Approved22 January 2018 
Applicable Section(s) 
Description of Change(s) 
Section 12.3.1 All 
Adverse Events/ 
Adverse Drug 
Reactions and 12.3.2, 
Serious adverse events/ 
Serious Adverse Drug 
Reactions 
During follow-up extension phase (Study Part III), all adverse events 
suspected to be related to the use of the drug (Adverse Drug Reactions, ADRs, 
Section 12.1.1) and deaths are recorded until final study visit of Study Part 
III.  
… 
All adverse events, regardless of seriousness, severity, or presumed relationship to 
study drug, and all adverse drug reactions regardless of seriousness and 
severity must be recorded using medical terminology in the source document and 
the eCRF. 
… 
During participation in Study Part III, the cause of death of a subject is also 
considered a serious adverse event. Death of a subject related to use of a medicinal 
product and meeting ADR definitions is a serious adverse drug reaction and will be 
reported correspondingly. 
Rationale: ADRs/SADRs will be reported during Study Part III. ADRs and subject death will be followed during 
Study Part III. 
Section 12.3.3, 
Pregnancy 
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 until end of Study Part II. 
Rationale: Specification of procedures. 
Section 14.5, Drug 
accountability 
Counting remaining FAE tablets during the study visits for compliance check is not 
considered as a return and re-dispense. 
Rationale: Specification of procedures. 
Section 16.2.3, 
Informed consent 
To meet the scope of this amendment two three separate ICFs have been developed to 
cover Study Parts I, and II and III. The ICF(s) must be signed before performance of any 
study-related activity (ICF I at screening, ICF II at Week 24 at the latest, ICF III at Week 
64 at the latest). 
… 
Before enrollment in the study or in Parts II or III of the study, if applicable, 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. 
Rationale: Implementation of Study Part III.
Section 17.5, Case 
report form completion 
Results of efficacy assessments performed by the blinded efficacy assessor (in Study Part 
I and II) will be entered in the eCRF by unblinded study personnel as described in Section 
9.2.3. 
Rationale: Implementation of Study Part III, specification of procedures.
 
 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
20 
Approved, Date: 22 January 2018 Approved22 January 2018 
SYNOPSIS 
Multicenter, randomized, open-label, efficacy assessor-blinded, active comparator-controlled phase 
3b study to compare the efficacy of guselkumab to fumaric acid esters (Fumaderm® initial/ 
Fumaderm®) for adult patients with moderate to severe plaque psoriasis who are candidates for and 
naive to systemic treatment  
Protocol Number: CNTO1959PSO3008 
CNTO 1959 (guselkumab) is a fully human immunoglobulin G1 lambda (IgG1λ) monoclonal 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-23p19 subunit blocks the binding of extracellular IL-23 to the cell 
surface IL-23 receptor, inhibiting IL-23 specific intracellular signaling and subsequent activation and 
cytokine production. Guselkumab has been studied in Phase 1, 2 and 3 studies for the treatment of moderate 
to severe psoriasis. 
EudraCT NUMBER: 2016-002135-15 
OBJECTIVES AND HYPOTHESIS  
Primary Objectives 
The primary objectives of the study are 
 
to compare the efficacy of guselkumab to fumaric acid esters (FAE) in systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis 
 
to assess the safety and tolerability of guselkumab in systemic treatment-naïve subjects with 
moderate to severe plaque-type psoriasis. 
Secondary Objectives 
The secondary objectives of the study are 
 
in Study Parts I and II: to compare improvement of health-related quality of life (QOL) and other 
patient-reported outcomes (PRO) when systemic treatment-naïve subjects with moderate to severe 
plaque-type psoriasis are treated with guselkumab compared to FAE. 
 
in Study Part II: to compare sustainability of response to treatment when systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis are treated with guselkumab compared to 
FAE. 
 
in Study Part III (guselkumab withdrawal): to investigate the maintenance of response in subjects 
withdrawn from study treatment, and to explore prediction parameters of disease modification.  
 
Hypotheses 
The primary hypothesis of this study is that guselkumab treatment is superior to FAE (Fumaderm® initial/ 
Fumaderm®) treatment as assessed by the proportion of subjects achieving a PASI 90 response at Week 24.  
The major secondary hypotheses are: 
 
Guselkumab treatment is superior to FAE treatment as assessed by the proportion of subjects 
achieving a PASI 75 response at Week 24. 
 
Guselkumab treatment is superior to FAE treatment as assessed by the proportion of subjects 
achieving a DLQI score of 0 or 1 at Week 24. 
If the primary hypothesis is accepted, the study will be considered positive. 
 
 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
21 
Approved, Date: 22 January 2018 Approved22 January 2018 
OVERVIEW OF STUDY DESIGN 
This is a randomized, open-label, efficacy assessor-blinded, single country, multicenter, active-comparator-
controlled phase 3b study of guselkumab in adult subjects with moderate to severe plaque-type psoriasis 
who have not yet received any systemic therapy. The study will be performed at about 30 to 45 sites in 
Germany.  
This study will have a 3-week screening phase, a 56-week treatment phase and a safety follow-up phase 
until Week 64, followed by a follow-up extension phase after withdrawal of guselkumab until loss of 
response or until Week 100 at the latest (as shown in Figure 1). The maximum duration of a subject’s 
participation in this study will be 103 weeks. With protocol Amendments INT-1 and INT-2, the study will 
be split into three parts (Study Part I, II and III): 
Study Part I (Core Study)—Week 0 through Week 24 
Subjects will be randomized in a 1:1 ratio to either the study drug (guselkumab) or to the active comparator 
(FAE). Efficacy of treatment will be assessed before any tests, procedures or other evaluations, first by the 
subject him/herself (1st DLQI, 2nd PSSD 7-day version, and 3rd SF-36), and subsequently, in Study Part I 
and II, by a blinded efficacy assessor (BSA%, IGA, ss-IGA, and PASI). Preferably the same efficacy 
assessor continues evaluation of the disease in Study Part III, but efficacy assessments are no longer blinded. 
A subject will be considered to have completed Study Part I if he or she has completed assessments at Week 
24 of the open-label phase. For subjects who discontinue study treatment or withdraw from study 
participation in Study Part I or who do not enter Study Part II, a safety follow-up visit (Study Part I) will 
be performed at Week 32 or 12 weeks after the last treatment (whatever comes first). For subjects enrolled 
in Study Part I only, maximum duration of study participation will be 35 weeks. 
Study Part II (Extension, Continuation/Switch of Study Treatment)—Week 24 through Week 56 
Subjects may enter the study extension at Week 24 only when the ICF for Study Part II was signed before 
or at Week 24, study treatment was not terminated prior to Week 24 and no protocol-prohibited 
medication/therapy was started. Study Part II is subdivided in two treatment periods: 
 
Part IIa – Week 24 through Week 32: All subjects who enter Study Part II will continue their 
assigned treatment (guselkumab or FAE) from Week 24 through Week 32.  
Study Part IIa is considered completed when the subject has completed assessments at Week 32. 
 
Part IIb – Week 32 through Week 56: Following Week 32, subjects with PASI 75 response will 
continue assigned treatment (guselkumab or FAE). For PASI 75 non-responders at Week 32 the 
following options will be available: 
- 
Guselkumab group: Subjects may continue guselkumab treatment, if the investigator 
considers therapy medically appropriate.  
- 
FAE group: Subjects will switch to guselkumab unless barred by safety reasons (based on 
lab values ≥Week 28). Subjects who terminate FAE treatment prior to Week 32 cannot 
continue study treatment but will enter safety follow-up per protocol. 
A subject will be considered to have completed Study Part II if he or she has completed assessments at 
Week 56 of the open-label phase. For Subjects who discontinue study treatment or withdraw from study 
participation in Study Part II, final study assessments are obtained and a final safety follow-up visit (Study 
Part II) is completed at Week 64 or 12 weeks after last treatment.  
For subjects completing Study Part II, and not entering Study Part III, maximum duration of study 
participation in this study will be 67 weeks including a 3-week screening phase.  
 
 
 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
22 
Approved, Date: 22 January 2018 Approved22 January 2018 
Study Part III (Follow-up extension, guselkumab withdrawal, no study treatment)—Week 64 
through Week 100 
Subjects who received guselkumab in Study Part II (subjects who started guselkumab treatment at Week 0 
or switched from FAE to guselkumab treatment in Week 32), had no psoriatic arthritis diagnosed at baseline 
and achieved a PASI 90 response at end of Study Part II (Week 56) may enter follow-up extension at Week 
64. To be eligible for follow-up extension subjects must have signed ICF for Study Part III before or at 
Week 64, must not have started a new psoriasis treatment (including commercially available guselkumab 
therapy) or started any other protocol-prohibited medication/therapy. In Study Part III, subjects are 
withdrawn from guselkumab treatment and will be followed until loss of response (defined as an increase 
in absolute PASI >5), but until Week 100 at the latest, which is almost 1 year after the last guselkumab 
treatment at visit Week 52.  
All other subjects may not enter Study Part III and complete the study at Week 64. 
Efficacy assessments will be performed first by the subject him/herself, and subsequently by an efficacy 
assessor. Preferably, in Study Part III the same efficacy assessor as in Study Parts I and II continues 
evaluation of the disease, but efficacy assessments are no longer blinded. 
The maximum duration of a subject’s participation will be 103 weeks including a 3-week screening phase.  
Safety Follow-up Phase 
 
Safety Follow-up (Part I) – Week 24 through Week 32 
For subjects who complete study treatment at Week 24 a final safety follow-up visit is completed at 
Week 32.  
 
Safety Follow-up (Part II) – Week 56 through Week 64 
All ongoing subjects complete the safety follow-up until Week 64. For subjects who complete study 
treatment at Week 56, a final safety follow-up visit is completed at Week 64. For subjects entering 
Study Part III the safety follow-up visit will be conducted as well and subjects will continue as 
described below. 
 
Safety Follow-up after discontinuation/withdrawal – 12 weeks after last treatment 
For subjects who discontinue study treatment or withdraw from study participation, final study 
assessments are obtained and a final safety follow-up visit is completed 12 weeks after last treatment.  
A subject will be considered to have completed Study Part I or Study Part II if he or she has completed 
assessments at Week 24 and Week 56, respectively. A subject will be considered to have completed Study 
Part III if he or she has completed assessments at Week 100 or completed final assessments after loss of 
response. 
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 transferred to the sponsor (or designee) after completion of the final subject 
visit at that study site, in the time specified in the Clinical Trial Agreement. The overall duration of the 
study is expected to be approximately 30 months (start in December 2016, stop in July 2019). The estimated 
frequency and timing of the study visits are summarized in the ‘Time and Events Schedule’ (TES). 
SUBJECT POPULATION 
The target population comprises adult men and women with a diagnosis of plaque-type psoriasis for at least 
6 months before the first administration of study drug. Subjects must have moderate to severe plaque-type 
psoriasis defined by Psoriasis Area and Severity Index (PASI) >10 or involved body surface area (BSA) 
>10%, and Dermatology Quality of Life Index (DLQI) >10. Subjects must be naïve but candidates for 
systemic therapy for psoriasis, and FAE must be considered as an appropriate treatment option. Subjects 
with 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, 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
23 
Approved, Date: 22 January 2018 Approved22 January 2018 
or lithium) are excluded. A total number of 114 subjects will be randomly assigned in this study with 57 
subjects planned per treatment group. 
DOSAGE AND ADMINISTRATION 
A 100 mg/mL solution of guselkumab will be provided in a single-use prefilled syringe (PFS) assembled 
with the UltraSafe PLUSTM Passive Needle Guard (PFS-U). Commercially available Fumaderm® initial/ 
Fumaderm® tablets will be supplied. 
Study Part I and Study Part IIa, active comparative treatment: Week 0 through Week 24 and Week 
24 through Week 32 
Subjects randomized to guselkumab will receive 100 mg guselkumab SC by trained study personnel at the 
study site, subjects randomized to FAE will receive commercially available Fumaderm® initial/ Fumaderm® 
tablets intended for self-administration at home, and specifically labeled for the study. 
The dose regimens are as follows: 
 Group I (Gus, n = 57): 100 mg guselkumab SC at Weeks 0, 4, 12 and 20 (Study Part I); every 8 weeks, 
ie, at Week 28 (Study Part IIa) 
Group II (FAE, n = 57): Fumaderm® initial/Fumaderm® tablets; individual dosing according to local 
prescribing information (SmPC) for each subject representing the optimal benefit-risk ratio; the maximum 
daily dosage of 3 × 2 tablets Fumaderm® must not be exceeded. 
Study Part IIb, continuation/switch of study treatment: Week 32 through Week 56 
Subjects with a PASI 75 response will continue treatment as before.  
 Group I (Gus): continue 100 mg guselkumab SC every 8 weeks (ie. at Weeks 36, 44, and Week 52)  
 Group II (FAE): continue Fumaderm® initial/Fumaderm® tablets, individual dosing according to 
local prescribing information (SmPC) (2) 
 
PASI 75 non-responders will be offered treatment as follows: 
 Group I (Gus): continue 100 mg guselkumab SC every 8 weeks (ie, at Weeks 36, 44 and Week 52). 
It is at the investigator’s discretion to continue therapy, if treatment is considered medically 
appropriate. 
 Group II (FAE): switch to 100 mg guselkumab SC at Weeks 32, 36, 44 and Week 52  
Safety follow-up phase, psoriasis treatment: Week 24 through Week 32 (Study Part I) or Week 56 
through Week 64 (Study Part II) 
Subjects who are not eligible for Study Part II will enter the safety follow-up phase after completion of all 
Study Part I assessments. For these subjects, the safety follow-up phase spans Week 24 to Week 32 and 
ends with a safety FUP visit at Week 32.   
Subjects who complete Study Part II enter the safety follow-up phase after completion of all Study Part II 
assessments at Week 56. For these subjects, the safety follow-up phase spans Week 56 to Week 64. All 
subjects, regardless whether they continue with Study Part III or not, complete the safety follow-up visit at 
Week 64. For all subjects who do not enter Study Part III, study participation ends with the safety FUP visit 
at Week 64.  
Subjects who discontinue study treatment or withdraw from study participation, safety follow-up visit is 
completed 12 weeks after last treatment.  
 
During the safety follow-up phase treatments for psoriasis may be administered at the investigator’s 
discretion as follows: 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
24 
Approved, Date: 22 January 2018 Approved22 January 2018 
 Group I (Gus): If commercially available, investigator may continue actual 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.  
Note: Subjects who start a new psoriasis treatment, including commercially available guselkumab, during 
safety follow-up phase are not eligible to enter Study Part III.   
 Group II (FAE): Investigator may either continue the actual FAE treatment with commercially available 
drug or switch to another commercially available treatment.   
Study Part III, follow-up extension phase, guselkumab withdrawal, no study treatment: Week 64 
through Week 100 
Subjects in the guselkumab group who are eligible to enter Study Part III are withdrawn from study 
treatment and followed until loss of response or until Week 100 at the latest. Eligible subjects in the 
guselkumab group may enter Study Part III after end of safety FUP. All subjects complete the safety FUP 
visit and eligible subjects continue with efficacy assessments at visit Week 64. Subjects may start a 
commercially available topical psoriasis treatment at Week 64 or later at the investigator’s discretion, 
except topical corticosteroids class IV (alone or in combination) and phototherapy. 
EFFICACY EVALUATIONS 
The chosen efficacy evaluations are consistent with those used to evaluate other therapies for psoriasis. 
Efficacy evaluations will be first done by subjects (PROs) and then by the blinded efficacy assessor: 
 
Dermatology Life Quality Index (DLQI) [PRO#1] 
 
Psoriasis Symptom and Sign Diary (PSSD 7-day version) [PRO#2] 
 
Medical Outcomes Study 36-Item Short Form (SF-36) [PRO#3] 
 
Involved Body Surface Area (BSA) 
 
Investigator’s Global Assessment (IGA) 
 
Scalp Specific Investigator’s Global Assessment (ss-IGA) 
 
Psoriasis Area and Severity Index (PASI) 
SAFETY EVALUATIONS 
Safety evaluations will include the monitoring of adverse events (AEs), including injection site and allergic 
reactions, physical examinations, measurement of body weight and vital signs, clinical laboratory testing 
(Hepatitis B and C, HIV, hematology, and chemistry), concomitant medication review, tuberculosis (TB) 
test and evaluation, urinalysis, and pregnancy testing. 
STATISTICAL METHODS 
The statistical analyses in this study will focus on the comparison of the two randomized treatment groups 
(ie, guselkumab vs. FAE). The analyses will be confirmatory for the primary endpoint and for the major 
secondary endpoints. They will be exploratory for all other secondary endpoints including Study Part II and 
Part III endpoints. Descriptive statistics will include counts and proportions for categorical data, and 
median, mean, interquartile range, and range for continuous data. Graphical data displays may also be used 
to summarize the data. 
The chi-square test 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 baseline value as a 
covariate. All statistical testing will be performed two-sided. The confirmatory significance level is fixed 
to a type 1 error rate alpha of 5% (two-sided). 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
25 
Approved, Date: 22 January 2018 Approved22 January 2018 
Primary Endpoint 
The primary endpoint is the proportion of subjects achieving at least a 90% improvement of their psoriasis 
according to the Psoriasis Area and Severity Index (PASI 90 response) at Week 24. 
Secondary Endpoints 
The major secondary endpoints are: 
 
The proportion of subjects achieving at least a 75% improvement of their psoriasis according to the 
PASI (PASI 75 response) at Week 24 
 
The proportion of subjects achieving a DLQI score of 0 or 1 at Week 24. 
Other secondary endpoints are: 
 
The proportion of subjects achieving a 100% improvement of their psoriasis according to the PASI 
(PASI 100 response) at Week 24  
 
The change from baseline in the signs and symptoms aggregate scores of the PSSD at Week 24 
 
The change from baseline in the individual scale scores for itch, pain and scaling of PSSD 
components at Week 24 
 
The proportion of subjects achieving an absolute PASI score ≤1 at Week 24 
 
The proportion of subjects achieving an IGA score of cleared (0) at Week 24 
 
The change from baseline of body surface area (BSA) psoriatic involvement at Week 24  
 
The change from baseline in DLQI score at Week 24 
 
The proportion of subjects achieving an ss-IGA score of absence of disease (0) at Week 24 in 
randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at baseline 
 
The change from baseline in the physical and mental component summary scores of SF-36 at Week 
24 
 
Maintenance of response. Proportion of subjects with a  
- PASI 75 response at Week 32 who maintain response at Week 56 
- PASI 90 response at Week 32 who maintain response at Week 56 
- DLQI score 0 or 1 at Week 32 who maintain response at Week 56 
- Proportion of subjects with a  
- PASI 75 response (compared to baseline) at Week 56 
- PASI 90 response (compared to baseline) at Week 56 
- PASI 100 response (compared to baseline) at Week 56 
- DLQI score 0 or 1 at Week 56 
- Proportion of subjects with a  
- PASI 75 response (compared to baseline) at Week 32 
- PASI 90 response (compared to baseline) at Week 32 
- PASI 100 response (compared to baseline) at Week 32 
- DLQI score 0 or 1 at Week 32 
- Maintenance of response after guselkumab withdrawal. Proportion of subjects of the guselkumab 
group (GUS-GUS and FAE-GUS) with a   
- PASI 90 response at Week 56 who maintain response at Week 100 
- Time to loss of response from Week 56 after guselkumab withdrawal at Week 100 
 
Safety and tolerability data will be summarized using descriptive statistics. 
 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
26 
Approved, Date: 22 January 2018 Approved22 January 2018 
Sample size 
In order to control the overall experiment wise type 1 error rate, the primary endpoint and the two major 
secondary endpoints will be tested in a fixed sequence as a-priori ordered hypotheses. That is, the first 
major secondary endpoint will be tested only if the primary endpoint is positive (ie, p <0.05), and the second 
major secondary endpoint will be tested only if the first major secondary endpoint is positive. Due to the 
testing of ordered hypotheses, no adjustment of the significance level with respect to the threefold test 
procedure is required. 
The assumptions for the sample size and power calculations using the threefold test procedure were based 
on guselkumab phase 2 data and unpublished data from the German PsoBest Registry and are as follows: 
PASI 90 responder rates for guselkumab and FAE in Week 24 are assumed to be 60% and 25%, 
respectively. PASI 75 responder rates are assumed to be 80% and 45%, respectively. DLQI responder rates 
are assumed to be 60% and 30%, respectively. 
Based on these assumptions, with a total of 114 subjects planned to be randomized in a 1:1 ratio to 
guselkumab (n = 57) and to FAE (n = 57), superiority of guselkumab vs. FAE can be demonstrated at a 5% 
significance level (two-sided) with power of at least 90% for each test of the threefold test procedure. 
Efficacy analyses 
For all efficacy analyses to compare guselkumab vs. FAE in Study Part I (Week 24 analysis), all randomized 
subjects will be included. For all the efficacy analyses, subjects will be analyzed according to the treatment 
group to which they were randomized regardless of the treatment they actually received (‘intent-to-treat 
principle’). Additionally, all efficacy analyses will be performed with all randomized subjects that received 
at least one dose of study drug. For all efficacy analyses to compare guselkumab vs. FAE in Study Part II 
(Week 64 analysis), subjects will be analyzed according to the treatment they actually received. For all 
efficacy analyses in the follow-up extension phase (Study Part III; Week 100 analysis), all subjects who 
entered Study Part III and received guselkumab from Week 0 and subjects who received FAE from Week 
0 to Week 32 and switched to guselkumab will be analyzed. 
Safety analyses 
Safety data, including but not limited to, AEs, SAEs, infections, serious infections, mortality, changes in 
laboratory assessments, and changes in vital signs will be summarized. Treatment-emergent AEs will be 
summarized by treatment group and Medical Dictionary for Regulatory Activities (MedDRA) system organ 
class and preferred terms. Details will be specified in the statistical analysis plan (SAP). 
For all safety analyses to compare guselkumab vs. FAE, all randomized 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.  
Data base locks (DBL) will be after the Week 24/64/100 visit data are ready for statistical analysis (ie, clean 
data). All analyses including all primary and secondary analyses as well as additional analyses as described 
in detail in the SAPs will be performed after the respective DBLs. 
  
 
 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
27 
Approved, Date: 22 January 2018Approved22 January 2018 
Table 1: Time and Events Schedule: From Screening through Week 24 (Study Part I) 
Phase 
Screen-
inga 
Active Treatment 
Safety FUP
(Final study 
visit Part I)h1
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7
Study Proceduresb 
Screening/Administrative 
Informed consent I 
(Study Part I) 
X 
 
 
 
 
 
 
 
 
 
 
Must be signed before first study-related activity 
Informed consent II 
(Study Part II)
------------------------------------------------------------------------------X 
 
 
ICF addendum for Study Part II to be signed at 
Week 24 at the latest
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Minimum criteria for the availability of 
documentation supporting the eligibility criteria 
are described in protocol, Section 4; check 
clinical status again before first dose of study 
medication
Study Drug Administration 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
All baseline study procedures and evaluations are 
to be completed before randomization
Study drug 
administration
 
   Xc-------------------------------------------------------------------…  
 
All study procedures and evaluations are to be 
completed before study drug administration
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before administration of study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
c: Subjects randomized to guselkumab will get guselkumab 100 mg on site at Weeks 0, 4, 12 and then every 8 weeks. Subjects randomized to FAEs will start with Fumaderm® 
initial regimen (0-0-1) at the day of the baseline visit; thereafter, FAE doses will be increased to find the optimal Fumaderm® dose for each subject as described in Section 
6.  
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit: for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.5 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
28 
Approved, Date: 22 January 2018Approved22 January 2018 
Phase 
Screen-
inga 
Active Treatment 
Safety FUP
(Final study 
visit Part I)h1
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7
Study Proceduresb 
Safety Assessments 
Physical examination  
X 
x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X  
X 
 
Tuberculosis evaluation 
X 
X 
   X--------------------------------------------------------… 
X 
X 
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 
(Section 9.3)
Chest radiograph 
X 
 
 
 
 
 
 
 
 
 
 
Taken within 3 months before the first 
administration of study drug and read by a 
qualified radiologist
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Women of childbearing potential must have a 
negative 
urine 
pregnancy 
test 
before 
randomization and at all study visits (prior to 
administration of study drug).
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
Weight 
 
X 
 
 
 
 
 
 
X 
X 
X 
 
Concomitant therapy 
      X--------------------------------------------------------------------------… 
X 
X 
 
Adverse events 
      X--------------------------------------------------------------------------… 
X 
X 
 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.5 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
29 
Approved, Date: 22 January 2018Approved22 January 2018 
Phase 
Screen-
inga 
Active Treatment 
Safety FUP
(Final study 
visit Part I)h1
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7
Study Proceduresb 
Efficacy Assessments 
DLQI 
X 
X 
 
X  
X 
 
X 
 
X 
 
X 
 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd 
SF-36; should be performed before any tests, 
procedures or other evaluations (PASI, IGA, ss-
IGA, BSA) for that visit; completion of the 
baseline 
PROs 
has 
to 
be 
done 
before 
randomization 
PSSD (7d) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
SF-36 
 
X 
 
 
X 
 
X 
 
X 
 
X 
IGAd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
PASId 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
ss-IGAd,e 
 
X 
 
 
X 
 
X 
 
X 
 
X 
BSA%d 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
d: Dermatological evaluation of the subjects will be done by a blinded assessor starting with the Baseline visit; assessments will be done before any study related procedure 
will take place 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.5 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
30 
Approved, Date: 22 January 2018Approved22 January 2018 
Phase 
Screen-
inga 
Active Treatment 
Safety FUP
(Final study 
visit Part I)h1
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7
Study Proceduresb 
Clinical Laboratory Assessment 
Tuberculosis testf 
X 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B and C 
Serologies
X 
 
 
 
 
 
 
 
 
 
 
 
HIV antibody test 
X 
 
 
 
 
 
 
 
 
 
 
 
Hematologyg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Laboratory tests are listed in Section 9.3 
Chemistryg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis by dipstick: glucose and protein; if 
there are signs of proteins and/or glucose on urine 
test strip, the urine sample must be analyzed 
centrally; here, protein and glucose levels must 
not exceed trace levels, eg,  +; one re-test 
(central urine analysis) is allowed.
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
f: The QuantiFERON-TB Gold Plus test will generally be performed by the central laboratory; however, if available, test results from local laboratory can be accepted 
g: All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled; fasting is not necessary; details will be 
provided in the Laboratory Manual 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.5 
 
 
 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
31 
Approved, Date: 22 January 2018Approved22 January 2018 
Table 2: Time and Events Schedule: From Week 24 through Week 64 (Study Part II) 
Phase 
Active Treatment 
Safety FUP 
(Final Study visit 
Part II)h3 
ETVh2
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the scheduled 
visit, Section 7 
Study Proceduresb 
Study Drug Administration 
Study drug administration 
…---------Xi--------------------------------------------------X 
 
 
Subjects may enter the study extension at Week 24 
when ICF for Study Part II was signed, study 
treatment was not terminated and no protocol-
prohibited medication/therapy was started.
Safety Assessments 
Physical examination  
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
Vital signs 
X 
X 
  
X 
 
X 
 
X 
X  
X 
Tuberculosis evaluation 
……----------------------------------------------------------X 
X 
X 
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 (Section 9.3)
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight 
 
 
 
 
 
 
 
 
X 
X 
 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.5. 
h3: Safety Follow-up/Final Study Visit Study Part II (≤Week 64): For subjects who complete Study Part II or discontinue study treatment or withdraw from study 
participation in Study Part II. Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
i: Week 24 to Week 32 (Study Part IIa): subjects continue assigned treatments through Week 32. Subjects treated with 100 mg SC guselkumab continue q8w (ie, at Week 
28). Subjects treated with FAE continue Fumaderm® tablets (individual dosing according to local SmPC) until Week 32. 
Week 32 to Week 56 (Study Part IIb): Treatment decision based on PASI assessment at Week 32 and safety assessment (≥Week 28): 
- PASI 75 responders at Week 32: subject continues assigned therapy. Subjects in the guselkumab group continue 100 mg guselkumab SC at Weeks 36, 44, 52. 
Subjects in the FAE group continue Fumaderm® treatment (individual dosing according to local SmPC) until Week 56. 
- PASI 75 non-responders at Week 32: subjects in the FAE group may switch to guselkumab treatment unless barred by safety reasons (see treatment criteria Section 
4.4). In case of safety concerns (based on lab values of Week ≥28), assessment can be repeated before Week 32. Subjects will receive guselkumab SC at Weeks 32, 
36, 44 and Week 52. Non-responders in the guselkumab group may continue guselkumab (continuation of therapy is at the investigator’s discretion). 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
32 
Approved, Date: 22 January 2018Approved22 January 2018 
Phase 
Active Treatment 
Safety FUP 
(Final Study visit 
Part II)h3 
ETVh2
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the scheduled 
visit, Section 7 
Study Proceduresb 
Safety Assessments (continued) 
Concomitant therapy 
…----------------------------------------------------------X 
X 
X 
 
Adverse events 
    …----------------------------------------------------------X 
X 
X 
 
Efficacy Assessments 
DLQI 
X 
X 
X* 
X  
 
X 
 
X 
 
X 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd SF-
36; should be performed before any tests, procedures 
or other evaluations (PASI, IGA, ss-IGA, BSA) for 
that visit. 
*ONLY applicable for subjects who switched to 
guselkumab at Week 32  
PSSD (7d) 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
SF-36 
 
X 
 
 
 
 
 
X 
 
X 
IGAd 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
PASId 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
ss-IGAd,e 
 
X 
X* 
X 
 
X 
 
X 
 
X 
BSA%d 
 
X 
 
 
 
 
 
X 
 
X 
 
Study Proceduresb  
 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
d: Dermatological evaluation of the subjects will be done by a blinded assessor as in Study Part I; assessments will be done before any study related procedure will take 
place 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.5. 
h3: Safety Follow-up/Final Study Visit Study Part II ≤Week 64: For subjects who complete Study Part II or discontinue study treatment or withdraw from study participation 
in Study Part II. Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
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Phase 
Active Treatment 
Safety FUP 
(Final Study visit 
Part II)h3 
ETVh2
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the scheduled 
visit, Section 7 
Study Proceduresb 
Clinical Laboratory Assessment 
Hematologyg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory tests are listed in Section 9.3 
NOT applicable for subjects continuing gusel-
kumab treatment since beginning of the study 
(Week 0) 
Chemistryg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X  
X 
X  
X 
X  
X 
X  
X 
X 
Urinalysis by dipstick: glucose and protein; if there are 
signs of proteins and/or glucose on urine test strip, the 
urine sample must be analyzed centrally; here, protein 
and glucose levels must not exceed trace levels, eg, 
+; one re-test (central urine analysis) is allowed. 
ONLY applicable for subjects treated with FAE 
 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
g: All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled; fasting is not necessary; details will be 
provided in the Laboratory Manual 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.5. 
h3: Safety Follow-up/Final Study Visit Study Part II ≤Week 64: For subjects who complete Study Part II or discontinue study treatment or withdraw from study participation 
in Study Part II. Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
 
 
 
 
 
 
 
 
 
 
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Clinical Protocol CNTO1959PSO3008  
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Table 3: Time and Events Schedule: Follow-Up Extension Week 64 through Week 100 (Study Part III) 
 
Study Part II 
Study Part III 
 
Phase 
Active 
treatment 
Safety FUP / 
FSV Part II
Guselkumab withdrawal 
FSVj  
Part III
Notes 
Week 
52 
56 
≤64 
64 
76 
88 
≤100 
After visit Week 64, all visits should occur within ±14 days of the scheduled 
visit, see Section 7
Study Procedures 
Administrative 
Informed consent III  
…-----------------------X 
 
 
ICF addendum for Study Part III signed at W64 at the latest (before efficacy 
assessments)
Eligibility criteria 
for Study Part III 
…-----------------------X 
 
 
Criteria include: subject treated with Gus in Study Part II (ie, last application at 
W52), no PsA diagnosis at baseline, PASI 90 response at W56, no start of new 
psoriasis treatment including commercially available guselkumab or any other 
prohibited treatment/therapy before W64; details see Section 4.5
Study Drug Administration 
Guselkumab 
 
X 
 
Not allowed for subjects participating in Study Part III 
Last study drug application at W52. Subjects may start a commercially available 
topical psoriasis treatment at Week 64 or later at the investigator’s discretion; 
topical corticosteroids class IV (alone or in combination) and phototherapy are 
prohibited 
Safety Assessments 
Concomitant therapy 
X, see Table 2 
X---------psoriasis therapy------------X 
In case any prohibited therapy is applied (for psoriasis or any other indication) 
the subject is withdrawn from study participation. Prohibited therapy is recorded 
at the end of study participation (FSV Part III). If already known, planned next 
psoriasis therapy is recorded at the end of study,
Physical examination 
X, see Table 2 
 
X 
X 
X 
 
Vital signs 
X, see Table 2 
 
X 
X 
X 
 
Weight 
X, see Table 2 
 
 
 
Adverse Events/ 
ADRs 
(S)AEs, see Table 2 
 
(S)ADRs and death -- X 
During Study Part III, Adverse Drug Reactions (ADRs) and deaths are recorded 
until FSV. Details see Section 12
Clinical Laboratory 
Assessments
X, see Table 2 
 
 
No lab assessments during Study Part III 
FSV=final study visit 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
j: FSV Study Part III ≤ Week 100; FSV is done at loss of response (defined as an increase in absolute PASI >5), upon withdrawal from study participation or at Week 100 
at the latest.  
 
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Clinical Protocol CNTO1959PSO3008  
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Study Part II 
Study Part III 
 
Phase 
Active 
treatment 
Safety FUP / 
FSV Part II
Guselkumab withdrawal 
FSVj  
Part III
Notes 
Week 
52 
56 
≤64 
64 
76 
88 
≤100 
After visit Week 64, all visits should occur within ±14 days of the scheduled 
visit, see Section 7
Study Procedures 
Efficacy Assessments 
DLQI 
 
X 
X 
X 
X 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd SF-36; should be performed 
before any other evaluations (PASI, IGA, ss-IGA, BSA) for that visit 
PSSD (7d) 
 
X 
X 
X 
X 
SF-36 
 
X 
X 
X 
X 
IGA 
 
X 
X 
X 
X 
As only subjects treated with guselkumab may enter follow-up extension phase, 
efficacy assessments are not blinded during Study Part III. However, it is 
recommended to have the efficacy assessments done by the same assessor as in 
Study Parts I and II. 
PASIj 
 
X 
X 
X 
X 
ss-IGAe 
 
X 
X 
X 
X 
BSA% 
 
X 
X 
X 
X 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
j: FSV Study Part III ≤Week 100: FSV is done at loss of response (defined as an increase in absolute PASI >5), upon withdrawal from study participation or at Week 100 
at the latest. FSV should also be performed for subjects who withdraw from study participation. 
 
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Clinical Protocol CNTO1959PSO3008  
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ABBREVIATIONS 
AE 
Adverse Event 
BSA 
Body Surface Area 
CRF 
Case Report Form(s)  
DBL 
Database Lock 
DLQI 
Dermatology Life Quality Index
DMC 
Data Monitoring Committee
FAE 
FSV 
FUP 
Fumaric Acid Esters 
Final Study Visit 
Follow-up Phase 
EDC 
Electronic Data Capture
eg 
example given 
GCP 
Good Clinical Practice
HBV/ HCV 
Hepatitis B virus/ Hepatitis C Virus
HIV 
Human Immunodeficiency Virus
ICF 
Informed Consent Form
ICH 
International Conference on Harmonization
ie 
that is
IEC 
Independent Ethics Committee
IGA 
Investigator´s Global Assessment
IGRA 
Interferon-gamma-release-assay
IL 
Interleukin 
IRB 
Institutional Review Board
mAB 
Monoclonal Antibody
MedDRA 
Medical Dictionary for Regulatory Activities
MTX 
Methotrexate 
NSAID 
Non-Steroidal Anti-Inflammatory Drugs
PASI 
Psoriasis Area and Severity Index
PFS-U 
Prefilled Syringe assembled with the UltraSafe PLUSTM Passive Needle Guard 
PGA 
Physician´s Global Assessment
PML 
Progressive Multifocal Leukoencephalopathy 
PQC 
Product Quality Complaint
PRO 
Patient-Reported Outcome(s) 
PSSD 
Psoriasis Symptom and Sign Diary
SAE 
Serious Adverse Event
SAP 
Statistical Analysis Plan
SC 
subcutaneous 
SF-36 
Short Form (36-item) health survey 
ss 
scalp-specific 
SUSAR 
Suspected Unexpected Serious Adverse Reaction
TB 
tuberculosis 
TES 
Time and Events Schedule
ULN 
Upper Limit of the Norm
 
 
 
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CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
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1. 
INTRODUCTION 
CNTO 1959 (guselkumab) is a fully human immunoglobulin G1 lambda (IgG1λ) monoclonal 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-23p19 subunit blocks the binding of extracellular IL-23 to the cell 
surface IL-23 receptor, inhibiting IL-23 specific intracellular signaling and subsequent activation and 
cytokine production. Guselkumab has been studied in Phase 1, 2 and 3 studies for the treatment of moderate 
to severe psoriasis.  
The term “sponsor” used throughout this document refers to the entities listed in the Contact Information 
page(s), which will be provided as a separate document. 
1.1. 
Background 
Clinical Studies 
The clinical development program for guselkumab includes studies in subjects with psoriasis, psoriatic 
arthritis, palmoplantar pustulosis, and rheumatoid arthritis as well as healthy subjects. As of 30 June 2017, 
18 clinical studies of guselkumab have been completed or are ongoing.  Ten clinical studies have been 
completed and eight studies are ongoing. One Phase 2 study and two Phase 1 studies of guselkumab for the 
treatment of moderate to severe psoriasis have been completed and demonstrated a favorable efficacy and 
safety profile for guselkumab. A Phase 1 pharmacokinetic (PK) study of guselkumab in healthy subjects 
has also been completed.  The different studies are summarized below; more details about the individual 
studies are provided in the Investigator’s Brochure. 
Phase 2 Study (CNTO1959PSO2001, X-PLORE) 
In the X-PLORE study, 293 subjects with moderate to severe plaque-type psoriasis were randomized to 
receive 1 of 5 guselkumab SC dose regimens (5 mg at Weeks 0, 4, and then every 12 weeks [q12w], 15 mg 
every 8 weeks [q8w], 50 mg at Weeks 0, 4, and then q12w, 100 mg q8w, or 200 mg at Weeks 0, 4, and then 
q12w), placebo, or adalimumab (HUMIRA®) 80 mg at Week 0, 40 mg at Week 1, and then 40 mg every 2 
weeks (q2w). 
The proportions of subjects who achieved a Physician’s Global Assessment (PGA) score of cleared (0) or 
minimal (1) were significantly higher at Week 16 in all guselkumab treatment groups compared with the 
placebo group. In addition, higher proportions of subjects in the guselkumab 50 mg q12w, 100 mg q8w, 
and 200 mg q12w groups achieved a PGA score of 0 or 1 compared with the adalimumab group at Week 
16. Improvements in psoriasis were demonstrated at Week 4 in the guselkumab groups and continued to 
improve through Week 16. A dose-response in efficacy was observed up to 100 mg q8w; the proportions 
of subjects who achieved a PGA of 0 or 1 were similar in the 100 mg q8w and 200 mg q12w dose groups. 
Results for improvements in Psoriasis Area and Severity Index (PASI) scores were generally similar to 
those observed for PGA. 
Treatment with guselkumab was generally well-tolerated through Week 52. The proportions of subjects 
with 1 or more adverse events (AEs) were comparable across the combined guselkumab, placebo, and the 
adalimumab groups through Week 16, with no evidence of a dose-response in the occurrence of AEs across 
the guselkumab groups. The most common events in the combined guselkumab group were 
nasopharyngitis, headache, and upper respiratory tract infection (URTI). Through Week 16, the proportion 
of subjects with 1 or more serious adverse events (SAEs) was low across all treatment groups. Two serious 
infections (guselkumab 50 mg group), no malignancies, and no major cardiovascular events (MACE) were 
reported. Similar patterns of AEs were observed through Week 52. Events of interest through Week 52 
included the 2 serious infections noted through Week 16, 1 malignancy in the 200 mg q12w group, and 3 
MACE (1 in the 5 mg q12w group and 2 in the 100 mg q8w group). 
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CNTO1959 (guselkumab)     
 
 
 
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Approximate dose-proportionality in serum guselkumab concentrations through Week 52 was observed 
after multiple SC administrations at dose levels ranging from 15 to 200 mg. Steady-state serum guselkumab 
concentrations were achieved by approximately Week 16 for both the q8w and q12w regimens. In each 
treatment group, mean or median trough serum guselkumab concentrations were maintained at steady state 
through Week 40 (q8w groups) or Week 52 (q12w groups). There was no evidence of accumulation in 
serum guselkumab concentrations over time with SC q8w or q12w administrations. Serum guselkumab 
concentrations appeared to be affected by body weight; higher-weight subjects (>90 kg) had lower mean 
steady-state trough serum guselkumab concentrations compared with lower-weight subjects (≤90 kg). 
The overall incidence of antibodies to guselkumab across all guselkumab treatment groups through Week 
52 was 6.3%, with generally low titers. None of the subjects who were positive for antibodies to guselkumab 
had antibodies that were able to neutralize the bioactivity of guselkumab in vitro. No consistent impact of 
antibodies to guselkumab on serum guselkumab concentrations was observed across the guselkumab 
treatment groups. 
Phase 3 Study (CNTO1959PSO3001, VOYAGE 1) 
CNTO1959PSO3001 is an ongoing Phase 3, randomized, double-blind, multicenter placebo- and active-
comparator-controlled study in subjects with moderate to severe plaque psoriasis. The target population is 
adult men or women with a diagnosis of plaque-type psoriasis (with or without PsA) for at least 6 months 
before the first administration of study drug. Subjects must have moderate to severe plaque-type psoriasis 
defined by Investigator’s Global Assessment (IGA). They must be candidates for either systemic therapy 
or phototherapy for psoriasis, and may have previously received some systemic therapies or phototherapy 
for psoriasis. Subjects with 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) are excluded. Subjects who have ever received guselkumab or 
adalimumab are also excluded. 
The primary analysis has been completed, follow-up is ongoing. A total of 837 subjects were randomized 
into the study. The co-primary endpoints and all major secondary endpoints were achieved (all p<0.001). 
Beginning at Week 8 and continuing through Week 48, guselkumab-treated subjects maintained higher 
rates of all 4 PASI responses (PASI 100, PASI 90, PASI 75, and PASI 50) compared with adalimumab-
treated subjects. The guselkumab group demonstrated a greater improvement compared with placebo at 
Week 16 in the following types of regional psoriasis: scalp psoriasis (ss-IGA), fingernail psoriasis (f-PGA, 
NAPSI), and hand and foot psoriasis (hf-PGA). The guselkumab group had also a significant and clinically 
meaningful improvement in health-related quality of life and psoriasis symptoms and signs as measured by 
DLQI and PSSD compared with the placebo and adalimumab groups. 
Phase 3 Study (CNTO1959PSO3002, VOYAGE 2) 
CNTO1959PSO3002 is an ongoing Phase 3, randomized, double-blind, multicenter, placebo- and active-
comparator-controlled study of guselkumab in subjects with moderate to severe plaque psoriasis with 
randomized withdrawal and retreatment. The target population is adult men or women with a diagnosis of 
plaque-type psoriasis (with or without PsA) for at least 6 months before the first administration of study 
drug. Subjects must have moderate to severe plaque-type psoriasis defined by IGA. Subjects must be 
candidates for either systemic therapy or phototherapy for psoriasis, and may have previously received 
some systemic therapies or phototherapy for psoriasis. Subjects with non-plaque forms of psoriasis (eg, 
erythrodermic, guttate, or pustular) or with current drug-induced psoriasis (eg, a new onset of psoriasis or 
an exacerbation of psoriasis from beta blockers, calcium channel blockers, or lithium) are excluded. 
Subjects who have ever received guselkumab or adalimumab are also excluded.  
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CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
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Primary analysis has been completed, follow-up is ongoing. A total of 992 subjects were randomized into 
the study. The guselkumab group demonstrated a greater improvement compared with placebo at Week 16 
in the following types of regional psoriasis: scalp psoriasis (ss-IGA), fingernail psoriasis (f-PGA, NAPSI), 
and hand and foot psoriasis (hf-PGA). More subjects of the guselkumab group achieved ss-IGA scores of 
0, and 0 or 1, and hf-PGA scores of 0 and 0 or 1 compared with adalimumab at Week 24, while no significant 
difference was observed in the proportion of subjects achieving an f-PGA score of 0/1 or the percent 
improvement in NAPSI between the guselkumab and adalimumab groups at Week 24. The guselkumab 
group demonstrated a significant and clinically meaningful improvement in health-related quality of life 
and psoriasis symptoms and signs as measured by DLQI and PSSD, compared with the placebo and 
adalimumab groups at Weeks 16 and 24, respectively. 
Phase 3 Study (CNTO1959PSO3003, NAVIGATE) 
This is a Phase 3, randomized, double-blind, multicenter study evaluating the efficacy and safety of 
guselkumab for the treatment of subjects with moderate to severe plaque-type psoriasis and an inadequate 
(IGA ≥ 2) response to ustekinumab at Week 16. The target population is adult men or women with a 
diagnosis of plaque-type psoriasis (with or without PsA) for at least 6 months before the first administration 
of study drug. Subjects must have moderate to severe plaque-type psoriasis, as defined by IGA ≥ 3, PASI 
≥ 12, and involved BSA ≥ 10%. Subjects must be candidates for either systemic therapy or phototherapy 
for psoriasis, and may have previously received some systemic therapies or phototherapy for psoriasis. 
Subjects with 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) are excluded. Subjects who have ever received guselkumab or ustekinumab are also 
excluded. A total of 871 subjects were enrolled into this study. The final analyses demonstrated that the 
guselkumab group achieved clinical responses approximately twice as often as the ustekinumab group. The 
proportion of randomized subjects in the guselkumab group with a PASI 90 response increased from Week 
16 through Week 36 and was maintained through Week 40. The difference of achieved response over time 
between the subjects randomized to the guselkumab group and the ustekinumab group was apparent as 
early as the first visit after randomization (Week 20). Difference increased over time reaching a maximum 
at Week 40. Randomized subjects treated with guselkumab also had a significantly greater mean number 
of visits at which subjects reported a score of 0 for both the PSSD sign and symptom scores and DLQI 
score of 0 or 1 between Week 28 and Week 40 as compared with subjects randomized to ustekinumab. 
Phase 1 Pharmacokinetic Results 
In the Phase 1 studies in subjects with psoriasis (CNTO1959PSO1001 [Part 2] and CNTO1959PSO1002) 
and in healthy subjects (CNTO1959PSO1001, Part 1 and CNTO1959NAP1001), guselkumab was slowly 
absorbed into the systemic circulation, with a median Tmax of approximately 3 to 6 days after a single SC 
administration. Systemic exposure (Cmax and AUC) increased in an approximately dose-proportional 
manner after a single intravenous (IV) administration at doses ranging from 0.03 to 10 mg/kg or after a 
single SC administration at doses ranging from 10 to 300 mg. After a single IV administration, the mean 
Vz values were approximately 6.7 to 10.1 L (98 to 123 mL/kg) and mean clearance (CL) values were 
approximately 0.288 to 0.479 L/day (3.6 to 6.0 mL/day/kg). The mean T1/2 values ranged from 
approximately 12.3 to 19.1 days after a single IV administration and approximately 14.7 to 17.2 days after 
a single SC administration. The mean absolute bioavailability of guselkumab after a single 100 mg SC 
administration was between 47.6% and 54.9%. Overall, the PK of guselkumab was comparable between 
Japanese (CNTO1959PSO1002) and non-Japanese (CNTO1959PSO1001) subjects with psoriasis. 
Phase 1 and Phase 2 Safety, Tolerability and Efficacy Results 
Improvements in PASI scores were observed in all dose groups in CNTO1959PSO1001 (Part 2), with the 
maximum clinical response between Weeks 8 and 16. Guselkumab SC was generally safe and well 
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CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
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Approved, Date: 22 January 2018Approved22 January 2018 
tolerated, with no dose-dependent response in the incidence of AEs; all AEs were considered to be mild to 
moderate in intensity by the investigator. In CNTO1959PSO1002, improvements in PASI scores and PGA 
were observed in all guselkumab dose groups and administration of guselkumab SC was generally safe and 
well tolerated. No dose-dependent response in the incidence of AEs was observed, and all AEs were 
considered mild in severity by the investigator. 
In Study CNTO1959PSO2001, treatment with guselkumab at doses ranging from 5 mg q12w to 200 mg 
q12w from Week 0 through Week 52 was generally well tolerated through the end of the study (Week 52) 
and improvements in PASI scores and PGA were observed in all guselkumab dose groups.  
1.2. 
Comparator 
Fumaderm® initial/Fumaderm® are mixtures of fumaric acid esters (FAE) that are approved for the 
treatment of moderate to severe plaque-type psoriasis in Germany. FAE consist of dimethylfumarate and 
monoethylfumarate salts, which can modulate the immune system; however, the exact mechanism of action 
is unclear (1). Detailed information about Fumaderm® initial/ Fumaderm® can be found in the current 
Summary of Product Characteristics (SmPC) (2). 
1.3. 
Overall Rationale for the Study 
Traditionally, biologic compounds like guselkumab with a precisely defined therapeutic target were used 
after failure of conventional systemic therapy such as MTX, FAE or cyclosporine. Years of experience with 
a variety of biologic compounds led to the assessment that the benefit-risk ratio of biologic compounds 
might also be favorable for psoriasis subjects without prior conventional systemic therapy (“1st line systemic 
subject population”). 
Guselkumab specifically targets IL-23, which contributes to the chronic inflammation underlying the 
pathophysiology of many immune-mediated diseases (3), (4). The clinical response to guselkumab 
observed in previous psoriasis studies demonstrates the specific importance of IL-23 in the pathogenesis of 
plaque psoriasis. 
In the current phase 3 program, guselkumab is compared to adalimumab in subjects suffering from 
moderate to severe psoriasis in two independent trials (CNTO1959PSO3001 and CNTO1959PSO3002). 
Additionally, the efficacy and safety of guselkumab is assessed in subjects with moderate to severe psoriasis 
and an inadequate response to ustekinumab (CNTO1959PSO3003). However, the phase 3 program lacks a 
head-to-head trial vs. conventional systemic compounds. In Germany, FAE are the most commonly 
prescribed 1st line systemic therapy (1) for moderate to severe plaque-type psoriasis. FAE are considered 
to be more effective in treating plaque-psoriasis than methotrexate and to be better suited for long-term 
treatment of psoriasis than cyclosporine (5). Therefore, FAE were selected as appropriate comparator to 
evaluate guselkumab in treating subjects with moderate to severe psoriasis who are candidates for and naïve 
to systemic treatment (1st line systemic subject population). 
The profile of side effects (eg, GI-symptoms and flush; lymphopenia) of FAE is very characteristic, will 
affect the majority of subjects and will lead to a de facto unblinding of treatment groups. Therefore, this 
clinical study will utilize an open-label design. To help improve objectivity and decrease bias, given the 
open-label design, efficacy assessments will be performed by a blinded assessor during Study Part I and II. 
Part II of this study is designed to exploratorily assess the sustainability of treatment efficacy (guselkumab 
and FAE), while non-responders will be offered to switch to or continue guselkumab. 
Finally, a withdrawal element has been incorporated into the study design (Study Part III) to assess the 
maintenance of response in subjects who discontinue guselkumab. Maintenance of response after drug 
withdrawal is indicative of disease modification. 
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CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
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Approved, Date: 22 January 2018Approved22 January 2018 
2. 
OBJECTIVES AND HYPOTHESES 
2.1. 
Objectives  
Primary Objectives 
The primary objectives of the study are 
 
to compare the efficacy of guselkumab to fumaric acid esters (FAE) in systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis. 
 
to assess the safety and tolerability of guselkumab in systemic treatment-naïve subjects with 
moderate to severe plaque-type psoriasis. 
Secondary Objectives 
The secondary objectives of the study are 
 
in Study Parts I and II: to compare improvement of health-related quality of life (QOL) and other 
patient-reported outcomes (PRO) when systemic treatment-naïve subjects with moderate to severe 
plaque-type psoriasis are treated with guselkumab compared to FAE. 
 
in Study Part II: to compare sustainability of response to treatment when systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis are treated with guselkumab compared to 
FAE. 
 
in Study Part III (guselkumab withdrawal): to investigate the maintenance of response in subjects 
withdrawn from study treatment, and to explore prediction parameters of disease modification. 
2.2. 
Hypotheses 
The primary hypothesis of this study is that guselkumab treatment is superior to FAE (Fumaderm® initial/ 
Fumaderm®) treatment as assessed by the proportion of subjects achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are: 
 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects achieving a 
PASI 75 response at Week 24 
 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects achieving a 
DLQI score of 0 or 1 at Week 24. 
If the primary hypothesis is accepted, the study will be considered positive. 
 
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CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
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3. 
STUDY DESIGN AND RATIONALE 
3.1. 
Overview of Study Design 
This is a randomized, open-label, efficacy assessor-blinded, single country, multicenter, active-comparator-
controlled phase 3b study of guselkumab in adult subjects with moderate to severe plaque-type psoriasis 
who have not yet received any systemic therapy. The study will be performed at about 30 to 45 sites in 
Germany. 
This study will have a 3-week screening phase, a 56-week treatment phase and a safety follow-up phase 
until Week 64, followed by a follow-up extension phase after withdrawal of guselkumab until loss of 
response or until Week 100 at the latest (as shown in Figure 1). The maximum duration of a subject’s 
participation in this study will be 103 weeks. With protocol Amendments INT-1 and INT-2, the study will 
be split into three parts (Study Part I, II and III): 
Study Part I (Core Study)—Week 0 through Week 24: 
Screening and treatment until primary endpoint is reached  
After screening, a total of 114 subjects will be randomized in a 1:1 ratio to either the study drug 
(guselkumab) or to the active comparator (FAE). Subjects of the guselkumab group will receive 100 mg 
guselkumab SC at Weeks 0, 4, 12, and 20. Subjects of the FAE group will receive commercially available 
Fumaderm® tablets specifically labeled for the study. An individual dosing for each subject representing 
the optimal benefit-risk ratio is aspired.  
A subject will be considered to have completed Study Part I if he or she has completed assessments at Week 
24 of the open-label phase. Subjects eligible for Study Part II at Week 24 (ICF Part II signed, study 
treatment ongoing, no protocol-prohibited treatment started) will enter study extension and continue study 
treatment. For subjects who discontinue study treatment or withdraw from study participation in Study Part 
I or who do not enter Study Part II, a safety follow-up visit (Study Part I) is completed at Week 32 or 12 
weeks after the last treatment (whatever comes first). For subjects enrolled in Study Part I only, maximum 
duration of study participation in this study will be 35 weeks. 
Study Part II (Extension, continuation/switch of study treatment)—Week 24 through Week 56: 
Treatment 
Subjects may enter the study extension at Week 24 only when the ICF for Study Part II was signed before 
or at Week 24, study treatment was not terminated prior to Week 24 and no protocol-prohibited 
medication/therapy was started. Study Part II is subdivided in two treatment periods: 
 
Part IIa—Week 24 through Week 32: All subjects who enter Study Part II will continue their 
assigned treatment (guselkumab or FAE) from Week 24 through Week 32. Study Part IIa is 
considered completed when the subject has completed assessments at Week 32. 
 
Part IIb—Week 32 through Week 56: Following Week 32, subjects with a PASI 75 response will 
continue assigned treatment (guselkumab or FAE). For PASI 75 non-responders at Week 32 the 
following options will be available: 
- 
Guselkumab group: Subjects may continue guselkumab treatment. It is at the investigator’s 
discretion to continue therapy, if it is considered medically appropriate. 
- 
FAE group: Subjects will switch to guselkumab unless barred by safety reasons (based on 
lab values ≥Week 28). Subjects who terminate FAE treatment prior to Week 32 cannot 
continue study treatment but will enter safety follow-up per protocol. 
A subject will be considered to have completed Study Part II if he or she has completed assessments at 
Week 56 of the open-label phase. For Subjects who discontinue study treatment or withdraw from study 
participation in Study Part II, final study assessments are obtained and a safety follow-up visit is completed 
at Week 64 or 12 weeks after last treatment (whatever comes first). For subjects completing Study Part II 
maximum duration of study participation in this study will be 67 weeks including a 3-week screening phase. 
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Study Part III (Follow-up extension after guselkumab withdrawal, no study treatment)—Week 64 
through Week 100 
Subjects who received guselkumab in Study Part II (subjects who started guselkumab treatment at Week 0 
or switched from FAE to guselkumab treatment in Week 32), had no psoriatic arthritis diagnosed at baseline 
and achieved a PASI 90 response at end of Study Part II (Week 56) may enter follow-up extension at Week 
64. To be eligible for follow-up extension subjects must have ICF for Study Part III before or at Week 64, 
must not have started a new psoriasis treatment (including commercially available guselkumab therapy) or 
started any other protocol-prohibited medication/therapy. In Study Part III, subjects are withdrawn from 
guselkumab treatment and will be followed until loss of response (defined as an increase in absolute PASI 
>5), but until Week 100 at the latest, which is almost 1 year after the last guselkumab treatment at visit 
Week 52.  
All other subjects may not enter Study Part III and complete the study at Week 64.  
Efficacy assessments will be performed first by the subject him/herself, and subsequently by an efficacy 
assessor. Preferably, in Study Part III the same efficacy assessor as in Study Parts I and II continues 
evaluation of the disease, but efficacy assessments are no longer blinded. 
A subject will be considered to have completed Study Part I or Study Part II if he or she has completed 
assessments at Week 24 and Week 56, respectively. A subject will be considered to have completed Study 
Part III if he or she has completed assessments at Week 100 or completed final assessments after loss of 
response. The maximum duration of a subject’s participation will be 103 weeks including a 3-week 
screening phase. 
Safety Follow-up Phase 
 
Safety FUP (Part I) – Week 24 through Week 32 
For subjects who complete study treatment at Week 24 a final safety follow-up visit is completed at 
Week 32.  
 
Safety Follow-up (Part II) – Week 56 through Week 64 
All ongoing subjects complete the safety follow-up until Week 64. For subjects who complete study 
treatment at Week 56 a final safety follow-up visit is completed at Week 64. For subjects entering 
Study Part III the safety follow-up visit will be conducted and subjects will continue as described 
below. 
 
Safety Follow-up after discontinuation/withdrawal – 12 weeks after last treatment 
For subjects who discontinue study treatment or withdraw from study participation, final study 
assessments are obtained and a final safety follow-up visit is completed 12 weeks after last treatment.  
 
Efficacy of treatment will be assessed before any tests, procedures or other evaluations, first by the subject 
him/herself (1st DLQI, 2nd PSSD 7-day version, and 3rd SF-36), and subsequently, in Study Part I and II, 
by a blinded efficacy assessor (BSA%, IGA, ss-IGA, and PASI). Preferably, the same efficacy assessor 
continues evaluation of the disease in Study Part III, but efficacy assessments are no longer blinded. 
Safety evaluations will include the monitoring of adverse events (including injection site and allergic 
reactions), physical examinations, measurement of body weight, vital sign measurement, clinical laboratory 
testing (HBV, HCV, HIV, hematology, chemistry), concomitant medication review, tuberculosis test and 
evaluation, urinalysis and pregnancy testing.  
The confirmatory analysis will be conducted after the primary endpoint at Week 24 is reached including 
subjects who have completed the Week 24 visit and subjects who have terminated the study prematurely 
(Section 11.3). The second and third statistical analyses will be performed after Week 64 and after Week 
100 (see Section 11). 
A subject will be considered to have completed Study Part I or Study Part II if he or she has completed 
assessments at Week 24 and Week 56, respectively. A subject will be considered to have completed Study 
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Part III if he or she has completed assessments at Week 100 or completed final assessments after loss of 
response. The maximum duration of a subject’s participation will be 103 weeks including a 3-week 
screening phase. 
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 transferred to the sponsor (or designee) after completion of the final subject 
visit at that site, in the time specified in the Clinical Trial Agreement. The overall duration of the study is 
expected to be approximately 30 months (start in December 2016, stop in July 2019). The estimated 
frequency and timing of the study visits are summarized in the ‘Time and Events Schedule’ (TES). Figure 
1: Schematic Overview of the Study 
 
 
 
 
 
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3.2. 
Study Design Rationale 
Blinding, Control, Study Phase/Periods, Treatment Groups 
FAE are the most commonly prescribed 1st line systemic therapy (1) for moderate to severe plaque-type 
psoriasis in Germany. For this reason, FAE were selected as appropriate comparator to evaluate guselkumab 
in treating subjects with moderate to severe psoriasis who are candidates for and naïve to systemic treatment 
(1st line systemic subject population). 
The profile of side effects (eg, GI-symptoms and flush; lymphopenia) of FAE is very characteristic, will 
affect the majority of subjects and will lead to a de facto unblinding of treatment groups. Therefore, this 
clinical study will utilize an open-label design. To help improve objectivity and decrease bias, given the 
open-label design, during Study Part I and II efficacy assessments will be performed by a blinded assessor, 
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meaning the assessor of dermatological evaluation will not know the treatment group the subject to be 
evaluated belongs to. Thus, investigators and investigational staff must not disclose the randomization table 
to the assessor. Additionally, it is prohibited to involve the assessor in study drug application and its 
preparation. The assessor must not have access to the electronic data capture (EDC) system or subject’s 
medical records or study drug administration information. 
Part I of this study (Week 0 to 24) is designed and powered to assess the efficacy of psoriasis therapy with 
guselkumab and FAE, respectively, after a 24-week treatment phase. This duration allows for an adequate 
treatment period. Part II of this study (Week 24 to 56) is designed to exploratorily assess the sustainability 
of treatment efficacy (guselkumab and FAE). So far, no randomized clinical trials evaluated the efficacy of 
FAE after Week 16. However, real-world data and anecdotal evidence suggest that the effectiveness of FAE 
treatment increases for up to 6 months. Part IIa of this study (Week 24 to 32) addresses the question if FAE 
efficacy might improve after Week 24. In Part IIb of this study (Week 32 to 56) the sustainability of 
response in subjects with a PASI 75 response will be addressed, while PASI 75 non-responders will be 
offered to switch to or continue guselkumab at Week 32. Part III of this study (Week 64 to 100) is designed 
to assess the maintenance of response after guselkumab withdrawal in subjects who responded well (PASI 
90 response) to guselkumab. Maintenance of response after drug withdrawal is indicative of disease 
modification. 
Randomization will be used to minimize bias in the assignment of subjects to treatment groups, 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. 
4. 
SUBJECT POPULATION 
The target population comprises adult men and women with a diagnosis of plaque-type psoriasis for at least 
6 months before the first administration of the study drug. Subjects must have moderate to severe plaque-
type psoriasis defined by Psoriasis Area and Severity Index (PASI) >10 or involved body surface area 
(BSA) >10%, and Dermatology Quality of Life Index (DLQI) >10. Subjects must be candidates for 
systemic psoriasis therapy, and FAE must be considered as an appropriate treatment option. Subjects with 
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) are excluded. 
A total number of 114 subjects will be randomly assigned in this study with 57 subjects planned per 
treatment group. 
The inclusion and exclusion criteria for enrolling subjects in this study are described in the following 
2 subsections. If there is a question about the inclusion or exclusion criteria below, the investigator must 
consult with the appropriate sponsor representative and resolve any issues before enrolling a subject in the 
study. Waivers are not allowed. 
4.1. 
Inclusion Criteria 
Each potential subject must satisfy all of the following criteria to be enrolled in the study: 
1. 
Male or female and ≥18 years of age 
2. 
Have a diagnosis of plaque-type psoriasis for at least 6 months before the first administration of study 
drug 
3. 
Have a PASI >10 or BSA >10 at screening and at baseline 
4. 
Have a DLQI >10 at screening and at baseline 
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5. 
Be a candidate for systemic treatment for psoriasis  
6. 
Topical psoriasis therapy is considered to be inadequate by the investigator due to  
o inadequate response to, intolerance to or contraindication against topical therapy in the 
subject’s medical history (documented or reported by the subject)  
o and/or disease severity at screening and at baseline
7. 
Must be eligible for Fumaderm® treatment according to the SmPC  
8. 
Fumaderm® is considered, in the opinion of the investigator, to be an appropriate treatment option 
9. 
Contraceptive use by men or women should be consistent with local regulations regarding the use of 
contraceptive methods for subject participating in clinical studies 
Before randomization, a woman must be either: 
a. Not of childbearing potential defined as:  
Premenarchal  
A premenarchal state is one in which menarche has not yet occurred. 
Postmenopausal  
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause. A high follicle stimulating hormone (FSH) level (>40 IU/L or mIU/mL) in the 
postmenopausal range may be used to confirm a postmenopausal state in women not using 
hormonal contraception or hormonal replacement therapy, however in the absence of 12 months 
of amenorrhea, a single FSH measurement is insufficient. 
Permanently sterile  
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, bilateral tubal 
occlusion/ligation procedures, and bilateral oophorectomy. 
b. Of childbearing potential and 
 practicing a highly effective method of contraception (failure rate of <1% per year when used 
consistently and correctly) 
Examples of highly effective contraceptives include: 
- user-independent methods: 
  implantable progestogen-only hormone contraception associated with inhibition of ovulation; 
intrauterine device (IUD); intrauterine hormone-releasing system (IUS); vasectomized partner; 
sexual abstinence (sexual abstinence is considered a highly effective method only if defined as 
refraining from heterosexual intercourse during the entire period of risk associated with the study 
drug. The reliability of sexual abstinence needs to be evaluated in relation to study duration and 
the preferred and usual lifestyle of the subject.) 
- user-dependent methods:  
 combined (estrogen- and progestogen-containing) hormonal contraception associated with 
inhibition of ovulation: oral, intravaginal, and transdermal; progestogen-only hormone 
contraception associated with inhibition of ovulation: oral and injectable 
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
participating in clinical studies. Hormonal contraception may be susceptible to interaction with 
the study drug, which may reduce the efficacy of the contraceptive method. 
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 agrees to remain on a highly effective method throughout the study and for at least 90 days after 
the last dose of study drug. A woman using oral contraceptives should use an additional birth 
control method. 
Note: If the childbearing potential changes after start of the study (eg, a premenarchal woman 
experiences menarche) or the risk of pregnancy changes (eg, a woman who is not heterosexually active 
becomes active) a woman must begin a highly effective method of contraception, as described 
throughout the inclusion criteria. 
If reproductive status is questionable, additional evaluation should be considered. 
10. A woman of childbearing potential must have a negative urine pregnancy test at screening and at Week 
0 
11. A woman must agree not to donate eggs (ova, oocytes) for the purpose of assisted reproduction during 
the study and for a period of at least 12 weeks after receiving the last administration of study treatment
12. During the study and for a minimum of 1 spermatogenesis cycle (defined as approximately 90 days) 
after receiving the last dose of study drug, in addition to the highly effective method of contraception, 
a man 
 who is sexually active with a woman of childbearing potential must agree to use a barrier method 
of contraception (eg, condom with spermicidal foam/gel/film/cream/suppository), during the study 
and for at least 12 weeks after receiving the last study treatment. 
 who is sexually active with a woman who is pregnant must use a condom, during the study and for 
at least 12 weeks after receiving the last administration of study treatment. 
 must agree not to donate sperm during the study and for at least 12 weeks after receiving the last 
administration of study treatment. 
13. Considered eligible according to the following tuberculosis (TB) screening criteria: 
 Have no history of latent or active TB before screening. 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. It is the responsibility of the investigator to verify the adequacy of previous anti-tuberculosis 
treatment and provide appropriate documentation. 
 Have no signs or symptoms suggestive of active TB upon medical history and/or physical 
examination 
 Have had no recent close contact with a person with active TB or, if there has been such contact, 
will be referred to a physician specializing in TB to undergo additional evaluation and, if warranted, 
receive appropriate treatment for latent TB before first administration of study drug 
 Within 2 months before the first administration of study drug, have a negative QuantiFERON®-TB 
Gold Plus test result (6) (7), or have a newly identified positive QuantiFERON®-TB Gold Plus test 
result (Attachment 3) in which active TB has been ruled out and for which appropriate treatment 
for latent TB (Section 9.1.2) has been initiated before the first administration of study drug. 
Indeterminate results should be handled as outlined in Section 9.1.2. 
Note: The QuantiFERON®-TB Gold Plus test is not required at screening for subjects with a history 
of latent TB and ongoing treatment for latent TB or documentation of having completed adequate 
treatment as described above; subjects with documentation of having completed adequate treatment 
as described above are not required to initiate additional treatment for latent TB. 
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14. Have a chest radiograph (posterior-anterior and lateral views), 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 
15. Agree not to receive a live virus or live bacterial vaccination during the study, or within 3 months after 
the last administration of study drug; for information on Bacille Calmette-Guérin (BCG) vaccination, 
see Inclusion Criterion 16 
16. Agree not to receive a BCG vaccination during the study, or within 12 months after the last 
administration of study drug 
17. Have screening laboratory test results within the following parameters, if one or more of the laboratory 
parameters is out of range, a single retest of laboratory values is permitted: 
 Hematology panel within normal limits 
 Serum creatinine ≤1 × upper limit of normal (ULN) 
 Aspartate aminotransferase (AST), alanine aminotransferase (ALT), gamma-GT, total bilirubin and 
alkaline phosphatase (AP) levels must be ≤2 × ULN 
18. No dipstick detection of proteins or glucose in urine. If there are signs of proteins and/or glucose on 
urine test strip, the urine sample must be analyzed centrally. Here, protein and glucose levels must not 
exceed trace levels, eg, (+); one re-test (central urine analysis) is allowed. 
19. Agree to avoid prolonged sun exposure and avoid use of tanning booths or other ultraviolet (UV) light 
sources during study 
20. Be willing and able to adhere to the prohibitions and restrictions specified in this protocol 
21. Sign an informed consent form (ICF) indicating that he or she understands the purpose of and 
procedures required for the study and is willing to participate in the study. 
4.2. 
Exclusion Criteria 
Any potential subject who meets any of the following criteria will be excluded from study participation: 
1. 
Has received prior systemic treatment of psoriasis including but not limited to 
- conventional systemic therapy (eg, methotrexate, cyclosporine, fumaric acid esters and acitretine)
- apremilast and tofacitinib 
- drugs targeted for reducing TNF (including but not limited to infliximab, adalimumab or 
etanercept) 
- drugs targeted for reducing IL-12, IL-17, or IL-23 (including but not limited to ustekinumab, 
tildrakizumab [MK3222], secukinumab [AIN457], ixekizumab [LY2439821], or brodalumab 
[AMG827])  
- alpha-4 integrin antagonists (including but not limited to natalizumab) 
2. 
Has a history or current signs or symptoms of severe, progressive, or uncontrolled liver or renal 
insufficiency, significant cardiac, vascular, pulmonary, gastrointestinal, endocrine, neurologic, 
hematologic, rheumatologic, psychiatric, or metabolic disturbances 
3. 
Has a history of malignancy within 5 years before screening (with the exception of a non-melanoma 
skin cancer that has been adequately treated with no evidence of recurrence for at least 3 months before 
the first study drug administration, or cervical carcinoma in situ that has been treated with no evidence 
of recurrence for at least 3 months before first study drug administration) 
4. 
Has a history of lymphoproliferative disease, including lymphoma; a history of monoclonal 
gammopathy of undetermined significance (MGUS); or signs and symptoms suggestive of possible 
lymphoproliferative disease, such as lymphadenopathy or splenomegaly 
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5. 
Has a transplanted organ (with exception of a corneal transplant >3 months before the first 
administration of study drug) 
6. 
Has a history of an infected joint prosthesis, or has received antibiotics for a suspected infection of a 
joint prosthesis, if that prosthesis has not been removed or replaced 
7. 
Has or has had a serious infection (eg, sepsis, pneumonia or pyelonephritis), or has been hospitalized 
or received IV antibiotics for an infection during the 2 months before screening 
8. 
Has or has had herpes zoster within the 2 months before screening 
9. 
Has current drug-induced psoriasis (eg, a new onset of psoriasis or an exacerbation of psoriasis from 
beta blockers, calcium channel blockers, or lithium) 
10. Has a non-plaque form of psoriasis (eg, erythrodermic, guttate, or pustular) 
11. Has a history of chronic or recurrent infectious disease, including but not limited to chronic renal 
infection, chronic chest infection (eg, bronchiectasis), recurrent urinary tract infection (recurrent 
pyelonephritis or chronic non-remitting cystitis), fungal infection (mucocutaneous candidiasis), or 
open, draining, or infected skin wounds or ulcers 
12. Known allergies, hypersensitivity, or intolerance to guselkumab or its excipients (more information 
can be found in the current version of the Investigator's Brochure) 
13. Contraindications to the use of Fumaderm® initial/ Fumaderm® per local prescribing information 
14. Has received phototherapy (including, but not limited to, PUVA, narrow-band UVB, 
balneophototherapy) within 4 weeks of the first administration of study drug 
15. Has used topical medications/ treatments that could affect psoriasis (including, but not limited to, 
corticosteroids, anthralin, calcipotriene, topical vitamin D derivatives, retinoids, tazarotene, 
methoxsalen, pimecrolimus, tacrolimus, or topical traditional Taiwanese, Korean, or Chinese 
medicines) within 2 weeks of the first administration of study drug 
16. Has received, or is expected to receive, any live virus or bacterial vaccination within 3 months before 
the first administration of study drug; for BCG vaccine, see Exclusion Criterion 17 
17. Has had a BCG vaccination within 12 months of screening 
18. Has known intolerance or hypersensitivity to any biologic medication, or known allergies or clinically 
significant reactions to murine, chimeric, or human proteins, mABs, or antibody fragments 
19. Has a history of active granulomatous infection, including histoplasmosis or coccidioidomycosis, 
before screening (regarding eligibility with a history of latent TB, see Inclusion Criterion 13) 
20. Has a chest radiograph within 3 months before the first administration of study drug that shows an 
abnormality suggestive of a malignancy or current active infection, including TB 
21. Has 
ever 
had 
a 
non-tuberculous 
mycobacterial 
infection 
or 
opportunistic 
infection
(eg, cytomegalovirus, pneumocystosis, or aspergillosis) 
22. Has persistently indeterminate (indeterminate on repeat sampling) IGRA, eg, QuantiFERON®-TB 
Gold Plus test results; indeterminate results should be handled as described in Section 9.1.2 
23. Is infected with human immunodeficiency virus (HIV, positive serology for HIV antibody) 
24. Tests positive for hepatitis B virus (HBV) infection or seropositive for antibodies to hepatitis C virus 
(HCV) at screening (Attachment 4) 
25. Received an investigational drug (including investigational vaccines) or used an invasive 
investigational medical device within 3 months before the planned first dose of study drug or is 
currently enrolled in an investigational study 
26. Is pregnant, or breast-feeding, or planning to become pregnant while enrolled in this study or within
12 weeks after the last dose of study drug 
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27. Plans to attempt to have a child while enrolled in this study or within 12 weeks after the last dose of 
study drug 
28. Is known to have had a substance abuse (drug or alcohol) problem within the previous 12 months 
29. Is unable or unwilling to undergo multiple venipunctures because of poor tolerability or lack of easy 
access to veins 
30. Lives in an institution on court or authority order 
31. Any condition for which, in the opinion of the investigator, participation would 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 
32. Had major surgery, (eg, requiring general anesthesia) within 8 weeks before screening, or will not 
have fully recovered from surgery, or has surgery planned during the time the subject is expected to 
participate in the study. 
Note: Subjects with planned surgical procedures to be conducted under local anesthesia may 
participate. 
33. Employee of the investigator or study site, with direct involvement in the proposed study or other 
studies under the direction of that investigator or study site, as well as family members of the 
employees or the investigator. 
Note: Investigators should ensure that all study enrollment criteria have been met at screening. If a subject's 
clinical status changes (including any available laboratory results or receipt of additional medical records) 
after screening but before the first dose of study drug is given such that he or she no longer meets all 
eligibility criteria, then the subject should be excluded from participation in the study. Section 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 course of the study to be eligible for participation: 
1. 
See Section “Prestudy and Concomitant Therapy” for details regarding prohibited and restricted 
therapy during the study. 
2. 
Agree to follow the contraceptive requirements as noted in the inclusion criteria. Women participating 
in Study Part III, who are of childbearing potential (e.g. not premenarchal, not postmenopausal and 
not permanently sterile) and use a highly effective method of contraception, have to agree to remain 
on a highly effective method of contraception throughout the study.  
3. 
Subjects must not receive a live virus or bacterial vaccination during the study and for 3 months after 
the last administration of any study drug; see Prohibition 5 for information regarding BCG vaccination
4. 
Avoid donating blood for at least 90 days after last study treatment (ie, safety follow-up visit) of the 
study. Subjects entering Study Part III should avoid donating blood until end of study (Final Study 
Visit). 
5.  Subjects must not receive a BCG vaccination during the study and for 12 months after the last 
administration of study drug. 
6. 
Subjects must avoid prolonged sun exposure and avoid use of tanning booths or other UV light sources 
during the study. 
 
 
 
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4.4. 
Treatment Assignment Criteria for Study Part II (Week 24 through Week 56) 
Study Part IIa: Week 24 through Week 32 
Subject may enter Study Part II at Week 24 when he/she did 
1. 
sign informed consent form (ICF) for Study Part II indicating that he or she understands the 
purpose of and procedures required for the study and is willing to participate in the study 
2. 
not terminate study treatment prior to Week 24 
3. 
not start a protocol-prohibited medication/therapy. 
Until Week 32, subjects will continue assigned treatment (guselkumab or FAE) as randomized at Week 0.  
Study Part IIb: Week 32 through Week 56 
At Week 32 the following treatment assignments will be performed based on the Week 32 PASI assessment 
and safety considerations: 
 
Subjects with a PASI 75 response in both groups will continue assigned treatment.  
 
PASI 75 non-responders in the guselkumab group may continue guselkumab treatment, if the 
investigator considers therapy medically appropriate. 
 
PASI 75 non-responders in the FAE group may switch to guselkumab when it is considered a safe 
treatment option (see Section 4.4.1). 
4.4.1. 
Study Part IIb: Treatment Switch Safety Criteria 
Subject of the FAE group with PASI 75 non-response may switch to guselkumab when he/she 
1. 
had laboratory results at Week 28 within the following ranges: 
Hemoglobin 
≥10 g/dL (SI: ≥100 g/L) 
Leukocytes 
≥3.5 × 103/μL (SI: ≥3.5 GI/L) 
Neutrophils 
≥1.5 × 103/μL (SI: ≥1.5 GI/L) 
Lymphocytes 
≥0.7 × 103/μL (SI: ≥0.7 GI/L) 
Platelets 
≥100 × 103/μL (SI: ≥100 GI/L)  
Serum creatinine 
≤1.5 mg/dL (SI: ≤129 μmol/L)  
Aspartate aminotransferase (AST) 
≤2 × upper limit of normal (ULN)* 
Alanine aminotransferase (ALT) 
≤2 × ULN* 
Alkaline phosphatase (AP) 
≤2 × ULN* 
* laboratory-specific 
Note: If one or more parameters are out of range, one single retest is permitted before the Week 
32 visit. 
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2. 
is eligible according to the following tuberculosis (TB) criteria: 
 
Have no signs or symptoms of an active TB infection according to the early detection 
guidelines for TB (Section 9.3) 
 
Subjects with a positive QuantiFERON®-TB Gold Plus test result must have completed 
appropriate treatment for latent TB within 5 years before the first administration of 
guselkumab, must continue appropriate treatment for latent, or must initiate appropriate 
treatment of latent TB before first administration of guselkumab. It is in the responsibility 
of the investigator to verify the adequacy of previous anti-tuberculosis treatment and 
provide appropriate documentation. 
4.5. 
Eligibility Criteria for Study Part III: Week 64 until loss of response or Week 100 
Subjects treated with guselkumab in Study Part II (subjects who started guselkumab treatment at Week 0 
or switched from FAE to guselkumab treatment in Week 32) may enter Study Part III at Week 64 when 
he/she: 
 
Signed ICF of Study Part III before or at Week 64  
 
Achieved a PASI 90 response at the end of Study Part II (Week 56) 
 
Had no diagnosis of psoriatic arthritis (PsA) at baseline 
 
Did not start a new psoriasis treatment before Week 64, including commercially available 
guselkumab 
 
Did not start any other protocol-prohibited medication/therapy 
 
Is a woman and used a highly effective method of contraception during Study Part I and II and 
agrees to remain on a highly effective method of contraception throughout the study. 
5. 
TREATMENT ALLOCATION AND BLINDING 
Procedures for Randomization  
Central randomization will be implemented in this study. Subjects will be randomly assigned to 1 of 2 
treatment groups (1:1 ratio) based on a computer-generated randomization schedule prepared before the 
study by or under the supervision of the sponsor. The randomization will be balanced by using randomly 
permuted blocks. The interactive web-based eCRF will assign a unique treatment code, which will dictate 
the treatment assignment at baseline visit of the subject. The investigator will not be provided with 
randomization codes. The randomization codes will be stored invisible for the investigator in a separate, 
blind part of the EDC system.  
Blinding 
As this is an open study, blinding procedures for the treatment are not applicable. However, a blinded 
efficacy evaluator will assess effectiveness of treatment as described in Section 9.2.3. During Study Part 
III, subjects who received guselkumab during Study Parts I or II only are eligible for Study Part III. During 
Study Part III subjects are no longer on study treatment, thus, efficacy assessments during Study Part III 
are no longer blinded. 
6. 
DOSAGE AND ADMINISTRATION 
A 100 mg/mL solution of guselkumab will be provided in a single-use prefilled syringe (PFS) assembled 
with the UltraSafe PLUSTM Passive Needle Guard (PFS-U). Commercially available Fumaderm® initial/ 
Fumaderm® tablets will be supplied. 
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Study-site personnel will instruct subjects on how to store study drug for at-home use (only Fumaderm® 
initial/ Fumaderm®) as indicated for this protocol. 
6.1. 
Study Drug Dosage 
6.1.1. 
Study Part I and Study Part IIa: Active Comparative Treatment 
Active comparative treatment phases are Week 0 through Week 24 (Study Part I) and Week 24 through 
Week 32 (Study Part IIa).  
Subjects randomized to guselkumab will receive 100 mg guselkumab SC by trained study personnel at the 
study site, subjects randomized to FAE will receive commercially available Fumaderm® initial/ Fumaderm® 
tablets intended for self-administration at home, and specifically labeled for the study. An individual FAE 
dosing for each subject representing the optimal benefit-risk ratio is aspired. The maximum daily dosage 
of 3 × 2 tablets Fumaderm® must not be exceeded. 
Subjects will receive study drug through Week 56 with a rescue option for FAE group PASI 75 non-
responders at Week 32. PASI evaluation will be used to decide if the current treatment can be considered 
satisfactory as defined by subject reaching a PASI 75 response. 
The dose regimens are as follows: 
Study Part I (Week 0 through Week 24): 
 
Group I (Gus, n = 57): 100 mg Guselkumab SC at weeks 0, 4, 12 and 20  
 
Group II (FAE, n = 57): Fumaderm® initial/Fumaderm® tablets; individual dosing according to 
local prescribing information (SmPC) (2) 
Study Part IIa (Week 24 through Week 32): 
Both groups continue their assigned treatment. 
 
Group I (Gus): 100 mg guselkumab SC every 8 weeks (ie, at Week 28)  
 
Group II (FAE): Fumaderm® initial/Fumaderm® tablets; individual dosing according to local 
prescribing information (SmPC) (2)  
6.1.2. 
Study Part IIb: Continuation/Switch of Study Treatment (Week 32 through Week 56) 
Study Part IIb is designed to assess sustainability of treatment efficacy and as rescue treatment phase for 
subjects of the FAE group with PASI 75 non-response. Part IIb spans Week 32 through Week 56. Treatment 
depends on PASI response.  
a. 
PASI 75 responders at Week 32:  
Both groups continue their assigned treatment. 
 
Group I (Gus): 100 mg guselkumab SC every 8 weeks (ie, at Weeks 36, 44 and Week 52)  
 
Group II (FAE): Fumaderm® initial/ Fumaderm® tablets; individual dosing according to local 
prescribing information (SmPC) (2)  
b. 
PASI 75 non-responders at Week 32:  
For non-responders of the guselkumab group, it is at the investigator’s discretion to continue 
guselkumab treatment, if it is considered medically appropriate. Non-responder subjects of the 
FAE group may switch to guselkumab treatment unless barred by safety reasons (for details see 
Section 4.4).  
 
Group I (Gus): continue 100 mg guselkumab SC every 8 weeks (ie, at Weeks 36, 44 and Week 52) 
 
Group II (FAE): switch to 100 mg guselkumab SC at Weeks 32, 36, 44 and Week 52 
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If the subject does not continue assigned treatment or does not switch to guselkumab, subject terminates 
study treatment and enters safety follow-up. 
6.1.3. 
Safety Follow-up Phase: Psoriasis Treatment  
During the safety follow-up period Week 24 through Week 32 (Study Part I) or Week 56 through Week 64 
(Study Part II) or 12 weeks after the last application of study drug (whatever comes first), concomitant 
treatments for psoriasis may be administered at the investigator’s discretion as follows: 
 Group I (Gus): If commercially available, investigator may continue actual 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. 
Note: Subjects who start a new psoriasis treatment, including commercially available guselkumab, 
during safety follow-up phase are not eligible to enter Study Part III. 
 Group II (FAE): Investigator may either continue the actual FAE treatment with commercially 
available drug or switch to another commercially available treatment. 
6.1.4. 
Study Part III, Follow-up Extension Phase: Guselkumab Withdrawal, No Study 
Treatment (Week 64 through Week 100) 
Subjects who are eligible to enter Study Part III are withdrawn from guselkumab treatment and are followed 
until loss of response (defined as an increase in absolute PASI >5) or until Week 100 at the latest. Subjects 
may start a commercially available topical psoriasis treatment after end of safety follow up (at Week 64 or 
later) at the investigator’s discretion, except topical corticosteroids class IV (alone or in combination) and 
phototherapy. 
6.2. 
Study Drug Administration 
6.2.1. 
Guselkumab 
A 100 mg/mL solution of guselkumab will be provided in a single-use prefilled syringe (PFS) assembled 
with the UltraSafe PLUSTM Passive Needle Guard (PFS-U).  
6.2.2. 
Fumaric Acid Esters  
Commercially available Fumaderm® initial/ Fumaderm® tablets will be repackaged and supplied as an 
active comparator to the study sites. Study-site personnel will instruct subjects on how to store study drug 
for at-home use as indicated for this protocol. 
Fumaderm® initial/ Fumaderm® tablets need to be swallowed unchewed during a meal or directly after a 
meal with plenty of liquid. Subjects will be instructed to drink at least 1½ to 2 liters per day. The optimal 
FAE dose representing the optimal benefit-risk ratio for each individual subject needs to be identified. All 
dose adjustments must be documented together with the reason for dose adjustment in the medical records. 
 
 
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Uptitration of FAE (Fumaderm® initial/ Fumaderm®) 
The FAE dose is increased starting with Fumaderm® initial (containing 30 mg dimethylfumarate) for the 
first 3 weeks according to Table 4 (40 tablets Fumaderm® initial total): 
Table 4: Uptitration of Fumaderm® initial 
Week 
Fumaderm® initial dose (tablets with 30 mg dimethylfumarate) 
in the morning 
at noon 
in the evening 
0 
0 
0 
1 
1 
1 
0 
1 
2* 
1 
1 
1 
* Until 40 tablets are consumed 
Directly after finishing the last tablet of Fumaderm® initial, subjects will continue with Fumaderm® tablets 
(containing 120 mg dimethylfumarate) starting with one tablet per day in the evening. Fumaderm® dose 
can be increased to a maximum of 3 × 2 tablets per day according to Table 5. In many cases, the maximum 
daily Fumaderm® dose is not necessary. First therapy effects usually can be detected after 4 to 6 weeks of 
treatment. 
Table 5: Uptitration of Fumaderm® 
Week 
Fumaderm® dose (tablets with 120 mg dimethylfumarate) 
in the morning 
at noon 
in the evening 
2*- 3 
0 
0 
1 
4 
1 
0 
1 
5 
1 
1 
1 
6 
1 
1 
2 
7 
2 
1 
2 
8 
2 
2 
2 
* Start at last day of Week 2 directly after finishing Fumaderm® initial (40 tablets) 
Uptitration of Fumaderm® may be stopped/interrupted/decelerated for one of the following reasons: 
a) The maximum of 3 × 2 tablets Fumaderm® per day has been reached.  
b) Reaching the therapeutic goal: When subjects achieved a reduction of the baseline PASI score of 
≥90% (PASI 90 response). See section “Maintenance/Tapering of Fumaderm®” below for further 
dosing instructions. 
c) Lack of tolerability: When subjects report side effects (eg, GI symptoms or flush), uptitration of FAE 
can be stopped/interrupted/decelerated at the discretion of the investigator. It may be necessary to 
taper FAE dose to increase tolerability again (see below). Additional safety/tolerability visits can be 
scheduled, if needed. After ceasing of the side effects/improvement of tolerability, it is at the 
discretion of the investigator to increase the FAE dose (again) according to Table 4 and Table 5. 
d) Laboratory findings: It is in the discretion of the investigator to stop/interrupt/decelerate uptitration 
of FAE due to laboratory findings. It may be feasible/necessary to taper FAE dose. Additional 
safety/tolerability visits can be scheduled. Some laboratory findings require tapering of FAE or 
termination of FAE treatment (see below). 
 
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Maintenance/tapering of Fumaderm® 
a) After achieving the therapeutic goal (PASI 90 response), it is at the discretion of the investigator to 
taper FAE dose slowly to the individually required maintenance dose. It is recommended, to verify 
sustainability of PASI 90 response at the subsequent visit before tapering the FAE dose unless safety 
findings or lack of tolerability demand FAE tapering. Instead of tapering, FAE dose may be 
maintained or even further increased to achieve higher efficacy levels (up to a maximum of 3 × 2 
tablets per day) as long as the benefit-risk ratio is considered to be positive. Reasons for 
maintaining/increasing/tapering the FAE dose after achieving a PASI 90 response need to be 
documented. If efficacy drops after FAE tapering, the Fumaderm® dose may be increased again 
according to Table 4 and Table 5. 
b) Tapering of the FAE dose due to side effects (eg, GI problems, flush, laboratory findings) is at the 
discretion of the investigator. It is suggested not to decrease the daily FAE dose by more than 1 tablet 
per week. However, the investigator may decide to taper FAE more rapidly. Reasons for tapering 
must be documented. After the side effects have ceased, FAE dose may be increased again according 
to Table 4 and Table 5. Additional safety/tolerability visits can be scheduled. Some laboratory 
findings require tapering of FAE or an end of FAE treatment (see below). 
Mandatory reasons to taper FAE dose or stop FAE treatment 
a) Leukopenia: After a pronounced drop of the leukocyte count and definitely if leukocyte count is less 
than 3000/µl, the FAE treatment must be terminated immediately.  
b) Lymphopenia: FAE treatment must be terminated immediately, if lymphocyte counts drop below 
500/µl. FAE dose must be tapered by 50% of the latest dosage immediately (not stepwise), if the 
lymphocyte count drops below 700/µl. If the lymphocyte count does not recover to at least 700/µl 
4 weeks later, FAE treatment must be terminated.  
c) A prolonged severe or moderate lymphopenia is considered to be a risk factor for progressive 
multifocal leukoencephalopathy (PML). Subjects developing lymphopenia should be screened for 
signs of opportunistic infections, especially signs indicative for PML including neurologic, cognitive 
and/or psychiatric symptoms. If a PML is suspected, FAE treatment must be terminated immediately 
and further appropriate neurologic/radiologic investigations need to be initiated. 
d) Other hematological findings: All other clinically relevant pathologic changes of the hematology 
panel should lead to immediate FAE treatment termination. One single retest is permitted. 
e) Creatinine: FAE treatment must be terminated when creatinine increases above ULN. One single 
retest is permitted. 
All pathological laboratory changes will be closely monitored until the parameters are within normal 
limits again. 
7. 
TREATMENT COMPLIANCE 
Subjects will receive instructions on compliance with study drug administration at the Week 0 visit. 
Subjects will be trained to self-administer study drug (only Fumaderm® initial/Fumaderm®) at their Week 0 
visit, and all subsequent Fumaderm® initial/Fumaderm® administrations will be performed at home. 
During the course of the study, the investigator or designated study-site personnel will be responsible for 
providing additional instruction to reeducate any subject who is not compliant with taking the study drug. 
Compliance with the treatment schedule is strongly encouraged. Study-site personnel will keep a log of 
study drug dispensed and will compare the amount of study drug dispensed with the amount returned. 
Additional details may be provided in the Site Investigational Product Manual that is provided separately. 
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Visits through Week 56 should occur within ±7 days of the scheduled visit. The subject should resume his 
or her normal dose schedule relative to the baseline visit (Week 0). During Study Part III visits should occur 
within ±14 days of the scheduled visit. 
8. 
PRESTUDY AND CONCOMITANT THERAPY 
Concomitant therapies must be recorded throughout the study from screening to Week 64. Concomitant 
therapies should be recorded beyond Week 64 only in conjunction with serious adverse events that meet 
the criteria outlined in Section 12.3.2. For patients entering Study Part III, psoriasis therapy/medication will 
be recorded until end of study. In case any protocol-prohibited therapy is applied (for psoriasis or any other 
indication), the subject is withdrawn from study participation. Prohibited therapy is recorded as well as any 
newly planned psoriasis therapy, if already known at the end of the study. 
All therapies different from the study drug (prescription or over-the-counter medications, including 
vaccines, vitamins, herbal supplements) must be recorded in the eCRF. Modification of an effective 
preexisting therapy should not be made for the explicit purpose of entering a subject into the study. 
8.1. 
Concomitant Medications for Treatment of Psoriasis 
8.1.1. 
Treatment Phase 
Topical Therapy 
Topical therapies that could affect psoriasis (eg, corticosteroids, tar, anthralin, calcipotriene, topical vitamin 
D derivatives, retinoids, tazarotene, methoxsalen, pimecrolimus, tacrolimus, and traditional Taiwanese, 
Korean, or Chinese medicines) are not permitted until Week 56, for subjects entering Study Part III until 
Week 64 (see Section 8.1.2. and 8.1.3). The only allowable concomitant treatments for psoriasis throughout 
the study are shampoos (containing tar or salicylic acid only) and topical moisturizers. Subjects should not 
use the topical agents on the day of a study visit; non-medicated shampoos may be used. 
Phototherapy or Systemic Therapy for Psoriasis 
The use of phototherapy or systemic anti-psoriatic medications is not permitted until the Week 56 visit, for 
subjects entering Study Part III until end of study (see Section 8.1.2 and 8.1.3). These medications include 
those targeted for reducing TNF (including but not limited to infliximab, adalimumab or etanercept), drugs 
targeted for reducing IL-12, IL-17, or IL-23 (including but not limited to ustekinumab, tildrakizumab 
[MK3222], secukinumab [AIN457], ixekizumab [LY2439821], or brodalumab [AMG827]), alpha-4 
integrin antagonists (including but not limited to natalizumab), steroids, any conventional systemic therapy 
that could affect psoriasis (including but not limited to MTX, cyclosporine, acitretin), herbal treatments, or 
traditional Taiwanese, Korean, or Chinese medicines, and any other biological agent or other systemic 
medication that could affect psoriasis. 
8.1.2. 
Safety Follow-Up Phase 
See section 6.1.3 for instructions regarding treatment of psoriasis during the follow-up phase. Furthermore, 
for subjects to be eligible for Study Part III all systemic treatments including commercially available 
guselkumab and topical therapies that could affect psoriasis (see Section 8.1.1) are prohibited. 
 
 
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8.1.3. 
Follow-up Extension Phase 
During Study Part III use of topical psoriasis treatment is allowed at the investigator’s discretion. However, 
topical corticosteroids class IV (alone or in combination) and phototherapy are prohibited until end of the 
study (Week 100). Systemic psoriasis therapies, including commercially available guselkumab and 
phototherapy, are prohibited during Study Part III. Patients starting any prohibited therapy, including 
medications for conditions other than psoriasis, will be withdrawn. 
8.2. 
Concomitant Medications for Conditions Other than Psoriasis 
Every effort should be made to keep subjects on stable concomitant medications. If the medication is 
temporarily discontinued because of abnormal laboratory values, side effects, concurrent illness, or the 
performance of a procedure, the change and reason for it should be clearly documented in the eCRF.  
If needed, the occasional use of nonsteroidal anti-inflammatory drugs (NSAID) is allowed. NSAID as well 
as acetaminophen (paracetamol) are not allowed as long-term medication, eg, as part of a treatment of a 
chronic inflammatory disease, but only for acute clinical situations. NSAID dosage and time of use should 
be kept as low and short as possible and should not exceed 2 weeks of daily NSAID administration. Disease-
modifying agents such as MTX, sulfasalazine, or IM gold, which may have an effect on psoriasis, are 
prohibited during the study.  
The use of corticosteroids for indications other than psoriasis should be limited to situations for which, in 
the opinion of the treating physician, there are no adequate alternatives. They should be used on a short-
term basis, preferably for ≤2 weeks. Longer-term use of corticosteroids should be discussed with the 
sponsor and may require discontinuation of study drug. Inhaled, otic, ocular, nasal or other routes of 
mucosal delivery of corticosteroids are allowed throughout the study. 
9. 
STUDY EVALUATIONS 
9.1. 
Study Procedures 
9.1.1. 
Overview 
The Time and Events Schedules (TES) (Table 1 [Part I], Table 2 [Part II] and Table 3 [Part III]) summarize 
frequency and timing of efficacy, immunogenicity, and safety measurements performed during this study. 
All subjects will be asked to sign the consent form(s) (ICF I, II and III) before any study-related procedures 
of the respective study part (I, II, III) are conducted.  
Note: At the time amendment INT-1 has been implemented all subjects were enrolled and had signed the 
ICF established at study initiation (identical to ICF I). All subjects on study treatment were asked to 
acknowledge and sign ICF II for Study Part II (study extension). ICF II had to be signed by Week 24 at the 
latest by all patients continuing to Study Part II.  
Adverse events and concomitant medication recording will start after ICF I has been signed and will 
continue until the last study-related procedure of Study Part I and II, respectively, has been completed. 
During Study Part III, adverse drug reactions and deaths will be recorded until end of study. Concomitant 
therapies will be recorded beyond Week 64 if they are in conjunction with serious adverse events that meet 
the criteria outlined in Section 12.3.2. Any topical psoriasis treatment will be recorded throughout Study 
Part III and all prohibited medication at subject’s withdrawal. 
All PRO assessments should be conducted/completed before any tests, procedures, or other consultations 
to prevent influencing subject perceptions. Completion of baseline PROs has to be done before 
randomization. All other efficacy evaluations should be completed before study drug administrations.  
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The following PRO assessments (1st DLQI, 2nd PSSD, and 3rd SF-36) and efficacy outcomes (BSA%, IGA, 
ss-IGA, and PASI) will be captured on paper sheets at the appropriate visits, as outlined by the TES. 
Study drug administration information will be captured at the appropriate visit through Week 56, as outlined 
by the TES. 
Details about who will perform and/or complete the assessments/data and the order of completion are 
provided in Section 9.2. 
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 
participation in the study. 
All blood samples must be collected before study drug administration (Table 6). Fasting is not necessary. 
For each subject, the total volume of blood drawn from each subject in this study is approximately 200 mL. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with the samples. 
Table 6: Volume of Blood to be Collected from Each Subject 
Type of Sample 
Volume per 
Sample (mL) 
Max. no. of  Samples 
per Subject 
Max. total 
Volume of 
Blood (mL)a 
Safety (including screening and posttreatment 
assessments) 
 
 
 
 - Hematology 
2.7 
17 
46 
 - Glucose (Plasma) 
2.7 
17 
46 
 - Chemistryb 
5.5 
17 
94 
 - Serology (HBV, HCV, HIV); HBV DNA testingc 
5.0 
1 
5 
 - TB testing 
4.0 
1 
4 
Approximate totald 
 
 
195 
a. Calculated as number of samples multiplied by amount of blood per sample. 
b. Includes FSH testing for selected female subjects to confirm postmenopausal state. 
c.  Performed only in subjects who test positive for core HBV antibody. 
d. Repeat or unscheduled samples may be taken for safety reasons or technical issues with the samples. 
Max.=maximum 
 
9.1.2. 
Screening Phase 
All subjects will have a screening visit that will occur within 3 weeks before their randomization visit 
(Week 0). The screening phase is designed to assess inclusion/exclusion criteria and to establish baseline 
characteristics for a subject’s psoriasis.  
The subjects will be asked to sign the consent form at the screening visit before any study related procedures 
are conducted (ICF I).  
With the exception of subjects with a history of appropriately treated latent TB within 5 years of the first 
administration of study drug (see Inclusion Criterion 13), subjects must undergo testing for TB (see 
Attachment 3) and their medical history assessment must include specific questions about a history of TB 
or known occupational or other personal exposure to individuals with active TB. The subject should be 
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asked about past testing for TB, including chest radiograph results and responses to tuberculin skin or other 
TB testing.  
The QuantiFERON-TB Gold Plus test will generally be performed by the central laboratory. However, if 
available, test results from local laboratory can be accepted. 
Subjects with a negative interferon-gamma-release-assay (IGRA) test result (eg, QuantiFERON®-TB Gold 
Plus test) (6), (7) are eligible to continue with pre-randomization procedures. Subjects with a newly 
identified positive IGRA test result (eg, QuantiFERON®-TB Gold Plus test) 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 Plus test result is indeterminate should have the test 
repeated. If the second QuantiFERON®-TB Gold Plus test result is also indeterminate, the subject has to be 
excluded from the study. 
Subjects will undergo screening for HBV (see Attachment 4) and antibodies to HCV and HIV. 
9.1.3. 
Screening Failure/Re-screening 
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 to be randomized 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 the screening period. 
In general, if a subject is a screening failure but at some point in the future meets all of the subject 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. 
9.1.4. 
Open-Label Assessor-blinded Treatment Phase 
Week 0/Randomization 
At Week 0, subjects who meet all inclusion criteria and do not demonstrate any exclusion criteria will be 
randomized. Randomization visit procedures will be performed as specified in the TES.  
Week 0 through Week 56: Study Part I and Study Part II 
During the treatment phase (Week 0 through Week 56), the site staff will be encouraged to contact subjects 
belonging to the FAE treatment group approximately 1 to 3 days prior to each scheduled visit with a 
reminder to bring their used study medication to the study site. 
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. End of Treatment/Early Withdrawal 
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 (see Section 9.1.5). 
For subjects who withdraw from study participation, every effort should be made to conduct final efficacy 
and safety evaluations as listed in the TES (FSV Part I or Part II; see Section 10.2).  
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9.1.5. 
Safety Follow-up Phase 
All subjects will enter a post-treatment safety follow-up phase. Subjects who prematurely stop taking the 
study drug should complete the ETV and safety follow-up should be conducted for 12 weeks after the last 
administration of study drug. The safety follow-up phase ends with a safety follow-up visit. The regular 
safety follow-up visit for subjects who completed Study Part I only and do not continue to Study Part II is 
scheduled for Week 32 at the latest. Subjects who continue in Study Part II through Week 56 will be 
followed for safety information through Week 64 at the latest.  
Subjects will be instructed that study drug will not be made available to them after they have completed/ 
discontinued the drug and that they should return to their physician to determine standard of care if not 
entering Study Part III.  
9.1.6. 
Follow-up Extension Phase after Guselkumab Withdrawal  
No study treatment is applied during the follow-up extension phase. During Study Part III, subjects may 
start a commercially available topical psoriasis treatment at Week 64 or later at the investigator’s discretion, 
except topical corticosteroids class IV (alone or in combination) and phototherapy. Subjects will be 
followed for safety information (ie, vital signs, physical examination, ADRs and death; no laboratory 
assessments) and unblinded efficacy assessments as specified in the TES until loss of response or until 
Week 100 at the latest. Subjects starting a systemic psoriasis treatment including commercially available 
guselkumab or other prohibited medication/therapy will be withdrawn. For subjects who withdraw from 
study participation, every eff 
ort should be made to conduct final efficacy and safety evaluations as listed in the TES (FSV Part III, see 
Section 10.2). 
9.2. 
Efficacy 
9.2.1. 
Evaluations 
Efficacy evaluations chosen for this study are consistent with those used to evaluate other therapies for 
psoriasis. Efficacy evaluations will be first done by subjects (PROs) and then by the blinded efficacy 
assessor Study Parts I and II; during Part III the assessor is no longer blinded. Completion of Baseline-
PROs has to be done before randomization. 
Efficacy evaluations include: 
 Dermatology Life Quality Index (DLQI) [PRO #1] 
 Psoriasis Symptom and Sign Diary (PSSD, 7-day version) [PRO #2] 
 Medical Outcomes Study 36-Item Short Form (SF-36) [PRO #3] 
 Involved Body Surface Area (BSA) 
 Investigator’s Global Assessment (IGA) 
 Scalp Specific Investigator’s Global Assessment (ss-IGA) 
 Psoriasis Area and Severity Index (PASI) 
9.2.2. 
Endpoints 
Primary Endpoint 
The primary endpoint is the proportion of subjects achieving at least a 90% improvement of their psoriasis 
according to the Psoriasis Area and Severity Index (PASI 90 response) at Week 24. 
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Secondary Endpoints 
The major secondary endpoints are: 
 The proportion of subjects achieving at least a 75% improvement of their psoriasis according to the 
PASI at Week 24 (PASI 75 response) 
 The proportion of subjects achieving a DLQI score of 0 or 1 at Week 24. 
Other secondary endpoints are: 
 The proportion of subjects achieving a 100% improvement of their psoriasis according to the PASI at 
Week 24 (PASI 100 response) 
 The change from baseline in the signs and symptoms aggregate scores of the PSSD at Week 24 
 The change from baseline in the individual scale scores for itch, pain, and scaling of PSSD components 
at Week 24 
 The proportion of subjects achieving an absolute PASI score ≤1 at Week 24 
 The proportion of subjects achieving an IGA score of cleared (0) at Week 24 
 The change from baseline of body surface area (BSA) psoriatic involvement at Week 24  
 The change from baseline in DLQI score at Week 24 
 The proportion of subjects achieving an ss-IGA score of absence of disease (0) at Week 24 in 
randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at baseline 
 The change from baseline in the physical and mental component summary scores of SF-36 at Week 24  
 Maintenance of response. Proportion of subjects with a 
- PASI 75 response at Week 32 who maintain response at Week 56 
- PASI 90 response at Week 32 who maintain response at Week 56 
- a DLQI score 0 or 1 at Week 32 who maintain response at Week 56Proportion of subjects with a  
- PASI 75 response (compared to baseline) at Week 56 
- PASI 90 response (compared to baseline) at Week 56 
- PASI 100 response (compared to baseline) at Week 56 
- DLQI score 0 or 1 at Week 56 
- Proportion of subjects with a  
- PASI 75 response (compared to baseline) at Week 32 
- PASI 90 response (compared to baseline) at Week 32 
- PASI 100 response (compared to baseline) at Week 32 
- DLQI score 0 or 1 at Week 32 
- Maintenance of response after guselkumab withdrawal. Proportion of subjects of the guselkumab group 
(GUS-GUS and FAE-GUS) with a  
- PASI 90 response at Week 56 who maintain response at Week 100 
- Time to loss of response from Week 56 after guselkumab withdrawal until Week 100 
- Safety and tolerability data will be summarized using descriptive statistics. 
 
9.2.3. 
Blinded Efficacy Assessment 
An independent, blinded efficacy assessor, approved by the Sponsor, will be designated at each study site 
to perform all efficacy assessments (BSA%, IGA, ss-IGA, and PASI) starting with baseline visit until end 
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of treatment phase (ie, Week 56). As only subjects treated with guselkumab may enter the follow-up 
extension phase, efficacy assessments are not blinded during Study Part III. It is recommended to have the 
efficacy assessments at screening be done by the same blinded assessor as the following assessments, 
including assessments during the follow-up extension phase. 
The blinded efficacy assessor should preferably be a dermatologist or, if a dermatologist is not available, a 
health care provider with at least 1 year of experience in performing the efficacy assessments. Health care 
providers with less than 1 year of experience may serve as a blinded efficacy assessor based upon the 
discretion and approval of the Sponsor. It is recommended that the designated blinded efficacy assessor 
identifies an appropriate back-up for coverage in the event of absences of the designated blinded efficacy 
assessor.  
It is strongly recommended that the same blinded efficacy assessor who performs the baseline efficacy 
assessments for a subject should also perform the efficacy assessments for that subject at every subsequent 
visit. The blinded efficacy assessor must have no contact with the subject during the study other than the 
efficacy assessments. Furthermore, the blinded efficacy assessor must not discuss the subject’s treatment 
with the subject, subject’s caregiver or any site personnel at any time. Reviewing the subject’s medical 
records, study drug administration documentation, questionnaires or the electronic CRF are not permitted. 
Documentation of the blinded efficacy assessment will be performed on separate forms provided by the 
sponsor and will be part of the source data. Data will be entered in the eCRF by the unblinded site staff. 
The sponsor will provide specific BSA%, IGA, ss-IGA, PASI trainings for each site’s designated efficacy 
assessor 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), this training will be considered adequate for the present study. However, repetition 
of training prior to study start is encouraged. Training documentation of each efficacy evaluator will be 
maintained at the site. All efficacy assessors at a site must be listed on the Delegation Log at the site. 
9.2.3.1. 
Involved 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 (7). Involved BSA is calculated by using the palm of the subject’s hand as equivalent 
to 1% of the BSA (rule of palm). In general, a BSA under 5% suggests mild psoriasis, a BSA of 5% to 10% 
is considered moderate, and an involved BSA of over 10% indicates severe psoriasis. 
9.2.3.2. 
Investigator’s Global Assessment (IGA) 
The Investigator’s Global Assessment (IGA) (8) documents the investigator’s assessment of the subject’s 
psoriasis at a given time (Attachment 1). Overall lesions are graded for induration, erythema, and scaling. 
The subject’s psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate (3), or severe (4). 
9.2.3.3. 
Scalp Specific Investigator Global Assessment (ss-IGA) 
The scalp-specific (ss-)IGA instrument is used to evaluate the disease severity of scalp psoriasis 
(Attachment 5). The lesions are assessed in terms of the clinical signs of redness, thickness, and scaliness 
which are scored as: absence of disease (0), very mild disease (1), mild disease (2), moderate disease (3), 
and severe disease (4). 
9.2.3.4. 
Psoriasis Area and Severity Index (PASI) 
The Psoriasis Area and Severity Index (PASI) (8), (9) is an instrument used for assessing and grading the 
severity of psoriatic lesions and their response to therapy (Attachment 2). In the PASI system, the body is 
divided into 4 regions: the head, trunk, upper extremities, and lower extremities. Each of these areas is 
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assessed separately for erythema, induration and scaling, which are each rated on a scale of 0 to 4. The 
PASI produces a numeric score that can range from 0 to 72. A higher score indicates more severe disease. 
9.2.4. 
Patient-reported outcomes (PROs) 
The patient-reported outcomes (PRO) assessments include DLQI, PSSD (7-day version), and SF-36. The 
current version valid at the time point of finalization of the protocol will be used. The questionnaires contain 
an instruction section and will be provided in German. They will be completed on paper sheets at the study 
site by subjects at the appropriate visits as outlined by the TES. The order of administration is 1st DLQI, 2nd 
PSSD, and 3rd SF-36. All visit-specific PRO assessments during a visit should be conducted before any 
tests, procedures or other consultations for that visit to prevent influencing subject perceptions. Completion 
of the baseline PROs has to be done before randomization. Data collected on the paper sheets will be 
handled as source data and will be entered in the eCRF by the unblinded site staff. 
9.2.4.1. 
Dermatology Life Quality Index 
The Dermatology Life Quality Index (DLQI) (10) 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 produces a numeric score that can range from 0 to 30. 
A higher score indicates a low quality of life due to more severe disease. The estimated time to complete 
the questionnaire will be 2 to 5 minutes. 
9.2.4.2. 
Psoriasis Symptom and Sign Diary 
The Psoriasis Symptom and Sign Diary (PSSD) is a 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 to 10 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 will be 
evaluated. The subjects will complete the 7-day recall version of the PSSD as indicated in the TES. The 
average completion time will be 5 to 10 minutes. 
9.2.4.3. 
Short Form Health Survey (SF-36) 
The Short Form Health Survey (SF-36) is a 36-item questionnaire used for subjects’ self-assessment of 
health-related quality of life, consisting of the following 8 dimensions: 1) limitations in physical functioning 
due to health problems, 2) limitations in usual role activities due to physical health problems, 3) bodily 
pain, 4) general mental health (psychological distress and well-being), 5) limitations in usual role activities 
due to personal or emotional problems, 6) limitations in social functioning due to physical or mental health 
problems, 7) vitality (energy and fatigue), and 8) general health perception.  
A physical component summary (PCS) score and a mental component summary (MCS) score can be 
derived. The concepts measured by the SF-36 are not specific to age, disease or treatment group, allowing 
comparison of relative burden of different diseases and the relative benefit of different treatments. The 
estimated completion time will be 10 minutes. 
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9.3. 
Safety Evaluations 
Safety will be monitored until end of study. Any clinically relevant health state changes occurring during 
the study must be recorded in the Adverse Event section of the eCRF. Any clinically significant 
abnormalities persisting at the end of the study/early withdrawal will be followed by the investigator until 
resolution or until a clinically stable endpoint is reached.  
The safety and tolerability of study drugs (guselkumab or FAE) will be monitored by collecting information 
on AEs, including injection site and allergic reactions, clinical laboratory testing (Hepatitis B and C, HIV, 
hematology, and chemistry), physical examinations, measurement of body weight and vital signs, 
concomitant medication review, TB test and evaluation, urinalysis, and pregnancy testing, as specified in 
the TES.  
The study will include the following evaluations of safety and tolerability according to the times provided 
in the TES: 
Adverse Events 
Adverse events will be reported by the subject (or, when appropriate, by a caregiver, surrogate, or the 
subject’s legally acceptable representative) until end of Study Part II (ie, Week 64). During Study Part III 
(after Week 64) only adverse drug reactions and deaths will be recorded. Adverse events/adverse drug 
reactions will be followed by the investigator as specified in Section 12. 
Early Detection of Active Tuberculosis (TB) 
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 the scheduled visits. The following series of 
questions is suggested for use during the evaluation: 
 Have you had a new cough of >14 days’ duration or a change in a chronic cough 
 Have you had any of the following symptoms: persistent fever/unintentional weight loss/night sweats 
 Have you had close contact with an individual with active TB? (If there is uncertainty as to whether a 
contact should be considered ‘close’, a physician specialized 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 immuno-compromised subjects 
may present as disseminated disease or with extra-pulmonary 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 Plus test (7), 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 IGRA test result (eg, 
QuantiFERON® TB Gold Plus test) should be considered detection of latent TB. If the IGRA test result 
(eg. QuantiFERON® TB Gold Plus test) is indeterminate the test should be repeated as outlined in Section 
9.1.2. Subjects in the guselkumab group 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 (see Attachment 3 for details of TB testing). 
Allergic Reactions 
The sponsor will proactively monitor reported AEs and query the injection site, if necessary, to capture 
anaphylactic reaction/serum sickness events in eCRFs. 
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Injection Site Reactions 
An injection site reaction is any unfavorable or unintended sign that occurs at the study drug injection site. 
After administration of study drug at Week 0, all subjects will be carefully observed at the study site for at 
least 30 minutes after the SC-injection of study drug for symptoms of an injection-site reaction. If an 
injection site reaction is observed, the subject should be treated at the investigator’s discretion. Any adverse 
reaction (eg, pain, erythema, and/or induration) should be noted in the Adverse Event section of the eCRF.  
Clinical Laboratory Tests  
Blood samples for serum chemistry and hematology, and a random urine sample for urinalysis will be 
collected at visits specified in the TES. Tests will be performed by a central laboratory. The investigator 
must review the laboratory results, document this review, and record any clinically relevant changes 
occurring during the study in the Adverse Event section of the eCRF. The laboratory reports must be filed 
with the source documents.  
All abnormal laboratory values will be evaluated for clinical significance by the investigator. If clinically 
significant abnormal laboratory values (in the opinion of the investigator) are detected, then the test(s) 
should be repeated until they return to normal or are otherwise explained by the Investigator. 
Instructions for collection, handling, and shipping of blood samples are provided in a Laboratory Manual. 
The following tests will be performed by the central laboratory (synlab Pharma Institute, Munich): 
 Hematology Panel 
- hemoglobin 
- lymphocytes [%, absolute]*  
- hematocrit 
- monocytes [%, absolute]* 
- red blood cell (RBC) count 
- eosinophils [%, absolute]* 
- white blood cell (WBC) count 
- basophils [%, absolute]* 
- platelet count 
- neutrophils [%, absolute]* 
*Subjects will be considered eligible if absolute counts are 
within normal limits 
 Serum Chemistry Panel 
- sodium 
- calcium 
- potassium 
- albumin 
- chloride 
- total protein 
- alkaline phosphatase (AP) 
- alanine aminotransferase (ALT) 
- urea 
- total bilirubin 
- creatinine 
- gamma-GT 
- glucose 
- follicle stimulating hormone (FSH*) 
- aspartate aminotransferase (AST) 
* Testing required for selected female subjects for confirmation 
of the postmenopausal state as defined for the Inclusion Criteria.
 
 Serology: HBV, including HBV serology and HBV DNA (see Attachment 4), and antibodies to HCV 
and HIV. 
 IGRA: eg, QuantiFERON®-TB Gold Plus test will generally be performed by the central laboratory. 
However, if available, test results from local laboratory can be accepted.  
 Urinalysis by dipstick (eg, Combur-Test 10): If there are signs of proteins and/or glucose on urine test 
strip, the urine sample must be analyzed centrally. 
 Central urinalysis: color, proteins, glucose, nitrites, pH, specific gravity, urobilirubin, bilirubin, ketones, 
blood, bacteria, yeast, crystals, casts, squamous epithelial cells, WBC, RBC 
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Pregnancy Testing 
Urine pregnancy testing is required for all women of childbearing potential at all study visits until end of 
Study Part II. Pregnancy tests must be completed and negative at the study visit prior to administration of 
study drug (guselkumab or FAE). All pregnancy test results must be recorded in study source documents. 
Vital Signs 
Blood pressure and pulse measurements will be done according to the TES. If any clinically significant 
changes in vital signs are noted, they must be reported as AEs (see Section 12) and followed to resolution, 
or until reaching a clinically stable endpoint. 
Physical Examination 
Physical examinations will be performed as part of safety evaluation by the investigator or designated 
physician at visits specified in the TES. Any abnormalities or changes in severity noted during the review 
of body systems should be documented in the source document and recorded in the eCRF. 
Height and weight  
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. 
9.4. 
Sample Collection and Handling 
The actual dates and times of sample collection must be recorded in the eCRF or laboratory requisition 
form. Details on timing and frequency of sample collections are listed in the TES. 
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 I if he or she has completed assessments at Week 
24 of the open-label phase. For subject who completed Study Part I but do not enter Study Part II the reason 
for not entering the extension phase will be documented in the eCRF and in source documents.  
A subject will be considered to have completed Study Part IIa when he or she has completed assessments 
at Week 32. A subject will be considered to have completed Study Part II if he or she has completed 
assessments at Week 56 of the open-label phase. Subjects who prematurely discontinue study treatment for 
any reason before completion of the corresponding treatment phase (Study Part I through Week 24 or Study 
Part II through Week 56) will not be considered to have completed this study part (discontinuation before 
Week 24), respectively the entire study.  
A subject will be considered to have completed Study Part III when he or she has completed last assessments 
after loss of response, withdrawal from study participation or at Week 100 at the latest. 
10.2. 
Discontinuation of Study Treatment/Withdrawal from the Study 
Discontinuation of Study Treatment 
A subject will not be automatically withdrawn from the study if he or she has to discontinue treatment 
before the end of the treatment regimen. 
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A subject’s study treatment must be discontinued if: 
 The investigator believes that for safety reasons or tolerability reasons (eg, adverse event) it is in the 
best interest of the subject to discontinue study treatment. 
 The subject becomes pregnant. 
 The subject is diagnosed with a malignancy, with the exception of no more than 2 localized basal cell 
skin cancers that are treated without evidence of recurrence or residual disease. 
 The subject is deemed ineligible according to the following TB screening criteria: 
- A diagnosis of active TB is made. 
- A subject has symptoms suggestive of active TB based on follow-up assessment questions and/or 
physical examination, or has had recent close contact with a person with active TB, and cannot or will 
not continue to undergo additional evaluation. 
- A subject undergoing evaluation has a chest radiograph with evidence of current active TB and/or a 
positive IGRA, eg QuantiFERON®-TB Gold Plus test result (and/or a positive tuberculin skin test 
result), unless active TB can be ruled out and appropriate treatment for latent TB can be initiated prior 
to the next administration of study drug and continued to completion. Indeterminate IGRA, eg 
QuantiFERON®-TB Gold Plus test results should be handled as described in Section 9.1.2. 
- A subject treated with guselkumab receiving treatment for latent TB discontinues this treatment 
prematurely or is noncompliant with the therapy. 
 The subject initiates a protocol-prohibited medication for his/her psoriasis (unless previously agreed to 
by the sponsor). 
 The subject withdraws consent for administration of study drug. 
 The subject is unable to adhere to the study visit schedule or to comply with protocol requirements. 
 The subject develops an allergic reaction like bronchospasm with wheezing and/or dyspnea requiring 
ventilatory support, or symptomatic hypotension that occurs following a study drug administration. 
 The subject has a reaction resulting in myalgia and/or arthralgia with fever and/or rash (suggestive of 
serum sickness and not representative of signs and symptoms of other recognized clinical syndromes) 
occurring 1 to 14 days after an injection of study drug. These may be accompanied by other events 
including pruritus, facial, hand, or lip edema, dysphagia, urticaria, sore throat, and/or headache. 
 The subject treated with FAE develops a laboratory finding that requires termination of treatment 
according to SmPC. 
Discontinuation of study treatment should be considered, and discussed with the sponsor for subjects who 
develop a serious or opportunistic infection, congestive heart failure, demyelinating disease, lupus-like 
syndrome, cytopenias (including pancytopenia) and liver abnormalities. 
If a subject discontinues study treatment for any reason before the end of the open-label phases of Study 
Part I or, when continuing to Study Part II, of Study Part II, end-of-treatment (Early Termination Visit) and 
post-treatment assessments (safety follow-up for 12 weeks after the last administration of study drug) 
should be obtained as indicated in the TES. However, regular safety follow-up ends for all subjects not 
entering Study Part III at Week 64. 
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 contribution of possible 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 
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source documents. Study drug assigned to a subject who discontinues may not be assigned to another 
subject. 
Withdrawal From the Study 
A subject will be withdrawn from the study for any of the following reasons: 
 Lost to follow-up 
 Withdrawal of consent 
 Death 
 Start of a protocol-prohibited medication/therapy during Study Part III  
If a subject discontinues study drug and withdraws from the study before the end of the open-label treatment 
phases of Study Part I or, when continuing to Study Part II, of Study Part II, end-of-treatment (Early 
Termination Visit) and post-treatment assessments (Safety Follow-up) should be obtained as indicated in 
the TES.  
A subject’s study participation from Study Part III must be discontinued if a protocol-prohibited 
medication/therapy (for his/her psoriasis or another indication) is started before completion of the final 
study visit after loss of response or at Week 100.  
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.  
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 e-mail addresses, and emphasize the importance of follow-up information to the 
subject, before randomization. 
For subjects not completing Study Part I, ie, who withdraw from study participation before or at Week 24 
as for subjects entering but not completing Study Part II, ie, who withdraw from study participation after 
Week 24 but before or at Week 56 every effort should be made to conduct the final assessments (Early 
Termination Visit) as indicated in the TES. For subjects who are not eligible for Study Part II and withdraw 
from the safety follow-up before Week 32 and for subjects enter Study Part II but withdraw from study 
participation after Week 56, every effort should be made to conduct the safety follow-up visit (Week 32 for 
Study Part I or Week 64 for Study Part II), as indicated in the TES. Similarly, for subjects who are not 
eligible for Study Part III, the Study Part II safety follow-up visit (Week 64) should be performed, as 
indicated in the TES. For subjects not completing Study Part III, every effort should be made to conduct a 
final study visit (FSV Part III) as indicated in the TES. 
Withdrawal of consent should be a very unusual occurrence in a clinical study. Thus, the investigator should 
make every effort to maintain good subject relationships to avoid withdrawals of consent. For subjects who 
truly request withdrawal of consent, it is recommended that the subject withdraw consent in writing. If the 
subject or the subject’s representative refuses to do so or is physically unavailable, the study site should 
document the reason for the subject’s failure to withdraw consent in writing, sign the documentation, and 
maintain it with the subject’s source records. 
When a subject withdraws before completing the study, the reason for withdrawal is to be documented in 
the eCRF and in the source document. Study drug assigned to the withdrawn subject may not be assigned 
to another subject. Subjects who withdraw will not be replaced. If a subject withdraws from the study before 
the end of the study, final study assessments should be obtained (Early Termination Visit, as outlined in 
TES). 
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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 will be divided in three separate 
documents describing analyses for the three study parts. Additional analyses may be performed for 
evaluations on health technology assessment (HTA). These analyses are not included in this clinical 
protocol and will be specified in a separate HTA SAP, if applicable. 
The statistical analyses in this study will focus on the comparison of the two randomized treatment groups 
(ie, guselkumab vs. FAE). The analyses will be confirmatory for the primary endpoint and the major 
secondary endpoints, and exploratory for all other secondary endpoints including Study Part II and Part III 
analyses.  
Descriptive statistics will include counts and proportions for categorical data, and median, mean, 
interquartile range, and range for continuous data. Graphical data displays may also be used to summarize 
the data. The chi-square test 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 baseline value 
as a covariate. All statistical testing will be performed two-sided. The confirmatory significance level is 
fixed to a type 1 error rate alpha of 5% (two-sided). 
11.1. 
Subject Information 
Descriptive statistics by randomized treatment group based on all randomized subjects will be provided for 
subject dispositions, demographics, baseline disease characteristics, and prior and concomitant 
medications. Details will be provided in the SAP. 
11.2. 
Sample Size Determination 
The primary hypothesis of this study is that guselkumab treatment is superior to FAE (Fumaderm® initial/ 
Fumaderm®) treatment as assessed by the proportion of subjects achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are:  
 Guselkumab treatment is superior to FAE as assessed by the proportion of subjects achieving a PASI 75 
response at Week 24. 
 Guselkumab treatment is superior to FAE as assessed by the proportion of subjects achieving a DLQI 
score of 0 or 1 at Week 24. 
In order to control the overall experiment wise type 1 error rate, the primary endpoint and the two major 
secondary endpoints will be tested in a fixed sequence as a-priori ordered hypotheses. That is, the first 
major secondary endpoint will be tested only if the primary endpoint is positive (ie, p <0.05), and the second 
major secondary endpoint will be tested only if the first major secondary endpoint is positive. Due to the 
testing of ordered hypotheses, no adjustment of the significance level with respect to the threefold test 
procedure is required. 
The assumptions for the sample size and power calculations using the threefold test procedure were based 
on guselkumab phase 2 data and unpublished data from the German PsoBest Registry and are as follows: 
PASI 90 responder rates for guselkumab and FAE in Week 24 are assumed to be 60% and 25%, 
respectively. PASI 75 responder rates are assumed to be 80% and 45%, respectively. DLQI responder rates 
are assumed to be 60% and 30%, respectively. 
Based on these assumptions, with a total of 114 subjects planned to be randomized in a 1:1 ratio to 
guselkumab (n = 57) and to FAE (n = 57), superiority of guselkumab vs. FAE can be demonstrated at a 5% 
significance level (two-sided) with power of at least 90% for each test of the threefold test procedure as 
displayed in the table below: 
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Table 7: 
Power to detect a treatment effect on expected proportions of subjects achieving the 
primary and the major secondary endpoints 
Order of 
testing 
Endpoint in  
Week 24 
Guselkumab 
(% responder) 
FAE 
(% responder) 
Power 
1 
PASI 90 
60 
25 
97% 
2 
PASI 75 
80 
45 
98% 
3 
DLQI 0/1 
60 
30 
90% 
type 1 error rate alpha 5% (two-sided) 
sequential testing with a-priori ordered hypotheses (only proceed with testing, if p <0.05)  
sample size n = 114 with 1:1 ratio guselkumab (n = 57) and FAE (n = 57) 
two group chi-square test; nQuery Advisor® Release 7.0
 
11.3. 
Efficacy Analyses 
Analysis Data Set 
For all efficacy analyses to compare guselkumab vs. FAE in Study Part I (Week 24 analysis), all randomized 
subjects will be included. For all the efficacy analyses, subjects will be analyzed according to the treatment 
group to which they were randomized regardless of the treatment they actually received (“intent-to-treat” 
principle). Additionally, all efficacy analyses will be performed with all randomized subjects that received 
at least one dose of study drug. For all efficacy analyses to compare guselkumab vs. FAE in Study Part 
II (Week 64 analysis), subjects will be analyzed according to the treatment they actually received. For all 
efficacy analyses in the follow-up extension phase (Study Part III, Week 100 analysis), subjects who entered 
Study Part III and received guselkumab from Week 0 and subjects who received FAE from Week 0 to Week 
32 and switched to guselkumab will be analyzed.  
The confirmatory statistical analysis of the primary and major secondary endpoints will be performed after 
all subjects have completed the Week 24 visit or have terminated the study prematurely. First data base 
lock (DBL) will be after the Week 24 visit data are ready for statistical analysis (ie, clean data). All analyses 
including all primary and secondary analyses as well as additional analyses as described in detail in the 
SAP for Week 24 analysis will be performed after DBL.  
The second statistical analysis will be performed after all subjects have completed the Week 64 visit or 
have terminated the study prematurely. Second data base lock (DBL) will be after the Week 64 visit data 
are ready for statistical analysis (ie, clean data). All analyses will be performed after DBL and will be 
described in detail in the SAP for Week 64 analysis. Following the rationale for Study Part II, the Week 64 
analysis will focus on PASI 75 responders and PASI 75 non-responders taking into account the switch 
decision. 
The third statistical analysis will be performed after all subjects have completed the Week 100 visit or have 
terminated the study prematurely or lost their response. Third data base lock (DBL) will be after the Final 
Study Visit/Week 100 visit data are ready for statistical analysis (ie, clean data). All analyses will be 
performed after DBL and will be described in detail in the SAP for Week 100 analysis. Following the 
rationale for Study Part III, the Week 100 analysis will focus on PASI 90 responders at Week 56 taking 
into account baseline disease characteristics and study treatment to explore prediction parameters of disease 
modification. 
 
 
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Primary Endpoint 
The proportion of subjects achieving at least a 90% improvement of their psoriasis according to the Psoriasis 
Area and Severity Index (PASI 90) at Week 24 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. Subjects who 
discontinue study treatment or who started a protocol-prohibited medication/therapy during the study 
(Section 11.4, Section 8.1.1) before Week 24 will be considered non-responders for the primary endpoint 
at Week 24. In addition, subjects who do not return for evaluation at Week 24 will be considered non-
responders at Week 24. 
To address the primary objective, a two-sided (α = 0.05) chi-square test will be used for the primary 
confirmatory comparison. In addition, two-sided 95% confidence intervals will be calculated for the 
PASI 90 response rate at Week 24 per treatment group and for the difference between the two groups.  
Major Secondary Endpoints 
The major secondary endpoints will comprise the endpoints as defined in Section 9.2.2. For the major 
secondary analyses, the chi-square test will be used to compare the proportion of subjects responding to 
treatment. Summary tabulation and analyses will be performed analogously to the primary endpoint. All 
statistical tests will be performed two-sided. In order to control the overall experiment-wise type 1 error 
rate, the primary endpoint and the two major secondary endpoints will be tested in a fixed sequence as a 
priori ordered hypotheses. That is, the first major secondary endpoint will be tested only if the primary 
endpoint is positive (ie, p <0.05), and the second major secondary endpoint will be tested only if the first 
major secondary endpoint is positive. 
 
 
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Other Secondary Endpoints 
The other secondary endpoints will comprise the endpoints as defined in Section 9.2.2. For the other 
secondary analyses including Study Part II and Part III analyses, the chi-square test will be used to compare 
the proportion of subjects responding to treatment. Summary tabulation will be performed analogously to 
the primary endpoint. Continuous response parameters will be compared using an analysis of variance 
model with 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. All statistical 
tests will be performed two-sided and are to be interpreted in the exploratory sense only. 
Subgroup and Sensitivity Analyses 
Subgroup analyses will be performed to evaluate consistency of the primary endpoint and selected major 
secondary endpoints over demographics and baseline disease characteristics. Additional subgroup and 
sensitivity analyses may be performed and will be documented in the SAPs. 
Handling of Missing Data 
All available data will be included in the analyses and will be summarized as far as possible. In general, 
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’). Subjects who discontinue 
study treatment or who do not return for evaluation at Week 24 or 56 will be considered non-responders at 
Week 24 and 56, respectively.  
In case of premature termination, the last available observation after baseline will be calculated and used 
for analysis for continuous response parameters (LOCF = Last Observation Carried Forward approach). 
LOCF will also be used as sensitivity analysis for binary response parameters. Additional sensitivity 
analyses may be done by applying different imputation rules for missing data. A more detailed description 
of the handling of missing data will be provided in the SAPs. 
11.4. 
Criteria for Endpoints 
PASI 75 Responders: Subjects with ≥75% improvement in PASI from baseline. 
PASI 90 Responders: Subjects with ≥90% improvement in PASI from baseline. 
PASI 100 Responders: Subjects with 100% improvement in PASI from baseline 
Loss of Response, Study Part III: Increase in absolute PASI >5  
11.5. 
Safety Analyses 
Safety data, including but not limited to, AEs, SAEs, ADRs, SADRs, infections, serious infections, 
mortality, changes in laboratory assessments, and changes in vital signs will be summarized. Treatment-
emergent AEs will be summarized by treatment group and Medical Dictionary for Regulatory Activities 
(MedDRA) system organ class and preferred terms. A general description of the planned safety analyses is 
provided below. Details will be specified in the SAPs. 
 
 
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Analysis Data Set 
For all safety analyses to compare guselkumab vs. FAE, all randomized subjects treated with at least one 
dose of study drug (guselkumab or FAE) will be included. For all the safety analyses, subjects will be 
analyzed according to the treatment they actually received. A main safety analysis will be performed after 
all subjects have completed their visit 24 weeks after randomization or discontinued earlier (with the 
confirmatory analysis). Safety analyses covering the time until Week 64 and until Week 100 safety visits 
will be performed separately with the Week 64 and Week 100 analyses. 
Adverse Events/Adverse Drug Reactions 
The verbatim terms used in the eCRF by investigators to identify adverse events (AEs) or adverse drug 
reactions (ADRs) will be coded using the Medical Dictionary for Regulatory Activities (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 AE, the percentage of subjects who 
experience at least 1 occurrence of the given event will be summarized by treatment group. (S)ADRs 
documented during Study Part III will be treated correspondingly. 
Summaries, listings, datasets, or subject narratives may be provided, as appropriate, for those subjects who 
die, who discontinue treatment due to an AE, or who experience a severe or a serious adverse event (SAE) 
or serious adverse drug reaction (SADR). The incidence of injection site reactions, SAEs, SADRs and 
premature discontinuations due to AEs/ADRs will be summarized separately. 
Clinical Laboratory Tests 
Laboratory data will be summarized by type of laboratory test. Reference ranges and markedly abnormal 
results (specified in the SAPs) will be used in the summary of laboratory data. Descriptive statistics will be 
calculated for each laboratory item at baseline and at each scheduled time. Changes from baseline results 
will be presented in pre- versus post-treatment cross-tabulations (with classes for below, within, and above 
normal ranges). A listing of subjects with any laboratory results outside the reference ranges will be 
provided. A listing of subjects with any markedly abnormal laboratory result (eg, CTCAE grade 3 or higher) 
will also be provided. 
Vital Signs 
Descriptive statistics of pulse and blood pressure (systolic and diastolic) values and changes from baseline 
will be summarized at each scheduled time. The percentage of subjects with values beyond clinically 
important limits (specified in the SAPs) will be summarized. 
Physical Examination 
Physical examination findings will be summarized at each scheduled time. Descriptive statistics will be 
calculated at baseline and for observed values and changes from baseline at each scheduled time. Frequency 
tabulations of the abnormalities will be made. 
11.6. 
Interim and Final Analyses 
The confirmatory analysis is planned to be performed at the end of Study Part I, ie, after all subjects have 
completed their visit at 24 weeks after randomization or discontinued earlier. This analysis will include the 
confirmatory analysis of the primary endpoint, the major secondary endpoints and all other predefined 
efficacy and safety analyses until Week 24. 
The second exploratory analysis will occur after all subjects have completed their visit at 64 weeks after 
randomization or discontinued earlier. This analysis will include the safety analysis and all efficacy 
measures after Week 24 and will cover the time until the Week 64 safety visit. 
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The third and final exploratory analysis will occur after all subjects have completed their visit at 100 weeks 
after randomization or discontinued earlier. This analysis will include the safety analysis and all efficacy 
measures after Week 64 and will cover the time until the Week 100 safety visit. 
12. 
ADVERSE EVENT/ADVERSE DRUG REACTION REPORTING 
Timely, accurate, and complete reporting and analysis of safety information from clinical studies are crucial 
for the protection of subjects, investigators, and the sponsor, and are mandated by regulatory agencies 
worldwide. The sponsor has established Standard Operating Procedures in conformity with regulatory 
requirements worldwide to ensure appropriate reporting of safety information; all clinical studies conducted 
by the sponsor or its affiliates will be conducted in accordance with those procedures. 
12.1. 
Definitions 
12.1.1. 
Adverse Event/Adverse Drug Reaction 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 adverse event does not necessarily have a 
causal relationship with the treatment. An adverse event can therefore be any unfavorable and unintended 
sign (including an abnormal finding), symptom, or disease temporally associated with the use of a medicinal 
(investigational or non-investigational) product, whether or not related to that medicinal (investigational or 
non-investigational) product (definition of International Conference on 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 will collect adverse events starting with signing of the ICF (see Section 12.3.1). 
Adverse Drug Reaction 
An ADR is defined as all untoward and unintended responses to an investigational medicinal product (IMP) 
related to any dose administered. ‘Response to a medicinal product’ means that a causal relationship 
between a medicinal product and an adverse event is possible, probable, or very likely. Thus, an ADR is 
characterized by the fact that a causal relationship between the medicinal product and the occurrence of the 
event is suspected. All adverse events judged by either the investigator or the sponsor as having a reasonable 
causal relationship to a medicinal product qualify as ADRs. 
Serious Adverse Event/Serious Adverse Drug Reaction 
A serious adverse event (SAE)/serious adverse drug reaction (SADR) based on ICH and EU Guidelines on 
Pharmacovigilance for Medicinal Products for Human Use is any untoward medical occurrence that at any 
dose: 
 Results in death 
 Is life-threatening  
(The subject was at risk of death at the time of the event. It does not refer to an event that 
hypothetically might have caused death if it were more severe.) 
 Requires inpatient hospitalization or prolongation of existing hospitalization 
 Results in persistent or significant disability/incapacity 
 Is a congenital anomaly/birth defect 
 Is a suspected transmission of any infectious agent via a medicinal product 
 Is Medically Important* 
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*Medical and scientific judgment should be exercised in deciding whether expedited reporting is also 
appropriate in other situations, such as important medical events that may not be immediately life 
threatening or result in death or hospitalization but may jeopardize the subject or may require 
intervention to prevent one of the other outcomes listed in the definition above. These should usually be 
considered serious. 
If a serious and unexpected adverse event/adverse drug reaction 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/ Adverse Drug Reaction/ Reference Safety Information 
An adverse event is considered unlisted, if the nature or severity is not consistent with the applicable product 
reference safety information. For guselkumab, the expectedness of an adverse event will be determined by 
whether or not it is listed in the Investigator's Brochure. For Fumaderm® initial/ Fumaderm® with a 
marketing authorization, the expectedness of an adverse event will be determined by whether or not it is 
listed in the prescribing information. 
Adverse Event Associated With the Use of the Drug/ Adverse Drug Reaction 
An adverse event is considered an Adverse Drug Reaction if it is associated with the use of the drug meaning 
if the attribution is possible, probable, or very likely by the definitions listed in the following Section 12.1.2. 
12.1.2. 
Attribution Definitions 
Not Related: An adverse event that is not related to the use of the drug. 
Doubtful: An adverse event 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 adverse event 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 adverse event 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 adverse event that is listed as a possible adverse reaction and cannot be reasonably 
explained by an alternative explanation, eg, concomitant drug(s), concomitant disease(s). The relationship 
in time is very suggestive (eg, it is confirmed by dechallenge and rechallenge). 
12.1.3. 
Severity Criteria  
An assessment of severity grade will be made using the following general categorical descriptors: 
Mild: Awareness of symptoms that are easily tolerated, causing minimal discomfort and not interfering 
with everyday activities. 
Moderate: Sufficient discomfort is present to cause interference with normal activity. 
Severe: Extreme distress, causing significant impairment of functioning or incapacitation; prevents normal 
everyday activities. 
The investigator should use clinical judgment in assessing the severity of events not directly experienced 
by the subject (eg, laboratory abnormalities). 
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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: 
 Overdose of a sponsor study drug 
 Suspected abuse/misuse of a sponsor study drug 
 Accidental or occupational exposure to a sponsor study drug 
 Medication error involving a sponsor product (with or without subject exposure to the sponsor study 
drug, eg, name confusion) 
 Exposure to a sponsor study drug from breastfeeding 
Special reporting situations should be recorded in the eCRF. Any special reporting situation that meets the 
criteria of a serious adverse event should be recorded in the Serious Adverse Event section of the eCRF. 
12.3. 
Procedures 
12.3.1. 
All Adverse Events/Adverse Drug Reactions 
All adverse events 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 
of Study Part II, which may include contact for follow-up of safety.  
Serious adverse events, including those spontaneously reported to the investigator within 12 weeks after 
the last dose of study drug, must be reported using the Serious Adverse Event Form. During follow-up 
extension phase (Study Part III), all adverse events suspected to be related to the use of the drug (Adverse 
Drug Reactions, ADRs, Section 12.1.1) and deaths are recorded until final study visit of Study Part III. 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 a serious adverse event will be reported as serious adverse events, 
regardless of whether they are protocol-specific assessments. 
All adverse events, regardless of seriousness, severity, or presumed relationship to study drug, and all 
adverse drug reactions regardless of seriousness and severity must be recorded using medical terminology 
in the source document and the eCRF. Whenever possible, diagnoses should be given when signs and 
symptoms are due to a common etiology (eg, cough, runny nose, sneezing, sore throat, and head congestion 
should be reported as “upper respiratory infection”). Investigators must record in the eCRF their opinion 
concerning the relationship of the adverse event to study therapy. All measures required for adverse event 
management must be recorded in the source document and reported according to sponsor instructions. 
The sponsor assumes responsibility for appropriate reporting of adverse events/adverse drug reactions 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.  
For all studies with an outpatient phase, including open-label studies, the subject must be provided with a 
“wallet (study) card” and instructed to carry this card with them for the duration of the study. 
The wallet card indicates the following: 
 Study number 
 Statement, in the local language(s), that the subject is participating in a clinical study 
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 Investigator's name and 24-hour contact telephone number 
 Local sponsor's name and 24-hour contact telephone number (for medical staff only) 
 Site number 
 Subject number 
12.3.2. 
Serious Adverse Events/Serious Adverse Drug Reactions 
All serious adverse events/adverse drug reactions 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 serious adverse events/adverse drug reactions will be transmitted to the sponsor using 
the Serious Adverse Event Form, which must be completed and signed by a physician from the study site, 
and transmitted to the sponsor within 24 hours. The initial and follow-up reports of a serious adverse 
event/adverse drug reactions should be made by facsimile (fax). 
All serious adverse events/adverse drug reactions that have not resolved by end of the study, or that have 
not resolved upon discontinuation of the subject’s study participation, must be followed until any of the 
following occurs: 
 The event resolves 
 The event stabilizes 
 The event returns to baseline, if a baseline value/status is available 
 The event can be attributed to agents other than the study drug or to factors unrelated to study conduct 
 It becomes unlikely that any additional information can be obtained (subject or health care practitioner 
refusal to provide additional information, lost to follow-up after demonstration of diligence with follow-
up efforts) 
Suspected transmission of an infectious agent by a medicinal product will be reported as a serious adverse 
event. Any event requiring hospitalization (or prolongation of hospitalization) that occurs during the course 
of a subject’s participation in a study must be reported as a serious adverse event, except hospitalizations 
for the following: 
 Hospitalizations not intended to treat an acute illness or adverse event/adverse drug reaction (eg, social 
reasons such as pending placement in long-term care facility) 
 Surgery or procedure planned before entry into the study (must be documented in the eCRF).  
Note: Hospitalizations that were planned before the signing of the ICF, and where the underlying condition 
for which the hospitalization was planned has not worsened, will not be considered serious adverse events. 
Any adverse event that results in a prolongation of the originally planned hospitalization is to be reported 
as a new serious adverse event. 
The cause of death of a 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 a serious adverse event. During 
participation in Study Part III, the cause of death of a subject is also considered a serious adverse event and 
must be reported using the Serious Adverse Event Form. 
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 serious adverse events and must be 
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reported using the Serious Adverse Event Form. Any subject who becomes pregnant during the study must 
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 until end of Study Part II. Follow-up information regarding the 
outcome of the pregnancy and any postnatal sequelae in the infant will be required. 
12.3.4. 
Events of Special Interest 
Any newly identified malignancy or case of active TB occurring after the first administration of study drug 
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 Germany. These events are to be considered serious only if they meet the definition of a serious adverse 
event. 
12.4. 
Contacting Sponsor Regarding Safety 
The names (and corresponding telephone numbers) of the individuals who should be contacted regarding 
safety issues or questions regarding the study are listed in the Contact Information page(s), which will be 
provided as a separate document. 
13. 
PRODUCT QUALITY COMPLAINT HANDLING 
A product quality complaint (PQC) is defined as any suspicion of a product defect related to manufacturing, 
labeling, or packaging, ie, any dissatisfaction relative to the identity, quality, durability, or reliability of a 
product, including its labeling or package integrity. A PQC may have an impact on the safety and efficacy 
of the product. Timely, accurate, and complete reporting and analysis of PQC information from studies are 
crucial for the protection of subjects, investigators, and the sponsor, and are mandated by regulatory 
agencies worldwide. The sponsor has established procedures in conformity with regulatory requirements 
worldwide to ensure appropriate reporting of PQC information; all studies conducted by the sponsor or its 
affiliates will be conducted in accordance with those procedures. 
13.1. 
Procedures 
All initial PQCs must be reported to the sponsor by the study-site personnel within 24 hours after being 
made aware of the event. If the defect is combined with a serious adverse event, the study-site personnel 
must report the PQC to the sponsor according to the serious adverse event reporting timelines (see Section 
12.3.2). A sample of the suspected product should be maintained for further investigation if requested by 
the sponsor. 
13.2. 
Contacting Sponsor Regarding Product Quality 
The names (and corresponding telephone numbers) of the individuals who should be contacted regarding 
product quality issues are listed in the Contact Information page(s), provided as a separate document. 
14. 
STUDY DRUG INFORMATION 
14.1. 
Physical Description of Study Drug(s) 
The guselkumab supplied for this study is a sterile liquid for SC injection in a single-use PFS assembled in 
an UltraSafe PLUS™ Passive Needle Guard (PFS-U). Each single-use PFS-U contains 100 mg (1 mL fill 
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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. The PFS-U is a passive safety needle guard that is permanently assembled on the syringe 
and incorporates a spring driven shield that automatically extends beyond the PFS needle following complete 
injection of the guselkumab PFS contents. Guselkumab will be manufactured and provided under the 
responsibility of the sponsor. A list of excipients can be found in the Investigator's Brochure. 
Commercially available Fumaderm® initial/ Fumaderm® blisters will be repackaged and supplied as an active 
comparator to the study sites. Details on the drug can be found in the Fumaderm® initial/ Fumaderm® SmPC, 
and details regarding the Fumaderm® initial/ Fumaderm® drug product are available in the Site Investigational 
Product Manual. 
14.2. 
Packaging 
The investigational supplies will be uniquely packaged to assure they will be properly managed throughout 
the supply chain process. 
Fumaderm® initial/ Fumaderm® is sourced as blisters in a commercial carton. The sponsor will take the 
Fumaderm® blisters out of the commercial cartons and will place them in a new package to ensure child 
resistant packaging for the take home Fumaderm® medication.  
14.3. 
Labeling 
Study drug labels will contain information to meet the applicable regulatory requirements. 
14.4. 
Preparation, Handling, and Storage  
Guselkumab must be stored at controlled temperatures ranging from 2°C to 8°C, and protected from light. 
Vigorous shaking of the product should be avoided. The sterile product does not contain preservatives and 
is designed for single use only. Protection from light is not required during administration.  
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.  
Further details regarding the storage of guselkumab will be provided in the Site Investigational Product 
Manual. 
Further details regarding the preparation and storage of FAE can be found in the Fumaderm® initial/ 
Fumaderm® SmPC. 
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14.5. 
Drug Accountability 
The investigator is responsible for ensuring that all study drugs received at the site are inventoried and 
accounted throughout the study. The dispensing of FAE to the subject, and the return of FAE from the 
subject (if applicable), must be documented on the drug accountability form. Subjects must be instructed 
to return all original containers, whether empty or containing study drug. Guselkumab administered to the 
subject must also 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 protocol and container label, and must be stored at 
the study site in a limited-access area or in a locked cabinet under appropriate environmental conditions. 
Unused study drug must be available for verification by the sponsor's study site monitor during on-site 
monitoring visits. The return of unused study drug to the sponsor, or used returned study drug for 
destruction, 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. The immediate destruction of these drug supplies should be documented in the 
drug accountability records on site. 
Study drug should be dispensed under supervision of the investigator or a qualified member of the 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. Counting remaining 
FAE tablets during the study visits for compliance check is not considered as a return and re-dispense. Study 
drug may not be relabeled or reassigned for use by other subjects. The investigator agrees neither to 
dispense the study drug from, nor store it at, any site other than the study sites agreed upon with the sponsor. 
15. 
STUDY-SPECIFIC MATERIALS 
The investigator will be provided with the following supplies: 
 Investigator’s Brochure for guselkumab 
 SmPC (“Fachinformation”) for Fumaderm® initial/Fumaderm® 
 Site investigational product manual 
 Laboratory manual 
 Paper PRO questionnaires including completion guideline section 
- DLQI 
- PSSD (7-days) 
- SF-36 
 Electronic Data Capture (EDC) Manual 
 Trial Center File 
 Sample ICFs 
 Paper forms to document efficacy assessment by blinded efficacy assessor (BSA, IGA, ss-IGA and 
PASI) 
 
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16. 
ETHICAL ASPECTS 
16.1. 
Study-Specific Design Considerations 
Thorough scientific evaluation of a new therapy is an ethical requirement. In the continuing search for 
medications with improved efficacy and safety profiles, it is necessary to compare new drugs with those 
already established on the market. This study is being conducted to compare SC administration of 
guselkumab with orally taken FAE tablets as treatment of moderate or severe psoriasis. 
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 adverse events of the study, and provide 
their consent voluntarily will be enrolled. 
16.2. 
Regulatory Ethics Compliance 
16.2.1. 
Investigator Responsibilities 
The investigator is responsible for ensuring that the study is performed in accordance with the protocol, 
current ICH guidelines on Good Clinical Practice (GCP), and applicable regulatory and country-specific 
requirements.  
Good Clinical Practice is an international ethical and scientific quality standard for designing, conducting, 
recording, and reporting studies that involve the participation of human subjects. Compliance with this 
standard provides public assurance that the rights, safety, and well-being of study subjects are protected, 
consistent with the principles that originated in the Declaration of Helsinki, and that the study data are 
credible. 
16.2.2. 
Independent Ethics Committee or Institutional Review Board 
Before the start of the study, the investigator (or sponsor where required) will provide the IEC/IRB with 
current and complete copies of the following documents (as required by local regulations): 
 Final protocol and, if applicable, amendments 
 Sponsor-approved ICF (and any other written materials to be provided to the subjects) 
 Investigator’s Brochure (or equivalent information) and amendments/addenda 
 Sponsor-approved subject recruiting materials 
 Information on compensation for study-related injuries or payment to subjects for participation in the 
study, if applicable 
 Investigator’s curriculum vitae or equivalent information (unless not required, as documented by the 
IEC/IRB) 
 Information regarding funding, name of the sponsor, institutional affiliations, other potential conflicts 
of interest, and incentives for subjects 
 Any other documents that the IEC/IRB requests to fulfill its obligation 
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This study will be undertaken only after the IEC/IRB has given full approval of the final protocol, 
amendments (if any, excluding the ones that are purely administrative, with no consequences for subjects, 
data or study conduct, unless required locally), the ICF, applicable recruiting materials, and subject 
compensation programs, and the sponsor has received a copy of this approval. This approval letter must be 
dated and must clearly identify the IEC/IRB and the documents being approved. 
During the study, the investigator (or sponsor where required) will send the following documents and 
updates to the IEC/IRB for their review and approval, where appropriate: 
 Protocol amendments (excluding the ones that are purely administrative, with no consequences for 
subjects, data or study conduct) 
 Revision(s) to ICF and any other written materials to be provided to subjects 
 If applicable, new or revised subject recruiting materials approved by the sponsor 
 Revisions to compensation for study-related injuries or payment to subjects for participation in the 
study, if applicable 
 New edition(s) of the Investigator's Brochure and amendments/addenda 
 Summaries of the study status at intervals stipulated in guidelines of the IEC/IRB (at least annually) 
 Reports of adverse events that are serious, unlisted/unexpected, and associated with the study drug 
 New information that may adversely affect the safety of the subjects or the conduct of the study 
 Deviations from or changes to the protocol to eliminate immediate hazards to the subjects 
 Report of deaths of subjects under the investigator's care 
 Notification if a new investigator is responsible for the study at the site 
 Development Safety Update Report and Line Listings, where applicable 
 Any other requirements of the IEC/IRB 
For all protocol amendments (excluding the ones that are purely administrative, with no consequences for 
subjects, data or study conduct), the amendment and applicable ICF revisions must be submitted promptly 
to the IEC/IRB for review and approval before implementation of the change(s). 
At least once a year, the IEC/IRB will be asked to review and reapprove this study, where required. 
At the end of the study, the investigator (or sponsor where required) will notify the IEC/IRB about the study 
completion. 
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. To meet the scope of this amendment three separate ICFs have been developed to 
cover Study Parts I, II and III. The ICF(s) must be signed before performance of any study-related activity 
(ICF I at screening, ICF II at Week 24 at the latest, ICF III at Week 64 at the latest). The ICF(s) that is/are 
used must be approved by both the sponsor and by the reviewing IEC/IRB and be in a language that the 
subject can read and understand. The informed consent should be in accordance with principles that 
originated in the Declaration of Helsinki, current ICH and GCP guidelines, applicable regulatory 
requirements, and sponsor policy. 
Before enrollment in the study or in Parts II or III of the study, if applicable, 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 
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to participate at any time. They will be informed that choosing not to participate will not affect any care the 
subject will receive for 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 re-contact the subject for the purpose of obtaining 
consent for additional safety evaluations, and subsequent disease-related treatments, if needed. The 
physician may also re-contact the subject for the purpose of obtaining consent to collect information about 
his or her survival status. 
The subject will be given sufficient time to read the ICF and the opportunity to ask questions. After this 
explanation and before study entry, consent will be appropriately recorded by means of the subject’s 
personally dated signature. After having obtained consent, a copy of the ICF must be given to the subject. 
If the subject is unable to read or write, an impartial witness should be present for the entire informed 
consent process (which includes reading and explaining all written information) and should personally date 
and sign the ICF after the oral consent of the subject is obtained. 
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 fulfil 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 the subject’s 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. 
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. If the changes involve only logistic or administrative aspects of 
the study, the IEC/IRB (where required) will only be notified. 
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During the study course, in situations where a departure from the protocol is unavoidable, the investigator 
or other physician in attendance will contact the appropriate sponsor representative listed in the Contact 
Information page(s), which will be provided as a separate document. Except in emergency situations, this 
contact should be made before implementing any departure from the protocol. In all cases, contact with the 
sponsor must be made as soon as possible to discuss the situation and agree on an appropriate course of 
action. The data recorded in the eCRF and source documents will reflect any departure from the protocol, 
and the source documents will describe this departure and the circumstances requiring it. 
17.2. 
Regulatory Documentation 
17.2.1. 
Regulatory Approval/Notification 
This protocol and any amendment(s) must be submitted to the Paul-Ehrlich Institute (PEI).   
A study may not be initiated until all local regulatory requirements are met. 
17.2.2. 
Required Pre-study Documentation 
The following documents must be provided to the sponsor before shipment of study drug to the study site: 
 Protocol and amendment(s), if any, signed and dated by the principal investigator 
 A copy of the dated and signed (or sealed, where appropriate per local regulations), written IEC/IRB 
approval of the protocol, amendments, ICFs, any recruiting materials, and if applicable, subject 
compensation programs. This approval must clearly identify the protocol by title and number and must 
be signed (or sealed, where appropriate per local regulations) by the chairman or authorized designee. 
 Name and address of the IEC/IRB, including a current list of the IEC/IRB members and their function, 
with a statement that it is organized and operates according to GCP and the applicable laws and 
regulations. If accompanied by a letter of explanation, or equivalent, from the IEC/IRB, a general 
statement may be substituted for this list. If an investigator or a member of the study-site personnel is a 
member of the IEC/IRB, documentation must be obtained to state that this person did not participate in 
the deliberations or in the vote/opinion of the study. 
 Regulatory authority approval or notification, if applicable 
 Signed and dated statement of investigator (eg, Form FDA 1572), if applicable 
 Documentation of investigator qualifications (eg, curriculum vitae) 
 Completed investigator financial disclosure form from the principal investigator, where required 
 Signed and dated clinical trial agreement, which includes the financial agreement 
 Any other documentation required by local regulations. 
The following documents must be provided to the sponsor before enrollment of the first subject: 
 Completed investigator financial disclosure forms from all subinvestigators 
 Documentation of subinvestigator qualifications (eg, curriculum vitae) 
 Name and address of any local laboratory conducting tests for the study, and a dated copy of current 
laboratory normal ranges for these tests, if applicable 
 Local laboratory documentation demonstrating competence and test reliability (eg, accreditation/ 
license), if applicable. 
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17.3. 
Subject Identification, Enrollment, and Screening Logs 
The investigator agrees to complete a subject identification and enrollment log to permit easy identification 
of each subject during and after the study. This document will be reviewed by the sponsor study-site contact 
for completeness. 
The subject identification and enrollment log will be treated as confidential and will be filed by the 
investigator in the study file. To ensure subject confidentiality, no copy will be made. All reports and 
communications relating to the study will identify subjects by subject identification number and year of 
birth.  
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. 
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 adverse events and follow-
up of adverse events; 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 following data will be recorded directly in the eCRF and will be considered source data:  
 Blood pressure and pulse 
 Height and weight  
 Investigator-completed scales and assessments  
The minimum source documentation requirements for Section 4.1 and Section 4.2 specifying the 
documentation of medical history are as follows: 
 Referral letter from treating physician or 
 Complete history of medical notes at the site 
 Discharge summaries 
Inclusion and exclusion criteria not requiring documented medical history must be verified at a minimum 
by subject interview or other protocol required assessment (eg, physical examination, laboratory 
assessment) and documented in the source documents. 
An electronic source system may be used, which contains data traditionally maintained in a hospital or 
clinic record to document medical care (eg, electronic source documents) as well as the clinical study-
specific data fields as determined by the protocol. This data is electronically extracted for use by the 
sponsor. If the electronic source system is utilized, references made to the eCRF in the protocol include the 
electronic source system but information collected through the electronic source system may not be limited 
to that found in the eCRF. Data in this system may be considered source documentation. 
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17.5. 
Case Report Form Completion 
Case report forms are prepared and provided by the sponsor for each subject in electronic format. All eCRF 
entries, corrections, and alterations must be made by the investigator or authorized study-site personnel. 
The investigator must verify that all data entries in the eCRF are accurate and correct. 
The study data will be transcribed by study-site personnel from the source documents onto an electronic 
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 eCRF. Any such 
worksheets will become part of the subject’s source documents. Data must be entered in the eCRF in 
English. The eCRF must be completed as soon as possible after a subject visit and the forms should be 
available for review at the next scheduled monitoring visit. 
All subjective measurements (eg, questionnaires) will be completed by the same individual (ie, blinded 
efficacy assessor) who made the initial baseline determinations whenever possible. Results of efficacy 
assessments performed by the blinded efficacy assessor (in Study Part I and II) will be entered in the eCRF 
by unblinded study personnel as described in Section 9.2.3. Corresponding documentation (separate forms) 
is part of the source data. 
If necessary, queries will be generated in the EDC tool. If corrections to data are needed after the initial 
entry in the eCRF, this can be done in either of the following ways: 
 Investigator and study-site personnel can make corrections in the EDC tool at their own initiative or as 
a response to an auto query (generated by the EDC tool). 
 Sponsor or sponsor delegate can generate queries for resolution by the investigator and site personnel. 
17.6. 
Data Quality Assurance/Quality Control 
Steps to be taken to ensure the accuracy and reliability of data include the selection of qualified investigators 
and appropriate study sites, review of protocol procedures with the investigator and study-site personnel 
before the study, periodic monitoring visits by the sponsor and direct transmission of clinical laboratory 
data from a central laboratory into the sponsor’s data base. Written instructions will be provided for 
collection, handling, storage, and shipment of samples. Guidelines for eCRF completion will be provided 
and reviewed with study-site personnel before start of the study. 
The sponsor will review eCRFs 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 eCRFs and all 
source documents that support the data collected from each subject, as well as all study documents as 
specified in ICH/GCP Section 8, Essential Documents for the Conduct of a Clinical Trial, and all study 
documents as specified by the applicable regulatory requirement(s). The investigator/institution will take 
measures to prevent accidental or premature destruction of these documents. 
Essential documents must be retained until at least 2 years after the last approval of a marketing application 
in an ICH region and until there are no pending or contemplated marketing applications in an ICH region 
or until at least 2 years have elapsed since the formal discontinuation of clinical development of the 
investigational product. These documents will be retained for a longer period if required by the applicable 
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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 use a combination of monitoring techniques (remote and on-site monitoring) to monitor 
this study. 
The sponsor will perform on-site monitoring visits as frequently as necessary. The monitor will record dates 
of the visits in a study site visit log that will be kept at the study site. 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 in the eCRF 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 eCRF are known to the sponsor and study-site personnel and are accessible for 
verification by the sponsor study-site contact. If electronic records are maintained at the study site, the 
method of verification must be discussed with the study-site personnel. 
Direct access to source documents (medical records) must be allowed for the purpose of verifying that the 
recorded data are consistent with the original source data. Findings from this review will be discussed with 
the study-site personnel. The sponsor expects that, during monitoring visits, the relevant study-site 
personnel will be available, the source documents will be accessible, and a suitable environment will be 
provided for review of study-related documents. The monitor will meet with the investigator on a regular 
basis during the study to provide feedback on the study conduct. 
In addition to on-site monitoring visits, remote contacts can occur. It is expected that during these remote 
contacts, study-site personnel will be available to provide an update on study progress at the site. 
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 transferred 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: 
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 Failure of the investigator to comply with the protocol, the requirements of the IEC/IRB or local health 
authorities, the sponsor’s procedures, or GCP guidelines 
 Inadequate recruitment of subjects by the investigator 
 Discontinuation of further study drug development 
17.10. 
On-Site Audits 
Representatives of the sponsor’s clinical quality assurance department may visit the study site at any time 
during or after completion of the study to conduct an audit of the study in compliance with regulatory 
guidelines and company policy. These audits will require access to all study records, including source 
documents, for inspection. Subject privacy must, however, be respected. The investigator and study-site 
personnel are responsible for being present and available for consultation during routinely scheduled study-
site audit visits conducted by the sponsor or its designees.  
Similar auditing procedures may also be conducted by agents of any regulatory body, either as part of a 
national GCP compliance program or to review the results of this study in support of a regulatory 
submission. The investigator should immediately notify the sponsor if he or she has been contacted by a 
regulatory agency concerning an upcoming inspection. 
17.11. 
Use of Information and Publication 
All information, including but not limited to information regarding guselkumab or the sponsor’s operations 
(eg, patent application, formulas, manufacturing processes, basic scientific data, prior clinical data, 
formulation information) supplied by the sponsor to the investigator and not previously published, and any 
data, including exploratory 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. Results of exploratory 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 
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will be arranged for abstracts, poster presentations, or other materials. If requested by the sponsor in writing, 
the investigator will withhold such publication for up to an additional 60 days to allow for filing of a patent 
application. In the event that issues arise regarding scientific integrity or regulatory compliance, the sponsor 
will review these issues with the investigator. The sponsor will not mandate modifications to scientific 
content and does not have the right to suppress information.  
For multicenter study designs and substudy approaches, secondary results generally should not be published 
before the primary endpoints of a study have been published. Similarly, investigators will recognize the 
integrity of a multicenter study by not submitting for publication data derived from the individual study site 
until the combined results from the completed study have been submitted for publication, within 12 months 
of the availability of the final data (tables, listings, graphs), or the sponsor confirms there will be no 
multicenter study publication.  
Authorship of publications resulting from this study will be based on the guidelines on authorship, such as 
those described in the Uniform Requirements for Manuscripts Submitted to Biomedical Journals, which 
state that the named authors must have made a significant contribution to the design of the study or analysis 
and interpretation of the data, provided critical review of the paper, and given final approval of the final 
version. 
Registration of Clinical Studies and Disclosure of Results 
The sponsor will register and disclose existence of and results of clinical studies as required by law. 
 
 
 
 
 
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REFERENCES 
1. Balak DMW. Fumaric acid esters in the management of psoriasis. Psoriasis: Targets and Therapy. 
2015, Bd. 5, S. 9-23. 
 
2. Summary of Product Characteristics – Fumaderm® Initial/Fumaderm®. s.l. : Biogen Idec GmbH, 
January 2016. 
 
3. Ouyang W, Kolls JK and Zehng Y. The biological functions of T helper 17 cell effector cytokines in 
inflammation. immunity. 28 (4), 2008, S. 454-467. 
 
4. Tato Cm and O`Shea JJ. Immunology: What does it mean to be just 17? Nature. 441 (7090), 2006, S. 
166-168. 
 
5. Pathirana D, Ormerod AD, Saiag P, et al. European S3-Guidelines on the systemic treatment of 
psoriasis vilgaris. 23 (2), 2009, S. 1-70. 
 
6. Manuel O and Kumar D. QuantiFERON-TB Gold assay for the diagnosis of latent tuberculosis 
infection. Expert Rev Mol Diagn. 8 (3), 2008, S. 247-256. 
 
7. Cellestis. QuantiFERON-TB Gold clinicans guide and QuantiFERON-TB Gold In-Tube Method 
package insert. downloaded from www.cellestis.com , 2009. 
 
8. Ramsay B and Lawrence CM. Measurement of involved surface area in patients with psoriasis. Br J 
Dermatol. 124, 1991, S. 565-570. 
 
9. Spuls PI, Lecluse LLA, Poulsen ML, et al. How good are clinical severity and outcome measures for 
psoriasis? J Invest Dermatol. 130, 2010, S. 933-943. 
 
10. Frederiksson T and Petterson U. Severe psoriasis- oral therapy with a new retinoid. Dermatologica. 
157, 1978, S. 238-244. 
 
11. Finlay AY and Khan GK. Dermatology Life Quality Index (DLQI)- a simple practical measure for 
routine clinical use. Clin Exp Dermatol. 19 (3), 1994, S. 210-216. 
 
12. Balasubramaniam P, Stevenson O and Berth-Jones J. Fumaric acid esters in severe psoriasis, 
including experience of use in combination with other systemic modalities. Br J Dermatol. 2004, Bd. 150, 
4, S. 741-746. 
 
13. Raschka C and Koch HJ. Longterm treatment of psoriasis using fumaric acid preparations can be 
associated with severe proximal tubublar damage. Hum Exp Toxicol. 1999, Bd. 18, 12, S. 738-739. 
 
14. Lowes MA, Bowcock Am and Krueger JG. Pathogenesis and therapy of psoriasis. Nature. 445 
(7130), 2007, S. 866-873. 
 
 
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ATTACHMENTS 
Attachment 1: Investigator´s Global Assessment (IGA) 
 
Induration (I) (averaged over all lesions; use the National Psoriasis Foundation Reference 
card for measurement) 
0 = no evidence of plaque elevation 
1 = minimal plaque elevation, = 0.25 mm 
2 = mild plaque elevation, = 0.5 mm 
3 = moderate plaque elevation, = 0.75 mm 
4 = severe plaque elevation, > 1 mm 
 
Erythema (E) (averaged over all lesions) 
0 = no evidence of erythema, hyperpigmentation may be present 
1 = faint erythema 
2 = light red coloration 
3 = moderate red coloration 
4 = bright red coloration 
 
Scaling (S) (averaged over all lesions) 
0 = no evidence of scaling 
1 = minimal; occasional fine scale over less than 5% of the lesion 
2 = mild; fine scale dominates 
3 = moderate; coarse scale predominates 
4 = severe; thick, scale predominates 
 
Total Average = ( I + E + S) / 3       
(Average will be calculated in the device but not displayed.  Numeric result will be included 
in data transfer.) 
 
Investigator’s Global Assessment based upon above Total Average 
0 = Cleared, except for residual discoloration 
1 = Minimal - majority of lesions have individual scores for I + E + S / 3 that averages 1 
2 = Mild - majority of lesions have individual scores for I + E + S / 3 that averages 2 
3 = Moderate - majority of lesions have individual scores for I + E + S / 3 that averages 3 
4 = Severe - majority of lesions have individual scores for I + E + S / 3 that averages 4 
 
Note: Scores should be rounded to the nearest whole number. If total ≤ 1.49, score = 1;  
if total ≥ 1.50, score = 2.  
 
 
 
 
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Attachment 2: Psoriasis Area and Severity Index (PASI) 
 
The Psoriasis Area and Severity Index (PASI) is a system used for assessing and grading the
severity of psoriatic lesions and their response to therapy.  The PASI produces a numeric
score that can range from 0 to 72.  The severity of the disease is calculated as follows. 
In the PASI system, the body is divided into 4 regions:  the head (h), trunk (t), upper
extremities (u), and lower extremities (l), which account for 10%, 30%, 20%, and 40% of the
total BSA, respectively.  Each of these areas is assessed separately for erythema, induration
and scaling, which are each rated on a scale of 0 to 4. 
The scoring system for the signs of the disease (erythema, induration, and scaling) are:
0 = none, 1 = slight, 2 = moderate, 3 = severe, and 4 = very severe. 
The scale for estimating the area of involvement for psoriatic lesions is outlined below. 
 
0 = no involvement 
 
1 = 1% to 9% involvement 
 
2 = 10% to 29% involvement 
 
3 = 30% to 49% involvement 
 
4 = 50% to 69% involvement 
 
5 = 70% to 89% involvement 
 
6 = 90% to 100% involvement 
To help with the area assessments, the following conventions should be noted: 
a. 
The neck is considered part of the head 
b. 
The axillae and groin are part of the trunk 
c. 
The buttocks are part of the lower extremities 
The PASI formula is: 
PASI = 0.1 (Eh + Ih + Sh) Ah + 0.3 (Et + It + St) At + 0.2 (Eu + Iu + Su) Au + 0.4 (El + Il + Sl) Al
 
Where E = erythema, I = induration, S = scaling, and A = area 
 
 
 
 
 
 
 
 
 
 
 
 
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Attachment 3: QuantiFERON TB Gold Plus Test 
The QuantiFERON®-TB Gold Plus (QFT®-Plus) test is one of the interferon-γ (IFN-γ) based blood assays for TB screening. It utilizes the
recently identified M. tuberculosis-specific antigens ESAT-6 and CFP-10 to detect in vitro cell-mediated immune responses in infected
individuals. The QFT®-Plus assay measures the amount of IFN-γ produced by sensitized T-cells when stimulated with the synthetic M.
tuberculosis-specific antigens.  In M. tuberculosis-infected persons, sensitized T lymphocytes will secrete IFN-γ in response to stimulation
with the M. tuberculosis-specific antigens and, thus, the QFT®-Plus test should be positive.  Because the antigens used in the test are specific
to M. tuberculosis and not found in BCG, the test is not confounded by BCG vaccination, unlike the tuberculin skin test.  However, there is
some cross-reactivity with the 3 Mycobacterium species, M. kansasii, M. marinum, and M. szulgai.  Thus, a positive test could be the result
of infection with one of these 3 species of Mycobacterium, in the absence of M. tuberculosis infection. 
In a study of a precursor of the QFT®-Plus test (QuantiFERON®-TB Gold test, QFT® test) in subjects with active TB, sensitivity has been
shown to be approximately 89% (Mori et al, 2004). Specificity of the test in healthy BCG-vaccinated individuals has been demonstrated to
be more than 98%.  In contrast, the sensitivity and specificity of the tuberculin skin test was noted to be only about 66% and 35% in a study
of Japanese patients with active TB and healthy BCG-vaccinated young adults, respectively.  However, sensitivity and specificity of the
tuberculin skin test depend on the population being studied, and the tuberculin skin test performs best in healthy young adults who have not
been BCG-vaccinated. 
Data from a limited number of published studies examining the performance of the QFT® assay in immunosuppressed populations suggest
that the sensitivity of the QFT® test is better than the tuberculin skin test even in immunosuppressed patients (Ferrara et al, 2005; Kobashi et
al, 2007; Matulis et al, 2008).  The ability of IFN-γ-based tests to detect latent infection has been more difficult to study due to the lack of a
gold standard diagnostic test; however, TB outbreak studies have demonstrated that the tests correlated better than the tuberculin skin test
with the degree of exposure that contacts had to the index TB case (Ewer et al, 2003).  In addition, TB contact tracing studies have shown
that patients who had a positive QFT® test result and were not treated for latent TB infection were much more likely to develop active TB
during longitudinal follow-up than those who had a positive tuberculin skin test and a negative QFT® test result (Diel et al, 2008). 
Although the performance of the new IFN-γ-based blood tests for active or latent M. tuberculosis infection have not been well validated in
the immunosuppressed population, experts believe these new tests will be at least as, if not more, sensitive, and definitely more specific, than
the tuberculin skin test (Barnes, 2004). 
Performing the QuantiFERON® TB Gold Plus Test (according to QFT®-Plus ELISA Package Insert 02/2015) 
The QuantiFERON® TB Gold Plus test  uses specialized blood collection tubes, which include a Nil tube (gray), TB1 tube (green), TB2 tube
(yellow), and a Mitogen tube (purple). The Mitogen tube is used with the QFT®-Plus test as a positive control and as a control for correct
blood handling and incubation. The Nil tube adjusts for background (e.g., excessive levels of circulating IFN-γ or presence of heterophile
antibodies). The IFN-γ level of the Nil tube is subtracted from the IFN-γ level for the TB Antigen tubes and Mitogen tube. 
To perform the test, blood is drawn through standard venipuncture into supplied tubes. A total of 4 tubes will be needed per subject, each
requiring 1 mL of blood. Tubes should be between 17°C to 25°C at the time of blood filling. Antigens have been dried onto the inner wall of
the blood collection tubes so it is essential that the contents of the tubes be thoroughly mixed with blood (shake them 10 times). The QFT®-
Plus tubes should be incubated at 37°C as soon as possible, and within 16 hours of collection.  
Following a 16 to 24 hour incubation period at 37°C, the tubes are shipped (ambient temperature) to the central laboratory. The central
laboratory will perform an ELISA to quantify the amount of IFN-γ present in the plasma using spectrophotometry and computer software
analysis.  
The central laboratory will analyze and report results for each subject, and sites will be informed of the results.  Subjects who have an
indeterminate result should have the test repeated. 
If available, test results from local laboratory can be accepted. 
References: 
Barnes, PF. (2004). Diagnosing latent tuberculosis infection: turning glitter to gold. Am J Respir Crit Care Med. 170(1):5-6 
Diel, R. et al. (2008) Predictive value of a whole-blood IFN-γ assay for the development of active TB disease. Am. J. Respir. Crit. Care Med.
177, 1164. 
Ewer, K. et al. (2003). Comparison of T-cell-based assay with tuberculin skin test for diagnosis of Mycobacterium tuberculosis infection in a
school tuberculosis outbreak. Lancet. 361(9364):1168-73. 
Ferrara, G. et al. (2005). Routine hospital use of a new commercial whole blood interferon-gamma assay for the diagnosis of tuberculosis
infection. Am J Respir Crit Care Med. 172(5):631-5 
Kobashi, Y. et al. (2007). Clinical evaluation of QuantiFERON TB-2G test for immunocompromised patients. Eur Respir J. 30(5):945-50. 
Matulis, G. et al. (2007). Detection of latent tuberculosis in immunosuppressed patients with autoimmune diseases performance of a
Mycobacterium tuberculosis antigen specific IFN-gamma assay. Ann. Rheum. Dis. 67, 84. 
Mori, T. et al. (2004). Specific detection of tuberculosis infection: an interferon-gamma-based assay using new antigens. Am J Respir Crit
Care Med. 170(1):59-64. 
 
 
 
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CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
96 
Approved, Date: 22 January 2018Approved22 January 2018 
Attachment 4: Hepatitis B Virus (HBV) Screening with HBV DNA 
 
Subjects must undergo screening for hepatitis B virus (HBV). At a minimum, this includes testing for 
HBsAg (HBV surface antigen), anti-HBs (HBV surface antibody), and anti-HBc total (HBV core 
antibody total):  
 
Subjects who test negative for all HBV screening tests (ie, HBsAg-, anti-HBc-, and anti-HBs-) 
are eligible for this study. 
 
Subjects who test negative for surface antigen (HBsAg-) and test positive for core antibody 
(anti-HBc+) and surface antibody (anti-HBs+) are eligible for this study. 
 
Subjects who test positive only for surface antibody (anti-HBs+) are eligible for this study. 
 
Subjects who test positive for surface antigen (HBsAg+) are NOT eligible for this study, 
regardless of the results of other hepatitis B tests. 
 
Subjects who test positive only for core antibody (anti-HBc+) must undergo further testing 
for the presence of hepatitis B virus deoxyribonucleic acid (HBV DNA test). If the HBV DNA 
test is positive, the subject is NOT eligible for this study. If the HBV DNA test is negative, 
the subject is eligible for this study. In the event the HBV DNA test cannot be performed, the 
subject is NOT eligible for this study.  
 
For subjects who are not eligible for this study due to HBV test results, consultation with a 
physician with expertise in the treatment of hepatitis B virus infection is recommended.   
Eligibility based on hepatitis B virus test results 
 
Hepatitis B test result 
Action 
Hepatitis B surface 
antigen 
(HBsAg) 
Hepatitis B surface 
antibody 
(anti-HBs) 
Hepatitis B core 
antibody 
(anti-HBc total) 
 
Include 
— 
— 
— 
— 
+ 
— 
— 
+ 
+ 
 
Exclude 
+ 
— or + 
— or + 
 
Require testing for presence 
HBV DNA* 
— 
— 
+ 
* If HBV DNA is detectable, exclude from the  clinical study. If HBV DNA testing cannot be performed, 
or there is evidence of chronic liver disease, exclude from the clinical study.   
 
 
 
 
NCT09251533


CNTO1959 (guselkumab)     
 
 
 
Clinical Protocol CNTO1959PSO3008  
97 
Approved, Date: 22 January 2018Approved22 January 2018 
Attachment 5: Scalp-specific IGA (ss-IGA) 
 
Subjects with psoriasis of the scalp will be assessed using the 5-point ss-IGA presented below. 
Only subjects with an ss-IGA score ≥2 at baseline will be included in the subset of subjects analyzed 
for efficacy. 
 
Details of the Scalp-Specific Investigator Global Assessment (ss-IGA) 
Score 
Category 
Description 
0 
Absence of Disease 
No evidence of redness, no evidence of thickness, and no evidence 
of scaliness on the scalp. 
1 
Very Mild Disease 
The overall clinical picture consists of flat lesions with barely 
perceptible erythema, with or without a trace of overlying fine scale 
2 
Mild Disease 
The overall clinical picture consists of lesions with mild erythema, 
slight, but definite, thickness, and a thin scale layer 
3 
Moderate Disease 
The overall clinical picture consists of lesions with moderate 
erythema, a moderate thickness, and a moderate scaled layer 
4 
Severe Disease 
The overall clinical picture consists of lesions with bright erythema, 
severe thickness and a severe, coarse thick scale 
 
 
  
 
 
 
NCT09251533


NCT09251533

SAP_003.pdf: 
Janssen-Cilag GmbH, Germany* 
 
Statistical Analysis Plans – Cover page 
 
Multicenter, randomized, open-label, efficacy assessor-blinded, active comparator-
controlled phase 3b study to compare the efficacy of guselkumab to fumaric acid esters 
(Fumaderm® initial/Fumaderm®) for adult patients with moderate to severe plaque 
psoriasis who are candidates for and naive to systemic treatment 
 
POLARIS  
 
Protocol CNTO1959PSO3008; Phase 3b 
 
CNTO1959 guselkumab  
 
*Janssen-Cilag is a regional organization that operates through different legal entities in Germany. 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 CSR. 
 
 
 
Content of this document 
 
This document consists of four statistical analysis plans, each pertaining to the analyses performed: 
• 
Week 24 analysis, document “Polaris_SAP_FINAL_signed_20170717.pdf”; 
• 
Week 32 analysis, document “Polaris_SAP_W32_V1.0_15Aug2018_signed.pdf”; 
• 
Week 64 analysis, document “Polaris_SAP_W64_V1.0_29Aug2018 signed.pdf”; 
• 
Week 100 analysis, document ”Polaris_SAP_W100_V1.0_09May2019_signed.pdf”. 
NCT09251533


 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 1 of 55 
 
Statistical Analysis Plan 
 
Multicenter, randomized, open-label, efficacy assessor-blinded, active 
comparator-controlled phase 3b study to compare the efficacy of 
guselkumab to fumaric acid esters (Fumaderm® initial/ Fumaderm®) for 
adult patients with moderate to severe plaque psoriasis who are 
candidates for and naive to systemic treatment 
POLARIS 
- Week 24 Analysis - 
 
Study Code 
CNTO1959PSO3008 
EudraCT Number 
2016-002135-15 
Development phase 
Phase 3b 
Study Design 
randomized, open-label, efficacy assessor-
blinded, single country, multicenter, 
active-comparator-controlled 
Sponsor 
Janssen-Cilag GmbH, Neuss 
Johnson & Johnson Platz 1, 
41470 Neuss, Germany 
Contract Research Organization 
acromion GmbH 
Europaallee 27 – 29 
50226 Frechen, Germany 
Version No., Date 
Final 1.0, 10-July-2017 
 
 
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CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 2 of 55 
Table of Contents 
 
 
1.0 
Signatures .................................................................................... 5 
2.0 
List of Abbreviations .................................................................... 6 
3.0 
Introduction ................................................................................. 7 
4.0 
Responsibilities ............................................................................ 7 
5.0 
Software Utilized .......................................................................... 8 
6.0 
Coding Systems Utilized ............................................................... 8 
7.0 
Study Objectives and Hypotheses ................................................ 9 
7.1 
Objectives ................................................................................................. 9 
7.2 
Hypotheses ............................................................................................... 9 
8.0 
Study Endpoints ......................................................................... 10 
9.0 
Study Design .............................................................................. 11 
9.1 
Overview ................................................................................................. 11 
9.2 
Sample Size Determination ........................................................................ 12 
9.3 
Randomization and Blinding ....................................................................... 13 
10.0 
Study Schedule........................................................................... 14 
11.0 
Analysis Sets .............................................................................. 18 
11.1 
Definition of Analysis Sets ......................................................................... 18 
11.2 
Protocol Deviations ................................................................................... 18 
11.3 
Screening Failures .................................................................................... 19 
12.0 
Definition and Calculation of Efficacy Endpoints ......................... 20 
12.1 
Involved Body Surface Area (BSA%) ........................................................... 20 
12.2 
Investigator's Global Assessment (IGA) ....................................................... 20 
12.3 
Scalp Specific Investigator's Global Assessment (ss-IGA) .............................. 20 
12.4 
Psoriasis Area and Severity Index (PASI) .................................................... 21 
12.5 
Dermatology Life Quality Index (DLQI) ....................................................... 21 
12.6 
Psoriasis Symptom and Sign Diary (PSSD) .................................................. 22 
12.7 
Short Form Health Survey (SF-36) ............................................................. 23 
13.0 
Statistical Methodology .............................................................. 24 
13.1 
Data Handling Rules ................................................................................. 24 
13.1.1 Baseline and Post-baseline Points in Time of Interest .................................... 24 
13.1.2 Definition of Within- and Between-Group Treatment Differences ..................... 24 
13.1.3 Visit Windows .......................................................................................... 24 
13.1.4 Treatment Failure Criteria .......................................................................... 25 
13.1.5 Treatment Failure Rules ............................................................................ 25 
13.1.6 Handling of Missing Values ........................................................................ 26 
13.1.7 Data Transformations ............................................................................... 26 
13.2 
Descriptive Statistics ................................................................................ 26 
13.2.1 Dichotomous and Categorical Variables ....................................................... 26 
13.2.2 Continuous and Quasi-Continuous Variables ................................................ 26 
13.2.3 Graphical Presentations ............................................................................. 27 
13.3 
Confirmatory Statistics .............................................................................. 27 
13.3.1 Statistical Hypotheses ............................................................................... 27 
13.3.2 Estimation, Confidence Intervals and Hypotheses Testing .............................. 27 
13.3.3 Significance Level ..................................................................................... 27 
13.4 
Exploratory Statistics ................................................................................ 28 
13.4.1 Binary Endpoints ...................................................................................... 28 
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CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 3 of 55 
 
13.4.2 Continuous Endpoints ............................................................................... 28 
13.5 
Adjustment for Covariates ......................................................................... 28 
13.6 
Interim Analyses ...................................................................................... 28 
13.7 
Multi-center Data ..................................................................................... 29 
13.8 
Subgroup Analyses ................................................................................... 29 
13.9 
Sensitivity Analyses .................................................................................. 30 
14.0 
Statistical Analyses .................................................................... 31 
14.1 
Study Subjects ......................................................................................... 31 
14.1.1 Disposition of Subjects .............................................................................. 31 
14.1.2 Discontinuation of Study Treatment ............................................................ 32 
14.1.3 Protocol Deviations ................................................................................... 32 
14.1.4 Analysis Sets ........................................................................................... 32 
14.2 
Demographic and Other Baseline Characteristics .......................................... 33 
14.2.1 Demographics .......................................................................................... 33 
14.2.2 Medical History ........................................................................................ 33 
14.2.3 Diagnosis of Psoriasis ................................................................................ 33 
14.2.4 Previous Psoriasis Therapy ........................................................................ 33 
14.2.5 Substance Use ......................................................................................... 34 
14.2.6 Physical Examination ................................................................................ 34 
14.2.7 Tuberculosis Evaluation ............................................................................. 34 
14.2.8 Chest Radiograph Result ........................................................................... 34 
14.2.9 Concomitant Medication and Therapy .......................................................... 34 
14.2.10 Shampoo and Moisturizer .......................................................................... 34 
14.3 
Treatment Compliance .............................................................................. 35 
14.3.1 Visit Windows .......................................................................................... 35 
14.3.2 Study Medication ...................................................................................... 35 
14.4 
Analysis of Efficacy ................................................................................... 36 
14.4.1 Primary Endpoint ...................................................................................... 37 
14.4.2 Major Secondary Endpoints ....................................................................... 37 
14.4.3 Other Secondary Endpoints ....................................................................... 38 
14.4.4 Other Efficacy Assessments ....................................................................... 40 
14.5 
Analysis of Safety ..................................................................................... 41 
14.5.1 Extent of Exposure ................................................................................... 41 
14.5.2 Adverse Events ........................................................................................ 41 
14.5.3 Clinical Laboratory Tests ........................................................................... 45 
14.5.4 Vital Signs ............................................................................................... 46 
14.5.5 Physical Examination ................................................................................ 46 
14.5.6 Body Weight ............................................................................................ 46 
14.5.7 Early Detection of Active Tuberculosis ......................................................... 46 
14.6 
Analysis of MedDRA Codes ......................................................................... 47 
14.7 
Analysis of WHO Drug Dictionary Codes ...................................................... 47 
15.0 
Changes to Planned Analyses ..................................................... 47 
16.0 
Tabulation .................................................................................. 48 
16.1 
General ................................................................................................... 48 
16.2 
Format of Data Displays ............................................................................ 48 
16.2.1 Tables ..................................................................................................... 48 
16.2.2 Listings ................................................................................................... 48 
16.2.3 Figures .................................................................................................... 49 
16.3 
Data Format ............................................................................................ 50 
17.0 
References ................................................................................. 51 
 
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CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 4 of 55 
18.0 
Appendices ................................................................................. 52 
18.1 
Table of Contents for Data Displays ............................................................ 52 
18.1.1 Tables ..................................................................................................... 53 
18.1.2 Listings ................................................................................................... 54 
18.1.3 Figures .................................................................................................... 55 
 
 
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NCT02473289


Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 6 of 55 
2.0 
List of Abbreviations 
 
 
 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
BSA 
Body Surface Area 
CRF 
Case Report Form(s)  
CSP 
Clinical Study Protocol 
DLQI 
Dermatology Life Quality Index 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
e.g. 
example given 
FAE 
Fumaric Acid Esters 
HBV/ HCV 
Hepatitis B virus/ Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HTA 
Health Technology Assessment 
ICH 
International Council on Harmonization 
i.e. 
that is 
IGA 
Investigator´s Global Assessment 
IL 
Interleukin 
LOCF 
Last Observation Carried Forward 
MCS 
Mental Component Summary 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
Methotrexate 
NTEAE 
Not Treatment Emergent Adverse Event 
NTESAE 
Not Treatment Emergent Serious Adverse Event 
PASI 
Psoriasis Area and Severity Index 
PCS 
Physical Component Summary 
PRO 
Patient-Reported Outcome(s)  
PSSD 
Psoriasis Symptom and Sign Diary 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous 
SF-36 
Short Form (36-item) health survey 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
ss 
scalp-specific 
TB 
tuberculosis 
TEAE 
Treatment Emergent Adverse Event 
TES 
Time and Events Schedule 
TESAE 
Treatment Emergent Serious Adverse Event 
 
 
 
 
 
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Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 7 of 55 
 
3.0 
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 and the relevant 
acromion SOPs and/or guidelines. This plan describes the statistical analyses planned to 
be performed for the Week 24 analysis of Janssen-Cilag GmbH Clinical Study Protocol 
CNTO1959PSO3008 and should be read in conjunction with the CSP and the electronic 
Case Report Form (eCRF). Statistical analyses of study data recorded after Week 24 will 
be specified in a separate SAP which will be based on protocol amendment 1 to the CSP. 
The Week 24 analysis will include the confirmatory analysis of the primary endpoint and 
the major secondary endpoints and exploratory analyses for all other predefined efficacy 
and safety analyses until Week 24. Evaluations on health technology assessment (HTA) 
will also be specified in this SAP. No separate HTA SAP will be provided. The Week 24 
analysis will be performed after all subjects have completed their visit at 24 weeks after 
randomization or discontinued earlier. Data base lock for the Week 24 analysis will be 
after the Week 24 visit data are ready for statistical analysis (i.e., clean data). 
This SAP is the core document for all statistical programming planned to be performed for 
the Week 24 analysis and is based on the following study documents to protocol no. 
CNTO1959PSO3008: 
Document 
Version, Date 
Protocol / Amendments 
Version 1.0, 03-AUG-2016 
eCRF 
Version 1.0, 12-DEC-2016 
Data Management Plan 
Version 1.0, 09-DEC-2016 
Data Validation Plan 
Version 1.0, 09-DEC-2016 
 
4.0 
Responsibilities 
The responsibilities for the biometrical tasks at acromion GmbH are assigned as follows: 
Name 
Function 
Task 
Statistician 
Statistical Programming and Analysis 
Statistician 
Statistical Programming and Analysis 
Statistical Programmer 
Statistical Programming and Analysis 
Medical Data Analyst 
Medical Data Review and Coding 
 
 
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CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 8 of 55 
5.0 
Software Utilized 
The statistical analysis and generation of tables, patient data listings and figures will be 
performed using the SAS® software package version 9.4 under the Microsoft Windows® 7 
operating system at the computer facilities of acromion GmbH. Additional analyses 
regarding health technology assessment (HTA) may be performed by or under the 
responsibility of Janssen-Cilag GmbH. 
 
6.0 
Coding Systems Utilized 
The MedDRA-dictionary version 19.1 is used for coding of prior and concomitant diseases 
and for coding of adverse events. The following items are coded. 
eCRF Module 
Item 
SDTM Domain/ Variable 
Name 
Medical History of Interest 
Medical History Term 
MH/MHTERM 
Previous Phototherapy 
Type of Phototherapy 
MH/MHTERM 
Concomitant Medication 
Indication 
CM/CMIND 
Concomitant Therapy 
Indication 
CM/CMIND 
Concomitant Therapy 
Therapy 
CM/CMTRT 
(S)AE  
Term 
AE/AETERM 
Prior and concomitant medications are coded according to the WHO terminology using the 
2016/1 version of the WHO-Drug Dictionary. The following items are coded. 
eCRF Module 
Item 
SDTM Domain/ Variable 
Name 
Previous Topical Therapy 
Medication/Therapy 
MH/MHTERM 
Concomitant Medication  
Compound 
CM/CMTRT 
Details are specified in the Data Management Plan. 
 
 
NCT02473289


Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 9 of 55 
 
7.0 
Study Objectives and Hypotheses 
7.1 
Objectives 
Primary Objectives 
The primary objectives of the study are 
• 
to compare the efficacy of guselkumab to fumaric acid esters (FAE) in systemic 
treatment-naïve subjects with moderate to severe plaque-type psoriasis. 
• 
to assess the safety and tolerability of guselkumab in systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis. 
Secondary Objective 
The secondary objective is to compare improvement of health-related quality of life (QOL) 
and other patient-reported outcomes (PRO) when systemic treatment-naïve subjects with 
moderate to severe plaque-type psoriasis are treated with guselkumab compared to FAE. 
7.2 
Hypotheses 
The primary hypothesis of this study is that guselkumab treatment is superior to FAE 
(Fumaderm® initial/ Fumaderm®) treatment as assessed by the proportion of subjects 
achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are: 
• Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a PASI 75 response at Week 24 
• Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a DLQI score of 0 or 1 at Week 24. 
If the primary hypothesis is accepted, the study will be considered positive. 
 
 
NCT02473289


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CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 10 of 55 
 
8.0 
Study Endpoints 
Primary Endpoint 
The primary endpoint is the proportion of subjects achieving at least a 90% improvement 
of their psoriasis according to the Psoriasis Area and Severity Index (PASI 90 response) at 
Week 24. 
Secondary Endpoints 
The major secondary endpoints are: 
• The proportion of subjects achieving at least a 75% improvement of their psoriasis 
according to the PASI at Week 24 (PASI 75 response) 
• The proportion of subjects achieving a DLQI score of 0 or 1 at Week 24. 
Other secondary endpoints are: 
• The proportion of subjects achieving a 100% improvement of their psoriasis according 
to the PASI at Week 24 (PASI 100 response) 
• The change from baseline in the signs and symptoms aggregate scores of the PSSD at 
Week 24 
• The change from baseline in the individual scale scores for itch, pain, and scaling of 
PSSD components at Week 24 
• The proportion of subjects achieving an absolute PASI score ≤1 at Week 24 
• The proportion of subjects achieving an IGA score of cleared (0) at Week 24 
• The change from baseline of body surface area (BSA) psoriatic involvement at Week 24  
• The change from baseline in DLQI score at Week 24 
• The proportion of subjects achieving an ss-IGA score of absence of disease (0) at Week 
24 in randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at baseline 
• The change from baseline in the physical and mental component summary scores of 
SF-36 at Week 24 
• Safety and tolerability data will be summarized using descriptive statistics. 
 
 
 
 
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CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 11 of 55 
9.0 
Study Design 
9.1 
Overview 
This is a randomized, open-label, efficacy assessor-blinded, single country, multicenter, 
active-comparator-controlled phase 3b study of guselkumab in adult subjects with 
moderate to severe plaque-type psoriasis who have not yet received any systemic 
therapy. The study will be performed at about 30 to 45 sites in Germany. 
A total of 114 subjects will be randomized in a 1:1 ratio to either the study drug 
(guselkumab) or to the active comparator (FAE). Subjects of the guselkumab group will 
receive 100 mg guselkumab SC at Weeks 0, 4, 12, and 20. Subjects of the FAE group will 
receive commercially available Fumaderm® tablets specifically labeled for the study. An 
individual dosing for each subject representing the optimal benefit-risk ratio is aspired. As 
shown in Figure 1, the study will be conducted with a 24-week treatment phase and a 
subsequent post-treatment safety follow-up phase until Week 32. Together with a 3-week 
screening phase, the maximum duration of a subject´s participation in this study will be 
35 weeks. 
Efficacy of treatment will be assessed before any tests, procedures or other evaluations, 
first by the subject him/herself (1st DLQI, 2nd PSSD 7 day version, and 3rd SF-36), and 
subsequently by a blinded efficacy assessor (BSA%, IGA, ss-IGA, and PASI). Safety 
evaluations will include the monitoring of adverse events (including injection site and 
allergic reactions), physical examinations, measurement of body weight, vital sign 
measurement, clinical laboratory testing (HBV, HCV, HIV, hematology, chemistry), 
concomitant medication review, tuberculosis test and evaluation, urinalysis and pregnancy 
testing. A confirmatory interim analysis will not be conducted. However, in addition to the 
main analysis after Week 24, a follow-up safety analysis will be performed. 
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 site, in the time frame specified in the Clinical 
Trial Agreement. The overall duration of the study is expected to be approximately 14 
months (start in December 2016, stop in February 2018). The estimated frequency and 
timing of the study visits are summarized in the 'Time and Events Schedule' (TES). 
Figure 1: Schematic Overview of the Study 
 
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CNTO1959 (guselkumab) 
 
Statistical Analysis Plan_Final 1.0_10Jul2017 
 
Page 12 of 55 
9.2 
 Sample Size Determination 
The primary hypothesis of this study is that guselkumab treatment is superior to FAE 
(Fumaderm® initial/ Fumaderm®) treatment as assessed by the proportion of subjects 
achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are:  
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a PASI 75 response at Week 24. 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a DLQI score of 0 or 1 at Week 24. 
In order to control the overall experiment wise type 1 error rate, the primary endpoint and 
the two major secondary endpoints will be tested in a fixed sequence as a-priori ordered 
hypotheses. That is, the first major secondary endpoint will be tested only if the primary 
endpoint is positive (i.e., p <0.05), and the second major secondary endpoint will be 
tested only if the first major secondary endpoint is positive (i.e., p <0.05). Due to the 
testing of ordered hypotheses, no adjustment of the significance level with respect to the 
threefold test procedure is required. 
The assumptions for the sample size and power calculations using the threefold test 
procedure were based on guselkumab phase 2 data and unpublished data from the 
German PsoBest Registry and are as follows: PASI 90 responder rates for guselkumab and 
FAE in Week 24 are assumed to be 60% and 25%, respectively. PASI 75 responder rates 
are assumed to be 80% and 45%, respectively. DLQI responder rates are assumed to be 
60% and 30%, respectively. 
Based on these assumptions, with a total of 114 subjects planned to be randomized in a 
1:1 ratio to guselkumab (n = 57) and to FAE (n = 57), superiority of guselkumab vs. FAE 
can be demonstrated at a 5% significance level (two-sided) with power of at least 90% for 
each test of the threefold test procedure as displayed in the table below. 
Table 1: Power to detect a treatment effect on expected proportions of subjects 
achieving the primary and the major secondary endpoints 
Order of 
testing 
Endpoint in  
Week 24 
Guselkumab 
(% responder) 
FAE 
(% responder) 
Power 
1 
PASI 90 
60 
25 
97% 
2 
PASI 75 
80 
45 
98% 
3 
DLQI 0/1 
60 
30 
90% 
type 1 error rate alpha 5% (two-sided) 
sequential testing with a-priori ordered hypotheses (only proceed with testing, if p <0.05)  
sample size n = 114 with 1:1 ratio guselkumab (n = 57) and FAE (n = 57) 
two group chi-square test; nQuery Advisor® Release 7.0 
 
 
 
 
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9.3 
 Randomization and Blinding 
Procedures for Randomization  
Central randomization is implemented in this study. Subjects will be randomly assigned to 
1 of 2 treatment groups (1:1 ratio) based on a computer-generated randomization 
schedule prepared before the study by or under the supervision of the sponsor. The 
randomization will be balanced by using randomly permuted blocks. The interactive web-
based eCRF will assign a unique treatment code, which will dictate the treatment 
assignment at baseline visit of the subject. The investigator will not be provided with 
randomization codes. The randomization codes will be stored invisible for the investigator 
in a separate, blind part of the EDC system.  
Blinding 
As this is an open study, blinding procedures for the treatment are not applicable. 
However, a blinded efficacy evaluator will assess effectiveness of treatment as described 
in Section 9.2.3 of the CSP. 
 
 
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10.0 Study Schedule 
An overview of the study procedures is displayed in the following time and events schedule of the CSP. 
Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final 
Study visit) 
ETVh 
Notes 
Week 
max. -3  
0 
2 
4 
8 
12 
16 
20 
24 
32 
 
All visits should occur within ±7 days 
of the scheduled visit, Section 7 
Study Proceduresb 
 
 
Screening/Administrative 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
Must be signed before first study-
related activity 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Minimum criteria for the availability 
of documentation supporting the 
eligibility criteria are described in 
protocol, Section 4; check clinical 
status again before first dose of study 
medication 
Study Drug Administration 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
All baseline study procedures and 
evaluations are to be completed 
before randomization 
Study drug 
administration 
 
  Xc ----------------------------------------------------------------X 
 
 
All study procedures and evaluations 
are to be completed before study drug 
administration 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before administration of study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
c: Subjects randomized to guselkumab will get guselkumab 100 mg on site at Weeks 0, 4, 12 and 20. Subjects randomized to FAEs will start with Fumaderm® initial 
regimen (0-0-1) at the day of the baseline visit; thereafter, FAE doses will be increased to find the optimal Fumaderm® dose for each subject as described in 
Section 6 
h: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before or at Week 24, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final 
Study visit) 
ETVh 
Notes 
Week 
max. -3  
0 
2 
4 
8 
12 
16 
20 
24 
32 
 
All visits should occur within ±7 days 
of the scheduled visit, Section 7 
Study Proceduresb 
 
 
Safety Assessments 
Physical examination  
X 
x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X  
X 
 
Tuberculosis evaluation 
X 
X 
X-------------------------------------------------------------------------X 
X 
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 (Section 9.3) 
Chest radiograph 
X 
 
 
 
 
 
 
 
 
 
 
Taken within 3 months before the 
first administration of study drug and 
read by a qualified radiologist 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Women of childbearing potential 
must have a negative urine pregnancy 
test before randomization and at all 
study visits (prior to administration of 
study drug). 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
Weight 
 
X 
 
 
 
 
 
 
X 
X 
X 
 
Concomitant therapy 
      X------------------------------------------------------------------------------------------X 
X 
 
Adverse events 
      X------------------------------------------------------------------------------------------X 
X 
 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration 
of study treatments, see Section 10.2 
h: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before or at Week 24, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final 
Study visit) 
ETVh 
Notes 
Week 
max. -3  
0 
2 
4 
8 
12 
16 
20 
24 
32 
 
All visits should occur within ±7 days 
of the scheduled visit, Section 7 
Study Proceduresb 
 
 
Efficacy Assessments 
DLQI 
X 
X 
 
X  
X 
 
X 
 
X 
 
X 
Order of assessment: 1st DLQI, 2nd 
PSSD, 
3rd 
SF-36; 
should 
be 
performed 
before 
any 
tests, 
procedures 
or 
other 
evaluations 
(PASI, IGA, ss-IGA, BSA) for that 
visit; completion of the baseline 
PROs 
has 
to 
be 
done 
before 
randomization 
PSSD (7d) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
SF-36 
 
X 
 
 
X 
 
X 
 
X 
 
X 
IGAd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
PASId 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
ss-IGAd,e 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
BSA%d 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration 
of study treatments, see Section 10.2 
d: Dermatological evaluation of the subjects will be done by a blinded assessor starting with the Baseline visit; assessments will be done before any study related 
procedure will take place 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
h: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before or at Week 24, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final 
Study visit) 
ETVh 
Notes 
Week 
max. -3  
0 
2 
4 
8 
12 
16 
20 
24 
32 
 
All visits should occur within ±7 days 
of the scheduled visit, Section 7 
Study Proceduresb 
 
 
Clinical Laboratory Assessment 
Tuberculosis testf 
X 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B and C 
Serologies 
X 
 
 
 
 
 
 
 
 
 
 
 
HIV antibody test 
X 
 
 
 
 
 
 
 
 
 
 
 
Hematologyg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory 
tests 
are 
listed 
in 
Section 9.3 
Chemistryg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Laboratory tests are listed in Section 
9.3 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis by dipstick: glucose and 
protein; if there are signs of proteins 
and/or glucose on urine test strip, the 
urine sample must be analyzed 
centrally; here, protein and glucose 
levels must not exceed trace levels, 
eg, ≤(+); one re-test (central urine 
analysis) is allowed. 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration 
of study treatments, see Section 10.2 
f: The QuantiFERON-TB Gold Plus test will generally be performed by the central laboratory; however, if available, test results from local laboratory can be 
accepted 
g: All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled; fasting is not necessary; details will 
be provided in the Laboratory Manual 
h: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before or at Week 24, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
 
 
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11.0 Analysis Sets 
In this study, subjects will be included in the efficacy analyses according to their assigned 
treatment. In contrast to the efficacy analysis set, safety analyses will be performed 
according to the actual treatment received during the study. 
11.1 
Definition of Analysis Sets 
The following analysis data sets will be defined: 
• 
Efficacy Analysis Set 
The efficacy analysis set is defined as the set of all subjects who were randomized to 
one of the two treatment groups (guselkumab or FAE) at Week 0 regardless of the 
treatment they actually received (“intent-to-treat” principle). 
• 
Per-Protocol Analysis Set 
The per-protocol analysis set will consist of all subjects in the efficacy 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.  
• 
Safety Analysis Set 
The safety analysis set is defined as the set of all subjects who were randomized to 
one of the two treatment groups (guselkumab or FAE) at Week 0 and who received at 
least one dose of study drug according to the actual treatment received during the 
study irrespective of the treatment assigned at randomization. 
Unless otherwise specified, data on study subjects (including subject disposition, reasons 
for discontinuation of study treatment, protocol deviations, analysis sets) will be analyzed 
based on data from all subjects randomized at Week 0 ('efficacy analysis set'). 
Demographic and other baseline characteristics as well as treatment compliance will be 
analyzed based on data from all subjects randomized at Week 0 ('efficacy analysis set') 
and on all treated subjects ('safety analysis set'). 
All efficacy analyses to compare guselkumab vs. FAE will be performed for all subjects 
randomized at Week 0 ('efficacy analysis set'). Additionally, all efficacy analysis will be 
performed for all treated subjects ('safety analysis set'). The primary and the major 
secondary endpoints will also be analyzed using the per-protocol analysis set. 
All safety analyses to compare guselkumab vs. FAE will be performed for all treated 
subjects ('safety analysis set'). The safety analysis will be performed after all subjects 
have completed their visit 24 weeks after randomization or discontinued earlier. 
If the efficacy analysis set and the safety analysis set will not be different, analyses of 
efficacy and safety will be performed on data from all subjects randomized at Week 0 
('efficacy analysis set'). 
11.2 
Protocol Deviations 
The determination of evaluability of subjects, especially in cases of protocol deviations, 
withdrawals or drop-outs and the assignment of subjects to the planned analysis sets will 
be performed according to the requirements of the study protocol. Minor and major and 
potentially major protocol deviations that can be expected based on the prescriptions in 
the protocol were defined by Janssen-Cilag GmbH during the trial set up period. A detailed 
description of major and potentially major protocol deviation criteria is included in a 
separate document. 
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Data on subjects who had a major protocol deviation will be documented continuously by 
Janssen-Cilag GmbH in a Clinical Trial Management System during the trial period. Final 
data on major protocol deviations regarding the Week 24 analysis will be transferred to 
the data management department of acromion GmbH as Excel spreadsheets and will be 
further processed for statistical analysis. 
 
11.3 
Screening Failures 
The data of subjects who were not randomized will not be included in the statistical 
analyses. However, a separate listing will be presented providing the site / subject no. and 
the reason for not being randomized. 
 
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12.0 Definition and Calculation of Efficacy Endpoints 
The following sections provide a detailed description of the definition and the planned 
calculation of the efficacy endpoints as defined in the CSP. The same applies also for 
additional endpoints not defined in the CSP. 
12.1 
Involved 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).  
12.2 
Investigator's Global Assessment (IGA) 
The Investigator’s Global Assessment (IGA) documents the investigator’s assessment of 
the subject’s psoriasis at a given time. Overall lesions are graded for induration, 
erythema, and scaling. The subject’s psoriasis is assessed as cleared (0), minimal (1), 
mild (2), moderate (3), or severe (4). 
The efficacy endpoint related to the IGA score is defined below: 
IGA cleared responder 
Subjects who achieve an IGA score of cleared (0) will be considered IGA cleared 
responders. 
12.3 
Scalp Specific Investigator's Global Assessment (ss-IGA) 
The scalp-specific (ss-)IGA instrument is used to evaluate the disease severity of scalp 
psoriasis. The lesions are assessed in terms of the clinical signs of redness, thickness, and 
scaliness which are scored as: absence of disease (0), very mild disease (1), mild disease 
(2), moderate disease (3), and severe disease (4). 
The analyses for ss-IGA will be based on subjects randomized at Week 0 with baseline ss-
IGA score ≥2.  
ss-IGA absence of disease responder 
Subjects with an ss-IGA score ≥2 at baseline who achieve ss-IGA score of absence of 
disease (0) will be considered ss-IGA absence of disease responders. 
 
 
 
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12.4 
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. 
In addition, the time to PASI 75/90/100 response defined as time from baseline to first 
onset of response will be calculated. In the absence of documented response the time to 
PASI 75/90/100 response will be censored at the date of Week 24 or the date of 
discontinuation in case of early treatment discontinuation. 
12.5 
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 (e.g., 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. 
In addition, the time to DLQI 0/1 response defined as time from baseline to first onset of 
response will be calculated. In the absence of documented response the time to DLQI 0/1 
response will be censored at the date of Week 24 or the date of discontinuation in case of 
early treatment discontinuation. 
 
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12.6 
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 (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. 
 
 
 
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12.7 
Short Form Health Survey (SF-36) 
The Short Form Health Survey (SF-36) is a 36-item questionnaire used for subjects’ self-
assessment of health-related quality of life, consisting of the following 8 dimensions: 1) 
limitations in physical functioning due to health problems, 2) limitations in usual role 
activities due to physical health problems, 3) bodily pain, 4) general mental health 
(psychological distress and well-being), 5) limitations in usual role activities due to 
personal or emotional problems, 6) limitations in social functioning due to physical or 
mental health problems, 7) vitality (energy and fatigue), and 8) general health perception.  
A physical component summary (PCS) score and a mental component summary (MCS) 
score can be derived. The concepts measured by the SF-36 are not specific to age, disease 
or treatment group, allowing comparison of relative burden of different diseases and the 
relative benefit of different treatments.  
Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating 
better health. Based on the scale scores, the summary scores, PCS and MCS, will be 
derived. These summary scores are also scaled with higher scores indicating better health. 
The QualityMetric Health Outcomes™ Scoring Software 5.0 offered by QualityMetric 
Incorporated will be used to score the SF-36. The Software is designed to provide users 
with standard scoring methods in an easy-to-use way. By using this Software, users will 
have the confidence that the data they obtain on their SF form are scored in accordance 
with standards set by the developers of the SF tools. The Software also provides 
evaluation of data quality and applies methods for missing data recovery. The PCS score 
can be calculated when seven scale scores are available and the Physical Functioning scale 
is not missing. The MCS score can be calculated when at least seven scale scores are 
available and the Mental Health scale is not missing. 
 
A more detailed description of the scoring procedure is provided in the User's Guide of 
QualityMetric Health Outcomes™ Scoring Software 5.0 (see especially Appendix F). 
 
 
 
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13.0 Statistical Methodology 
The statistical analyses in this study will focus on the comparison of the two randomized 
treatment groups (i.e., guselkumab vs. FAE). The analyses will be confirmatory for the 
primary endpoint and the major secondary endpoints, and exploratory for all other 
secondary endpoints. 
The biometrical evaluation will be carried out by acromion GmbH under the authority of 
the sponsor. Statistical programming and analyses will be performed using the statistical 
software system SAS®. 
The following sections provide a more detailed description of the planned statistical 
methodology. 
13.1 
Data Handling Rules 
 
13.1.1 
Baseline and Post-baseline Points in Time of Interest 
Baseline Definition 
In general, the values of the Week 0 visit (= day of randomization = first day of week 1) 
or the values of the screening visit (= day within 3 weeks before their randomization visit) 
will be used as baseline values, as applicable. If data for the same variable are available 
from both (i.e., screening and Week 0) visits then the result of the Week 0 visit will be 
used as baseline value, i.e., for each variable the baseline measurement is defined as the 
closest measurement taken prior to or at the Week 0 visit. 
Definition of Post-baseline Points in Time of Interest 
The primary point in time for efficacy assessment will be the Week 24 visit (= end of 
treatment visit 24 weeks after randomization). Secondary points in time for efficacy 
assessment will be the study visits scheduled at Week 4 and Week 16 during the 
treatment phase. Handling of missing values is described in SAP section 13.1.6. 
The safety analysis will cover the time period until Week 24.  
13.1.2 
Definition of Within- and Between-Group Treatment 
Differences 
Within-group treatment differences will be computed as differences of the post-baseline 
visits as compared to the baseline visit, if applicable: 
• 
post-baseline visit minus baseline visit 
 
The following between-group treatment difference to assess the treatment effect will be 
computed, if applicable: 
• 
guselkumab minus FAE 
 
13.1.3 
Visit Windows 
Nominal visits (i.e., visits as recorded in the eCRF) will be used for all by-visit analyses in 
the study. The study visits scheduled post randomization should occur at the times 
delineated in the Time and Events Schedule. No visit windows will be defined and used for 
analysis. 
 
 
 
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13.1.4 
Treatment Failure Criteria 
Subjects who discontinue study treatment due to lack of efficacy or an AE of worsening of 
psoriasis, or who started a protocol-prohibited medication/therapy during the study that 
could improve psoriasis are considered treatment failures. 
By time period the particular protocol-prohibited medications/therapies include: 
Topical Therapy  
Topical therapies that could affect psoriasis (e.g., corticosteroids, tar, anthralin, 
calcipotriene, 
topical 
vitamin 
D 
derivatives, 
retinoids, 
tazarotene, 
methoxsalen, 
pimecrolimus, tacrolimus, and traditional Taiwanese, Korean, or Chinese medicines) are 
not permitted until Week 24. 
(The only allowable concomitant treatments for psoriasis throughout the study are 
shampoos (containing tar or salicylic acid only) and topical moisturizers. (Subjects should 
not use the topical agents on the day of a study visit; non-medicated shampoos may be 
used.))  
Phototherapy 
Phototherapy including, but not limited to PUVA, narrow-band UVB, balneophototherapy is 
not permitted until Week 24. 
Systemic Therapy for Psoriasis  
Systemic Therapy for Psoriasis is not permitted until the Week 24 visit.  
These medications include those targeted for reducing TNF (including but not limited to 
infliximab, adalimumab or etanercept), drugs targeted for reducing IL-12, IL-17, or IL-23 
(including but not limited to ustekinumab, tildrakizumab [MK3222], secukinumab 
[AIN457], ixekizumab [LY2439821], or brodalumab [AMG827]), alpha-4 integrin 
antagonists (including but not limited to natalizumab), steroids, any conventional systemic 
therapy that could affect psoriasis (including but not limited to MTX, cyclosporine, 
acitretin), herbal treatments, or traditional Taiwanese, Korean, or Chinese medicines, and 
any other biological agent or other systemic medication that could affect psoriasis. 
 
13.1.5 
Treatment Failure Rules 
No treatment failure rules will be applied.  
 
 
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13.1.6 
Handling of Missing Values 
All available data will be included in the analyses and will be summarized descriptively as 
far as possible. If not otherwise specified, there will be no substitution of missing data, 
i.e., missing data will not be replaced, missing data will be handled as ‘missing’ in the 
statistical evaluation (‘observed cases analysis’). 
Missing data for the efficacy endpoints at key visits Week 4, 16, and 24 will be handled as 
follows for all inferential statistical analyses (confirmatory or exploratory). 
Missing data imputation for the efficacy endpoints at Week 4, 16, and 24: 
• 
Nonresponder imputation will be applied for binary endpoints 
o 
i.e., subjects with missing data at Week 4/16/24 will be considered non-
responders at Week 4/16/ 24. 
• 
Last observation carried forward (LOCF) will be applied for continuous endpoints 
o 
i.e., in subjects with missing data at Week 4/16/24 the last available 
observation after baseline will be calculated and used for analysis for 
continuous response variables at Week 4/16/24. 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. 
Sensitivity analyses with respect to the handling of missing values at Week 24 are 
described in SAP section 13.9. 
13.1.7 
Data Transformations 
No data transformations (e.g. square root, logarithmic) to confirm basic statistical 
assumptions will be performed. All variables will be used in the analysis as reported. 
 
13.2 
Descriptive Statistics 
 
13.2.1 
Dichotomous and Categorical Variables 
Categorical data will be presented in frequency tables using counts and percentages. 
Percentages will be based on the total number of subjects in the respective analysis set 
(i.e., missing values will be included in percentage calculation). Besides presentation of 
absolute values cross tabulation vs. baseline by study visit will be provided, if appropriate. 
 
13.2.2 
Continuous and Quasi-Continuous Variables 
Standard descriptive summary statistics will be calculated for continuous and quasi-
continuous variables: arithmetic mean, standard deviation, minimum value, lower quartile, 
median, upper quartile, maximum value, number of non-missing values. Besides 
presentation of absolute values tabulation for differences to baseline by study visit will be 
provided, if appropriate. 
 
 
 
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13.2.3 
Graphical Presentations 
Graphical presentation of pertinent data will be given by means of box plots, bar charts, 
and survival graphs, as appropriate. Additional forms of graphical presentations may be 
specified. Descriptions of graphical presentations are included in the appendix of this 
document. 
 
13.3 
Confirmatory Statistics 
The statistical analyses will be confirmatory for the primary endpoint and the major 
secondary endpoints. 
13.3.1 
Statistical Hypotheses 
The primary hypothesis of this study is that guselkumab treatment is superior to FAE 
(Fumaderm® initial/ Fumaderm®) treatment as assessed by the proportion of subjects 
achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are:  
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a PASI 75 response at Week 24. 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a DLQI score of 0 or 1 at Week 24. 
 
13.3.2 
Estimation, Confidence Intervals and Hypotheses Testing 
In order to control the overall experiment wise type 1 error rate, the primary endpoint and 
the two major secondary endpoints will be tested in a fixed sequence as a-priori ordered 
hypotheses. That is, the first major secondary endpoint will be tested only if the primary 
endpoint is positive (i.e., p <0.05), and the second major secondary endpoint will be 
tested only if the first major secondary endpoint is positive (i.e., p <0.05). 
A two-sided (α = 0.05) chi-square test will be used for the confirmatory comparisons. In 
addition, two-sided 95% confidence intervals will be calculated for the response rates at 
Week 24 per treatment arm and for the difference between the two arms. 
13.3.3 
Significance Level 
All statistical testing will be performed two-sided. The confirmatory significance level is 
fixed to a type 1 error rate alpha of 5% (two-sided). 
Due to the testing of ordered hypotheses, no adjustment of the significance level with 
respect to the threefold test procedure is required. 
 
 
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13.4 
Exploratory Statistics 
Exploratory statistical analyses will be performed for the primary endpoint, the major 
secondary endpoints and the other secondary endpoints at Week 24, and at Week 4 and 
Week 16. All statistical tests and confidence intervals will be calculated two-sided and are 
to be interpreted in the exploratory sense only. 
13.4.1 
Binary Endpoints 
For binary endpoints counts and percentage of subjects per treatment group along with 
odds ratio (OR), relative risk (RR) and risk difference (RD), 95% confidence intervals 
(95% CIs) and p-values for treatment effect using the chi-square test will be provided. 
Time-to-event analyses will be performed for binary endpoints PASI 75/90/100 response, 
DLQI 0/1 response, onset of any TEAE, serious TEAE, and treatment discontinuation due 
to TEAE using Kaplan-Meier product limit method and Cox proportional hazards model. 
Summary tables will provide counts and percentage of subjects per treatment 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 factor treatment group). 
The survival curves will also be displayed graphically. Time-to-event analyses of binary 
endpoints will be performed on the observed cases only (i.e., missing data will not be 
replaced for time-to-event analyses). 
A logistic regression model will be used for subgroup analyses of selected binary endpoints 
(i.e., PASI 75/90/100 response, DLQI 0/1 response, onset of any TEAE, serious TEAE, and 
treatment discontinuation due to TEAE) at Week 24 with factors for treatment group, the 
respective subgroup and the interaction term between treatment and subgroup. Only the 
p-value of the interaction term will be provided from these analyses. 
13.4.2 
Continuous Endpoints 
The change from baseline of continuous endpoints will be analyzed by an analysis of 
covariance model (ANCOVA) with the fixed effect factor for treatment group 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 95% CI and two-sided p-value will be provided from the ANCOVA model. For subgroup 
analyses of continuous endpoints the ANCOVA model will be extended by the respective 
subgroup and the interaction term between treatment and subgroup. 
 
13.5 
Adjustment for Covariates 
The baseline value will be used as covariate in the analysis of variance model (ANCOVA) 
for the change from baseline of continuous response parameters. 
13.6 
Interim Analyses 
No confirmatory interim analysis is planned to be performed.  
 
 
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13.7 
Multi-center Data 
Exploration of possible heterogeneity of treatment effects across centers for the primary 
efficacy endpoint (i.e., the proportion of subjects achieving a PASI 90 response at Week 
24) using nonresponder imputation 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. 
13.8 
 Subgroup Analyses 
The following subgroup analyses at Week 24 are planned to be performed to evaluate 
consistency over demographics and baseline disease characteristics of the primary 
endpoint, all secondary efficacy endpoints and as well of the following safety endpoints: 
onset of any TEAE, serious TEAE, treatment discontinuation due to TEAE. 
• 
Gender 
o 
male 
o 
female 
• 
Age at baseline in years 
o 
< 45 
o 
≥ 45 - < 65  
o 
≥ 65 
• 
PASI 
o 
< 20 
o 
≥ 20 
The subgroup analyses will also include time-to-event analyses for the binary endpoints 
PASI 75/90/100 response, DLQI 0/1 response, onset of any TEAE, serious TEAE, and 
treatment discontinuation due to TEAE. 
Subgroup analyses for the primary endpoint and all secondary efficacy endpoints will be 
performed using the following different imputation rules of missing values at Week 24 (see 
SAP sections 13.1.6 and 13.9): 
• 
Binary endpoint: 
o 
Nonresponder imputation 
o 
LOCF (only PASI 75/90 response, and DLQI 0/1 response) 
o 
Multiple imputation 
• 
Continuous endpoint: 
o 
Multiple Imputation 
Subgroup analyses will NOT be performed for the per-protocol analysis set. 
 
 
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13.9 
Sensitivity Analyses 
The following sensitivity analyses at Week 24 with respect to the handling of missing 
values are planned to be performed: 
• 
Multiple imputation will be used for all binary and continuous endpoints. 
o 
For the multiple imputation, the repeated nature of the analysis is restricted 
to the imputation step (procedure "MI" in SAS). Basic premise is the 
creation of several datasets in which missing data is imputed in a random 
fashion and then analyses are performed to check for changes for the 
conclusion. The analysis will be done with SAS Proc MIANALYZE. 
• 
LOCF imputation will be used for all binary endpoints (see SAP section 13.1.6). 
• 
An 'observed cases analysis' for all binary and continuous endpoints without 
substitution of missing data will be used (see SAP section 13.1.6). 
Sensitivity analyses at Week 24 with respect to the handling of missing values will be 
performed for all binary and all continuous efficacy endpoints. 
Sensitivity analyses at Week 24 with respect to the handling of missing values will NOT be 
performed for the per-protocol analysis set. 
 
 
 
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14.0 Statistical Analyses 
A table of contents of planned data displays is provided in section 18.1 of this document. 
The following sections are intended to provide more details of the planned analyses. In 
addition, mock tables will be created and will be used as template for statistical 
programming. 
Data will be appropriately summarized and analyzed using tabulation and graphs with 
respect to demographic/baseline characteristics and efficacy/safety observations and 
measurements. Standard descriptive summary statistics (i.e., n, arithmetic mean, 
standard deviation, median, minimum/maximum value, quartiles) will be calculated for 
continuous variables. Categorical data will be presented in frequency tables using counts 
and percentages. In general, summary tables will be displayed by treatment group as the 
main classification variable and for the total of the sample in the respective analysis set. 
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, center, subject number and study visit, if applicable. 
14.1 Study Subjects 
Unless otherwise specified, data on study subjects will be analyzed based on data from all 
subjects randomized at Week 0 ('efficacy analysis set').  
14.1.1 
Disposition of Subjects 
The overview of subject disposition will provide the respective frequency counts and 
percentages regarding the following subjects: 
• 
Treatment phase until Week 24 
o 
Subjects who were enrolled (i.e., signed informed consent) 
o 
Subjects who were randomized 
o 
Subjects who were treated 
o 
Subjects with premature discontinuation of study treatment 
o 
Subjects who completed the treatment phase 
The table will also include the total number of study sites and the dates of the enrolment 
of the first subject and the last visit of the last subject. Moreover, the overview of subject 
disposition will be broken down by center. A flow diagram (according to the CONSORT 
statement) giving an overview of subject disposition will also be provided. 
In addition, the number and percentage of randomized subjects continuing and attending 
by study visit will be displayed in a separate table. Subjects will be counted as continuing 
at the time of visit whether they attend the visit or not. Only those subjects that 
prematurely discontinued before the visit will not be counted as attending.  
 
 
 
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14.1.2 
Discontinuation of Study Treatment 
The number and percentage of randomized subjects who discontinued study treatment 
prematurely within the 24 Weeks treatment period of the study will be tabulated for each 
reason of premature discontinuation (including tabulation of specifications for category 
‘other’). Moreover, the number of subjects enrolled but not randomized (i.e., screening 
failures) and the reasons for not being randomized will be given. 
14.1.3 
Protocol Deviations 
In general, the following list of major protocol deviations may have the potential to impact 
subjects’ rights, safety or well-being, or the integrity and/or result of the clinical trial. 
Subjects with major protocol deviations will be summarized by category for all randomized 
subjects. 
• 
Developed withdrawal criteria but not withdrawn 
• 
Entered but did not satisfy criteria 
• 
Received a disallowed concomitant treatment 
• 
Received wrong treatment or incorrect dose 
• 
Other 
The summary table will provide the number of subjects per major protocol deviation and 
will also provide the number of major protocol deviations. 
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.  
 
14.1.4 
Analysis Sets 
The number and percentage of randomized subjects included in each analysis set, 
together with a breakdown of the reasons for exclusion for non-evaluable subjects, will be 
provided. 
 
 
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14.2  Demographic and Other Baseline Characteristics 
Generally, assessments made at the screening visit and the baseline visit will be 
summarized by treatment group and overall. These assessments will include demographic 
characteristics and other parameters (such as medical history, previous psoriasis therapy 
by type (phototherapy and topical therapy)) substance use alcohol/tobacco, previous and 
concomitant diseases, prior and concomitant medication, physical examination). By-
treatment summaries will serve to identify any imbalances between the treatment groups 
at baseline. Summary tables will be provided by means of descriptive statistics and 
frequency tables, where appropriate. Demographic and other baseline characteristics will 
be analyzed based on data from all subjects randomized at Week 0 ('efficacy analysis set') 
and on all treated subjects ('safety analysis set'). No analyses for baseline balance using 
statistical hypothesis tests or confidence intervals will be done. 
14.2.1 
Demographics 
Age (categorized), gender, and race will be presented in a frequency table. Age group 
categories will be chosen as < 45; ≥ 45 - < 65; ≥ 65years. Descriptive summary statistics 
will be calculated for age, body height, body weight and body mass index (BMI).  
Tables for demographic data will also be stratified by gender. Age and gender distribution 
will be presented in a bar chart. 
Note: Age is documented as 'age at date of informed consent signature' at the screening visit. Body 
height and body weight data will be taken from the vital signs eCRF form at the Week 0 visit. BMI 
will be calculated as body weight in kg / body height in m². 
 
14.2.2 
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 terminology as described in SAP section 14.6. 
Summary tabulation will also consider whether the disease is ongoing or not at screening 
visit. 
 
14.2.3 
Diagnosis of Psoriasis 
The time from date of initial diagnosis of psoriasis to date of screening visit will be 
calculated and will be displayed by descriptive statistics. If the day is unknown the day will 
be set to day = 1. If the month is unknown the month will be set to month = July. 
In addition, the disease characteristics will be summarized by providing the following 
relevant results: descriptive summary statistics of the PASI and the DLQI index at 
baseline, frequency distribution of the IGA categories and the PASI < 20 and PASI ≥ 20 
subgroups at baseline. 
14.2.4 
Previous Psoriasis Therapy 
Categorical data on previous psoriasis therapy (including data on previous phototherapy 
and previous topical therapy) will be displayed in frequency tables providing the number 
and percentage of subjects per category. Summary tabulation of data on previous 
phototherapy will consider the type of phototherapy. The number and percentage of 
subjects with use of other previous topical psoriasis therapy will be displayed in WHO-DD 
terminology as described in SAP section 14.7.  
 
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14.2.5 
Substance Use  
Categorical data on substance use (alcohol or tobacco) will be displayed in a frequency 
table providing the number and percentage of subjects per category. Summary tabulation 
will also consider whether the substance usage is current or former. 
 
14.2.6 
Physical Examination 
Abnormal findings in physical examination (additional to psoriasis findings) at screening 
and baseline visit 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. 
14.2.7 
Tuberculosis Evaluation 
Categorical data on tuberculosis evaluation at screening and baseline visit will be displayed 
in a frequency table providing the number and percentage of subjects per category. 
14.2.8 
Chest Radiograph Result 
Categorical data on chest radiograph result at screening visit will be displayed in a 
frequency table providing the number and percentage of subjects per category. Details on 
findings in verbatim terms will be displayed in individual data listings. 
 
14.2.9 
Concomitant Medication and Therapy 
Analyses of concomitant medication and therapy will only consider the data recorded 
within the 24 Weeks treatment period of the study. In case of early treatment 
discontinuation before Week 24 concomitant medication and therapy with a start date at 
or after the discontinuation date will not be considered. 
Concomitant Medication 
The number and percentage of subjects with use of concomitant medication will be 
displayed in WHO-DD terminology as described in SAP section 14.7. Concomitant 
medication will be identified from the Concomitant Medication form of the eCRF. 
The number and percentage of subjects with indication for concomitant medication will be 
displayed in MedDRA terminology as described in SAP section 14.6. 
Concomitant Therapy 
The number and percentage of subjects with use of concomitant therapy will be displayed 
in MedDRA terminology as described in SAP section 14.6. Concomitant therapy will be 
identified from the Concomitant Therapy form of the eCRF. 
The number and percentage of subjects with indication for concomitant therapy will be 
displayed in MedDRA terminology as described in SAP section 14.6. 
 
14.2.10 
Shampoo and Moisturizer 
The number and percentage of subjects with use of shampoo or moisturizer will be 
displayed in a frequency table. 
 
 
 
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14.3  Treatment Compliance 
Treatment compliance will be analyzed based on data from all subjects randomized at 
Week 0 ('efficacy analysis set') and on all treated subjects ('safety analysis set'). 
14.3.1 
Visit Windows 
The number of days between the scheduled study visits and the baseline visit will be 
calculated using the reported visit dates per scheduled study visit and will be displayed by 
summary descriptive statistics. 
 
14.3.2 
Study Medication 
Categorical data on guselkumab administration recorded at Week 0, 4, 12, 20 will be 
summarized by frequency tabulation providing the number and percentage of subjects per 
category. Frequency tabulation and descriptive statistics will be presented for the overall 
number of guselkumab administrations. 
Compliance to guselkumab administration will be calculated as follows based on the eCRF 
data: 
• 
Compliance guselkumab in % = (number of actual administrations x 100 / number 
of planned adminstrations)  
Categorical data on Fumaderm® initial/ Fumaderm® administration during initial uptitration 
and/or maintenance period (including data on reasons for end of uptitration and reasons 
for dose selection) recorded at each week until Week 24 will be summarized by frequency 
tabulation providing the number and percentage of subjects per category. The number of 
planned tablets to be taken in the morning, at noon, and in the evening will also be 
summed up and analyzed descriptively. 
The number of dispensed and returned tablets of Fumaderm® initial/ Fumaderm® 
(including the difference of dispensed - returned tablets = actual tablets) will be displayed 
by descriptive summary statistics. 
Compliance to Fumaderm® initial and Fumaderm® administration will be calculated as 
follows based on the eCRF data: 
• 
Compliance FAE in % = (number of actual tablets x 100 / total number of tablets 
supposed to be taken)  
Treatment compliance will also be assessed by protocol deviations related to study drug 
administration (i.e., incorrect study drug received and missed administrations).  
For subjects who completed the Week 24 visit the dose of Fumaderm® in mg at Week 24 
will be summarized by descriptive statistics and frequency tabulation. In addition, the 
maximum dose of Fumaderm® initial and Fumaderm® in mg will be calculated for all 
subjects and will be summarized by descriptive statistics and frequency tabulation. 
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14.4  Analysis of Efficacy 
All efficacy analyses to compare guselkumab vs. FAE will be performed for all subjects 
randomized at Week 0 ('efficacy analysis set'). Additionally, all efficacy analysis will be 
performed for all treated subjects ('safety analysis set'). The primary and the major 
secondary endpoints will also be analyzed using the per-protocol analysis set. However, 
subgroup and sensitivity analyses at Week 24 will NOT be performed for the per-protocol 
analysis set. 
All statistical tests will be performed two-sided. In order to control the overall experiment 
wise type 1 error rate, the primary endpoint and the two major secondary endpoints will 
be tested in a fixed sequence as a-priori ordered hypotheses. That is, the first major 
secondary endpoint will be tested only if the primary endpoint is positive (i.e., p <0.05), 
and the second major secondary endpoint will be tested only if the first major secondary 
endpoint is positive (i.e., p <0.05). 
Handling of missing values, exploratory statistics, subgroup analyses, and sensitivity 
analyses will be performed as described in detail in the following sections of this SAP: 
SAP Section No. 
Topic 
13.1.6 
Handling of missing values 
13.4.1 
Exploratory statistics - binary endpoints 
13.4.2 
Exploratory statistics - continuous endpoints 
13.8 
Subgroup analyses 
13.9 
Sensitivity analyses 
Data at the scheduled points Week 4 and Week 16 during the active treatment period will 
be analyzed analogously to the Week 24 data. However, no subgroup or sensitivity 
analyses will be performed for these points in time. 
 
 
 
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14.4.1 
Primary Endpoint 
The proportion of subjects achieving at least a 90% improvement of their psoriasis 
according to the Psoriasis Area and Severity Index (PASI 90 response) at Week 24 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 address the primary objective, a two-sided (α = 0.05) chi-square test will be used for 
the primary confirmatory comparison. In addition, two-sided 95% confidence intervals will 
be calculated for the PASI 90 response rate at Week 24 per treatment arm and for the 
difference between the two arms. 
Exploratory statistical analyses (also including analyses of time to PASI 90 response) will 
be performed as described in SAP section 13.4.1. 
 
14.4.2 
Major Secondary Endpoints 
14.4.2.1 
Endpoint related to PASI 
The proportion of subjects achieving at least a 75% improvement of their psoriasis 
according to the PASI at Week 24 (PASI 75 response) 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. 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 24 per treatment arm and for the difference between the two arms. 
Exploratory statistical analyses (also including analyses of time to PASI 75 response) will 
be performed as described in SAP section 13.4.1. 
 
14.4.2.2 
Endpoint related to DLQI 
The proportion of subjects achieving a DLQI score of 0 or 1 at Week 24 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. 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 24 per treatment arm and for the difference between the two arms. 
Exploratory statistical analyses (also including analyses of time to DLQI 0/1 response) will 
be performed as described in SAP section 13.4.1. 
 
 
 
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14.4.3 
Other Secondary Endpoints 
14.4.3.1 
Endpoints related to PASI 
Other secondary endpoints related to PASI are: 
• The proportion of subjects achieving a 100% improvement of their psoriasis according 
to the PASI at Week 24 (PASI 100 response) 
• The proportion of subjects achieving an absolute PASI score ≤1 at Week 24 
The proportion of responding 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. 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 24 per treatment arm and for the difference between the two arms. 
Additional exploratory statistical analyses (also including analyses of time to PASI 100 
response) will be performed as described in SAP section 13.4.1. 
 
14.4.3.2 
Endpoints related to PSSD 
Other secondary endpoints related to PSSD are: 
• The change from baseline in the signs and symptoms aggregate scores of the PSSD at 
Week 24 
• The change from baseline in the individual scale scores for itch, pain, and scaling of 
PSSD components at Week 24 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 24 value and the change from the 
baseline value will be displayed. 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2). 
In addition, the other individual scale scores will be analyzed analogously. 
 
 
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14.4.3.3 
Endpoints related to IGA 
Other secondary endpoints related to IGA are: 
• The proportion of subjects achieving an IGA score of cleared (0) at Week 24 
The proportion of responding 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.  
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 24 per treatment arm and for the difference between the two arms. 
Additional exploratory statistical analyses will be performed as described in SAP section 
13.4.1. 
 
14.4.3.4 
Endpoints related to BSA 
Other secondary endpoints related to BSA are: 
• The change from baseline of body surface area (BSA) psoriatic involvement at Week 24  
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 24 value and the change from the 
baseline value will be displayed. 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2).  
14.4.3.5 
Endpoints related to DLQI 
Other secondary endpoints related to DLQI are: 
• The change from baseline in DLQI score at Week 24 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 24 value and the change from the 
baseline value will be displayed. 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2). 
 
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14.4.3.6 
Endpoints related to ss-IGA 
Other secondary endpoints related to ss-IGA are: 
• The proportion of subjects achieving an ss-IGA score of absence of disease (0) at Week 
24 in randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at baseline 
The proportion of responding 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. 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for response rate at 
Week 24 per treatment arm and for the difference between the two arms. 
Additional exploratory statistical analyses will be performed as described in SAP section 
13.4.1. 
 
14.4.3.7 
Endpoints related to SF-36 
Other secondary endpoints related to SF-36 are: 
• The change from baseline in the physical and mental component summary scores of 
SF-36 at Week 24 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 24 value and the change from the 
baseline value will displayed. 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2). 
 
14.4.4 
Other Efficacy Assessments 
In addition to the efficacy analyses described above all efficacy data related to PASI, DLQI, 
PSSD, IGA, ss-IGA, and SF-36 at all scheduled study visits during the active treatment 
period until Week 24 will be summarized descriptively without any imputation of missing 
data (‘observed cases analysis’; see SAP section 13.1.6). 
 
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14.5  Analysis of Safety 
Safety data, including but not limited to, adverse events (AEs), serious adverse events 
(SAEs), infections, serious infections, mortality, changes in laboratory assessments, and 
changes in vital signs will be summarized using descriptive statistics. All safety analyses to 
compare guselkumab vs. FAE will be performed for all treated subjects ('safety analysis 
set'). 
 
14.5.1 
Extent of Exposure  
Extent of exposure will be defined as the total number of days from baseline to Week 24 
(for all patients still under treatment) or to study discontinuation. 
Descriptive summary statistics and frequency tables (using appropriate categories) will be 
provided for the extent of exposure.  
 
14.5.2 
Adverse Events 
Adverse events data will be processed in the statistical analysis after coding according to 
the MedDRA dictionary version 19.1. All reported AEs with onset date during the active 
treatment period until Week 24 (i.e., treatment emergent AEs) will be included in the 
analysis. In case of early treatment discontinuation before Week 24 all reported AEs with 
onset date during the safety follow-up period until Week 24 (i.e., treatment emergent 
AEs) will be included in the analysis. AEs reported after Week 24 will NOT be considered in 
the analysis. 
 
14.5.2.1 
Definitions 
The following definitions will be applied in the present study 
Crude Incidence Rate 
Where percentages of subjects are reported in summary tables, incidences provide 
information on the proportion of subjects experiencing adverse events in relation to the 
total number of subjects exposed, i.e., if not otherwise specified, the crude incidence rate 
will be used.  
The crude incidence rate is defined as the number of subjects experiencing a certain 
event, divided by the number of subjects exposed to study treatment, regardless of 
duration of use: 
 
exposed
 
patients
 
of
number 
events
 
adverse
 with 
patients
 
of
number 
 *
100
 
rate
 
incidence
 
Crude
=
 
 
Treatment Emergent Adverse Events 
Treatment emergent adverse events (TEAEs) are those AEs that occurred during the 
active treatment period until Week 24 after the start of initial study drug administration 
and those AEs that were present at baseline but worsened in severity after the start of 
initial study drug administration. AEs reported after Week 24 will NOT be considered in the 
analysis. 
In case of early treatment discontinuation before Week 24 all reported AEs with onset date 
during the safety follow-up period until Week 24 will be included in the analyses. Thus, 
identification of TEAEs (distinguished by subjects who completed or discontinued the 
treatment period until Week 24) will be performed as follows: 
 
 
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• 
TEAE for Completer: Date of Week 0 < Start Date of AE < Date of Week 24 
• 
TEAE for Non-Completer: Date of Week 0 < Start Date of AE < Date of Week 0 + 
168 Days 
AEs which are not classified as TEAEs will be considered as not treatment emergent 
adverse events (NTEAEs). 
 
14.5.2.2 
Analyses 
Overview of adverse events 
For summary presentation of the overall adverse event experience overview tables will be 
provided for AEs and SAEs including the following information: 
Adverse events: 
• 
n (%) of subjects with AEs *) 
• 
n (%) of subjects with NTEAEs *) 
• 
n (%) of subjects with TEAEs *) 
• 
n (%) of subjects with TEAEs by highest causality to study medication 
• 
n (%) of subjects with TEAEs by worst severity 
• 
n (%) of subjects with TEAEs leading to dose modification *) 
• 
n (%) of subjects with TEAEs leading to permanent stop of study medication *) 
Serious Adverse events: 
• 
n (%) of subjects with SAEs *) 
• 
n (%) of subjects with NTESAEs *) 
• 
n (%) of subjects with TESAEs *) 
• 
n (%) of subjects with TESAEs leading to death *) 
• 
n (%) of subjects with TESAEs by highest causality to study medication 
• 
n (%) of subjects with TESAEs by worst severity 
• 
n (%) of subjects with TESAEs leading to permanent stop of study medication *) 
*) the number of events (i.e., number of coded preferred terms) will also be given. 
TEAEs/TESAEs leading to dose modification will be defined as all events with 'Action taken 
with study treatment' is not equal to 'DOSE NOT CHANGED'. 
In addition, the number of TEAEs will be displayed for the following investigator’s ratings: 
• 
severity  
• 
seriousness 
• 
causality 
• 
action taken 
• 
outcome 
 
 
 
 
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Detailed display of adverse events 
For a more detailed display, adverse events will be presented in summary tables, listing 
these events in code form according to the preferred term. These tables will show the 
number of subjects per group presenting an adverse event and the incidence of its 
occurrence. Adverse events will be grouped by primary SOC (System Organ Class) and will 
be stratified additionally by highest causality to study treatment (not related, doubtful, 
possible, probable, or very likely) and by worst severity (mild, moderate, or severe). The 
incidence of adverse events will be presented by decreasing order of frequency at 
preferred term level within the primary SOC. 
The following tables will be provided for the detailed display of adverse events: 
Adverse events: 
• 
TEAEs by primary SOC and preferred term *) 
• 
TEAEs by primary SOC and preferred term stratified by highest causality 
• 
TEAEs by primary SOC and preferred term stratified by worst severity 
 thereof 
o 
Drug related TEAEs 
o 
Not drug related TEAEs 
• 
TEAEs leading to permanent stop of study medication by primary SOC and 
preferred term *) 
Serious Adverse events: 
• 
TESAEs by primary SOC and preferred term *) 
• 
TESAEs by primary SOC and preferred term stratified by highest causality 
• 
TESAEs by primary SOC and preferred term stratified by worst severity 
• 
TESAEs leading to permanent stop of study medication by primary SOC and 
preferred term *) 
• 
TESAEs leading to death by primary SOC and preferred term *) 
Not treatment emergent adverse events: 
• 
NTEAEs by primary SOC and preferred term *) 
*) These tables will show additionally the number of events (i.e., number of coded preferred terms). 
Summary tabulation of TEAEs and TESAEs by primary SOC and preferred term will also be 
provided for the following types of adverse events: 
• 
injection site reactions (according to the tick box in the e-CRF) 
• 
infections (according to the tick box in the e-CRF) 
o 
thereof, infections treated with oral or parenteral antibiotics 
• 
adverse events of psoriasis (adverse events of psoriasis include any event of 
erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, inverse psoriasis, 
palmo-plantar psoriasis and worsening or exacerbation of psoriasis; final allocation 
will be performed after blinded data review). 
Note that the summary tables will provide the number of subjects per event (i.e., coded as 
preferred term) and will also provide the number of events for certain tables. 
 
 
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For calculation of the number of subjects per event each preferred term will be counted 
only once per subject and will be linked to the primary SOC. A subject may contribute with 
more than one different adverse event (at preferred term level); however, a subject with 
more than one occurrence of the same adverse event (at preferred term level) is displayed 
and counted only once for this event in the tables. 
Tables that are stratified by the severity of adverse events will summarize the worst 
severity per subject and preferred term.  
Tables that are stratified by the relationship of adverse events will summarize the highest 
relationship per subject and preferred term. 
For presentation of drug related/ not drug related adverse events the following categories 
will be used: 
• 
drug related   
=  
very likely, probable, possible 
• 
not drug related  
=  
doubtful, not related 
For summarization of severity of drug related TEAEs, events with a causality assessment 
of 'doubtful/not related' will be excluded and the worst severity will be tabulated as 
described above. Summarization of severity of not drug related TEAEs will be performed 
likewise. 
 
The following safety endpoints will be defined and used for the statistical analyses for HTA 
purposes:  
• The proportion of subjects with any TEAE within the 24 Weeks treatment period 
• The proportion of subjects with serious TEAE within the 24 Weeks treatment period 
• The proportion of subjects with treatment discontinuation due to TEAE within the 24 
Weeks treatment period 
• The proportion of subjects with any TEAE by preferred term and SOC within the 24 
Weeks treatment period  
Counts and percentage of subjects per treatment group along with odds ratio (OR), 
relative risk (RR) and risk difference (RD), 95% confidence intervals (95% CIs) and p-
values for treatment effect using the chi-square test will be provided. In addition, time-to-
event-analyses and logistic regression analyses as described in SAP section 13.4.1 will be 
conducted for the onset of any TEAE, serious TEAE, and treatment discontinuation due to 
TEAE. 
Subgroup analyses will be performed for the subgroups defined in SAP section 13.8 for the 
proportion of subjects with any TEAE, serious TEAE, and treatment discontinuation due to 
TEAE. 
The cut-off ≥ 5% (i.e., percentage of subjects ≥ X% in at least one treatment group) will 
be used for analyses of TEAEs by preferred term for any TEAE. 
 
 
 
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Listings 
All adverse events (AEs) and serious adverse events (SAEs) will be listed in the individual 
subject data listings by treatment group, study center and subject number including all 
information documented on the respective form of the eCRF. Separate listings of subjects 
with the following AEs will be provided: SAEs, SAEs leading to death, AEs of severe 
intensity, AEs leading to permanent discontinuation of study medication. 
Verbatim description of the adverse event reported by the investigator, MedDRA preferred 
terms and primary SOCs (system organ class) for all adverse events will be contained in 
the data listings. Non treatment emergent adverse events will be flagged in the respective 
listings. 
 
14.5.3 
Clinical Laboratory Tests 
Laboratory data will be summarized by type of laboratory test. Reference ranges will be 
used in the summary of laboratory data. Descriptive statistics will be calculated for each 
laboratory item at each scheduled time. Changes from baseline results will be presented in 
pre- versus post-treatment cross-tabulations (with classes for below, within, and above 
normal ranges).  
Results of tuberculosis testing, serology, urine pregnancy testing and local urinalysis 
(glucose, protein) will be displayed in frequency tables providing the number and 
percentage of subjects per category (i.e., negative or positive) at each scheduled time. 
The results of all laboratory tests will be provided in individual subject data listings 
including the reference ranges. Abnormal values will be identified by flagging all values 
below and above the reference range. 
A listing of subjects with any laboratory results outside the reference ranges will be 
provided.  
For the lymphocyte count the following subjects will be listed and summarized in a 
frequency table:  
• 
lowest lymphocyte count  < 500/µl 
• 
500/µl ≤ lowest lymphocyte count <700/µl  
• 
700/µl ≤ lowest lymphocyte count < lower limit of normal range 
Graphical presentation of quantitative laboratory data will be given by means of box plots. 
 
 
 
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14.5.4 
Vital Signs 
Descriptive statistics of pulse and blood pressure (systolic and diastolic) values and 
changes from baseline will be summarized at each scheduled time. Subjects reporting vital 
signs findings beyond clinically important limits will be identified using the following 
criteria.  
Criteria for Identifying Potentially Clinically Significant Vital Signs Findings 
Variable (units) 
Criterion Valuea 
Change from Baseline 
Systolic Blood Pressure (mmHg) 
 
>200 
 
<80 
Increase of >40 
Decrease of >40 
Diastolic Blood Pressure (mmHg) 
 
>120 
 
<40 
Increase of >30 
Decrease of >30 
Heart Rate (bpm) 
 
>110 
 
<40 
 
a 
In order to be identified as an abnormality of potential clinical importance, a value would 
need to meet the criterion value or also represent a change of at least the magnitude noted in the 
change column. 
Vital signs values of potentially clinically significant importance will be analyzed by 
providing the number and percentages of subjects with values of potential clinical 
importance per scheduled study visit, overall during the study and with first occurrence 
after baseline. 
 
14.5.5 
Physical Examination 
Physical examination findings will be tabulated by the body systems given in the eCRF at 
each scheduled time. Moreover, abnormal findings with first occurrence after baseline 
reported during the treatment phase and follow-up phase will be presented. Details on 
abnormal findings in verbatim terms will be displayed in individual subject data listings. 
 
14.5.6 
Body Weight 
For body weight absolute values and changes from baseline values will be presented by 
descriptive statistics at each scheduled time. 
 
14.5.7 
Early Detection of Active Tuberculosis 
Categorical data on early detection of active tuberculosis will be presented in a frequency 
table providing the number and percentage of subjects per category at each scheduled 
time. 
 
 
 
 
 
 
 
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14.6 Analysis of MedDRA Codes 
Previous / concomitant diseases (including indications for use of concomitant and other 
medications) and adverse events will be coded with version 19.1 of the MedDRA-
dictionary. 
In general, tabulation will be displayed by preferred term and primary SOC. 
 
14.7 Analysis of WHO Drug Dictionary Codes 
The use of concomitant and other medications will be coded using the WHO Drug 
Dictionary (version 2016/1). Medications will be tabulated by preferred name (i.e., the 
decode of the code which results when SEQ1 and SEQ2 are set to 01 and 001, respectively 
(usually resulting in a decode close to the generic drug name)) and they will be grouped 
by level 2 of the Anatomical Therapeutic Chemical (ATC) code. Codes being linked to more 
than one ATC code at this level will be assigned to one primary ATC code by medical data 
analysts. 
15.0 Changes to Planned Analyses 
This statistical analysis plan includes the following relevant changes to the planned 
analyses which are described in the clinical study protocol. 
• 
Evaluations on health technology assessment (HTA) will also be specified in this 
SAP. No separate SAP for evaluations on health technology assessment will be 
provided (see SAP section 3.0 and CSP section 11) 
• 
A per-protocol analysis will be performed for the primary and the major secondary 
endpoints (see SAP section 11.0). 
• 
No treatment failure imputation rules will be applied (see to SAP section 13.1.5 and 
CSP section 11.4) 
• 
The following safety endpoints will be defined and used for the statistical analyses 
for HTA purposes:  
o 
The proportion of subjects with any TEAE within the 24 Weeks treatment 
period 
o 
The proportion of subjects with serious TEAE within the 24 Weeks treatment 
period 
o 
The proportion of subjects with treatment discontinuation due to TEAE 
within the 24 Weeks treatment period 
o 
The proportion of subjects with any TEAE, serious TEAE, treatment 
discontinuation due to TEAE by preferred term and SOC within the 24 
Weeks treatment period 
• 
Time-to-event analyses for binary endpoints PASI 75/90/100 response, DLQI 0/1 
response, onset of TEAE, serious TEAE, and treatment discontinuation due to TEAE 
will be performed using Kaplan-Meier product limit method and Cox proportional 
hazards model. 
Any major changes to this plan after sign-off of the latest final version will be specified in 
the clinical study report. 
 
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16.0 Tabulation 
 
16.1  General 
The statistical output will be prepared in American English. No separate statistical report 
will be written. 
 
16.2 Format of Data Displays 
The layout of all tables, listings and figures will be drafted by acromion GmbH when 
providing the first draft tables, listings and figures on final data. No sponsor or other 
requirements for layout specifications have to be followed. 
 
The SAS outputs will be post-processed within Microsoft Word®. SAS tables and listings 
will be integrated into Microsoft Word® using the SAS Monospace 8 points font. 
 
Separate appendices will be provided for tables, listings, and figures. For each appendix a 
corresponding table of contents will be generated. All pages within one appendix will be 
numbered consecutively. Tables, listings and figures generally should be self-explaining. 
Abbreviations will be described in the footnote if necessary. 
 
16.2.1 
Tables 
SAS summary tables will be produced using a landscape page. The maximum number of 
lines per page will be pagesize = 40 and the number of characters in one line will be 
linesize = 140.  
 
16.2.2 
Listings  
SAS subject data listings will be produced using a landscape page. The maximum number 
of lines per page will be pagesize = 40 and the number of characters in one line will be 
linesize = 140.  
 
Data listings will be created for groups of variables which logically belong together (e.g. 
demographic variables) and will be sorted by treatment group, center, subject and visit (if 
applicable). 
 
 
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16.2.3 
Figures  
Figures will be created using the following graphical SAS options, if not otherwise 
specified: 
 
 
GOPTIONS  
    RESET   = ALL  
    NOBORDER 
    KEYMAP = WINANSI  
    DEVMAP = WINANSI  
    DEV       = EMF 
    TARGET = WINPRTC  
    GUNIT   = CM  
    CTEXT   = BLACK  
    FTEXT   = 'Arial/bold'  
    HTEXT   = 0.5 CM  
    LFACTOR= 1  
    HSIZE   = 6 IN  
    VSIZE   = 5 IN; 
 
Variables may be presented in the following graphical formats, if applicable: 
 
Box plot 
Box plots summarize the data by a box reaching from the 1st to the 3rd quartile. The 
median is displayed inside this box by a horizontal line. Above the box a vertical line 
indicates the region from the 3rd quartile to the max. value below the upper fence ; below 
the box a vertical line indicates the region from the 1st  quartile to the min. value above 
the lower fence. The upper fence lies 1.5 interquartile-ranges above the 3rd quartile, the 
lower fence lies 1.5 interquartile ranges below the 1st quartile. Values outside the fences 
are displayed by a distinct marker. 
A graphical presentation is given below: 
 
 
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Bar chart 
A bar chart displays a categorical variable. A sample display is provided below. 
 
 
Survival Graph 
A survival graph displays the survival distribution functions according to Kaplan-Meier. A 
sample display is provided below. 
 
 
 
 
16.3  Data Format 
Unless otherwise specified, percentage values will be printed with one digit to the right of 
the decimal point. 
In general, minima and maxima will be quoted to the number of decimal places as 
recorded in the eCRF; means, standard deviations and medians will be quoted to one 
further decimal place. 
All p-values will be given by four digits to the right of the decimal point. Verbatim terms 
documented in the eCRFs will be presented as entered in the clinical data base. 
0
10
20
30
40
50
25
35
45
55
% 
AGE 
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17.0 References 
Study Documents: 
Document 
Version, Date 
Protocol / Amendments 
Version 1.0, 03-AUG-2016 
eCRF 
Version 1.0, 12-DEC-2016 
Data Management Plan 
Version 1.0, 09-DEC-2016 
Data Validation Plan 
Version 1.0, 09-DEC-2016 
SOPs and Guidelines acromion: 
Document 
Title, Date 
acromion SOP BM04 
Statistical Analysis Plans, Oct-2016 
acromion SOP BM05 
Determination of Availability of Data for Analysis, Oct-2016 
acromion SOP BM06 
Generation and Release of Blinded Randomization Code, Oct-
2016 
acromion SOP BM07 
Programming of Derived Data Sets, Oct-2016 
acromion SOP BM08  
Programming of SAS Data Displays, Oct-2016 
acromion SOP BM11  
Documentation and Project Close-Out, Oct-2016 
acromion Guideline 
BM01  
SAS Programming Guideline, Oct-2016 
acromion Guideline 
BM02  
Biometrics Naming Conventions for SAS Datasets and SAS 
Programs, Oct-2016 
Other Documents: 
Document 
Title, Date 
ICH Guideline E 9 
Statistical Principles for Clinical Trials, final approval 1998 
 
 
 
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18.0 Appendices 
 
18.1  Table of Contents for Data Displays 
The tables, subject data listings and figures will be provided using the following numbering 
system, which will be updated after start of programming the data displays. However, this 
section does not include the HTA analyses for the topline results described in SAP section 
14.6. The numbering system for the HTA analyses will be provided with the HTA mock 
tables. 
All summary tables will start with the one-character identifier for the displayed analysis 
set followed by the one-digit identifier for the displayed analysis chapter as listed below. 
Identifier for displayed analysis set: 
• 
A: Efficacy analysis set 
• 
B: Safety analysis set 
• 
C: Per-protocol analysis set 
 
Identifier for displayed analysis chapter: 
• 
1: Study subjects 
• 
2: Demographics and other baseline characteristics 
• 
3: Treatment compliance 
• 
4: Analysis of efficacy 
• 
5: Analysis of safety 
Data displays will be provided for the following analysis sets: 
 
Chapter 
No. 
Chapter Title 
Analysis set 
1 
Study subjects 
• A: efficacy analysis set 
2 
Demographic and other baseline 
characteristics 
• A: efficacy analysis set 
• B: safety analysis set 
3 
Treatment compliance 
• A: efficacy analysis set 
• B: safety analysis set 
4 
Analysis of efficacy 
• A: efficacy analysis set 
• B: safety analysis set 
• C: per-protocol analysis set 
5 
Analysis of safety 
• B: safety analysis set 
All individual subject data listings will start with the one-digit identifier for the displayed 
chapter analogously as for the summary tables. Data displays and subject data listings will 
be provided in separate appendices and pages will be numbered for each appendix 
separately starting with page no. 1. 
 
 
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18.1.1 
Tables 
Study Subjects, Prefix A 
No. 
Analysis Chapter 
1.1 
Disposition of subjects 
1.2 
Discontinuation of study treatment 
1.3 
Protocol deviations 
1.4 
Analysis sets 
 
Demographic and Other Baseline Characteristics, Prefix A, B 
No. 
Analysis Chapter 
2.1 
Demographics 
2.2 
Medical history 
2.3 
Diagnosis of Psoriasis 
2.4 
Previous Psoriasis Therapy 
2.5 
Substance Use 
2.6 
Physical Examination 
2.7 
Tuberculosis Evaluation 
2.8 
Chest Radiograph Result 
2.9 
Concomitant Medication and Therapy 
2.10 
Shampoo and Moisturizer 
 
Treatment Compliance, Prefix A, B 
No. 
Analysis Chapter 
3.1 
Visit windows 
3.2 
Study medication 
 
Analysis of Efficacy, Prefix A, B, C 
No. 
Analysis Chapter 
 
- Primary Endpoint - 
4.1 
PASI 90% Response 
 
- Major Secondary Endpoints - 
4.2.1 
Endpoint Related to PASI 
4.2.2 
Endpoint Related to DLQI 
 
- Other Secondary Endpoints - 
4.3.1 
Endpoints related to PASI 
4.3.2 
Endpoints related to PSSD 
4.3.3 
Endpoints related to IGA 
4.3.4 
Endpoints related to BSA 
4.3.5 
Endpoints related to DLQI 
4.3.6 
Endpoints related to ss-IGA 
4.3.7 
Endpoints related to SF-36 
 
- Other Efficacy Assessments - 
4.4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, BSA, ss-IGA, SF-36) 
 
Analysis of Safety, Prefix B 
No. 
Analysis Chapter 
5.1 
Extent of Exposure 
5.2 
Adverse Events  
5.3 
Clinical Laboratory Tests 
5.4 
Vital Signs 
5.5 
Physical Examination 
5.6  
Body Weight 
5.7 
Early Detection of Active Tuberculosis 
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18.1.2 
Listings 
Study Subjects  
No. 
Analysis Chapter 
1.1 
Disposition of subjects 
1.2 
Discontinuation of study treatment  
1.3 
Protocol deviations 
1.4 
Analysis sets 
 
Demographic and Other Baseline Characteristics 
No. 
Analysis Chapter 
2.1 
Demographics 
2.2 
Medical history 
2.3 
Diagnosis of Psoriasis 
2.4 
Previous Psoriasis Therapy 
2.5 
Substance Use 
2.6 
Physical Examination 
2.7 
Tuberculosis Evaluation 
2.8 
Chest Radiograph Result 
2.9 
Concomitant Medication and Therapy 
2.10 
Shampoo and Moisturizer 
 
Treatment Compliance 
No. 
Analysis Chapter 
3.1 
Visit windows 
3.2 
Study medication 
 
Analysis of Efficacy 
No. 
Analysis Chapter 
 
- Primary Endpoint - 
4.1 
PASI 90% Response 
 
- Major Secondary Endpoints - 
4.2.1 
Endpoint Related to PASI 
4.2.2 
Endpoint Related to DLQI 
 
- Other Secondary Endpoints - 
4.3.1 
Endpoints related to PASI 
4.3.2 
Endpoints related to PSSD 
4.3.3 
Endpoints related to IGA 
4.3.4 
Endpoints related to BSA 
4.3.5 
Endpoints related to DLQI 
4.3.6 
Endpoints related to ss-IGA 
4.3.7 
Endpoints related to SF-36 
 
- Other Efficacy Assessments - 
4.4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, BSA, ss-IGA, SF-36) 
 
Analysis of Safety 
No. 
Analysis Chapter 
5.1 
Extent of Exposure 
5.2 
Adverse Events  
5.3 
Clinical Laboratory Tests 
5.4 
Vital Signs 
5.5 
Physical Examination 
5.6  
Body Weight 
5.7 
Early Detection of Active Tuberculosis 
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18.1.3 
Figures 
 
Analysis of Efficacy, Prefix A, B, C 
No. 
Analysis Chapter 
Type of Figure 
 
- Primary Endpoint - 
 
1 
PASI 90% Response 
Bar Chart, 
Survival Graph 
 
- Major Secondary Endpoints - 
 
2.1 
Endpoint Related to PASI 
Bar Chart, 
Survival Graph 
2.2 
Endpoint Related to DLQI 
Bar Chart, 
Survival Graph 
 
- Other Secondary Endpoints - 
 
3.1 
Endpoints related to PASI 
Bar Chart,  
Survival Graph 
3.2 
Endpoints related to PSSD 
Box Plot 
3.3 
Endpoints related to IGA 
Bar Chart 
3.4 
Endpoints related to BSA 
Box Plot 
3.5 
Endpoints related to DLQI 
Bar Chart 
3.6 
Endpoints related to ss-IGA 
Bar Chart 
3.7 
Endpoints related to SF-36 
Box Plot 
 
- Other Efficacy Assessments - 
 
4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, 
BSA, ss-IGA, SF-36) 
Bar Chart,  
Box Plot 
 
Analysis of Safety, Prefix B 
No. 
Analysis Chapter 
Type of Figure 
5 
Clinical Laboratory Tests 
Box Plot 
6 
Vital Signs 
Box Plot 
7 
Body Weight 
Box Plot 
 
NCT02473289


 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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Statistical Analysis Plan 
 
Multicenter, randomized, open-label, efficacy assessor-blinded, active 
comparator-controlled phase 3b study to compare the efficacy of 
guselkumab to fumaric acid esters (Fumaderm® initial/ Fumaderm®) for 
adult patients with moderate to severe plaque psoriasis who are 
candidates for and naive to systemic treatment 
POLARIS 
- Study Part IIa: Week 32 Analysis - 
 
Study Code 
CNTO1959PSO3008 
EudraCT Number 
2016-002135-15 
Development phase 
Phase 3b 
Study Design 
randomized, open-label, efficacy assessor-
blinded, single country, multicenter, 
active-comparator-controlled 
Sponsor 
Janssen-Cilag GmbH, Neuss 
Johnson & Johnson Platz 1, 
41470 Neuss, Germany 
Contract Research Organization 
acromion GmbH 
Europaallee 27 – 29 
50226 Frechen, Germany 
Version No., Date 
Final Version 1.0, 15-Aug-2018 
 
 
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Table of Contents 
 
1.0 
Signatures .................................................................................... 4 
2.0 
List of Abbreviations .................................................................... 5 
3.0 
Introduction ................................................................................. 6 
4.0 
Responsibilities ............................................................................ 6 
5.0 
Software Utilized .......................................................................... 7 
6.0 
Coding Systems Utilized ............................................................... 7 
7.0 
Study Objectives and Hypotheses ................................................ 8 
7.1 
Objectives ................................................................................................. 8 
7.2 
Hypotheses ............................................................................................... 8 
8.0 
Study Endpoints ........................................................................... 9 
9.0 
Study Design .............................................................................. 10 
9.1 
Overview ................................................................................................. 10 
9.2 
Sample Size Determination ........................................................................ 13 
9.3 
Randomization and Blinding ....................................................................... 14 
10.0 
Study Schedule........................................................................... 15 
11.0 
Analysis Sets .............................................................................. 22 
11.1 
Definition of Analysis Sets ......................................................................... 22 
11.2 
Protocol Deviations ................................................................................... 23 
11.3 
Screening Failures .................................................................................... 23 
12.0 
Definition and Calculation of Efficacy Endpoints ......................... 24 
12.1 
Involved Body Surface Area (BSA%) ........................................................... 24 
12.2 
Investigator's Global Assessment (IGA) ....................................................... 24 
12.3 
Scalp Specific Investigator's Global Assessment (ss-IGA) .............................. 24 
12.4 
Psoriasis Area and Severity Index (PASI) .................................................... 25 
12.5 
Dermatology Life Quality Index (DLQI) ....................................................... 25 
12.6 
Psoriasis Symptom and Sign Diary (PSSD) .................................................. 26 
12.7 
Short Form Health Survey (SF-36) ............................................................. 27 
13.0 
Statistical Methodology .............................................................. 28 
13.1 
Data Handling Rules ................................................................................. 28 
13.1.1 Baseline and Post-baseline Points in Time of Interest .................................... 28 
13.1.2 Definition of Within- and Between-Group Treatment Differences ..................... 28 
13.1.3 Visit Windows .......................................................................................... 28 
13.1.4 Treatment Failure Criteria .......................................................................... 28 
13.1.5 Treatment Failure Rules ............................................................................ 28 
13.1.6 Handling of Missing Values ........................................................................ 29 
13.1.7 Data Transformations ............................................................................... 29 
13.2 
Descriptive Statistics ................................................................................ 29 
13.2.1 Dichotomous and Categorical Variables ....................................................... 29 
13.2.2 Continuous and Quasi-Continuous Variables ................................................ 29 
13.2.3 Graphical Presentations ............................................................................. 29 
13.3 
Confirmatory Statistics .............................................................................. 30 
13.4 
Exploratory Statistics ................................................................................ 30 
13.4.1 Binary Endpoints ...................................................................................... 30 
13.4.2 Continuous Endpoints ............................................................................... 30 
13.5 
Adjustment for Covariates ......................................................................... 31 
13.6 
Planned Analyses ..................................................................................... 31 
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13.7 
Multi-center Data ..................................................................................... 31 
13.8 
Subgroup Analyses ................................................................................... 32 
13.9 
Sensitivity Analyses .................................................................................. 33 
14.0 
Statistical Analyses .................................................................... 34 
14.1 
Study Subjects ......................................................................................... 34 
14.1.1 Disposition of Subjects .............................................................................. 34 
14.1.2 Discontinuation of Study Treatment ............................................................ 35 
14.1.3 Protocol Deviations ................................................................................... 35 
14.1.4 Analysis Sets ........................................................................................... 35 
14.2 
Demographic and Other Baseline Characteristics .......................................... 36 
14.2.1 Demographics .......................................................................................... 36 
14.2.2 Medical History ........................................................................................ 36 
14.2.3 Diagnosis of Psoriasis ................................................................................ 36 
14.2.4 Previous Psoriasis Therapy ........................................................................ 36 
14.2.5 Substance Use ......................................................................................... 36 
14.2.6 Physical Examination ................................................................................ 36 
14.2.7 Tuberculosis Evaluation ............................................................................. 36 
14.2.8 Chest Radiograph Result ........................................................................... 37 
14.2.9 Concomitant Medication and Therapy .......................................................... 37 
14.2.10 Shampoo and Moisturizer .......................................................................... 37 
14.3 
Treatment Compliance .............................................................................. 38 
14.3.1 Visit Windows .......................................................................................... 38 
14.3.2 Study Medication ...................................................................................... 38 
14.4 
Analysis of Efficacy ................................................................................... 39 
14.4.1 Primary Endpoint ...................................................................................... 40 
14.4.2 Major Secondary Endpoints ....................................................................... 40 
14.4.3 Other Secondary Endpoints ....................................................................... 40 
14.4.4 Other Efficacy Assessments ....................................................................... 42 
14.5 
Analysis of Safety ..................................................................................... 43 
14.5.1 Extent of Exposure ................................................................................... 43 
14.5.2 Adverse Events ........................................................................................ 43 
14.5.3 Clinical Laboratory Tests ........................................................................... 47 
14.5.4 Vital Signs ............................................................................................... 48 
14.5.5 Physical Examination ................................................................................ 48 
14.5.6 Body Weight ............................................................................................ 48 
14.5.7 Early Detection of Active Tuberculosis ......................................................... 48 
14.6 
Analysis of MedDRA Codes ......................................................................... 48 
14.7 
Analysis of WHO Drug Dictionary Codes ...................................................... 48 
15.0 
Changes to Planned Analyses ..................................................... 49 
16.0 
Tabulation .................................................................................. 51 
16.1 
General ................................................................................................... 51 
16.2 
Format of Data Displays ............................................................................ 51 
16.2.1 Tables ..................................................................................................... 51 
16.2.2 Listings ................................................................................................... 51 
16.2.3 Figures .................................................................................................... 52 
16.3 
Data Format ............................................................................................ 53 
17.0 
References ................................................................................. 54 
18.0 
Appendices ................................................................................. 55 
18.1 
Table of Contents for Data Displays ............................................................ 55 
18.1.1 Tables ..................................................................................................... 56 
18.1.2 Listings ................................................................................................... 57 
18.1.3 Figures .................................................................................................... 58 
 
 
NCT09251533


NCT09251533


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NCT09251533


Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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2.0 
List of Abbreviations 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
BSA 
Body Surface Area 
CRF 
Case Report Form(s)  
CSP 
Clinical Study Protocol 
DLQI 
Dermatology Life Quality Index 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
e.g. 
example given 
FAE 
Fumaric Acid Esters 
HBV/ HCV 
Hepatitis B virus/ Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HTA 
Health Technology Assessment 
ICH 
International Council on Harmonization 
i.e. 
that is 
IGA 
Investigator´s Global Assessment 
IL 
Interleukin 
LOCF 
Last Observation Carried Forward 
MCS 
Mental Component Summary 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
Methotrexate 
NTEAE 
Non Treatment Emergent Adverse Event 
NTESAE 
Non Treatment Emergent Serious Adverse Event 
PASI 
Psoriasis Area and Severity Index 
PCS 
Physical Component Summary 
PRO 
Patient-Reported Outcome(s)  
PSSD 
Psoriasis Symptom and Sign Diary 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous 
SF-36 
Short Form (36-item) health survey 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
ss 
scalp-specific 
TB 
tuberculosis 
TEAE 
Treatment Emergent Adverse Event 
TES 
Time and Events Schedule 
TESAE 
Treatment Emergent Serious Adverse Event 
 
 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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3.0 
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 and the relevant 
acromion SOPs and/or guidelines. This plan describes the statistical analyses planned to 
be performed for the Week 32 analysis Study Part IIa of Janssen-Cilag GmbH Clinical 
Study Protocol CNTO1959PSO3008 and should be read in conjunction with the statistical 
analysis plan for the Week 24 analysis, the protocol amendment INT-1 to the CSP and the 
electronic Case Report Form (eCRF).  
An overview about all planned analyses is given in Section 13.6. The Week 32 analysis 
summarizes the study data unit Week 32 (Study Part IIa; Week 24 through Week 32) and 
will be conducted as part of the Week 64 analysis once all data of Study Part II are 
available. The Week 32 analysis will include the safety analysis and all efficacy measures 
after Week 24 and will cover the time until the Week 32 visit. All statistical analyses will 
be descriptive and exploratory only for the predefined efficacy and safety analyses until 
Week 32. Statistical analyses of study data until Week 64 (Study Part IIb; active 
treatment from Week 32 through Week 56 and safety follow-up until Week 64) will be 
provided in a separate SAP. 
Confirmatory analyses for the primary endpoint and the major secondary endpoints were 
already performed at the Week 24 analysis as described in the statistical analysis plan for 
Week 24 (Final 1.0, 10-July-2017). Evaluations on health technology assessment (HTA) 
will also be specified in this SAP. No separate HTA SAP will be provided. The Week 32 
analysis will be performed after all subjects have completed their visit at 64 weeks after 
randomization or discontinued earlier. Data base lock for the Week 32 analysis will be 
after the Week 64 visit data are ready for statistical analysis (i.e., clean data). 
This SAP is the core document for all statistical programming planned to be performed for 
the Week 32 analysis and is based on the following study documents to protocol no. 
CNTO1959PSO3008: 
Document 
Version, Date 
Protocol / Amendments 
Protocol Amendment INT-1, Version 2.0, 25-APR-2017 
eCRF 
Version 2.0, 08-JUN-2017 
Data Management Plan 
Version 1.0, 09-DEC-2016 
Data Validation Plan 
Version 1.0, 09-DEC-2016 
Statistical Analysis Plan - 
Week 24 Analysis 
Version 1.0, 10-JUL-2017 
4.0 
Responsibilities 
The responsibilities for the biometrical tasks at acromion GmbH are assigned as follows: 
Name 
Function 
Task 
Statistician 
Statistical Programming and Analysis 
Statistician 
Statistical Programming and Analysis 
Statistical Programmer 
Statistical Programming and Analysis 
Statistical Programmer 
Statistical Programming and Analysis 
Medical Data Analyst 
Medical Data Review and Coding 
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Polaris_SAP_W32_V1.0_15Aug2018 
 
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5.0 
Software Utilized 
The statistical analysis and generation of tables, patient data listings and figures will be 
performed using the SAS® software package version 9.4 under the Microsoft Windows® 7 
operating system at the computer facilities of acromion GmbH. Additional analyses 
regarding health technology assessment (HTA) may be performed by or under the 
responsibility of Janssen-Cilag GmbH. 
 
6.0 
Coding Systems Utilized 
The MedDRA-dictionary version 19.1 is used for coding of prior and concomitant diseases 
and for coding of adverse events. The following items are coded. 
eCRF Module 
Item 
SDTM Domain/ Variable 
Name 
Medical History of Interest 
Medical History Term 
MH/MHTERM 
Previous Phototherapy 
Type of Phototherapy 
MH/MHTERM 
Concomitant Medication 
Indication 
CM/CMIND 
Concomitant Therapy 
Indication 
CM/CMIND 
Concomitant Therapy 
Therapy 
CM/CMTRT 
(S)AE  
Term 
AE/AETERM 
Prior and concomitant medications are coded according to the WHO terminology using the 
2016/1 version of the WHO-Drug Dictionary. The following items are coded. 
eCRF Module 
Item 
SDTM Domain/ Variable 
Name 
Previous Topical Therapy 
Medication/Therapy 
MH/MHTERM 
Concomitant Medication  
Compound 
CM/CMTRT 
Details are specified in the Data Management Plan. 
 
 
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7.0 
Study Objectives and Hypotheses 
7.1 
Objectives 
Primary Objectives 
The primary objectives of the study are 
• 
to compare the efficacy of guselkumab to fumaric acid esters (FAE) in systemic 
treatment-naïve subjects with moderate to severe plaque-type psoriasis. 
• 
to assess the safety and tolerability of guselkumab in systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis. 
Secondary Objective 
The secondary objectives of the study are 
• 
in Study Parts I and II: to compare improvement of health-related quality of life 
(QOL) and other patient-reported outcomes (PRO) when systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis are treated with 
guselkumab compared to FAE. 
• 
in Study Part II: to compare sustainability of response to treatment when systemic 
treatment naïve subjects with moderate to severe plaque-type psoriasis are 
treated with guselkumab compared to FAE. 
 
7.2 
Hypotheses 
The primary hypothesis of this study is that guselkumab treatment is superior to FAE 
(Fumaderm® initial/Fumaderm®) treatment as assessed by the proportion of subjects 
achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are: 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of 
subjects achieving a PASI 75 response at Week 24 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of 
subjects achieving a DLQI score of 0 or 1 at Week 24. 
If the primary hypothesis is accepted, the study will be considered positive. 
 
 
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8.0 
Study Endpoints 
This section provides a description of all study endpoints as pre-specified in the CSP 
(Protocol Amendment INT-1) for the Week 24 and the Week 64 analyses. The Week 64 
analysis includes the Week 32 analysis which is described in the present SAP. 
Primary Endpoint 
The primary endpoint is the proportion of subjects achieving at least a 90% improvement 
of their psoriasis according to the Psoriasis Area and Severity Index (PASI 90 response) at 
Week 24. 
Secondary Endpoints 
The major secondary endpoints are: 
• 
The proportion of subjects achieving at least a 75% improvement of their psoriasis 
according to the PASI at Week 24 (PASI 75 response) 
• 
The proportion of subjects achieving a DLQI score of 0 or 1 at Week 24. 
 
Other secondary endpoints are: 
• 
The proportion of subjects achieving a 100% improvement of their psoriasis 
according to the PASI at Week 24 (PASI 100 response) 
• 
The change from baseline in the signs and symptoms aggregate scores of the PSSD 
at Week 24 
• 
The change from baseline in the individual scale scores for itch, pain, and scaling of 
PSSD components at Week 24 
• 
The proportion of subjects achieving an absolute PASI score ≤1 at Week 24 
• 
The proportion of subjects achieving an IGA score of cleared (0) at Week 24 
• 
The change from baseline of body surface area (BSA) psoriatic involvement at 
Week 24 
• 
The change from baseline in DLQI score at Week 24 
• 
The proportion of subjects achieving an ss-IGA score of absence of disease (0) at 
Week 24 in randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at 
baseline 
• 
The change from baseline in the physical and mental component summary scores 
of SF-36 at Week 24 
• 
Maintenance of response. Proportion of subjects with a 
− 
PASI 75 response at Week 32 who maintain response at Week 56 
− 
PASI 90 response at Week 32 who maintain response at Week 56 
− 
a DLQI score 0 or 1 at Week 32 who maintain response at Week 56 
• 
Proportion of subjects of the FAE group who were PASI 75 non-responders at Week 
32 and switched to guselkumab with a 
− 
PASI 75 response (compared to Week 0) at Week 56 
− 
PASI 90 response (compared to Week 0) at Week 56 
− 
PASI 100 response (compared to Week 0) at Week 56 
− 
DLQI score 0 or 1 at Week 56 
• 
Proportion of subjects with a 
− 
PASI 75 response at Week 32 
− 
PASI 90 response at Week 32 
− 
PASI 100 response at Week 32 
− 
DLQI score 0 or 1 at Week 32 
• 
Safety and tolerability data will be summarized using descriptive statistics. 
 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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9.0 
Study Design 
This section provides a description of the study design as defined in the CSP (Protocol 
Amendment INT-1) for the Week 24 and the Week 64 analyses. The Week 64 analysis 
includes the Week 32 analysis which is described in the present SAP. 
The description is written in future tense according to the wording in the CSP, even though 
some of the planned actions, analyses and procedures have been carried out meanwhile. 
Note: References to 'Section' always refer to the respective section in the CSP (Protocol 
Amendment INT-1). 
9.1 
Overview 
This is a randomized, open-label, efficacy assessor-blinded, single country, multicenter, 
active comparator-controlled phase 3b study of guselkumab in adult subjects with 
moderate to severe plaque-type psoriasis who have not yet received any systemic 
therapy. The study will be performed at about 30 to 45 sites in Germany. 
This study will have a 3-week screening phase, a 56-week treatment phase and a safety 
follow-up phase until Week 64 (as shown in Figure 1). The maximum duration of a 
subject’s participation in this study will be 67 weeks including the 3-week screening phase. 
With protocol Amendment 1, the study will be split into two parts (Study Part I and II): 
 
Study Part I (Core Study)—Week 0 through Week 24: 
Screening and treatment until Week 24 
After screening, a total of 114 subjects will be randomized in a 1:1 ratio to either the 
study drug (guselkumab) or to the active comparator (FAE). Subjects of the guselkumab 
group will receive 100 mg guselkumab SC at Weeks 0, 4, 12, and 20. Subjects of the FAE 
group will receive commercially available Fumaderm® tablets specifically labeled for the 
study. An individual dosing for each subject representing the optimal benefit-risk ratio is 
aspired. 
A subject will be considered to have completed Study Part I if he or she has completed 
assessments at Week 24 of the open-label phase. Subjects eligible for Study Part II at 
Week 24 (ICF Part II signed, study treatment ongoing, no protocol-prohibited treatment 
started) will enter study extension and continue study treatment. For subjects who 
discontinue study treatment or withdraw from study participation in Study Part I or who 
do not enter Study Part II, a safety follow-up visit (Study Part I) is completed at Week 32 
or 12 weeks after the last treatment (whatever comes first). For subjects enrolled in Study 
Part I only, maximum duration of study participation in this study will be 35 weeks. 
 
Study Part II (Extension)—Week 24 through Week 56: 
Treatment 
Subjects may enter the study extension at Week 24 only when the ICF for Study Part II 
was signed before or at Week 24, study treatment was not terminated prior to Week 24 
and no protocol-prohibited medication/therapy was started. Study Part II is subdivided in 
two treatment periods: 
• 
Part IIa—Week 24 through Week 32: All subjects who enter Study Part II will 
continue their assigned treatment (guselkumab or FAE) from Week 24 through 
Week 32. Study Part IIa is considered completed when the subject has completed 
assessments at Week 32. 
Part IIb—Week 32 through Week 56: Following Week 32, subjects with a PASI 75 
response will continue assigned treatment (guselkumab or FAE). For PASI 75 non-
responders at Week 32 the following options will be available: 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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− 
Guselkumab group: Subjects may continue guselkumab treatment. It is at 
the investigator’s discretion to continue therapy, if it is considered medically 
appropriate. 
− 
FAE group: Subjects will switch to guselkumab unless barred by safety 
reasons (based on lab values ≥Week 28). Subjects who terminate FAE 
treatment prior to Week 32 cannot continue study treatment but will enter 
safety follow-up per protocol. 
A subject will be considered to have completed Study Part II if he or she has completed 
assessments at Week 56 of the open-label phase. For Subjects who discontinue study 
treatment or withdraw from study participation in Study Part II, final study assessments 
are obtained and a safety follow-up visit is completed at Week 64 or 12 weeks after last 
treatment (whatever comes first). For subjects completing Study Part II maximum 
duration of study participation in this study will be 67 weeks including a 3-week screening 
phase. 
Efficacy of treatment will be assessed before any tests, procedures or other evaluations, 
first by the subject him/herself (1st DLQI, 2nd PSSD 7-day version, and 3rd SF-36), and 
subsequently by a blinded efficacy assessor (BSA%, IGA, ss-IGA, and PASI). Safety 
evaluations will include the monitoring of adverse events (including injection site and 
allergic reactions), physical examinations, measurement of body weight, vital sign 
measurement, clinical laboratory testing (HBV, HCV, HIV, hematology, chemistry), 
concomitant medication review, tuberculosis test and evaluation, urinalysis and pregnancy 
testing. The confirmatory analysis will be conducted after the primary endpoint at Week 
24 is reached including subjects who have completed the Week 24 visit and subjects who 
have terminated the study prematurely (Section 11.3). The second statistical analysis will 
be performed after Week 64 (see Section 11). 
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 transferred to the sponsor (or 
designee) after completion of the final subject visit at that site, in the time specified in the 
Clinical Trial Agreement. The overall duration of the study is expected to be approximately 
21 months (start in December 2016, stop in October2018). The estimated frequency and 
timing of the study visits are summarized in the ‘Time and Events Schedule’ (TES). 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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Figure 1: Schematic Overview of the Study 
 
 
 
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Polaris_SAP_W32_V1.0_15Aug2018 
 
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9.2 
 Sample Size Determination 
As described in the CSP, the primary hypothesis of this study is that guselkumab 
treatment is superior to FAE (Fumaderm® initial/ Fumaderm®) treatment as assessed by 
the proportion of subjects achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are:  
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a PASI 75 response at Week 24. 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a DLQI score of 0 or 1 at Week 24. 
In order to control the overall experiment wise type 1 error rate, the primary endpoint and 
the two major secondary endpoints will be tested in a fixed sequence as a-priori ordered 
hypotheses. That is, the first major secondary endpoint will be tested only if the primary 
endpoint is positive (i.e., p <0.05), and the second major secondary endpoint will be 
tested only if the first major secondary endpoint is positive (i.e., p <0.05). Due to the 
testing of ordered hypotheses, no adjustment of the significance level with respect to the 
threefold test procedure is required. 
The assumptions for the sample size and power calculations using the threefold test 
procedure were based on guselkumab phase 2 data and unpublished data from the 
German PsoBest Registry and are as follows: PASI 90 responder rates for guselkumab and 
FAE in Week 24 are assumed to be 60% and 25%, respectively. PASI 75 responder rates 
are assumed to be 80% and 45%, respectively. DLQI responder rates are assumed to be 
60% and 30%, respectively. 
Based on these assumptions, with a total of 114 subjects planned to be randomized in a 
1:1 ratio to guselkumab (n = 57) and to FAE (n = 57), superiority of guselkumab vs. FAE 
can be demonstrated at a 5% significance level (two-sided) with power of at least 90% for 
each test of the threefold test procedure as displayed in the table below. 
Table 1: Power to detect a treatment effect on expected proportions of subjects 
achieving the primary and the major secondary endpoints 
Order of 
testing 
Endpoint in  
Week 24 
Guselkumab 
(% responder) 
FAE 
(% responder) 
Power 
1 
PASI 90 
60 
25 
97% 
2 
PASI 75 
80 
45 
98% 
3 
DLQI 0/1 
60 
30 
90% 
type 1 error rate alpha 5% (two-sided) 
sequential testing with a-priori ordered hypotheses (only proceed with testing, if p <0.05)  
sample size n = 114 with 1:1 ratio guselkumab (n = 57) and FAE (n = 57) 
two group chi-square test; nQuery Advisor® Release 7.0 
 
 
 
 
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9.3 
 Randomization and Blinding 
Procedures for Randomization  
Central randomization is implemented in this study as described in Section 5 of the CSP. 
Subjects will be randomly assigned to 1 of 2 treatment groups (1:1 ratio) based on a 
computer-generated randomization schedule prepared before the study by or under the 
supervision of the sponsor. The randomization will be balanced by using randomly 
permuted blocks. The interactive web-based eCRF will assign a unique treatment code, 
which will dictate the treatment assignment at baseline visit of the subject. The 
investigator will not be provided with randomization codes. The randomization codes will 
be stored invisible for the investigator in a separate, blind part of the EDC (Electronic Data 
Capture) system.  
Blinding 
As this is an open study, blinding procedures for the treatment are not applicable. 
However, a blinded efficacy evaluator will assess effectiveness of treatment as described 
in Section 9.2.3 of the CSP. 
 
 
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10.0 Study Schedule 
An overview of the study procedures is displayed in the following time and events schedule of the CSP. References to 'Section' always refer 
to the respective section in the CSP. 
Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Screening/Administrative 
Informed consent I 
(Study Part I) 
X 
 
 
 
 
 
 
 
 
 
 
Must be signed before first study-related activity 
Informed consent II 
(Study Part II) 
------------------------------------------------------------------------------X 
 
 
ICF addendum for Study Part II to be signed at 
Week 24 at the latest 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Minimum criteria for the availability of 
documentation supporting the eligibility criteria 
are described in protocol, Section 4; check 
clinical status again before first dose of study 
medication 
Study Drug Administration 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
All baseline study procedures and evaluations 
are to be completed before randomization 
Study drug 
administration 
 
   Xc-------------------------------------------------------------------…  
 
All study procedures and evaluations are to be 
completed before study drug administration 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before administration of study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
c: Subjects randomized to guselkumab will get guselkumab 100 mg on site at Weeks 0, 4, 12 and then every 8 weeks. Subjects randomized to FAEs will start with 
Fumaderm® initial regimen (0-0-1) at the day of the baseline visit; thereafter, FAE doses will be increased to find the optimal Fumaderm® dose for each subject as 
described in Section 6.  
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit: for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
Safety Assessments 
Physical examination  
X 
x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X  
X 
 
Tuberculosis evaluation 
X 
X 
   X--------------------------------------------------------… 
X 
X 
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 
(Section 9.3) 
Chest radiograph 
X 
 
 
 
 
 
 
 
 
 
 
Taken within 3 months before the first 
administration of study drug and read by a 
qualified radiologist 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Women of childbearing potential must have a 
negative 
urine 
pregnancy 
test 
before 
randomization and at all study visits (prior to 
administration of study drug). 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
Weight 
 
X 
 
 
 
 
 
 
X 
X 
X 
 
Concomitant therapy 
      X--------------------------------------------------------------------------… 
X 
X 
 
Adverse events 
      X--------------------------------------------------------------------------… 
X 
X 
 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Efficacy Assessments 
DLQI 
X 
X 
 
X  
X 
 
X 
 
X 
 
X 
 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd 
SF-36; should be performed before any tests, 
procedures or other evaluations (PASI, IGA, ss-
IGA, BSA) for that visit; completion of the 
baseline 
PROs 
has 
to 
be 
done 
before 
randomization 
PSSD (7d) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
SF-36 
 
X 
 
 
X 
 
X 
 
X 
 
X 
IGAd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
PASId 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
ss-IGAd,e 
 
X 
 
 
X 
 
X 
 
X 
 
X 
 
BSA%d 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
d: Dermatological evaluation of the subjects will be done by a blinded assessor starting with the Baseline visit; assessments will be done before any study related 
procedure will take place 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Clinical Laboratory Assessment 
Tuberculosis testf 
X 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B and C 
Serologies 
X 
 
 
 
 
 
 
 
 
 
 
 
HIV antibody test 
X 
 
 
 
 
 
 
 
 
 
 
 
Hematologyg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Laboratory tests are listed in Section 9.3 
Chemistryg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis by dipstick: glucose and protein; if 
there are signs of proteins and/or glucose on 
urine test strip, the urine sample must be 
analyzed centrally; here, protein and glucose 
levels must not exceed trace levels, eg, ≤ +; one 
re-test (central urine analysis) is allowed. 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
f: The QuantiFERON-TB Gold Plus test will generally be performed by the central laboratory; however, if available, test results from local laboratory can be accepted 
g: All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled; fasting is not necessary; details will be 
provided in the Laboratory Manual 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
 
 
 
 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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Phase 
Active Treatment 
Safety FUP 
(Final Study 
visit Part II)h3 
ETVh2 
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Study Drug Administration 
Study drug administration 
…---------Xi--------------------------------------------------X 
 
 
Subjects may enter the study extension at Week 24 
when ICF for Study Part II was signed, study 
treatment was not terminated and no protocol-
prohibited medication/therapy was started. 
Safety Assessments 
Physical examination  
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
Vital signs 
X 
X 
  
X 
 
X 
 
X 
X  
X 
Tuberculosis evaluation 
……----------------------------------------------------------X 
X 
X 
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 (Section 9.3) 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight 
 
 
 
 
 
 
 
 
X 
X 
 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4. 
h3: Safety Follow-up/Final Study Visit Study Part II (≤Week 64): For subjects who discontinue study treatment or withdraw from study participation in Study Part II. 
Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
i: Week 24 to Week 32 (Study Part IIa): subjects continue assigned treatments through Week 32. Subjects treated with 100 mg SC guselkumab continue q8w (ie, at Week 
28). Subjects treated with FAE continue Fumaderm® tablets (individual dosing according to local SmPC) until Week 32. 
Week 32 to Week 56 (Study Part IIb): Treatment decision based on PASI assessment at Week 32 and safety assessment (≥Week 28): 
- PASI 75 responders at Week 32: subject continues assigned therapy. Subjects in the guselkumab group continue 100 mg guselkumab SC at Weeks 36, 44, 52. 
Subjects in the FAE group continue Fumaderm® treatment (individual dosing according to local SmPC) until Week 56. 
- PASI 75 non-responders at Week 32: subjects in the FAE group may switch to guselkumab treatment unless barred by safety reasons (see treatment criteria 
Section 4.4). In case of safety concerns (based on lab values of Week ≥28), assessment can be repeated before Week 32. Subjects will receive guselkumab SC at 
Weeks 32, 36, 44 and Week 52. Non-responders in the guselkumab group may continue guselkumab (continuation of therapy is at the investigator’s discretion). 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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Phase 
Active Treatment 
Safety FUP 
(Final Study 
visit Part II)h3 
ETVh2 
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Safety Assessments (continued) 
Concomitant therapy 
…----------------------------------------------------------X 
X 
X 
 
Adverse events 
    …----------------------------------------------------------X 
X 
X 
 
Efficacy Assessments 
DLQI 
X 
X 
X* 
X  
 
X 
 
X 
 
X 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd SF-
36; should be performed before any tests, procedures 
or other evaluations (PASI, IGA, ss-IGA, BSA) for 
that visit. 
*ONLY applicable for subjects who switched to 
guselkumab at Week 32  
PSSD (7d) 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
SF-36 
 
X 
 
 
 
 
 
X 
 
X 
IGAd 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
PASId 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
ss-IGAd,e 
 
X 
X* 
X 
 
X 
 
X 
 
X 
BSA%d 
 
X 
 
 
 
 
 
X 
 
X 
 
Study Proceduresb  
 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
d: Dermatological evaluation of the subjects will be done by a blinded assessor as in Study Part I; assessments will be done before any study related procedure will take 
place 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4. 
h3: Safety Follow-up/Final Study Visit Study Part II ≤Week 64: For subjects who discontinue study treatment or withdraw from study participation in Study Part II. 
Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
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Polaris_SAP_W32_V1.0_15Aug2018 
 
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Phase 
Active Treatment 
Safety FUP 
(Final Study 
visit Part II)h3 
ETVh2 
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Clinical Laboratory Assessment 
Hematologyg 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X 
Laboratory tests are listed in Section 9.3 
∆  NOT applicable for subjects continuing gusel-
kumab treatment since beginning of the study 
(Week 0) 
Chemistryg 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X 
Urinalysis 
X 
Xβ  
X 
Xβ  
X 
Xβ  
X 
Xβ  
X 
X 
Urinalysis by dipstick: glucose and protein; if there 
are signs of proteins and/or glucose on urine test 
strip, the urine sample must be analyzed centrally; 
here, protein and glucose levels must not exceed 
trace levels, eg, ≤+; one re-test (central urine 
analysis) is allowed. 
β  ONLY applicable for subjects treated with FAE 
  
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
g: All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled; fasting is not necessary; details will be 
provided in the Laboratory Manual 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4. 
h3: Safety Follow-up/Final Study Visit Study Part II ≤Week 64: For subjects who discontinue study treatment or withdraw from study participation in Study Part II. 
Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
 
 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W32_V1.0_15Aug2018 
 
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11.0 Analysis Sets 
In this study, subjects will be included in the efficacy analyses according to their assigned 
treatment. In contrast to the efficacy analysis set, safety analyses will be performed 
according to the actual treatment received during the study. 
 
11.1 
Definition of Analysis Sets 
The following analysis data sets will be defined analogously to the definitions of the Week 
24 analysis: 
• 
Efficacy Analysis Set 
The efficacy analysis set is defined as the set of all subjects who were randomized to 
one of the two treatment groups (guselkumab or FAE) at Week 0 regardless of the 
treatment they actually received (“intent-to-treat” principle). 
• 
Per-Protocol Analysis Set 
The per-protocol analysis set will consist of all subjects in the efficacy analysis set 
terminating the study without any major deviation of the protocol and its procedures. 
Subjects with major protocol deviations until Week 32 will be excluded from the per-
protocol analysis.  
• 
Safety Analysis Set 
The safety analysis set is defined as the set of all subjects who were randomized to 
one of the two treatment groups (guselkumab or FAE) at Week 0 and who received at 
least one dose of study drug according to the actual treatment received during the 
study irrespective of the treatment assigned at randomization. 
Unless otherwise specified, data on study subjects (including subject disposition, reasons 
for discontinuation of study treatment, protocol deviations, analysis sets) will be analyzed 
based on data from all subjects randomized at Week 0 ('efficacy analysis set'). 
If not otherwise specified, demographic and other baseline characteristics as well as 
treatment compliance will be analyzed based on data from all subjects randomized at 
Week 0 ('efficacy analysis set'). 
All efficacy analyses to compare guselkumab vs. FAE will be performed for all subjects 
randomized at Week 0 ('efficacy analysis set'). The PASI 90, PASI 75 and DLQI 0/1 
response rates will also be analyzed using the per-protocol analysis set. 
All safety analyses to compare guselkumab vs. FAE will be performed for all treated 
subjects ('safety analysis set'). 
Since the safety analysis set differed only by one patient from the efficacy analysis set, it 
was decided that the efficacy analyses were not to be performed for all treated patients 
('safety analysis set'). 
 
 
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11.2 
Protocol Deviations 
The determination of evaluability of subjects, especially in cases of protocol deviations, 
withdrawals or drop-outs and the assignment of subjects to the planned analysis sets will 
be performed according to the requirements of the study protocol. Minor and major and 
potentially major protocol deviations that can be expected based on the prescriptions in 
the protocol were defined by Janssen-Cilag GmbH during the trial set up period and 
adapted during the study conduct. A detailed description of major and potentially major 
protocol deviation criteria is included in a separate document. 
Data on subjects who had a major protocol deviation will be documented continuously by 
Janssen-Cilag GmbH in a Clinical Trial Management System during the trial period. Final 
data on major protocol deviations regarding the Week 32 analysis will be transferred to 
the data management department of acromion GmbH as Excel spreadsheets and will be 
further processed for statistical analysis. 
 
11.3 
Screening Failures 
The data of subjects who were not randomized will not be included in the statistical 
analyses. However, a separate listing will be presented providing the site/subject no. and 
the reason for not being randomized. 
 
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CNTO1959 (guselkumab) 
 
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12.0 Definition and Calculation of Efficacy Endpoints 
The following sections provide a detailed description of the definition and the planned 
calculation of the efficacy endpoints as defined in the CSP. The same applies also for 
additional endpoints not defined in the CSP. 
 
12.1 
Involved 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).  
 
12.2 
Investigator's Global Assessment (IGA) 
The Investigator’s Global Assessment (IGA) documents the investigator’s assessment of 
the subject’s psoriasis at a given time. Overall lesions are graded for induration, 
erythema, and scaling. The subject’s psoriasis is assessed as cleared (0), minimal (1), 
mild (2), moderate (3), or severe (4). 
The efficacy endpoint related to the IGA score is defined below: 
IGA cleared responder 
Subjects who achieve an IGA score of cleared (0) will be considered IGA cleared 
responders. 
 
12.3 
Scalp Specific Investigator's Global Assessment (ss-IGA) 
The scalp-specific (ss-)IGA instrument is used to evaluate the disease severity of scalp 
psoriasis. The lesions are assessed in terms of the clinical signs of redness, thickness, and 
scaliness which are scored as: absence of disease (0), very mild disease (1), mild disease 
(2), moderate disease (3), and severe disease (4). 
The analyses for ss-IGA will be based on subjects randomized at Week 0 with baseline ss-
IGA score ≥2.  
ss-IGA absence of disease responder 
Subjects with an ss-IGA score ≥2 at baseline who achieve ss-IGA score of absence of 
disease (0) will be considered ss-IGA absence of disease responders. 
 
 
 
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12.4 
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. 
In addition, the time to PASI 75/90/100 response defined as time from baseline to first 
onset of response will be calculated. In the absence of documented response the time to 
PASI 75/90/100 response will be censored at the date of Week 32 or the date of 
discontinuation in case of early treatment discontinuation. 
 
12.5 
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 (e.g., 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. 
In addition, the time to DLQI 0/1 response defined as time from baseline to first onset of 
response will be calculated. In the absence of documented response, the time to DLQI 0/1 
response will be censored at the date of Week 32 or the date of discontinuation in case of 
early treatment discontinuation. 
 
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12.6 
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 (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. 
 
 
 
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12.7 
Short Form Health Survey (SF-36) 
The Short Form Health Survey (SF-36) is a 36-item questionnaire used for subjects’ self-
assessment of health-related quality of life, consisting of the following 8 dimensions: 1) 
limitations in physical functioning due to health problems, 2) limitations in usual role 
activities due to physical health problems, 3) bodily pain, 4) general mental health 
(psychological distress and well-being), 5) limitations in usual role activities due to 
personal or emotional problems, 6) limitations in social functioning due to physical or 
mental health problems, 7) vitality (energy and fatigue), and 8) general health perception.  
A physical component summary (PCS) score and a mental component summary (MCS) 
score can be derived. The concepts measured by the SF-36 are not specific to age, disease 
or treatment group, allowing comparison of relative burden of different diseases and the 
relative benefit of different treatments. The estimated completion time will be 10 minutes. 
Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating 
better health. Based on the scale scores, the summary scores, PCS and MCS, will be 
derived. These summary scores are also scaled with higher scores indicating better health. 
The QualityMetric Health Outcomes™ Scoring Software 5.0 offered by QualityMetric 
Incorporated will be used to score the SF-36. The Software is designed to provide users 
with standard scoring methods in an easy-to-use way. By using this Software, users will 
have the confidence that the data they obtain on their SF form are scored in accordance 
with standards set by the developers of the SF tools. The Software also provides 
evaluation of data quality and applies methods for missing data recovery. The PCS score 
can be calculated when seven scale scores are available and the Physical Functioning scale 
is not missing. The MCS score can be calculated when at least seven scale scores are 
available and the Mental Health scale is not missing. 
 
A more detailed description of the scoring procedure is provided in the User's Guide of 
QualityMetric Health Outcomes™ Scoring Software 5.0 (see especially Appendix F). 
 
 
 
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13.0 Statistical Methodology 
The present Week 32 analysis of Study Part IIa summarizes the study data until Week 32 
(Study Part IIa; Week 24 through Week 32) and will be part of the Week 64 analysis of 
Study Part II. This analysis will include the safety analysis and all efficacy measures after 
Week 24 and will cover the time until the Week 32 visit. All statistical analyses will be 
descriptive and exploratory only for the predefined efficacy and safety analyses until Week 
32. 
The biometrical evaluation will be carried out by acromion GmbH under the authority of 
the sponsor. Statistical programming and analyses will be performed using the statistical 
software system SAS®. 
The following sections provide a more detailed description of the planned statistical 
methodology. 
 
13.1 
Data Handling Rules 
13.1.1 
Baseline and Post-baseline Points in Time of Interest 
Baseline Definition 
In general, the values of the Week 0 visit (= day of randomization = first day of week 1) 
or the values of the screening visit (= day within 3 weeks before their randomization visit) 
will be used as baseline values, as applicable. If data for the same variable are available 
from both (i.e., screening and Week 0) visits then the result of the Week 0 visit will be 
used as baseline value, i.e., for each variable the baseline measurement is defined as the 
closest measurement taken prior to or at the Week 0 visit. 
Definition of Post-baseline Points in Time of Interest 
The primary point in time for efficacy assessment will be the Week 32 visit (= the 
treatment visit 32 weeks after randomization). Secondary points in time for efficacy 
assessment will be the study visits scheduled at Week 28 during the treatment phase. 
Handling of missing values is described in SAP section 13.1.6. 
The safety analysis will cover the time period until Week 32.  
13.1.2 
Definition of Within- and Between-Group Treatment 
Differences 
Within-group treatment differences will be computed as differences of the post-baseline 
visits as compared to the baseline visit, if applicable: 
• 
post-baseline visit minus baseline visit 
The following between-group treatment difference to assess the treatment effect will be 
computed, if applicable: 
• 
guselkumab minus FAE 
13.1.3 
Visit Windows 
Nominal visits (i.e., visits as recorded in the eCRF) will be used for all by-visit analyses in 
the study. The study visits scheduled post randomization should occur at the times 
delineated in the Time and Events Schedule. No visit windows will be defined and used for 
analysis. 
13.1.4 
Treatment Failure Criteria 
Not applicable. 
13.1.5 
Treatment Failure Rules 
No treatment failure rules will be applied. 
 
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13.1.6 
Handling of Missing Values 
All available data will be included in the analyses and will be summarized descriptively as 
far as possible. If not otherwise specified, there will be no substitution of missing data, 
i.e., missing data will not be replaced, missing data will be handled as ‘missing’ in the 
statistical evaluation (‘observed cases analysis’). 
Missing data for the efficacy endpoints at key visits Week 28 and 32 will be handled as 
follows for all exploratory inferential statistical analyses. 
Missing data imputation for the efficacy endpoints at Week 28 and 32: 
• 
Nonresponder imputation will be applied for binary endpoints 
o 
i.e., subjects with missing data at Week 28/32 will be considered non-
responders at Week 28/32. 
• 
Last observation carried forward (LOCF) will be applied for continuous endpoints 
o 
i.e., in subjects with missing data at Week 28/32 the last available 
observation after baseline will be calculated and used for analysis for 
continuous response variables at Week 28/32. 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. 
Sensitivity analyses with respect to the handling of missing values at Week 32 are 
described in SAP section 13.9. 
 
13.1.7 
Data Transformations 
No data transformations (e.g. square root, logarithmic) to confirm basic statistical 
assumptions will be performed. All variables will be used in the analysis as reported. 
 
13.2 
Descriptive Statistics 
13.2.1 
Dichotomous and Categorical Variables 
Categorical data will be presented in frequency tables using counts and percentages. 
Percentages will be based on the total number of subjects in the respective analysis set 
(i.e., missing values will be included in percentage calculation). Besides presentation of 
absolute values cross tabulation vs. baseline by study visit will be provided, if appropriate. 
 
13.2.2 
Continuous and Quasi-Continuous Variables 
Standard descriptive summary statistics will be calculated for continuous and quasi-
continuous variables: arithmetic mean, standard deviation, minimum value, lower quartile, 
median, upper quartile, maximum value, number of non-missing values. Besides 
presentation of absolute values tabulation for differences to baseline by study visit will be 
provided, if appropriate. 
 
13.2.3 
Graphical Presentations 
Graphical presentation of pertinent data will be given by means of box plots, bar charts, 
and survival graphs, as appropriate. Additional forms of graphical presentations may be 
specified. Descriptions of graphical presentations are included in the appendix of this 
document. 
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13.3 
Confirmatory Statistics 
Not applicable for the present Week 32 analysis of Study Part IIa. The confirmatory 
analysis is described in the SAP for the Week 24 analysis (Final 1.0, 10-July-2017). 
 
13.4 
Exploratory Statistics 
Exploratory statistical analyses will be performed for the other secondary endpoints at 
Week 32, and at Week 28. All statistical tests and confidence intervals will be calculated 
two-sided and will be interpreted in the exploratory sense only.  
 
13.4.1 
Binary Endpoints 
For binary endpoints counts and percentage of subjects per treatment group along with 
odds ratio (OR), relative risk (RR) and risk difference (RD), 95% confidence intervals 
(95% CIs) and p-values for treatment effect using the chi-square test will be provided. 
Time-to-event analyses will be performed for binary endpoints PASI 75/90/100 response, 
DLQI 0/1 response, onset of any TEAE, serious TEAE, and treatment discontinuation due 
to TEAE using Kaplan-Meier product limit method and Cox proportional hazards model. 
Summary tables will provide counts and percentage of subjects per treatment 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 factor treatment group). 
The survival curves will also be displayed graphically. Time-to-event analyses of binary 
endpoints will be performed on the observed cases only (i.e., missing data will not be 
replaced for time-to-event analyses). 
A logistic regression model will be used for subgroup analyses of selected binary endpoints 
(i.e., PASI 75/90/100 response, DLQI 0/1 response, onset of any TEAE, serious TEAE, and 
treatment discontinuation due to TEAE) at Week 32 with factors for treatment group, the 
respective subgroup and the interaction term between treatment and subgroup. Only the 
p-value of the interaction term will be provided from these analyses. 
 
13.4.2 
Continuous Endpoints 
The change from baseline of continuous endpoints will be analyzed by an analysis of 
covariance model (ANCOVA) with the fixed effect factor for treatment group 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 95% CI and two-sided p-value will be provided from the ANCOVA model. For subgroup 
analyses of continuous endpoints, the ANCOVA model will be extended by the respective 
subgroup and the interaction term between treatment and subgroup. 
 
 
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13.5 
Adjustment for Covariates 
The baseline value will be used as covariate in the analysis of variance model (ANCOVA) 
for the change from baseline of continuous response parameters. 
 
13.6 
Planned Analyses 
The following analyses are planned to be performed. 
1. Main Analysis (Confirmatory Week 24 Analysis) 
The confirmatory main analysis was performed at the end of Study Part I, i.e., after all 
subjects had completed their visit at 24 weeks after randomization or discontinued earlier. 
This analysis, described in a separate SAP (‘SAP Week 24’, final version 1.0, 10-July-
2017), included the confirmatory analysis of the primary endpoint and the major 
secondary endpoints as well as all other exploratory predefined efficacy and safety 
analyses until Week 24. The results of the analysis are described in the Clinical Study 
Report Week 24, dated 14.05. 2018. 
2. Interim Analysis (Exploratory Week 64 Analysis)  
No confirmatory analysis is planned to be performed. The (exploratory) interim analysis 
will be performed at the end of Study Part II, i.e. after all subjects had completed their 
visits at 64 weeks after randomization or discontinued earlier. The Week 64 analysis will 
be split into 2 parts, the Week 32 analysis and the Week 64 analysis. 
- 
The Week 32 analysis, described in this SAP (‘SAP Week 32’), summarizes the 
study data until Week 32 (Study Part IIa; continuation of assigned treatment from 
Week 24 through Week 32). All statistical analyses will be descriptive and 
exploratory only for the predefined efficacy and safety analyses until Week 32.  
- 
The Week 64 analysis, described in a separate SAP (‘SAP Week 64’), summarizes 
the study data until Week 64 (Study Part IIb). The analysis will include all efficacy 
measures until Week 56 and safety measures until the Week 64 safety visit.  
3. Final Analysis (Exploratory Week 100 Analysis) 
No confirmatory analysis is planned to be performed. The (exploratory) final analysis will 
be performed at the end of Study Part III, i.e. after all subjects had completed their visits 
at 100 weeks after randomization or completed earlier (i.e., subjects meet the definition of 
loss of response) or discontinued earlier. 
 
13.7 
Multi-center Data 
Exploration of possible heterogeneity of treatment effects across centers for the proportion 
of subjects achieving a PASI 90 response at Week 32 using nonresponder imputation 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. 
 
 
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13.8 
Subgroup Analyses 
The following subgroup analyses are planned to be performed to evaluate consistency over 
demographics and baseline disease characteristics of all efficacy endpoints and as well of 
the 
following 
safety 
endpoints: 
onset 
of 
any 
TEAE, 
serious 
TEAE, 
treatment 
discontinuation due to TEAE. 
• 
Gender 
o 
male 
o 
female 
• 
Age at baseline in years 
o 
< 45 
o 
≥ 45 - < 65  
o 
≥ 65 
• 
PASI 
o 
< 20 
o 
≥ 20 
The subgroup analyses will also include time-to-event analyses for the binary endpoints 
PASI 75/90/100 response, DLQI 0/1 response, onset of any TEAE, serious TEAE, and 
treatment discontinuation due to TEAE. 
Subgroup analyses for all efficacy endpoints will be performed using the following different 
imputation rules of missing values at Week 32 (see SAP sections 13.1.6 and 13.9): 
• 
Binary endpoint: 
o 
Nonresponder imputation 
o 
LOCF (only PASI 75/90 response, and DLQI 0/1 response) 
o 
Multiple imputation 
• 
Continuous endpoint: 
o 
Multiple Imputation 
Subgroup analyses will NOT be performed for the per-protocol analysis set. 
 
 
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13.9 
Sensitivity Analyses 
The following sensitivity analyses at Week 32 with respect to the handling of missing 
values are planned to be performed: 
• 
Multiple imputation will be used for all binary and continuous endpoints. 
o 
For the multiple imputation, the repeated nature of the analysis is restricted 
to the imputation step (procedure "MI" in SAS). Basic premise is the 
creation of several datasets in which missing data is imputed in a random 
fashion and then analyses are performed to check for changes for the 
conclusion. The analysis will be done with SAS Proc MIANALYZE. 
• 
LOCF imputation will be used for all binary endpoints (see SAP section 13.1.6). 
• 
An 'observed cases analysis' for all binary and continuous endpoints without 
substitution of missing data will be used (see SAP section 13.1.6). 
Sensitivity analyses at Week 32 with respect to the handling of missing values will be 
performed for all binary and all continuous efficacy endpoints. 
Sensitivity analyses at Week 32 with respect to the handling of missing values will NOT be 
performed for the per-protocol analysis set. 
 
 
 
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14.0 Statistical Analyses 
A table of contents of planned data displays is provided in section 18.1 of this document. 
The following sections are intended to provide more details of the planned analyses. In 
addition, mock tables were created and were used as template for statistical programming 
at the Week 24 analysis. This mock tables will be used analogously for the present Week 
32 analysis of Study Part IIa. 
Data will be appropriately summarized and analyzed using tabulation and graphs with 
respect to demographic/baseline characteristics and efficacy/safety observations and 
measurements. Standard descriptive summary statistics (i.e., n, arithmetic mean, 
standard deviation, median, minimum/maximum value, quartiles) will be calculated for 
continuous variables. Categorical data will be presented in frequency tables using counts 
and percentages. In general, summary tables will be displayed by treatment group as the 
main classification variable and for the total of the sample in the respective analysis set. 
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, center, subject number and study visit, if applicable. 
14.1 
Study Subjects 
Unless otherwise specified, data on study subjects will be analyzed based on data from all 
subjects randomized at Week 0 ('efficacy analysis set').  
14.1.1 
Disposition of Subjects 
The overview of subject disposition will provide the respective frequency counts and 
percentages regarding the following subjects: 
• 
Treatment phase from Week 0 until Week 32 
o 
Subjects who were enrolled (i.e., signed informed consent Part I) 
o 
Subjects who were randomized 
o 
Subjects who were treated 
o 
Subjects with premature discontinuation of study treatment until Week 24 
o 
Subjects who completed the treatment phase until Week 24 
o 
Subject who entered Study Part II (i.e., signed informed consent Part II) 
o 
Subjects with premature discontinuation of study treatment until Week 32 
o 
Subjects who completed the treatment phase until Week 32 
The table will also include the total number of study sites and the dates of the enrolment 
of the first subject and the last visit of the last subject in Study Part IIa scheduled at Week 
32. Moreover, the overview of subject disposition will be broken down by center. A flow 
diagram (according to the CONSORT statement) giving an overview of subject disposition 
will also be provided. 
In addition, the number and percentage of randomized subjects continuing and attending 
by study visit will be displayed in a separate table. Subjects will be counted as continuing 
at the time of visit whether they attend the visit or not. Only those subjects that 
prematurely discontinued before the visit will not be counted as attending.  
 
 
 
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14.1.2 
Discontinuation of Study Treatment 
The number and percentage of randomized subjects who discontinued study treatment 
prematurely within the 32 Weeks treatment period of the study will be tabulated for each 
reason of premature discontinuation (including tabulation of specifications for category 
‘other’). Moreover, the number of subjects enrolled but not randomized (i.e., screening 
failures) and the reasons for not being randomized will be given. 
 
14.1.3 
Protocol Deviations 
In general, the following list of major protocol deviations may have the potential to impact 
subjects’ rights, safety or well-being, or the integrity and/or result of the clinical trial. 
Subjects with major protocol deviations will be summarized by category for all randomized 
subjects. 
• 
Developed withdrawal criteria but not withdrawn 
• 
Entered but did not satisfy criteria 
• 
Received a disallowed concomitant treatment 
• 
Received wrong treatment or incorrect dose 
• 
Other 
The summary table will provide the number of subjects per major protocol deviation and 
will also provide the number of major protocol deviations. 
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. 
14.1.4 
Analysis Sets 
The number and percentage of randomized subjects included in each analysis set, 
together with a breakdown of the reasons for exclusion for non-evaluable subjects, will be 
provided. 
 
 
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14.2  Demographic and Other Baseline Characteristics 
In the Week 24 analysis, assessments made at the screening visit and the baseline visit 
were summarized by treatment group and overall. These assessments included 
demographic characteristics and other parameters (such as medical history, previous 
psoriasis 
therapy 
by 
type 
(phototherapy 
and 
topical 
therapy)) 
substance 
use 
alcohol/tobacco, previous and concomitant diseases, prior and concomitant medication, 
physical examination). By-treatment summaries should serve to identify any imbalances 
between the treatment groups at baseline. Summary tables were provided by means of 
descriptive statistics and frequency tables, where appropriate. Demographic and other 
baseline characteristics were analyzed based on data from all subjects randomized at 
Week 0 ('efficacy analysis set'). No analyses for baseline balance using statistical 
hypothesis tests or confidence intervals were done. 
For the present Week 32 analysis only data on concomitant medication, concomitant 
therapy and shampoo and moisturizer will be analyzed including the time period from 
Week 0 until Week 32. 
 
14.2.1 
Demographics 
Not applicable for the Week 32 analysis. The analysis was already performed at the Week 
24 analysis. 
 
14.2.2 
Medical History 
Not applicable for the Week 32 analysis. The analysis was already performed at the Week 
24 analysis. 
 
14.2.3 
Diagnosis of Psoriasis 
Not applicable for the Week 32 analysis. The analysis was already performed at the Week 
24 analysis. 
 
14.2.4 
Previous Psoriasis Therapy 
Not applicable for the Week 32 analysis. The analysis was already performed at the Week 
24 analysis. 
 
14.2.5 
Substance Use  
Not applicable for the Week 32 analysis. The analysis was already performed at the Week 
24 analysis. 
 
14.2.6 
Physical Examination 
Not applicable for the Week 32 analysis. The analysis was already performed at the Week 
24 analysis. 
 
14.2.7 
Tuberculosis Evaluation 
Not applicable for the Week 32 analysis. The analysis was already performed at the Week 
24 analysis. 
 
 
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14.2.8 
Chest Radiograph Result 
Not applicable for the Week 32 analysis. The analysis was already performed at the Week 
24 analysis. 
 
14.2.9 
Concomitant Medication and Therapy 
Analyses of concomitant medication and therapy will consider the data recorded within the 
32 Weeks treatment period of the study. In case of early treatment discontinuation before 
Week 32, concomitant medication and therapy with a start date at or after the 
discontinuation date will not be considered. 
Concomitant Medication 
The number and percentage of subjects with use of concomitant medication until Week 32 
will be displayed in WHO-DD terminology as described in SAP section 14.7. Concomitant 
medication will be identified from the Concomitant Medication form of the eCRF. 
The number and percentage of subjects with indication for concomitant medication will be 
displayed in MedDRA terminology as described in SAP section 14.6. 
Concomitant Therapy 
The number and percentage of subjects with use of concomitant therapy until Week 32 
will be displayed in MedDRA terminology as described in SAP section 14.6. Concomitant 
therapy will be identified from the Concomitant Therapy form of the eCRF. 
The number and percentage of subjects with indication for concomitant therapy until Week 
32 will be displayed in MedDRA terminology as described in SAP section 14.6. 
 
14.2.10 
Shampoo and Moisturizer 
The number and percentage of subjects with use of shampoo or moisturizer until Week 32 
will be displayed in a frequency table. 
 
 
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14.3  Treatment Compliance 
Treatment compliance will be analyzed based on data from all subjects randomized at 
Week 0 ('efficacy analysis set'). 
 
14.3.1 
Visit Windows 
The number of days between the scheduled study visits and the baseline visit will be 
calculated using the reported visit dates per scheduled study visit and will be displayed by 
summary descriptive statistics until Week 32. 
 
14.3.2 
Study Medication 
Categorical data on guselkumab administration recorded until Week 32 will be summarized 
by frequency tabulation providing the number and percentage of subjects per category. 
Frequency tabulation and descriptive statistics will be presented for the overall number of 
guselkumab administrations until Week 32. 
Compliance to guselkumab administration will be calculated as follows based on the eCRF 
data until Week 32: 
• 
Compliance guselkumab in % = (number of actual administrations x 100 / number 
of planned adminstrations)  
Categorical data on Fumaderm® initial/ Fumaderm® administration during initial uptitration 
and/or maintenance period (including data on reasons for end of uptitration and reasons 
for dose selection) recorded at each week until Week 32 and will be summarized by 
frequency tabulation providing the number and percentage of subjects per category. The 
number of planned tablets to be taken in the morning, at noon, and in the evening will 
also be summed up and analyzed descriptively. 
The number of dispensed and returned tablets of Fumaderm® initial/ Fumaderm® until 
Week 32 is not documented in the eCRF. Therefore the compliance to Fumaderm® initial 
and Fumaderm® administration in % cannot be calculated.  
Treatment compliance will also be assessed by protocol deviations related to study drug 
administration (i.e., incorrect study drug received and missed administrations).  
For subjects who completed the Week 32 visit the dose of Fumaderm® in mg at Week 32 
will be summarized by descriptive statistics and frequency tabulation. In addition, the 
maximum dose of Fumaderm® initial and Fumaderm® in mg will be calculated for all 
subjects and will be summarized by descriptive statistics and frequency tabulation. 
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14.4  Analysis of Efficacy 
All efficacy analyses to compare guselkumab vs. FAE will be performed for all subjects 
randomized at Week 0 ('efficacy analysis set'). The PASI 90, PASI 75, and DLQI 0/1 
response rates will also be analyzed using the per-protocol analysis set. However, 
subgroup and sensitivity analyses at Week 32 will NOT be performed for the per-protocol 
analysis set. 
All statistical analyses will be descriptive and exploratory only for the predefined efficacy 
and safety analyses until Week 32. All statistical tests will be performed two-sided in an 
exploratory sense.  
Handling of missing values, exploratory statistics, subgroup analyses, and sensitivity 
analyses will be performed as described in detail in the following sections of this SAP: 
SAP Section No. 
Topic 
13.1.6 
Handling of missing values 
13.4.1 
Exploratory statistics - binary endpoints 
13.4.2 
Exploratory statistics - continuous endpoints 
13.8 
Subgroup analyses 
13.9 
Sensitivity analyses 
Data at the scheduled point Week 28 during the active treatment period will be analyzed 
analogously to the Week 32 data. However, no subgroup or sensitivity analyses will be 
performed for this point in time. 
 
 
 
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14.4.1 
Primary Endpoint 
Not applicable for the Week 32 analysis. The confirmatory statistical analysis was already 
performed at the Week 24 analysis. 
 
14.4.2 
Major Secondary Endpoints 
14.4.2.1 
Endpoint related to PASI 
Not applicable for the Week 32 analysis. The confirmatory statistical analysis was already 
performed at the Week 24 analysis. 
 
14.4.2.2 
Endpoint related to DLQI 
Not applicable for the Week 32 analysis. The confirmatory statistical analysis was already 
performed at the Week 24 analysis. 
 
14.4.3 
Other Secondary Endpoints 
The following sections provide a description of the planned statistical analyses of the other 
secondary endpoints as reported in the CSP (Protocol Amendment INT-1) and as well of 
additional endpoints not explicitly stated in the CSP (see SAP section 15.0). 
 
14.4.3.1 
Endpoints related to PASI 
Other secondary endpoints related to PASI are: 
• The proportion of subjects achieving a 75%/90%/100% improvement of their psoriasis 
according to the PASI at Week 32 (PASI 75/90/100 response) 
• The proportion of subjects achieving an absolute PASI score ≤1, ≤2, ≤3, ≤5 at Week 
32 
The proportion of responding 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. 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 32 per treatment arm and for the difference between the two arms. 
Additional 
exploratory 
statistical 
analyses 
(also 
including 
analyses 
of 
time 
to 
PASI 75/90/100 response) will be performed as described in SAP section 13.4.1. 
 
14.4.3.2 
Endpoints related to PSSD 
Other secondary endpoints related to PSSD are: 
• The change from baseline in the signs and symptoms aggregate scores of the PSSD at 
Week 32 
• The change from baseline in the individual scale scores for itch, pain, and scaling of 
PSSD components at Week 32 
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The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 32 value and the change from the 
baseline value will be displayed. 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2). 
In addition, the other individual scale scores will be analyzed analogously. 
 
14.4.3.3 
Endpoints related to IGA 
Other secondary endpoints related to IGA are: 
• The proportion of subjects achieving an IGA score of cleared (0) at Week 32 
The proportion of responding 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.  
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 32 per treatment arm and for the difference between the two arms. 
Additional exploratory statistical analyses will be performed as described in SAP section 
13.4.1. 
In addition, the proportion of subjects achieving an IGA score of cleared (0) or minimal (1) 
at Week 32 will be analyzed analogously. 
 
14.4.3.4 
Endpoints related to BSA 
Other secondary endpoints related to BSA are: 
• The change from baseline of body surface area (BSA) psoriatic involvement at Week 32  
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 32 value and the change from the 
baseline value will be displayed. 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2).  
 
14.4.3.5 
Endpoints related to DLQI 
Other secondary endpoints related to DLQI are: 
• The proportion of subjects achieving a DLQI score of 0 or 1 at Week 32 
• The change from baseline in DLQI score at Week 32 
The proportion of subjects achieving a DLQI score of 0 or 1 at Week 32 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. 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 32 per treatment arm and for the difference between the two arms. 
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Exploratory statistical analyses (also including analyses of time to DLQI 0/1 response) will 
be performed as described in SAP section 13.4.1. 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 32 value and the change from the 
baseline value will be displayed. 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2). 
 
14.4.3.6 
Endpoints related to ss-IGA 
Other secondary endpoints related to ss-IGA are: 
• The proportion of subjects achieving an ss-IGA score of absence of disease (0) at Week 
32 in randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at baseline 
The proportion of responding 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. 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for response rate at 
Week 32 per treatment arm and for the difference between the two arms. 
Additional exploratory statistical analyses will be performed as described in SAP section 
13.4.1. 
In addition, the proportion of subjects achieving an ss-IGA score of absence of disease (0) 
or very mild disease (1) at Week 32 will be analyzed analogously. 
 
14.4.3.7 
Endpoints related to SF-36 
Other secondary endpoints related to SF-36 are: 
• The change from baseline in the physical and mental component summary scores of 
SF-36 at Week 32 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 32 value and the change from the 
baseline value will displayed. 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2). 
 
14.4.4 
Other Efficacy Assessments 
In addition to the efficacy analyses described above all efficacy data related to PASI, DLQI, 
PSSD, IGA, ss-IGA, and SF-36 at all scheduled study visits during the active treatment 
period until Week 32 will be summarized descriptively without any imputation of missing 
data (‘observed cases analysis’; see SAP section 13.1.6). 
 
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14.5  Analysis of Safety 
Safety data, including but not limited to, adverse events (AEs), serious adverse events 
(SAEs), infections, serious infections, mortality, changes in laboratory assessments, and 
changes in vital signs will be summarized using descriptive statistics. All safety analyses to 
compare guselkumab vs. FAE will be performed for all treated subjects ('safety analysis 
set'). 
 
14.5.1 
Extent of Exposure  
Extent of exposure will be defined as the total number of days from baseline to Week 32 
(for all patients still under treatment) or to study discontinuation. 
Descriptive summary statistics and frequency tables (using appropriate categories) will be 
provided for the extent of exposure.  
 
14.5.2 
Adverse Events 
Adverse events data will be processed in the statistical analysis after coding according to 
the MedDRA dictionary version 19.1. All reported AEs with onset date during the active 
treatment period until Week 32 (i.e., treatment emergent AEs) will be included in the 
analysis. In case of early treatment discontinuation before Week 32, all reported AEs with 
onset date during the safety follow-up period until Week 32 (i.e., treatment emergent 
AEs) will be included in the analysis. AEs reported after Week 32 will NOT be considered in 
the analysis. 
 
14.5.2.1 
Definitions 
The following definitions will be applied in the present study 
Crude Incidence Rate 
Where percentages of subjects are reported in summary tables, incidences provide 
information on the proportion of subjects experiencing adverse events in relation to the 
total number of subjects exposed, i.e., if not otherwise specified, the crude incidence rate 
will be used.  
The crude incidence rate is defined as the number of subjects experiencing a certain 
event, divided by the number of subjects exposed to study treatment, regardless of 
duration of use: 
 
exposed
 
patients
 
of
number 
events
 
adverse
 with 
patients
 
of
number 
 *
100
 
rate
 
incidence
 
Crude
=
 
 
Treatment Emergent Adverse Events 
Treatment emergent adverse events (TEAEs) are those AEs that occurred during the 
active treatment period until Week 32 after the start of initial study drug administration 
and those AEs that were present at baseline but worsened in severity after the start of 
initial study drug administration. AEs reported after Week 32 will NOT be considered in the 
present analysis.  
In case of early treatment discontinuation before Week 32, all reported AEs with onset 
date during the safety follow-up period until Week 32 will be included in the analyses. 
Thus, identification of TEAEs (distinguished by subjects who completed or discontinued the 
treatment period until Week 32) will be performed as follows: 
 
 
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• 
TEAE for Completer of Study Part IIa: Date of Week 0 ≤ Start Date of AE ≤ Date of 
Week 32 
• 
TEAE for Non-Completer of Study Part IIa: Date of Week 0 ≤ Start Date of AE ≤ 
Date of Final Study Visit 
AEs which are not classified as TEAEs will be considered as not treatment emergent 
adverse events (NTEAEs). 
 
14.5.2.2 
Analyses 
Overview of adverse events 
For summary presentation of the overall adverse event experience overview tables will be 
provided for AEs and SAEs including the following information: 
Adverse events: 
• 
n (%) of subjects with AEs *) 
• 
n (%) of subjects with NTEAEs *) 
• 
n (%) of subjects with TEAEs *) 
• 
n (%) of subjects with TEAEs by highest causality to study medication 
• 
n (%) of subjects with TEAEs by worst severity 
• 
n (%) of subjects with TEAEs leading to dose modification *) 
• 
n (%) of subjects with TEAEs leading to permanent stop of study medication *) 
Serious Adverse events: 
• 
n (%) of subjects with SAEs *) 
• 
n (%) of subjects with NTESAEs *) 
• 
n (%) of subjects with TESAEs *) 
• 
n (%) of subjects with TESAEs leading to death *) 
• 
n (%) of subjects with TESAEs by highest causality to study medication 
• 
n (%) of subjects with TESAEs by worst severity 
• 
n (%) of subjects with TESAEs leading to permanent stop of study medication *) 
*) the number of events (i.e., number of coded preferred terms) will also be given. 
TEAEs/TESAEs leading to dose modification will be defined as all events with 'Action taken 
with study treatment' is not equal to 'DOSE NOT CHANGED'. 
In addition, the number of TEAEs will be displayed for the following investigator’s ratings: 
• 
severity  
• 
seriousness 
• 
causality 
• 
action taken 
• 
outcome 
 
 
 
 
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Detailed display of adverse events 
For a more detailed display, adverse events will be presented in summary tables, listing 
these events in code form according to the preferred term. These tables will show the 
number of subjects per group presenting an adverse event and the incidence of its 
occurrence. Adverse events will be grouped by primary SOC (System Organ Class) and will 
be stratified additionally by highest causality to study treatment (not related, doubtful, 
possible, probable, or very likely) and by worst severity (mild, moderate, or severe). The 
incidence of adverse events will be presented by decreasing order of frequency at 
preferred term level within the primary SOC. 
The following tables will be provided for the detailed display of adverse events: 
Adverse events: 
• 
TEAEs by primary SOC and preferred term *) 
• 
TEAEs by primary SOC and preferred term stratified by highest causality 
• 
TEAEs by primary SOC and preferred term stratified by worst severity 
 thereof 
o 
Drug related TEAEs 
o 
Not drug related TEAEs 
• 
TEAEs leading to permanent stop of study medication by primary SOC and 
preferred term *) 
Serious Adverse events: 
• 
TESAEs by primary SOC and preferred term *) 
• 
TESAEs by primary SOC and preferred term stratified by highest causality 
• 
TESAEs by primary SOC and preferred term stratified by worst severity 
• 
TESAEs leading to permanent stop of study medication by primary SOC and 
preferred term *) 
• 
TESAEs leading to death by primary SOC and preferred term *) 
Not treatment emergent adverse events: 
• 
NTEAEs by primary SOC and preferred term *) 
*) These tables will show additionally the number of events (i.e., number of coded preferred terms). 
Summary tabulation of TEAEs and TESAEs by primary SOC and preferred term will also be 
provided for the following types of adverse events: 
• 
injection site reactions (according to the tick box in the e-CRF) 
• 
infections (according to the tick box in the e-CRF) 
o 
thereof, infections treated with oral or parenteral antibiotics 
• 
adverse events of psoriasis (adverse events of psoriasis include any event of 
erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, inverse psoriasis, 
palmo-plantar psoriasis and worsening or exacerbation of psoriasis; final allocation 
will be performed after blinded data review). 
Note that the summary tables will provide the number of subjects per event (i.e., coded as 
preferred term) and will also provide the number of events for certain tables. 
 
 
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For calculation of the number of subjects per event each preferred term will be counted 
only once per subject and will be linked to the primary SOC. A subject may contribute with 
more than one different adverse event (at preferred term level); however, a subject with 
more than one occurrence of the same adverse event (at preferred term level) is displayed 
and counted only once for this event in the tables. 
Tables that are stratified by the severity of adverse events will summarize the worst 
severity per subject and preferred term.  
Tables that are stratified by the relationship of adverse events will summarize the highest 
relationship per subject and preferred term. 
For presentation of drug related/ not drug related adverse events the following categories 
will be used: 
• 
drug related   
=  
very likely, probable, possible 
• 
not drug related  
=  
doubtful, not related 
For summarization of severity of drug related TEAEs, events with a causality assessment 
of 'doubtful/not related' will be excluded and the worst severity will be tabulated as 
described above. Summarization of severity of not drug related TEAEs will be performed 
likewise. 
 
The following safety endpoints will be defined:  
• The proportion of subjects with any TEAE within the 32 Weeks treatment period 
• The proportion of subjects with serious TEAE within the 32 Weeks treatment period 
• The proportion of subjects with treatment discontinuation due to TEAE within the 32 
Weeks treatment period 
• The proportion of subjects with any TEAE by preferred term and SOC within the 32 
Weeks treatment period  
Counts and percentage of subjects per treatment group along with odds ratio (OR), 
relative risk (RR) and risk difference (RD), 95% confidence intervals (95% CIs) and p-
values for treatment effect using the chi-square test will be provided. In addition, time-to-
event-analyses and logistic regression analyses as described in SAP section 13.4.1 will be 
conducted for the onset of any TEAE, serious TEAE, and treatment discontinuation due to 
TEAE. 
Subgroup analyses will be performed for the subgroups defined in SAP section 13.8 for the 
proportion of subjects with any TEAE, serious TEAE, and treatment discontinuation due to 
TEAE. 
The cut-off ≥ 5% (i.e., percentage of subjects ≥ X% in at least one treatment group) will 
be used for analyses of TEAEs by preferred term for any TEAE. 
In addition, the rate of infections TEAEs (according to the tick box in the e-CRF) per 
subject per week for the treatment period Week 0-32 will be estimated using Poisson 
regression. Tabulated summaries will also display 95% CIs for the respective rates. The 
treatment duration will be calculated as time span (weeks) between baseline (week 0) and 
week 32 (for all subjects still under treatment) or to study discontinuation. 
 
 
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Listings 
All adverse events (AEs) and serious adverse events (SAEs) will be listed in the individual 
subject data listings by treatment group, study center and subject number including all 
information documented on the respective form of the eCRF. Separate listings of subjects 
with the following AEs will be provided: SAEs, SAEs leading to death, AEs of severe 
intensity, AEs leading to permanent discontinuation of study medication. 
Verbatim description of the adverse event reported by the investigator, MedDRA preferred 
terms and primary SOCs (system organ class) for all adverse events will be contained in 
the data listings. Non treatment emergent adverse events will be flagged in the respective 
listings. 
 
14.5.3 
Clinical Laboratory Tests 
Laboratory data will be summarized by type of laboratory test. Reference ranges will be 
used in the summary of laboratory data. Descriptive statistics will be calculated for each 
laboratory item at each scheduled time. Changes from baseline results will be presented in 
pre- versus post-treatment cross-tabulations (with classes for below, within, and above 
normal ranges).  
Results of tuberculosis testing, serology, urine pregnancy testing and local urinalysis 
(glucose, protein) will be displayed in frequency tables providing the number and 
percentage of subjects per category (i.e., negative or positive) at each scheduled time. 
The results of all laboratory tests will be provided in individual subject data listings 
including the reference ranges. Abnormal values will be identified by flagging all values 
below and above the reference range. 
A listing of subjects with any laboratory results outside the reference ranges will be 
provided.  
For the lymphocyte count the following subjects will be listed and summarized in a 
frequency table:  
• 
lowest lymphocyte count < 500/µl 
• 
500/µl ≤ lowest lymphocyte count <700/µl  
• 
700/µl ≤ lowest lymphocyte count < lower limit of normal range 
Graphical presentation of quantitative laboratory data will be given by means of box plots. 
 
 
 
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14.5.4 
Vital Signs 
Descriptive statistics of pulse and blood pressure (systolic and diastolic) values and 
changes from baseline will be summarized at each scheduled time. Subjects reporting vital 
signs findings beyond clinically important limits will be identified using the following 
criteria.  
Criteria for Identifying Potentially Clinically Significant Vital Signs Findings 
Variable (units) 
Criterion Valuea 
Change from Baseline 
Systolic Blood Pressure (mmHg) 
 
>200 
 
<80 
Increase of >40 
Decrease of >40 
Diastolic Blood Pressure (mmHg) 
 
>120 
 
<40 
Increase of >30 
Decrease of >30 
Heart Rate (bpm) 
 
>110 
 
<40 
 
In order to be identified as an abnormality of potential clinical importance, a value would need to meet the 
criterion value or also represent a change of at least the magnitude noted in the change column. 
Vital signs values of potentially clinically significant importance will be analyzed by 
providing the number and percentages of subjects with values of potential clinical 
importance per scheduled study visit, overall during the study and with first occurrence 
after baseline. 
 
14.5.5 
Physical Examination 
Physical examination findings will be tabulated by the body systems given in the eCRF at 
each scheduled time. Moreover, abnormal findings with first occurrence after baseline 
reported during the treatment phase and follow-up phase will be presented. Details on 
abnormal findings in verbatim terms will be displayed in individual subject data listings. 
 
14.5.6 
Body Weight 
Not applicable for the Week 32 analysis. Body weight ist not documented at Week 32. The 
analysis until Week 24 was already performed at the Week 24 analysis. 
 
14.5.7 
Early Detection of Active Tuberculosis 
Not applicable for the Week 32 analysis. Data on early detection of active tuberculosis is 
not documented at Week 32. The analysis until Week 24 was already performed at the 
Week 24 analysis. 
14.6 Analysis of MedDRA Codes 
Previous / concomitant diseases (including indications for use of concomitant and other 
medications) and adverse events will be coded with version 19.1 of the MedDRA-
dictionary. 
In general, tabulation will be displayed by preferred term and primary SOC. 
14.7 Analysis of WHO Drug Dictionary Codes 
The use of concomitant and other medications will be coded using the WHO Drug 
Dictionary (version 2016/1). Medications will be tabulated by preferred name (i.e., the 
decode of the code which results when SEQ1 and SEQ2 are set to 01 and 001, respectively 
(usually resulting in a decode close to the generic drug name)) and they will be grouped 
by level 2 of the Anatomical Therapeutic Chemical (ATC) code. Codes being linked to more 
than one ATC code at this level will be assigned to one primary ATC code by medical data 
analysts. 
 
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15.0 Changes to Planned Analyses 
This statistical analysis plan includes the following relevant changes to the planned 
analyses which are described in the clinical study protocol. 
• 
Evaluations on health technology assessment (HTA) will also be specified in this 
SAP. No separate SAP for evaluations on health technology assessment will be 
provided (see SAP section 3.0 and CSP section 11) 
• 
A per-protocol analysis will be performed for the PASI 90, PASI 75, and DLQI 0/1 
response rates (see SAP section 11.0). 
• 
No treatment failure imputation rules will be applied (see to SAP section 13.1.5 and 
CSP section 11.4) 
• 
The following safety endpoints will be defined and used for the statistical analyses 
for HTA purposes:  
o The proportion of subjects with any TEAE within the 32 Weeks treatment period 
o The proportion of subjects with serious TEAE within the 32 Weeks treatment 
period 
o The proportion of subjects with treatment discontinuation due to TEAE within the 
32 Weeks treatment period 
o The 
proportion 
of 
subjects 
with 
any 
TEAE, 
serious 
TEAE, 
treatment 
discontinuation due to TEAE by preferred term and SOC within the 32 Weeks 
treatment period 
• 
Time-to-event analyses for binary endpoints PASI 75/90/100 response, DLQI 0/1 
response, onset of TEAE, serious TEAE, and treatment discontinuation due to TEAE 
will be performed using Kaplan-Meier product limit method and Cox proportional 
hazards model. 
The following additional efficacy endpoints will be defined and used for the statistical 
analyses: 
o The change from baseline in the signs and symptoms aggregate scores of the 
PSSD at Week 32 
o The change from baseline in the individual scale scores for itch, pain and scaling 
of PSSD components at Week 32 
o The proportion of subjects achieving an absolute PASI score ≤1, ≤2, ≤3, ≤5 at 
Week 32 
o Time to event analysis for PASI score ≤1, ≤2, ≤3, ≤5 
o The proportion of subjects achieving an IGA score of cleared (0) at Week 32 
o The proportion of subjects achieving an IGA score of cleared (0) or  
minimal (1) at Week 32 
o The change from baseline of body surface area (BSA) psoriatic involvement at 
Week 32 
o The change from baseline in DLQI score at Week 32 
o The proportion of subjects achieving an ss-IGA score of absence of  
disease (0) at Week 32 in randomized subjects with scalp psoriasis and an ss-
IGA score ≥2 at baseline 
o The proportion of subjects achieving an ss-IGA score of absence of  
disease (0) or very mild disease (1) at Week 32 in randomized subjects with 
scalp psoriasis and an ss-IGA score ≥2 at baseline 
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o The change from baseline in the physical and mental component summary 
scores of SF-36 at Week 32  
Any major changes to this plan after sign-off of the latest final version will be specified in 
the clinical study report. 
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16.0 Tabulation 
16.1  General 
The statistical output will be prepared in American English. No separate statistical report 
will be written. 
 
16.2 Format of Data Displays 
The layout of all tables, listings and figures will be drafted by acromion GmbH when 
providing the first draft tables, listings and figures on final data. No sponsor or other 
requirements for layout specifications have to be followed. 
 
The SAS outputs will be post-processed within Microsoft Word®. SAS tables and listings 
will be integrated into Microsoft Word® using the SAS Monospace 8 points font. 
 
Separate appendices will be provided for tables, listings, and figures. For each appendix a 
corresponding table of contents will be generated. All pages within one appendix will be 
numbered consecutively. Tables, listings and figures generally should be self-explaining. 
Abbreviations will be described in the footnote if necessary. 
 
16.2.1 
Tables 
SAS summary tables will be produced using a landscape page. The maximum number of 
lines per page will be pagesize = 40 and the number of characters in one line will be 
linesize = 140.  
 
16.2.2 
Listings  
SAS subject data listings will be produced using a landscape page. The maximum number 
of lines per page will be pagesize = 40 and the number of characters in one line will be 
linesize = 140.  
 
Data listings will be created for groups of variables which logically belong together (e.g. 
demographic variables) and will be sorted by treatment group, center, subject and visit (if 
applicable). 
 
 
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16.2.3 
Figures  
Figures will be created using the following graphical SAS options, if not otherwise 
specified: 
 
 
GOPTIONS  
    RESET   = ALL  
    NOBORDER 
    KEYMAP = WINANSI  
    DEVMAP = WINANSI  
    DEV       = EMF 
    TARGET = WINPRTC  
    GUNIT   = CM  
    CTEXT   = BLACK  
    FTEXT   = 'Arial/bold'  
    HTEXT   = 0.5 CM  
    LFACTOR= 1  
    HSIZE   = 6 IN  
    VSIZE   = 5 IN; 
 
Variables may be presented in the following graphical formats, if applicable: 
 
Box plot 
Box plots summarize the data by a box reaching from the 1st to the 3rd quartile. The 
median is displayed inside this box by a horizontal line. Above the box a vertical line 
indicates the region from the 3rd quartile to the max. value below the upper fence ; below 
the box a vertical line indicates the region from the 1st quartile to the min. value above the 
lower fence. The upper fence lies 1.5 interquartile-ranges above the 3rd quartile, the lower 
fence lies 1.5 interquartile ranges below the 1st quartile. Values outside the fences are 
displayed by a distinct marker. 
A graphical presentation is given below: 
 
 
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Bar chart 
A bar chart displays a categorical variable. A sample display is provided below. 
 
 
Survival Graph 
A survival graph displays the survival distribution functions according to Kaplan-Meier. A 
sample display is provided below. 
 
 
 
 
16.3  Data Format 
Unless otherwise specified, percentage values will be printed with one digit to the right of 
the decimal point. 
In general, minima and maxima will be quoted to the number of decimal places as 
recorded in the eCRF; means, standard deviations and medians will be quoted to one 
further decimal place. 
All p-values will be given by four digits to the right of the decimal point. Verbatim terms 
documented in the eCRFs will be presented as entered in the clinical data base. 
0
10
20
30
40
50
25
35
45
55
% 
AGE 
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17.0 References 
Study Documents: 
Document 
Version, Date 
Protocol Amendment 
INT-1s 
Version 2.0, 25-APR-2017 
eCRF 
Version 2.0, 08-JUN-2017 
Data Management Plan 
Version 1.0, 09-DEC-2016 
Data Validation Plan 
Version 1.0, 09-DEC-2016 
Statistical Analysis Plan 
- Week 24 Analysis 
Version 1.0, 10-JUL-2017 
SOPs and Guidelines acromion: 
Document 
Title, Date 
acromion SOP BM04 
Statistical Analysis Plans, Oct-2016 
acromion SOP BM05 
Determination of Availability of Data for Analysis, Oct-2016 
acromion SOP BM06 
Generation and Release of Blinded Randomization Code, Oct-
2016 
acromion SOP BM07 
Programming of Derived Data Sets, Oct-2016 
acromion SOP BM08  
Programming of SAS Data Displays, Oct-2016 
acromion SOP BM11  
Documentation and Project Close-Out, Oct-2016 
acromion Guideline 
BM01  
SAS Programming Guideline, Oct-2016 
acromion Guideline 
BM02  
Biometrics Naming Conventions for SAS Datasets and SAS 
Programs, Oct-2016 
Other Documents: 
Document 
Title, Date 
ICH Guideline E 9 
Statistical Principles for Clinical Trials, final approval 1998 
 
 
 
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18.0 Appendices 
18.1  Table of Contents for Data Displays 
The tables, subject data listings and figures will be provided using the following numbering 
system, which will be updated after start of programming the data displays. However, this 
section does not include the HTA analyses for the topline results described in SAP section 
14.6. The numbering system for the HTA analyses will be provided with the HTA mock 
tables. 
All summary tables will start with the one-character identifier for the displayed analysis 
set followed by the one-digit identifier for the displayed analysis chapter as listed below. 
Identifier for displayed analysis set: 
• 
A: Efficacy analysis set 
• 
B: Safety analysis set 
• 
C: Per-protocol analysis set 
 
Identifier for displayed analysis chapter: 
• 
1: Study subjects 
• 
2: Demographics and other baseline characteristics 
• 
3: Treatment compliance 
• 
4: Analysis of efficacy 
• 
5: Analysis of safety 
Data displays will be provided for the following analysis sets: 
 
Chapter 
No. 
Chapter Title 
Analysis set 
1 
Study subjects 
• A: efficacy analysis set 
2 
Demographic and other baseline 
characteristics 
• A: efficacy analysis set 
3 
Treatment compliance 
• A: efficacy analysis set 
4 
Analysis of efficacy 
• A: efficacy analysis set 
• C: per-protocol analysis set 
5 
Analysis of safety 
• B: safety analysis set 
All individual subject data listings will start with the one-digit identifier for the displayed 
chapter analogously as for the summary tables. Data displays and subject data listings will 
be provided in separate appendices and pages will be numbered for each appendix 
separately starting with page no. 1. 
 
 
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18.1.1 
Tables 
Study Subjects, Prefix A 
No. 
Analysis Chapter 
1.1 
Disposition of subjects 
1.2 
Discontinuation of study treatment 
1.3 
Protocol deviations 
1.4 
Analysis sets 
 
Demographic and Other Baseline Characteristics, Prefix A 
No. 
Analysis Chapter 
2.1 
Demographics – Not applicable 
2.2 
Medical history – Not applicable 
2.3 
Diagnosis of Psoriasis – Not applicable 
2.4 
Previous Psoriasis Therapy – Not applicable 
2.5 
Substance Use – Not applicable 
2.6 
Physical Examination – Not applicable 
2.7 
Tuberculosis Evaluation – Not applicable 
2.8 
Chest Radiograph Result – Not applicable 
2.9 
Concomitant Medication and Therapy 
2.10 
Shampoo and Moisturizer 
 
Treatment Compliance, Prefix A 
No. 
Analysis Chapter 
3.1 
Visit windows 
3.2 
Study medication 
 
Analysis of Efficacy, Prefix A, C 
No. 
Analysis Chapter 
 
- Other Secondary Endpoints - 
4.1 
PASI 90% Response 
4.2.1 
PASI 75% Response 
4.2.2 
DLQI 0/1 Response 
4.3.1 
Other Endpoints related to PASI  
4.3.2 
Endpoints related to PSSD 
4.3.3 
Endpoints related to IGA 
4.3.4 
Endpoints related to BSA 
4.3.5 
Other Endpoints related to DLQI 
4.3.6 
Endpoints related to ss-IGA 
4.3.7 
Endpoints related to SF-36 
 
- Other Efficacy Assessments - 
4.4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, BSA, ss-IGA, SF-36) 
 
Analysis of Safety, Prefix B 
No. 
Analysis Chapter 
5.1 
Extent of Exposure 
5.2 
Adverse Events  
5.3 
Clinical Laboratory Tests 
5.4 
Vital Signs 
5.5 
Physical Examination 
5.6  
Body Weight – Not applicable 
5.7 
Early Detection of Active Tuberculosis – Not applicable 
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18.1.2 
Listings 
Study Subjects  
No. 
Analysis Chapter 
1.1 
Disposition of subjects 
1.2 
Discontinuation of study treatment  
1.3 
Protocol deviations 
1.4 
Analysis sets 
 
Demographic and Other Baseline Characteristics 
No. 
Analysis Chapter 
2.1 
Demographics – Not applicable 
2.2 
Medical history – Not applicable 
2.3 
Diagnosis of Psoriasis – Not applicable 
2.4 
Previous Psoriasis Therapy – Not applicable 
2.5 
Substance Use – Not applicable 
2.6 
Physical Examination – Not applicable 
2.7 
Tuberculosis Evaluation – Not applicable 
2.8 
Chest Radiograph Result – Not applicable 
2.9 
Concomitant Medication and Therapy 
2.10 
Shampoo and Moisturizer 
 
Treatment Compliance 
No. 
Analysis Chapter 
3.1 
Visit windows 
3.2 
Study medication 
 
Analysis of Efficacy 
No. 
Analysis Chapter 
 
- Other Secondary Endpoints - 
4.1 
PASI 90% Response 
4.2.1 
PASI 75% Response 
4.2.2 
DLQI 0/1 Response 
4.3.1 
Other Endpoints related to PASI 
4.3.2 
Endpoints related to PSSD 
4.3.3 
Endpoints related to IGA 
4.3.4 
Endpoints related to BSA 
4.3.5 
Other Endpoints related to DLQI 
4.3.6 
Endpoints related to ss-IGA 
4.3.7 
Endpoints related to SF-36 
 
- Other Efficacy Assessments - 
4.4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, BSA, ss-IGA, SF-36) 
 
Analysis of Safety 
No. 
Analysis Chapter 
5.1 
Extent of Exposure 
5.2 
Adverse Events  
5.3 
Clinical Laboratory Tests 
5.4 
Vital Signs 
5.5 
Physical Examination 
5.6  
Body Weight – Not applicable 
5.7 
Early Detection of Active Tuberculosis – Not applicable 
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18.1.3 
Figures 
Analysis of Efficacy, Prefix A, B, C 
No. 
Analysis Chapter 
Type of Figure 
 
- Other Secondary Endpoints - 
 
1 
PASI 90% Response 
Bar Chart, 
Survival Graph 
2.1 
PASI 75% Response 
Bar Chart, 
Survival Graph 
2.2 
DLQI 0/1 Response 
Bar Chart, 
Survival Graph 
3.1 
Other Endpoints related to PASI 
Bar Chart,  
Survival Graph 
3.2 
Endpoints related to PSSD 
Box Plot 
3.3 
Endpoints related to IGA 
Bar Chart 
3.4 
Endpoints related to BSA 
Box Plot 
3.5 
Other Endpoints related to DLQI 
Bar Chart 
3.6 
Endpoints related to ss-IGA 
Bar Chart 
3.7 
Endpoints related to SF-36 
Box Plot 
 
- Other Efficacy Assessments - 
 
4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, 
BSA, ss-IGA, SF-36) 
Bar Chart,  
Box Plot 
 
Analysis of Safety, Prefix B 
No. 
Analysis Chapter 
Type of Figure 
5 
Clinical Laboratory Tests 
Box Plot 
6 
Vital Signs 
Box Plot 
7 
Body Weight – Not applicable 
Box Plot 
 
NCT09251533


 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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Statistical Analysis Plan 
 
Multicenter, randomized, open-label, efficacy assessor-blinded, active 
comparator-controlled phase 3b study to compare the efficacy of 
guselkumab to fumaric acid esters (Fumaderm® initial/ Fumaderm®) for 
adult patients with moderate to severe plaque psoriasis who are 
candidates for and naive to systemic treatment 
POLARIS 
- Study Part IIb: Week 64 Analysis - 
 
Study Code 
CNTO1959PSO3008 
EudraCT Number 
2016-002135-15 
Development phase 
Phase 3b 
Study Design 
randomized, open-label, efficacy assessor-
blinded, single country, multicenter, 
active-comparator-controlled 
Sponsor 
Janssen-Cilag GmbH, Neuss 
Johnson & Johnson Platz 1, 
41470 Neuss, Germany 
Contract Research Organization 
acromion GmbH 
Europaallee 27 – 29 
50226 Frechen, Germany 
Version No., Date 
Final Version 1.0, 29-Aug-2018 
 
 
NCT09251533


Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
Page 2 of 66 
Table of Contents 
1.0 
Signatures .................................................................................... 4 
2.0 
List of Abbreviations .................................................................... 5 
3.0 
Introduction ................................................................................. 6 
4.0 
Responsibilities ............................................................................ 7 
5.0 
Software Utilized .......................................................................... 7 
6.0 
Coding Systems Utilized ............................................................... 7 
7.0 
Study Objectives and Hypotheses ................................................ 8 
7.1 
Objectives ................................................................................................. 8 
7.2 
Hypotheses ............................................................................................... 8 
8.0 
Study Endpoints ........................................................................... 9 
9.0 
Study Design .............................................................................. 10 
9.1 
Overview ................................................................................................. 10 
9.2 
Sample Size Determination ........................................................................ 13 
9.3 
Randomization and Blinding ....................................................................... 14 
10.0 
Study Schedule........................................................................... 15 
11.0 
Analysis Sets .............................................................................. 22 
11.1 
Definition of Analysis Sets ......................................................................... 22 
11.2 
Protocol Deviations ................................................................................... 23 
11.3 
Screening Failures .................................................................................... 23 
12.0 
Definition and Calculation of Efficacy Endpoints ......................... 24 
12.1 
Involved Body Surface Area (BSA%) ........................................................... 24 
12.2 
Investigator's Global Assessment (IGA) ....................................................... 24 
12.3 
Scalp Specific Investigator's Global Assessment (ss-IGA) .............................. 24 
12.4 
Psoriasis Area and Severity Index (PASI) .................................................... 25 
12.5 
Dermatology Life Quality Index (DLQI) ....................................................... 25 
12.6 
Psoriasis Symptom and Sign Diary (PSSD) .................................................. 26 
12.7 
Short Form Health Survey (SF-36) ............................................................. 27 
13.0 
Statistical Methodology .............................................................. 28 
13.1 
Data Handling Rules ................................................................................. 28 
13.1.1 Baseline and Post-baseline Points in Time of Interest .................................... 28 
13.1.2 Definition of Within- and Between-Group Treatment Differences ..................... 29 
13.1.3 Visit Windows .......................................................................................... 29 
13.1.4 Treatment Failure Criteria .......................................................................... 29 
13.1.5 Treatment Failure Rules ............................................................................ 29 
13.1.6 Handling of Missing Values ........................................................................ 30 
13.1.7 Data Transformations ............................................................................... 30 
13.2 
Descriptive Statistics ................................................................................ 30 
13.2.1 Dichotomous and Categorical Variables ....................................................... 30 
13.2.2 Continuous and Quasi-Continuous Variables ................................................ 30 
13.2.3 Graphical Presentations ............................................................................. 31 
13.3 
Confirmatory Statistics .............................................................................. 31 
13.4 
Exploratory Statistics ................................................................................ 31 
13.4.1 Binary Endpoints ...................................................................................... 31 
13.4.2 Continuous Endpoints ............................................................................... 31 
13.5 
Adjustment for Covariates ......................................................................... 31 
13.6 
Interim Analyses ...................................................................................... 32 
13.7 
Multi-center Data ..................................................................................... 32 
NCT09251533


Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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13.8 
Subgroup Analyses ................................................................................... 33 
13.9 
Sensitivity Analyses .................................................................................. 34 
14.0 
Statistical Analyses .................................................................... 35 
14.1 
Study Subjects ......................................................................................... 35 
14.1.1 Disposition of Subjects .............................................................................. 35 
14.1.2 Discontinuation of Study Treatment ............................................................ 36 
14.1.3 Protocol Deviations ................................................................................... 36 
14.1.4 Analysis Sets ........................................................................................... 36 
14.2 
Demographic and Other Baseline Characteristics .......................................... 37 
14.2.1 Demographics .......................................................................................... 37 
14.2.2 Medical History ........................................................................................ 37 
14.2.3 Diagnosis of Psoriasis ................................................................................ 37 
14.2.4 Previous Psoriasis Therapy ........................................................................ 37 
14.2.5 Substance Use ......................................................................................... 37 
14.2.6 Physical Examination ................................................................................ 37 
14.2.7 Tuberculosis Evaluation ............................................................................. 38 
14.2.8 Chest Radiograph Result ........................................................................... 38 
14.2.9 Concomitant Medication and Therapy .......................................................... 38 
14.2.10 Shampoo and Moisturizer .......................................................................... 38 
14.3 
Treatment Compliance .............................................................................. 39 
14.3.1 Visit Windows .......................................................................................... 39 
14.3.2 Study Medication ...................................................................................... 39 
14.4 
Analysis of Efficacy ................................................................................... 40 
14.4.1 Primary Endpoint ...................................................................................... 41 
14.4.2 Major Secondary Endpoints ....................................................................... 41 
14.4.3 Other Secondary Endpoints ....................................................................... 41 
14.4.4 Other Efficacy Assessments ....................................................................... 44 
14.4.5 Additional Efficacy Analyses ....................................................................... 45 
14.5 
Analysis of Safety ..................................................................................... 49 
14.5.1 Extent of Exposure ................................................................................... 49 
14.5.2 Adverse Events ........................................................................................ 49 
14.5.3 Clinical Laboratory Tests ........................................................................... 55 
14.5.4 Vital Signs ............................................................................................... 56 
14.5.5 Physical Examination ................................................................................ 56 
14.5.6 Body Weight ............................................................................................ 56 
14.5.7 Early Detection of Active Tuberculosis ......................................................... 56 
14.6 
Analysis of MedDRA Codes ......................................................................... 57 
14.7 
Analysis of WHO Drug Dictionary Codes ...................................................... 57 
15.0 
Changes to Planned Analyses ..................................................... 58 
16.0 
Tabulation .................................................................................. 59 
16.1 
General ................................................................................................... 59 
16.2 
Format of Data Displays ............................................................................ 59 
16.2.1 Tables ..................................................................................................... 59 
16.2.2 Listings ................................................................................................... 59 
16.2.3 Figures .................................................................................................... 60 
16.3 
Data Format ............................................................................................ 61 
17.0 
References ................................................................................. 62 
18.0 
Appendices ................................................................................. 63 
18.1 
Table of Contents for Data Displays ............................................................ 63 
18.1.1 Tables ..................................................................................................... 64 
18.1.2 Listings ................................................................................................... 65 
18.1.3 Figures .................................................................................................... 66 
 
 
NCT09251533


NCT09251533


NCT09251533


Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
Page 5 of 66 
2.0 
List of Abbreviations 
 
AE 
Adverse Event 
ANCOVA 
Analysis of Covariance 
BSA 
Body Surface Area 
CRF 
Case Report Form(s)  
CSP 
Clinical Study Protocol 
DLQI 
Dermatology Life Quality Index 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
e.g. 
example given 
FAE 
Fumaric Acid Esters 
HBV/ HCV 
Hepatitis B virus/ Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HTA 
Health Technology Assessment 
ICH 
International Council on Harmonization 
i.e. 
that is 
IGA 
Investigator´s Global Assessment 
IL 
Interleukin 
LOCF 
Last Observation Carried Forward 
MCS 
Mental Component Summary 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
Methotrexate 
NTEAE 
Non Treatment Emergent Adverse Event 
NTESAE 
Non Treatment Emergent Serious Adverse Event 
PASI 
Psoriasis Area and Severity Index 
PCS 
Physical Component Summary 
PRO 
Patient-Reported Outcome(s)  
PSSD 
Psoriasis Symptom and Sign Diary 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous 
SF-36 
Short Form (36-item) health survey 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
ss 
scalp-specific 
TB 
tuberculosis 
TEAE 
Treatment Emergent Adverse Event 
TES 
Time and Events Schedule 
TESAE 
Treatment Emergent Serious Adverse Event 
 
 
 
 
 
 
 
NCT09251533


Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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3.0 
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 and the relevant 
acromion SOPs and/or guidelines. This plan describes the statistical analyses planned to 
be performed for the Week 64 analysis of Study Part IIb of Janssen-Cilag GmbH Clinical 
Study Protocol CNTO1959PSO3008 and should be read in conjunction with the statistical 
analysis plan for the Week 24 analysis, the protocol amendment INT-1 to the CSP and the 
electronic Case Report Form (eCRF).  
An overview about all planned analyses is given in Section 13.6. The Week 64 analysis of 
Study Part IIb summarizes the study data in Study Part IIb from Week 32 until Week 64 
(Study Part IIb: active treatment period from Week 32 through Week 56 and safety 
follow-up period from Week 56 through Week 64) and will be the second part of the Week 
64 analysis of Study Part II (first part of the Week 64 analysis ist the Week 32 analysis of 
Study Part IIa). The Week 64 analysis of Study Part IIb will include the safety analysis and 
all efficacy measures beyond Week 32 and will cover the time until the Week 64 visit. All 
statistical analyses will be descriptive and exploratory and will be conducted only for the 
predefined efficacy and safety analyses until Week 64. Statistical analyses of study data 
until Week 32 (Study Part IIa; Week 24 through Week 32) have been laid out in a 
separate SAP. 
Confirmatory analyses for the primary endpoint and the major secondary endpoints were 
already perfomed at the Week 24 analysis as described in the statistical analysis plan for 
Week 24 (Final 1.0, 10-July-2017). Evaluations on health technology assessment (HTA) 
were also specified in this SAP. No separate HTA SAP was provided. The Week 64 analysis 
of Study Part IIb will be performed after all subjects have completed their visit at 64 
weeks after randomization or discontinued earlier. Data base lock for the Week 64 analysis 
will be after the Week 64 visit data are ready for statistical analysis (i.e., clean data). 
This SAP is the core document for all statistical programming planned to be performed for 
the Week 64 analysis of Study Part IIb and is based on the following study documents to 
protocol no. CNTO1959PSO3008: 
Document 
Version, Date 
Protocol / Amendments 
Protocol Amendment INT-1, Version 2.0, 25-APR-2017 
eCRF 
Version 2.0, 08-JUN-2017 
Data Management Plan 
Version 1.0, 09-DEC-2016 
Data Validation Plan 
Version 1.0, 09-DEC-2016 
Statistical Analysis Plan - 
Week 24 Analysis 
Version 1.0, 10-JUL-2017 
 
 
 
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CNTO1959 (guselkumab) 
 
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4.0 
Responsibilities 
The responsibilities for the biometrical tasks at acromion GmbH are assigned as follows: 
Name 
Function 
Task 
Statistician 
Statistical Programming and Analysis 
Statistician 
Statistical Programming and Analysis 
Statistical Programmer 
Statistical Programming and Analysis 
Statistical Programmer 
Statistical Programming and Analysis 
Medical Data Analyst 
Medical Data Review and Coding 
5.0 
Software Utilized 
The statistical analysis and generation of tables, patient data listings and figures will be 
performed using the SAS® software package version 9.4 under the Microsoft Windows® 7 
operating system at the computer facilities of acromion GmbH. Additional analyses 
regarding health technology assessment (HTA) may be performed by or under the 
responsibility of Janssen-Cilag GmbH. 
 
6.0 
Coding Systems Utilized 
The MedDRA-dictionary version 19.1 is used for coding of prior and concomitant diseases 
and for coding of adverse events. The following items are coded. 
eCRF Module 
Item 
SDTM Domain/ Variable 
Name 
Medical History of Interest 
Medical History Term 
MH/MHTERM 
Previous Phototherapy 
Type of Phototherapy 
MH/MHTERM 
Concomitant Medication 
Indication 
CM/CMIND 
Concomitant Therapy 
Indication 
CM/CMIND 
Concomitant Therapy 
Therapy 
CM/CMTRT 
(S)AE  
Term 
AE/AETERM 
Prior and concomitant medications are coded according to the WHO terminology using the 
2016/1 version of the WHO-Drug Dictionary. The following items are coded. 
eCRF Module 
Item 
SDTM Domain/ Variable 
Name 
Previous Topical Therapy 
Medication/Therapy 
MH/MHTERM 
Concomitant Medication  
Compound 
CM/CMTRT 
Details are specified in the Data Management Plan. 
 
 
NCT09251533


Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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7.0 
Study Objectives and Hypotheses 
7.1 
Objectives 
Primary Objectives 
The primary objectives of the study are 
• 
to compare the efficacy of guselkumab to fumaric acid esters (FAE) in systemic 
treatment-naïve subjects with moderate to severe plaque-type psoriasis. 
• 
to assess the safety and tolerability of guselkumab in systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis. 
Secondary Objective 
The secondary objectives of the study are 
• 
in Study Parts I and II: to compare improvement of health-related quality of life 
(QOL) and other patient-reported outcomes (PRO) when systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis are treated with 
guselkumab compared to FAE. 
• 
in Study Part II: to compare sustainability of response to treatment when systemic 
treatment naïve subjects with moderate to severe plaque-type psoriasis are 
treated with guselkumab compared to FAE. 
 
7.2 
Hypotheses 
The primary hypothesis of this study is that guselkumab treatment is superior to FAE 
(Fumaderm® initial/Fumaderm®) treatment as assessed by the proportion of subjects 
achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are: 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of 
subjects achieving a PASI 75 response at Week 24 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of 
subjects achieving a DLQI score of 0 or 1 at Week 24. 
If the primary hypothesis is accepted, the study will be considered positive. 
 
 
NCT09251533


Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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8.0 
Study Endpoints 
This section provides a description of all study endpoints as pre-specified in the CSP 
(Protocol Amendment INT-1) for the Week 24 and Week 64 analyses. The Week 64 
analysis includes the Week 32 and the Week 64 analysis, the latter is described in the 
present SAP. 
Primary Endpoint 
The primary endpoint is the proportion of subjects achieving at least a 90% improvement 
of their psoriasis according to the Psoriasis Area and Severity Index (PASI 90 response) at 
Week 24. 
Secondary Endpoints 
The major secondary endpoints are: 
• 
The proportion of subjects achieving at least a 75% improvement of their psoriasis 
according to the PASI at Week 24 (PASI 75 response) 
• 
The proportion of subjects achieving a DLQI score of 0 or 1 at Week 24. 
 
Other secondary endpoints are: 
• 
The proportion of subjects achieving a 100% improvement of their psoriasis 
according to the PASI at Week 24 (PASI 100 response) 
• 
The change from baseline in the signs and symptoms aggregate scores of the PSSD 
at Week 24 
• 
The change from baseline in the individual scale scores for itch, pain, and scaling of 
PSSD components at Week 24 
• 
The proportion of subjects achieving an absolute PASI score ≤1 at Week 24 
• 
The proportion of subjects achieving an IGA score of cleared (0) at Week 24 
• 
The change from baseline of body surface area (BSA) psoriatic involvement at 
Week 24 
• 
The change from baseline in DLQI score at Week 24 
• 
The proportion of subjects achieving an ss-IGA score of absence of disease (0) at 
Week 24 in randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at 
baseline 
• 
The change from baseline in the physical and mental component summary scores 
of SF-36 at Week 24 
• 
Maintenance of response. Proportion of subjects with a 
− 
PASI 75 response at Week 32 who maintain response at Week 56 
− 
PASI 90 response at Week 32 who maintain response at Week 56 
− 
a DLQI score 0 or 1 at Week 32 who maintain response at Week 56 
• 
Proportion of subjects of the FAE group who were PASI 75 non-responders at Week 
32 and switched to guselkumab with a 
− 
PASI 75 response (compared to Week 0) at Week 56 
− 
PASI 90 response (compared to Week 0) at Week 56 
− 
PASI 100 response (compared to Week 0) at Week 56 
− 
DLQI score 0 or 1 at Week 56 
• 
Proportion of subjects with a 
− 
PASI 75 response at Week 32 
− 
PASI 90 response at Week 32 
− 
PASI 100 response at Week 32 
− 
DLQI score 0 or 1 at Week 32 
• 
Safety and tolerability data will be summarized using descriptive statistics 
 
 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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9.0 
Study Design 
This section provides a description of the study design as defined in the CSP (Protocol 
Amendment INT-1) for the Week 24 and the Week 64 analyses. The Week 64 analysis 
includes Week 32 analysis and the Week 64 analysis, the latter is described in the present 
SAP. 
The description is written in future tense according to the wording in the CSP, even though 
some of the planned actions, analyses and procedures have been carried out meanwhile. 
Note: References to 'Section' always refer to the respective section in the CSP (Protocol 
Amendment INT-1). 
9.1 
Overview 
This is a randomized, open-label, efficacy assessor-blinded, single country, multicenter, 
active comparator-controlled phase 3b study of guselkumab in adult subjects with 
moderate to severe plaque-type psoriasis who have not yet received any systemic 
therapy. The study will be performed at about 30 to 45 sites in Germany. 
This study will have a 3-week screening phase, a 56-week treatment phase and a safety 
follow-up phase until Week 64 (as shown in Figure 1). The maximum duration of a 
subject’s participation in this study will be 67 weeks including the 3-week screening phase. 
With protocol Amendment 1, the study will be split into two parts (Study Part I and II): 
 
Study Part I (Core Study)—Week 0 through Week 24: 
Screening and treatment until Week 24 
After screening, a total of 114 subjects will be randomized in a 1:1 ratio to either the 
study drug (guselkumab) or to the active comparator (FAE). Subjects of the guselkumab 
group will receive 100 mg guselkumab SC at Weeks 0, 4, 12, and 20. Subjects of the FAE 
group will receive commercially available Fumaderm® tablets specifically labeled for the 
study. An individual dosing for each subject representing the optimal benefit-risk ratio is 
aspired. 
A subject will be considered to have completed Study Part I if he or she has completed 
assessments at Week 24 of the open-label phase. Subjects eligible for Study Part II at 
Week 24 (ICF Part II signed, study treatment ongoing, no protocol-prohibited treatment 
started) will enter study extension and continue study treatment. For subjects who 
discontinue study treatment or withdraw from study participation in Study Part I or who 
do not enter Study Part II, a safety follow-up visit (Study Part I) is completed at Week 32 
or 12 weeks after the last treatment (whatever comes first). For subjects enrolled in Study 
Part I only, maximum duration of study participation in this study will be 35 weeks. 
 
Study Part II (Extension)—Week 24 through Week 56: 
Treatment 
Subjects may enter the study extension at Week 24 only when the ICF for Study Part II 
was signed before or at Week 24, study treatment was not terminated prior to Week 24 
and no protocol-prohibited medication/therapy was started. Study Part II is subdivided in 
two treatment periods: 
• 
Part IIa—Week 24 through Week 32: All subjects who enter Study Part II will 
continue their assigned treatment (guselkumab or FAE) from Week 24 through 
Week 32. Study Part IIa is considered completed when the subject has completed 
assessments at Week 32. 
Part IIb—Week 32 through Week 56: Following Week 32, subjects with a PASI 75 
response will continue assigned treatment (guselkumab or FAE). For PASI 75 non-
responders at Week 32 the following options will be available: 
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Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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− 
Guselkumab group: Subjects may continue guselkumab treatment. It is at 
the investigator’s discretion to continue therapy, if it is considered medically 
appropriate. 
− 
FAE group: Subjects will switch to guselkumab unless barred by safety 
reasons (based on lab values at Week 28 or up to Week 32). Subjects who 
terminate FAE treatment prior to Week 32 cannot continue study treatment 
but will enter safety follow-up per protocol. 
A subject will be considered to have completed Study Part II if he or she has completed 
assessments at Week 56 of the open-label phase. For Subjects who discontinue study 
treatment or withdraw from study participation in Study Part II, final study assessments 
are obtained and a safety follow-up visit is completed at Week 64 or 12 weeks after last 
treatment (whatever comes first). For subjects completing Study Part II the maximum 
duration of study participation in this study will be 67 weeks including a 3-week screening 
phase. 
Efficacy of treatment will be assessed before any tests, procedures or other evaluations, 
first by the subject him/herself (1st DLQI, 2nd PSSD 7-day version, and 3rd SF-36), and 
subsequently by a blinded efficacy assessor (BSA%, IGA, ss-IGA, and PASI). Safety 
evaluations will include the monitoring of adverse events (including injection site and 
allergic reactions), physical examinations, measurement of body weight, vital sign 
measurement, clinical laboratory testing (HBV, HCV, HIV, hematology, chemistry), 
concomitant medication review, tuberculosis test and evaluation, urinalysis and pregnancy 
testing. The confirmatory analysis will be conducted after the primary endpoint at Week 
24 is reached including subjects who have completed the Week 24 visit and subjects who 
have terminated the study prematurely (Section 11.3). The second statistical analysis will 
be performed after Week 64 (see Section 11). 
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 transferred to the sponsor (or 
designee) after completion of the final subject visit at that site, in the time specified in the 
Clinical Trial Agreement. The overall duration of the study is expected to be approximately 
21 months (start in December 2016, stop in October 2018). The estimated frequency and 
timing of the study visits are summarized in the ‘Time and Events Schedule’ (TES). 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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Figure 1: Schematic Overview of the Study 
 
 
 
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Polaris_SAP_W64_V1.0_29Aug2018 
 
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9.2 
 Sample Size Determination 
As decribed in the CSP, the primary hypothesis of this study is that guselkumab treatment 
is superior to FAE (Fumaderm® initial/ Fumaderm®) treatment as assessed by the 
proportion of subjects achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are:  
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a PASI 75 response at Week 24. 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a DLQI score of 0 or 1 at Week 24. 
In order to control the overall experiment wise type 1 error rate, the primary endpoint and 
the two major secondary endpoints will be tested in a fixed sequence as a-priori ordered 
hypotheses. That is, the first major secondary endpoint will be tested only if the primary 
endpoint is positive (i.e., p <0.05), and the second major secondary endpoint will be 
tested only if the first major secondary endpoint is positive (i.e., p <0.05). Due to the 
testing of ordered hypotheses, no adjustment of the significance level with respect to the 
threefold test procedure is required. 
The assumptions for the sample size and power calculations using the threefold test 
procedure were based on guselkumab phase 2 data and unpublished data from the 
German PsoBest Registry and are as follows: PASI 90 responder rates for guselkumab and 
FAE in Week 24 are assumed to be 60% and 25%, respectively. PASI 75 responder rates 
are assumed to be 80% and 45%, respectively. DLQI responder rates are assumed to be 
60% and 30%, respectively. 
Based on these assumptions, with a total of 114 subjects planned to be randomized in a 
1:1 ratio to guselkumab (n = 57) and to FAE (n = 57), superiority of guselkumab vs. FAE 
can be demonstrated at a 5% significance level (two-sided) with power of at least 90% for 
each test of the threefold test procedure as displayed in the table below. 
Table 1: Power to detect a treatment effect on expected proportions of subjects 
achieving the primary and the major secondary endpoints 
Order of 
testing 
Endpoint in  
Week 24 
Guselkumab 
(% responder) 
FAE 
(% responder) 
Power 
1 
PASI 90 
60 
25 
97% 
2 
PASI 75 
80 
45 
98% 
3 
DLQI 0/1 
60 
30 
90% 
type 1 error rate alpha 5% (two-sided) 
sequential testing with a-priori ordered hypotheses (only proceed with testing, if p <0.05)  
sample size n = 114 with 1:1 ratio guselkumab (n = 57) and FAE (n = 57) 
two group chi-square test; nQuery Advisor® Release 7.0 
 
 
 
 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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9.3 
 Randomization and Blinding 
Procedures for Randomization  
Central randomization is implemented in this study as described in Section 5 of the CSP. 
Subjects will be randomly assigned to 1 of 2 treatment groups (1:1 ratio) based on a 
computer-generated randomization schedule prepared before the study by or under the 
supervision of the sponsor. The randomization will be balanced by using randomly 
permuted blocks. The interactive web-based eCRF will assign a unique treatment code, 
which will dictate the treatment assignment at baseline visit of the subject. The 
investigator will not be provided with randomization codes. The randomization codes will 
be stored invisible for the investigator in a separate, blind part of the EDC (Electronic Data 
Capture) system.  
Blinding 
As this is an open study, blinding procedures for the treatment are not applicable. 
However, a blinded efficacy evaluator will assess effectiveness of treatment as described 
in Section 9.2.3 of the CSP. 
 
 
NCT09251533


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CNTO1959 (guselkumab) 
Polaris_SAP_W64_V1.0_29Aug2018 
 
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10.0 Study Schedule 
An overview of the study procedures is displayed in the following time and events schedule of the CSP. References to 'Section' always refer 
to the respective section in the CSP. 
Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Screening/Administrative 
Informed consent I 
(Study Part I) 
X 
 
 
 
 
 
 
 
 
 
 
Must be signed before first study-related activity 
Informed consent II 
(Study Part II) 
------------------------------------------------------------------------------X 
 
 
ICF addendum for Study Part II to be signed at 
Week 24 at the latest 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Minimum criteria for the availability of 
documentation supporting the eligibility criteria 
are described in protocol, Section 4; check 
clinical status again before first dose of study 
medication 
Study Drug Administration 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
All baseline study procedures and evaluations 
are to be completed before randomization 
Study drug 
administration 
 
   Xc-------------------------------------------------------------------…  
 
All study procedures and evaluations are to be 
completed before study drug administration 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before administration of study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
c: Subjects randomized to guselkumab will get guselkumab 100 mg on site at Weeks 0, 4, 12 and then every 8 weeks. Subjects randomized to FAEs will start with 
Fumaderm® initial regimen (0-0-1) at the day of the baseline visit; thereafter, FAE doses will be increased to find the optimal Fumaderm® dose for each subject as 
described in Section 6.  
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit: for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
Safety Assessments 
Physical examination  
X 
x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X  
X 
 
Tuberculosis evaluation 
X 
X 
   X--------------------------------------------------------… 
X 
X 
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 
(Section 9.3) 
Chest radiograph 
X 
 
 
 
 
 
 
 
 
 
 
Taken within 3 months before the first 
administration of study drug and read by a 
qualified radiologist 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Women of childbearing potential must have a 
negative 
urine 
pregnancy 
test 
before 
randomization and at all study visits (prior to 
administration of study drug). 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
Weight 
 
X 
 
 
 
 
 
 
X 
X 
X 
 
Concomitant therapy 
      X--------------------------------------------------------------------------… 
X 
X 
 
Adverse events 
      X--------------------------------------------------------------------------… 
X 
X 
 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Efficacy Assessments 
DLQI 
X 
X 
 
X  
X 
 
X 
 
X 
 
X 
 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd 
SF-36; should be performed before any tests, 
procedures or other evaluations (PASI, IGA, ss-
IGA, BSA) for that visit; completion of the 
baseline 
PROs 
has 
to 
be 
done 
before 
randomization 
PSSD (7d) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
SF-36 
 
X 
 
 
X 
 
X 
 
X 
 
X 
IGAd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
PASId 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
ss-IGAd,e 
 
X 
 
 
X 
 
X 
 
X 
 
X 
BSA%d 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
d: Dermatological evaluation of the subjects will be done by a blinded assessor starting with the Baseline visit; assessments will be done before any study related 
procedure will take place 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Clinical Laboratory Assessment 
Tuberculosis testf 
X 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B and C 
Serologies 
X 
 
 
 
 
 
 
 
 
 
 
 
HIV antibody test 
X 
 
 
 
 
 
 
 
 
 
 
 
Hematologyg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Laboratory tests are listed in Section 9.3 
Chemistryg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis by dipstick: glucose and protein; if 
there are signs of proteins and/or glucose on 
urine test strip, the urine sample must be 
analyzed centrally; here, protein and glucose 
levels must not exceed trace levels, eg, ≤ +; one 
re-test (central urine analysis) is allowed. 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
f: The QuantiFERON-TB Gold Plus test will generally be performed by the central laboratory; however, if available, test results from local laboratory can be accepted 
g: All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled; fasting is not necessary; details will be 
provided in the Laboratory Manual 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4 
 
 
 
 
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Phase 
Active Treatment 
Safety FUP 
(Final Study 
visit Part II)h3 
ETVh2 
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Study Drug Administration 
Study drug administration 
…---------Xi--------------------------------------------------X 
 
 
Subjects may enter the study extension at Week 24 
when ICF for Study Part II was signed, study 
treatment was not terminated and no protocol-
prohibited medication/therapy was started. 
Safety Assessments 
Physical examination  
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
Vital signs 
X 
X 
  
X 
 
X 
 
X 
X  
X 
Tuberculosis evaluation 
……----------------------------------------------------------X 
X 
X 
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 (Section 9.3) 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight 
 
 
 
 
 
 
 
 
X 
X 
 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4. 
h3: Safety Follow-up/Final Study Visit Study Part II (≤Week 64): For subjects who discontinue study treatment or withdraw from study participation in Study Part II. 
Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
i: Week 24 to Week 32 (Study Part IIa): subjects continue assigned treatments through Week 32. Subjects treated with 100 mg SC guselkumab continue q8w (ie, at Week 
28). Subjects treated with FAE continue Fumaderm® tablets (individual dosing according to local SmPC) until Week 32. 
Week 32 to Week 56 (Study Part IIb): Treatment decision based on PASI assessment at Week 32 and safety assessment (≥Week 28): 
- PASI 75 responders at Week 32: subject continues assigned therapy. Subjects in the guselkumab group continue 100 mg guselkumab SC at Weeks 36, 44, 52. 
Subjects in the FAE group continue Fumaderm® treatment (individual dosing according to local SmPC) until Week 56. 
- PASI 75 non-responders at Week 32: subjects in the FAE group may switch to guselkumab treatment unless barred by safety reasons (see treatment criteria 
Section 4.4). In case of safety concerns (based on lab values of Week ≥28), assessment can be repeated before Week 32. Subjects will receive guselkumab SC at 
Weeks 32, 36, 44 and Week 52. Non-responders in the guselkumab group may continue guselkumab (continuation of therapy is at the investigator’s discretion). 
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Phase 
Active Treatment 
Safety FUP 
(Final Study 
visit Part II)h3 
ETVh2 
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Safety Assessments (continued) 
Concomitant therapy 
…----------------------------------------------------------X 
X 
X 
 
Adverse events 
    …----------------------------------------------------------X 
X 
X 
 
Efficacy Assessments 
DLQI 
X 
X 
X* 
X  
 
X 
 
X 
 
X 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd SF-
36; should be performed before any tests, procedures 
or other evaluations (PASI, IGA, ss-IGA, BSA) for 
that visit. 
*ONLY applicable for subjects who switched to 
guselkumab at Week 32  
PSSD (7d) 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
SF-36 
 
X 
 
 
 
 
 
X 
 
X 
IGAd 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
PASId 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
ss-IGAd,e 
 
X 
X* 
X 
 
X 
 
X 
 
X 
BSA%d 
 
X 
 
 
 
 
 
X 
 
X 
 
Study Proceduresb  
 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
d: Dermatological evaluation of the subjects will be done by a blinded assessor as in Study Part I; assessments will be done before any study related procedure will take 
place 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4. 
h3: Safety Follow-up/Final Study Visit Study Part II ≤Week 64: For subjects who discontinue study treatment or withdraw from study participation in Study Part II. 
Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
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Phase 
Active Treatment 
Safety FUP 
(Final Study 
visit Part II)h3 
ETVh2 
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the 
scheduled visit, Section 7 
Study Proceduresb 
Clinical Laboratory Assessment 
Hematologyg 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X 
Laboratory tests are listed in Section 9.3 
∆  NOT applicable for subjects continuing gusel-
kumab treatment since beginning of the study 
(Week 0) 
Chemistryg 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X 
Urinalysis 
X 
Xβ  
X 
Xβ  
X 
Xβ  
X 
Xβ  
X 
X 
Urinalysis by dipstick: glucose and protein; if there 
are signs of proteins and/or glucose on urine test 
strip, the urine sample must be analyzed centrally; 
here, protein and glucose levels must not exceed 
trace levels, eg, ≤+; one re-test (central urine 
analysis) is allowed. 
β  ONLY applicable for subjects treated with FAE 
  
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of 
study treatments, see Section 10.2 
g: All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled; fasting is not necessary; details will be 
provided in the Laboratory Manual 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section 9.1.4. 
h3: Safety Follow-up/Final Study Visit Study Part II ≤Week 64: For subjects who discontinue study treatment or withdraw from study participation in Study Part II. 
Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
 
 
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11.0 Analysis Sets 
For all efficacy and safety analyses to compare guselkumab vs. FAE in Study Part IIb 
(active treatment period from Week 32 through Week 56 and safety follow-up period from 
Week 56 through Week 64), subjects will be analyzed according to the treatment they 
actually received. If not otherwise specified, the following 4 treatment groups which are 
defined in the CSP will be analyzed in Study Part IIb.  
o 
GUSresp-GUS: PASI 75 responder at Week 32 who continue guselkumab 100 
mg  
o 
GUSnon-resp-GUS: PASI 75 non-responder at Week 32 who continue 
guselkumab 100 mg  
o 
FAEresp-FAE: PASI 75 responder at Week 32 who continue FAE, individual 
dose  
o 
FAEnon-resp-GUS: PASI 75 non-responder at Week 32 who switch to 
guselkumab 100 mg (‘Switcher’) 
Statistical analyses on combined treatment groups in Study Part IIb (e.g., GUSresp/non-resp-
GUS: PASI 75 responder or non-responder at Week 32 who continue guselkumab 100 mg) 
or additional statistical analyses using the randomized treatment groups in Study Part I 
are explicitly mentioned and described in the respective chapters of Section 14. 
11.1 
Definition of Analysis Sets 
Subjects in Study Part IIb will be analyzed according to the treatment they actually 
received. The following analysis data sets will be defined: 
• 
Study Part IIb Analysis Set 
The Study Part IIb analysis set is defined as the set of all subjects who entered Study 
Part IIb and were treated with one of the two treatments (guselkumab or FAE) at least 
once during the treatment period from Week 32 to Week 56. 
• 
Study Part IIb Per-Protocol Analysis Set 
The Study Part IIb per-protocol analysis set will consist of all subjects in the Study Part 
IIb 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. 
Data on study subjects, demographic and baseline characteristics, treatment compliance, 
as well as all efficacy and safety analyses will be analyzed for the Study Part IIb analysis 
set. In addition, the PASI 90, PASI 75 and DLQI 0/1 response rates will also be analyzed 
using the Study Part IIb per-protocol analysis set. 
 
Exploratory inferential statistical analyses to compare guselkumab vs. FAE in Study Part 
IIb will only be performed in the PASI 75 responder treatment arms at Week 32. The FAE 
PASI 75 non-responder and the GUS combined responder or non-responder arms will be 
analyzed with descriptive statistics only. 
In addition, statistical analyses using the randomized treatment groups in Study Part I will 
also be performed using the safety analysis set as defined in the SAP - Week 24 Analysis. 
Such analyses are explicitly mentioned and described in the respective chapters of Section 
14. 
 
 
 
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11.2 
Protocol Deviations 
The determination of evaluability of subjects, especially in cases of protocol deviations, 
withdrawals or drop-outs and the assignment of subjects to the planned analysis sets will 
be performed according to the requirements of the study protocol. Minor and major and 
potentially major protocol deviations that can be expected based on the prescriptions in 
the protocol were defined by Janssen-Cilag GmbH during the trial set up period and 
adapted during the study conduct. A detailed description of major and potentially major 
protocol deviation criteria is included in a separate document. 
Data on subjects who had a major protocol deviation will be documented continuously by 
Janssen-Cilag GmbH in a Clinical Trial Management System during the trial period. Final 
data on major protocol deviations regarding the Week 64 analysis of Study Part IIb will be 
transferred to the data management department of acromion GmbH as Excel spreadsheets 
and will be further processed for statistical analysis. 
 
11.3 
Screening Failures 
Not applicable for the present analysis. 
 
 
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12.0 Definition and Calculation of Efficacy Endpoints 
The following sections provide a detailed description of the definition and the planned 
calculation of the efficacy endpoints as defined in the CSP. The same applies also for 
additional endpoints not defined in the CSP. 
 
12.1 
Involved 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).  
 
12.2 
Investigator's Global Assessment (IGA) 
The Investigator’s Global Assessment (IGA) documents the investigator’s assessment of 
the subject’s psoriasis at a given time. Overall lesions are graded for induration, 
erythema, and scaling. The subject’s psoriasis is assessed as cleared (0), minimal (1), 
mild (2), moderate (3), or severe (4). 
The efficacy endpoint related to the IGA score is defined below: 
IGA cleared responder 
Subjects who achieve an IGA score of cleared (0) will be considered IGA cleared 
responders. 
 
12.3 
Scalp Specific Investigator's Global Assessment (ss-IGA) 
The scalp-specific (ss-)IGA instrument is used to evaluate the disease severity of scalp 
psoriasis. The lesions are assessed in terms of the clinical signs of redness, thickness, and 
scaliness which are scored as: absence of disease (0), very mild disease (1), mild disease 
(2), moderate disease (3), and severe disease (4). 
The analyses for ss-IGA will be based on subjects randomized at Week 0 with baseline ss-
IGA score ≥2.  
ss-IGA absence of disease responder 
Subjects with an ss-IGA score ≥2 at baseline who achieve ss-IGA score of absence of 
disease (0) will be considered ss-IGA absence of disease responders. 
 
 
 
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12.4 
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. 
In addition, the time to PASI 75/90/100 response defined as time from baseline to first 
onset of response will be calculated. In the absence of documented response the time to 
PASI 75/90/100 response will be censored at the date of Week 64 or the date of 
discontinuation in case of early treatment discontinuation. 
 
12.5 
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 (e.g., 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. 
In addition, the time to DLQI 0/1 response defined as time from baseline to first onset of 
response will be calculated. In the absence of documented response the time to DLQI 0/1 
response will be censored at the date of Week 64 or the date of discontinuation in case of 
early treatment discontinuation. 
 
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12.6 
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 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. 
 
 
 
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12.7 
Short Form Health Survey (SF-36) 
The Short Form Health Survey (SF-36) is a 36-item questionnaire used for subjects’ self-
assessment of health-related quality of life, consisting of the following 8 dimensions: 1) 
limitations in physical functioning due to health problems, 2) limitations in usual role 
activities due to physical health problems, 3) bodily pain, 4) general mental health 
(psychological distress and well-being), 5) limitations in usual role activities due to 
personal or emotional problems, 6) limitations in social functioning due to physical or 
mental health problems, 7) vitality (energy and fatigue), and 8) general health perception.  
A physical component summary (PCS) score and a mental component summary (MCS) 
score can be derived. The concepts measured by the SF-36 are not specific to age, disease 
or treatment group, allowing comparison of relative burden of different diseases and the 
relative benefit of different treatments. The estimated completion time will be 10 minutes. 
Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating 
better health. Based on the scale scores, the summary scores, PCS and MCS, will be 
derived. These summary scores are also scaled with higher scores indicating better health. 
The QualityMetric Health Outcomes™ Scoring Software 5.0 offered by QualityMetric 
Incorporated will be used to score the SF-36. The Software is designed to provide users 
with standard scoring methods in an easy-to-use way. By using this Software, users will 
have the confidence that the data they obtain on their SF form are scored in accordance 
with standards set by the developers of the SF tools. The Software also provides 
evaluation of data quality and applies methods for missing data recovery. The PCS score 
can be calculated when seven scale scores are available and the Physical Functioning scale 
is not missing. The MCS score can be calculated when at least seven scale scores are 
available and the Mental Health scale is not missing. 
 
A more detailed description of the scoring procedure is provided in the User's Guide of 
QualityMetric Health Outcomes™ Scoring Software 5.0 (see especially Appendix F). 
 
 
 
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13.0 Statistical Methodology 
The present Week 64 analysis of Study Part IIb summarizes the study data in Study Part 
IIb from Week 32 until Week 64 (Study Part IIb: active treatment period from Week 32 
through Week 56 and safety follow-up period from Week 56 through Week 64) and will be 
part of the Week 64 analysis of Study Part II. This analysis will include the safety analysis 
and all efficacy measures after Week 32 and will cover the time from Week 32 until the 
Week 64 visit. All statistical analyses will be descriptive and exploratory only for the 
predefined efficacy and safety analyses from Week 32 until Week 64. 
In addition, statistical analyses using the data of from Week 0 to Week 32 will also be 
perfomed. Such analyses are explicitly mentioned and described in the respective chapters 
of Section 14. 
The biometrical evaluation will be carried out by acromion GmbH under the authority of 
the sponsor. Statistical programming and analyses will be performed using the statistical 
software system SAS®. 
The following sections provide a more detailed description of the planned statistical 
methodology. 
13.1 
Data Handling Rules 
13.1.1 
Baseline and Post-baseline Points in Time of Interest 
Baseline Definition 
In general, the values of the Week 0 visit (= day of randomization = first day of week 1) 
or the values of the screening visit (= day within 3 weeks before their randomization visit) 
will be used as baseline values, as applicable. If data for the same variable are available 
from both (i.e., screening and Week 0) visits then the result of the Week 0 visit will be 
used as baseline value, i.e., for each variable the baseline measurement is defined as the 
closest measurement taken prior to or at the Week 0 visit. 
For the treatment group FAEnon-resp-GUS (PASI 75 non-responder at Week 32 who switch to 
guselkumab 100 mg (‘Switcher’)) the values of the Week 32 visit will also be used as 
baseline values for some analyses. If data for the Week 32 visit are missing then the 
result of the Week 28 visit will be used as baseline value. Such analyses are explicitly 
mentioned and described in the respective chapters of Section 14. 
Definition of Post-baseline Points in Time of Interest 
The primary point in time for efficacy assessment will be the Week 56 visit (= the 
treatment visit 56 weeks after randomization). Secondary points in time for efficacy 
assessment will be the study visits scheduled at Week 40 and Week 48 during the 
treatment phase. Handling of missing values is described in SAP section 13.1.6. 
The safety analysis will cover the time period from Week 32 through 64.  
In addition, statistical analyses using the data from Week 0 to Week 32 will also be 
perfomed. Such analyses are explicitly mentioned and described in the respective chapters 
of Section 14. 
 
 
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13.1.2 
Definition of Within- and Between-Group Treatment 
Differences 
Within-group treatment differences will be computed as differences of the post-baseline 
visits as compared to the baseline visit, if applicable: 
• 
post-baseline visit minus baseline visit 
 
The following between-group treatment difference to assess the treatment effect will be 
computed in the PASI 75 responder treatment groups, if applicable: 
• 
guselkumab minus FAE 
 
13.1.3 
Visit Windows 
Nominal visits (i.e., visits as recorded in the eCRF) will be used for all by-visit analyses in 
the study. The study visits scheduled post randomization should occur at the times 
delineated in the Time and Events Schedule. No visit windows will be defined and used for 
analysis. 
13.1.4 
Treatment Failure Criteria 
Not applicable. 
 
13.1.5 
Treatment Failure Rules 
No treatment failure rules will be applied.  
 
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13.1.6 
Handling of Missing Values 
All available data will be included in the analyses and will be summarized descriptively as 
far as possible. If not otherwise specified, there will be no substitution of missing data, 
i.e., missing data will not be replaced, missing data will be handled as ‘missing’ in the 
statistical evaluation (‘observed cases analysis’). 
Missing data for the efficacy endpoints at key visits Week 40, 48 and 56 will be handled as 
follows for all exploratory inferential statistical analyses (only for PASI 75 responders at 
Week 32). 
Missing data imputation for the efficacy endpoints at Week 40, 48 and 56: 
• 
Nonresponder imputation will be applied for binary endpoints 
o 
i.e., subjects with missing data at Week 40/48/56 will be considered non-
responders at Week 40/48/56. 
• 
Last observation carried forward (LOCF) will be applied for continuous endpoints 
o 
i.e., in subjects with missing data at Week 40/48/56 the last available 
observation after Week 32 will be calculated and used for analysis for 
continuous response variables at Week 40/48/56. 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. 
Sensitivity analyses with respect to the handling of missing values at Week 56 are 
described in SAP section 13.9. 
Deviations from this general plan for missing data imputation are explicitly mentioned and 
described in the respective chapters of Section 14. 
13.1.7 
Data Transformations 
No data transformations (e.g. square root, logarithmic) to confirm basic statistical 
assumptions will be performed. All variables will be used in the analysis as reported. 
 
13.2 
Descriptive Statistics 
13.2.1 
Dichotomous and Categorical Variables 
Categorical data will be presented in frequency tables using counts and percentages. 
Percentages will be based on the total number of subjects in the respective analysis set 
(i.e., missing values will be included in percentage calculation). Besides presentation of 
absolute values cross tabulation vs. baseline by study visit will be provided, if appropriate. 
 
13.2.2 
Continuous and Quasi-Continuous Variables 
Standard descriptive summary statistics will be calculated for continuous and quasi-
continuous variables: arithmetic mean, standard deviation, minimum value, lower quartile, 
median, upper quartile, maximum value, number of non-missing values. Besides 
presentation of absolute values tabulation for differences to baseline by study visit will be 
provided, if appropriate. 
 
 
 
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13.2.3 
Graphical Presentations 
Graphical presentation of pertinent data will be given by means of box plots, bar charts, 
and survival graphs, as appropriate. Additional forms of graphical presentations may be 
specified. Descriptions of graphical presentations are included in the appendix of this 
document. 
 
13.3 
Confirmatory Statistics 
Not applicable for the present Week 64 analysis of Study Part IIb.  The confirmatory 
analysis is described in the SAP for the Week 24 analysis (Final 1.0, 10-July-2017). 
 
13.4 
Exploratory Statistics 
Exploratory statistical analyses will be performed for the endpoints listed under 'other 
secondary endpoints' relevant for Study Part IIb at Week 56, and at Week 40 and Week 
48. All statistical tests and confidence intervals will be calculated two-sided and will be 
interpreted in the exploratory sense only.  
Exploratory inferential statistical analyses to compare guselkumab vs. FAE in Study Part 
IIb will only be performed in the PASI 75 responder treatment arms at Week 32. The other 
arms will be analyzed with descriptive statistics only. 
13.4.1 
Binary Endpoints 
For binary endpoints counts and percentage of subjects per treatment group along with 
odds ratio (OR), relative risk (RR) and risk difference (RD), 95% confidence intervals 
(95% CIs) and p-values for treatment effect using the chi-square test will be provided. 
 
13.4.2 
Continuous Endpoints 
The change from baseline of continuous endpoints will be analyzed by an analysis of 
covariance model (ANCOVA) with the fixed effect factor for treatment group 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 95% CI and two-sided p-value will be provided from the ANCOVA model. 
 
13.5 
Adjustment for Covariates 
The baseline value will be used as covariate in the analysis of variance model (ANCOVA) 
for the change from baseline of continuous response parameters. 
 
 
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13.6 
Interim Analyses 
The following analyses are planned to be performed. 
1. Main Analysis (Confirmatory Week 24 Analysis) 
The confirmatory main analysis was performed at the end of Study Part I, i.e., after all 
subjects had completed their visit at 24 weeks after randomization or discontinued earlier. 
This analysis, described in a separate SAP (‘SAP Week 24’, final version 1.0, 10-July-
2017), included the confirmatory analysis of the primary endpoint and the major 
secondary endpoints as well as all other exploratory predefined efficacy and safety 
analyses until Week 24. The results of the analysis are described in the Clinical Study 
Report Week 24, dated 14.05. 2018. 
2. Interim Analysis (Exploratory Week 64 Analysis)  
No confirmatory analysis is planned to be performed. The (exploratory) interim analysis 
will be performed at the end of Study Part II, i.e. after all subjects had completed their 
visits at 64 weeks after randomization or discontinued earlier. The Week 64 analysis will 
be split into 2 parts, the Week 32 analysis and the Week 64 analysis. 
- 
The Week 32 analysis, described in this SAP (‘SAP Week 32’), summarizes the 
study data until Week 32 (Study Part IIa; continuation of assigned treatment from 
Week 24 through Week 32). All statistical analyses will be descriptive and 
exploratory only for the predefined efficacy and safety analyses until Week 32.  
- 
The Week 64 analysis, described in a separate SAP (‘SAP Week 64’), summarizes 
the study data until Week 64 (Study Part IIb). The analysis will include all efficacy 
measures until Week 56 and safety measures until the Week 64 safety visit.  
3. Final Analysis (Exploratory Week 100 Analysis) 
No confirmatory analysis is planned to be performed. The (exploratory) final analysis will 
be performed at the end of Study Part III, i.e. after all subjects had completed their visits 
at 100 weeks after randomization or completed earlier (i.e., subjects meet the definition of 
loss of response) or discontinued earlier. 
13.7 
Multi-center Data 
Exploration of possible heterogeneity of treatment effects across centers for the proportion 
of subjects achieving a PASI 90 response at Week 56 using nonresponder imputation 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. 
 
 
 
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13.8 
 Subgroup Analyses 
The following subgroup analyses are planned to be performed for the treatment group 
GUSresp-GUS (PASI 75 responder at Week 32 who continue guselkumab 100 mg)  to 
evaluate consistency over demographics and baseline disease characteristics of the 
endpoints PASI 75/90/100 response, PASI ≤ 1, PASI ≤ 3, DLQI score 0 or 1, PSSD sign 
score, and PSSD symptom score: 
• 
Gender 
o 
male 
o 
female 
• 
Age at baseline in years 
o 
< 45 
o 
≥ 45 - < 65  
o 
≥ 65 
• 
PASI 
o 
< 20 
o 
≥ 20 
Subgroup analyses for these efficacy endpoints will be performed using the following 
different imputation rules of missing values at Week 56 (see SAP sections 13.1.6 and 
13.9): 
• 
Binary endpoint: 
o 
Nonresponder imputation 
o 
LOCF (only PASI 75/90 response, and DLQI 0/1 response) 
o 
Multiple imputation 
• 
Continuous endpoint: 
o 
Multiple Imputation 
Subgroup analyses will NOT be performed for the Study Part IIb per-protocol analysis set. 
 
 
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13.9 
Sensitivity Analyses 
The following sensitivity analyses at Week 56 with respect to the handling of missing 
values are planned to be performed: 
• 
Multiple imputation will be used for all binary and continuous endpoints. 
o 
For the multiple imputation, the repeated nature of the analysis is restricted 
to the imputation step (procedure "MI" in SAS). Basic premise is the 
creation of several datasets in which missing data is imputed in a random 
fashion and then analyses are performed to check for changes for the 
conclusion. The analysis will be done with SAS Proc MIANALYZE. 
• 
LOCF imputation will be used for all binary endpoints (see SAP section 13.1.6). 
• 
An 'observed cases analysis' for all binary and continuous endpoints without 
substitution of missing data will be used (see SAP section 13.1.6). 
Sensitivity analyses at Week 56 with respect to the handling of missing values will be 
performed for all binary and all continuous efficacy endpoints. 
Sensitivity analyses at Week 56 with respect to the handling of missing values will NOT be 
performed for the Study Part IIb per-protocol analysis set. 
 
 
 
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14.0 Statistical Analyses 
A table of contents of planned data displays is provided in section 18.1 of this document. 
The following sections are intended to provide more details of the planned analyses. In 
addition, mock tables were created and were used as template for statistical programming 
at the Week 24 analysis. The mock tables will be used analogously at the present Week 64 
analysis of Study Part IIb. 
Data will be appropriately summarized and analyzed using tabulation and graphs with 
respect to demographic/baseline characteristics and efficacy/safety observations and 
measurements. Standard descriptive summary statistics (i.e., n, arithmetic mean, 
standard deviation, median, minimum/maximum value, quartiles) will be calculated for 
continuous variables. Categorical data will be presented in frequency tables using counts 
and percentages. In general, summary tables will be displayed by the four treatment 
groups in Study Part IIb (see SAP section 11.0) as the main classification variable and for 
the total of the sample in the respective analysis set. Additional classification variables or 
statistical analyses on combined treatment groups in Study Part IIb or statistical analyses 
using the randomized treatment groups in Study Part I are explicitly mentioned in the 
following text. Individual subject data listings will be presented parameter wise and will be 
sorted by treatment group, center, subject number and study visit, if applicable. 
14.1 
Study Subjects 
Unless otherwise specified, data on study subjects will be analyzed based on data from all 
subjects who entered Study Part IIb and were treated with one of the two treatments 
(guselkumab or FAE) at least once in the four treatment groups during the treatment 
period from Week 32 to Week 56 ('Study Part IIb analysis set').  
14.1.1 
Disposition of Subjects 
The overview of subject disposition from Week 0 to Week 32 and from Week 32 to Week 
56 will provide the respective frequency counts and percentages regarding the following 
subjects: 
• 
Treatment phase from Week 0 until Week 32 
o 
Subjects who were enrolled (i.e., signed informed consent Part I) 
o 
Subjects who were randomized 
o 
Subjects who were treated 
o 
Subjects with premature discontinuation of study treatment until Week 24 
o 
Subjects who completed the treatment phase until Week 24 
o 
Subject who entered Study Part II (i.e., signed informed consent Part II) 
o 
Subjects with premature discontinuation of study treatment until Week 32 
o 
Subjects who completed the treatment phase until Week 32 
• 
Treatment phase from Week 32 to Week 56 
o 
Subjects who were treated 
o 
Subjects with premature discontinuation of study treatment until Week 56 
o 
Subjects who completed the treatment phase until Week 56 
The table will also include the total number of study sites and the dates of the entry of the 
first subject and the last visit of the last subject in Study Part IIb. A flow diagram 
(according to the CONSORT statement) giving an overview of subject disposition will also 
be provided. 
In addition, the number and percentage of treated subjects continuing and attending by 
study visit will be displayed in a separate table. Subjects will be counted as continuing at 
the time of visit whether they attend the visit or not. Only those subjects that prematurely 
discontinued before the visit will not be counted as attending.  
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14.1.2 
Discontinuation of Study Treatment 
The number and percentage of treated subjects who discontinued study treatment 
prematurely within the treatment period from Week 32 to Week 56 will be tabulated for 
each reason of premature discontinuation (including tabulation of specifications for 
category ‘other’). Moreover, the number of subjects not included in Study Part IIb and the 
reasons for not being included will be given. 
 
14.1.3 
Protocol Deviations 
In general, the following list of major protocol deviations may have the potential to impact 
subjects’ rights, safety or well-being, or the integrity and/or result of the clinical trial. 
Subjects with major protocol deviations will be summarized by category for all randomized 
subjects. 
• 
Developed withdrawal criteria but not withdrawn 
• 
Entered but did not satisfy criteria 
• 
Received a disallowed concomitant treatment 
• 
Received wrong treatment or incorrect dose 
• 
Other 
The summary table will provide the number of subjects per major protocol deviation and 
will also provide the number of major protocol deviations in Study Part IIb. 
The treatment assignment criteria deviations (Study Part IIb) will also be given.  
14.1.4 
Analysis Sets 
The number and percentage of treated subjects included in each analysis set, together 
with a breakdown of the reasons for exclusion for non-evaluable subjects, will be provided. 
 
 
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14.2  Demographic and Other Baseline Characteristics 
Generally, assessments made at the screening visit and the baseline visit will be 
summarized by treatment group in Study Part IIb (i.e. 4 treatment arms) and overall. 
Note that this summary is different to the summary of the two randomized treatment 
groups in Study Part I. These assessments will include demographic characteristics and 
other parameters (such as medical history, diagnosis of psoriasis, concomitant diseases, 
and concomitant medication). By-treatment summaries will serve to identify any 
imbalances between the treatment groups at baseline. Summary tables will be provided by 
means of descriptive statistics and frequency tables, where appropriate. Demographic and 
other baseline characteristics will be analyzed based on data from all treated subjects in 
Study Part IIb ('Study Part IIb analysis set'). No analyses for baseline balance using 
statistical hypothesis tests or confidence intervals will be done. 
 
14.2.1 
Demographics 
Age (categorized), gender, and race will be presented in a frequency table. Age group 
categories will be chosen as < 45; ≥ 45 - < 65; ≥ 65years. Descriptive summary statistics 
will be calculated for age, body height, body weight and body mass index (BMI).  
Tables for demographic data will also be stratified by gender. Age and gender distribution 
will be presented in a bar chart. 
Note: Age is documented as 'age at date of informed consent signature' at the screening visit. Body 
height and body weight data will be taken from the vital signs eCRF form at the Week 0 visit. BMI 
will be calculated as body weight in kg / body height in m². 
14.2.2 
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 terminology as described in SAP section 14.6. 
Summary tabulation will also consider whether the disease is ongoing or not at screening 
visit. 
 
14.2.3 
Diagnosis of Psoriasis 
The time from date of initial diagnosis of psoriasis to date of screening visit will be 
calculated and will be displayed by descriptive statistics. If the day is unknown the day will 
be set to day = 1. If the month is unknown the month will be set to month = July. 
In addition, the disease characteristics at baseline Week 32 will be summarized for the 
treatment group FAEnon-resp-GUS (PASI 75 non-responder at Week 32 who switch to 
guselkumab 100 mg (‘Switcher’)) by providing the following relevant results: descriptive 
summary statistics of the PASI and the DLQI index, frequency distribution of the IGA 
categories and the PASI < 20 and PASI ≥ 20 subgroups.  
 
14.2.4 
Previous Psoriasis Therapy 
No statistical analysis will be performed.  
14.2.5 
Substance Use  
No statistical analysis will be performed.  
 
14.2.6 
Physical Examination 
No statistical analysis will be performed.  
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14.2.7 
Tuberculosis Evaluation 
No statistical analysis will be performed.  
14.2.8 
Chest Radiograph Result 
No statistical analysis will be performed.  
14.2.9 
Concomitant Medication and Therapy 
Analyses of concomitant medication and therapy will consider the data recorded within the 
treatment periods from Week 0 to Week 32 and from Week 32 to Week 56 and recorded 
during the safety follow-up period from Week 56 to Week 64.  
Concomitant Medication 
The number and percentage of subjects with use of concomitant medication from Week 32 
to Week 56 will be displayed in WHO-DD terminology as described in SAP section 14.7. 
Concomitant medication will be identified from the Concomitant Medication form of the 
eCRF. 
The number and percentage of subjects with indication for concomitant medication from 
Week 32 to Week 56 will be displayed in MedDRA terminology as described in SAP section 
14.6. 
Analyses of data recorded from week 0 to week 64 and of data recorded during the safety 
follow-up period from Week 56 to Week 64 will be performed analogously. 
Concomitant Therapy 
The number and percentage of subjects with use of concomitant therapy from Week 32 to 
Week 56 will be displayed in MedDRA terminology as described in SAP section 14.6. 
Concomitant therapy will be identified from the Concomitant Therapy form of the eCRF. 
The number and percentage of subjects with indication for concomitant therapy from 
Week 32 to Week 56 will be displayed in MedDRA terminology as described in SAP section 
14.6. 
Analyses of data recorded from week 0 to week 64 and of data recorded during the safty 
follow-up period from Week 56 to Week 64 will be performed analogously. 
 
14.2.10 
Shampoo and Moisturizer 
The number and percentage of subjects with use of shampoo or moisturizer from Week 32 
to Week 56 will be displayed in a frequency table. 
 
 
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14.3  Treatment Compliance 
Treatment compliance will be analyzed based on data from all treated subjects of the four 
treatment arms in Study Part IIb ('efficacy analysis set'). 
14.3.1 
Visit Windows 
The number of days between the scheduled study visits and the baseline visit will be 
calculated using the reported visit dates per scheduled study visit and will be displayed by 
summary descriptive statistics from Week 32 to Week 56 and from Week 56 to Week 64. 
 
14.3.2 
Study Medication 
Categorical data on guselkumab administration recorded from Week 32 to Week 56 will be 
summarized by frequency tabulation providing the number and percentage of subjects per 
category. Frequency tabulation and descriptive statistics will be presented for the overall 
number of guselkumab administrations from Week 32 to Week 56. 
Compliance to guselkumab administration will be calculated as follows based on the eCRF 
data from Week 32 to Week 56: 
• 
Compliance guselkumab in % = (number of actual administrations x 100 / number 
of planned administrations)  
Categorical data on Fumaderm® initial/ Fumaderm® administration recorded at each week 
from Week 32 to Week 56 and will be summarized by frequency tabulation providing the 
number and percentage of subjects per recorded category in the eCRF. The number of 
planned tablets to be taken in the morning, at noon, and in the evening will also be 
summed up and analyzed descriptively. 
The number of dispensed and returned tablets of Fumaderm® initial/ Fumaderm® 
(including the difference of dispensed - returned tablets = actual tablets) will be displayed 
by descriptive summary statistics from Week 32 to Week 56. 
Compliance to Fumaderm® initial and Fumaderm® administration will be calculated as 
follows based on the eCRF data from Week 32 to Week 56: 
• 
Compliance FAE in % = (number of actual tablets x 100 / total number of tablets 
supposed to be taken)  
Treatment compliance will also be assessed by protocol deviations related to study drug 
administration (i.e., incorrect study drug received and missed administrations).  
For subjects who completed the Week 56 visit the dose of Fumaderm® in mg at Week 56 
will be summarized by descriptive statistics and frequency tabulation. In addition, the 
maximum dose of Fumaderm® initial and Fumaderm® in mg will be calculated for all 
subjects and will be summarized by descriptive statistics and frequency tabulation. 
For patients starting with guselkumab and staying on guselkumab and for patients starting 
with Fumaderm® and staying on Fumaderm®, compliance will also be calculated for the 
Week 0 to Week 56 period. For patients switching from Fumaderm® to guselkumab, 
compliance will be analyzed separately from Week 0 to Week 32 and from Week 32 to 
Week 56. 
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14.4  Analysis of Efficacy 
All efficacy analyses to compare guselkumab vs. FAE will be performed for all treated 
subjects of the four treatment in Study Part IIb ('Study Part IIb analysis set'). The PASI 
90, PASI 75, and DLQI 0/1 response rates will also be analyzed using the Study Part IIb 
per-protocol analysis set. However, subgroup and sensitivity analyses at Week 56 will NOT 
be performed for the Study Part IIb per-protocol analysis set. 
All statistical analyses will be descriptive and exploratory only for the predefined efficacy 
analyses from Week 32 through Week 56. All statistical tests will be performed two-sided 
in an exploratory sense.  
Exploratory inferential statistical analyses to compare guselkumab vs. FAE in Study Part 
IIb will only be performed in the PASI 75 responder treatment arms at Week 32. The PASI 
75 non-responder arms will be analyzed with descriptive statistics only. 
Handling of missing values, exploratory statistics, subgroup analyses, and sensitivity 
analyses will be performed as described in detail in the following sections of this SAP: 
SAP Section No. 
Topic 
13.1.6 
Handling of missing values 
13.4.1 
Exploratory statistics - binary endpoints 
13.4.2 
Exploratory statistics - continuous endpoints 
13.8 
Subgroup analyses 
13.9 
Sensitivity analyses 
Data at the scheduled points Week 40 and Week 48 during the active treatment period will 
be analyzed analogously to the Week 56 data. However, no subgroup or sensitivity 
analyses will be performed for these points in time. 
 
 
 
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14.4.1 
Primary Endpoint 
Not applicable for the present analysis. The confirmatory statistical analysis was already 
performed at the Week 24 analysis. 
 
14.4.2 
Major Secondary Endpoints 
14.4.2.1 
Endpoint related to PASI 
Not applicable for the present analysis. The confirmatory statistical analysis was already 
performed at the Week 24 analysis. 
 
14.4.2.2 
Endpoint related to DLQI 
Not applicable for the present analysis. The confirmatory statistical analysis was already 
performed at the Week 24 analysis. 
 
14.4.3 
Other Secondary Endpoints 
The following sections provide a description of the planned statistical analyses of the other 
secondary endpoints as reported in the CSP and as well as of additional endpoints not 
explicitly stated in the CSP (see SAP section 15.0). 
 
14.4.3.1 
Endpoints related to PASI 
Other secondary endpoints related to PASI are: 
• The proportion of subjects achieving a 75%/90%/100% improvement of their psoriasis 
according to the PASI at Week 56 (PASI 75/90/100 response) compared to baseline 
• The proportion of subjects achieving an absolute PASI score ≤1, ≤2, ≤3, ≤5 at Week 
56 
• The proportion of subjects with a PASI 75/90 response at Week 32 who maintain 
response at Week 56 
The proportion of responding 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. 
Exploratory statistical analyses for PASI 75 responder treatment arms at Week 32: 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 56 per treatment arm and for the difference between the two arms. 
Additional exploratory statistical analyses will be performed as described in SAP section 
13.4.1. 
 
 
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14.4.3.2 
Endpoints related to PSSD 
Other secondary endpoints related to PSSD are: 
• The change from baseline in the signs and symptoms aggregate scores of the PSSD at 
Week 56 
• The change from baseline in the individual scale scores for itch, pain, and scaling of 
PSSD components at Week 56 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 56 value and the change from the 
baseline value will be displayed. 
Exploratory statistical analyses for PASI 75 responder treatment arms at Week 32: 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2). 
 
14.4.3.3 
Endpoints related to IGA 
Other secondary endpoints related to IGA are: 
• The proportion of subjects achieving an IGA score of cleared (0) at Week 56. 
The proportion of responding 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.  
Exploratory statistical analyses for PASI 75 responder treatment arms at Week 32: 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 56 per treatment arm and for the difference between the two arms. 
Additional exploratory statistical analyses will be performed as described in SAP section 
13.4.1. 
In addition, the proportion of subjects achieving an IGA score of cleared (0) or minimal (1) 
at Week 56 will be analyzed analogously. 
 
14.4.3.4 
Endpoints related to BSA 
Other secondary endpoints related to BSA are: 
• The change from baseline of body surface area (BSA) psoriatic involvement at Week 56 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 56 value and the change from the 
baseline value will be displayed. 
Exploratory statistical analyses for PASI 75 responder treatment arms at Week 32: 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2).  
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14.4.3.5 
Endpoints related to DLQI 
Other secondary endpoints related to DLQI are: 
• The proportion of subjects achieving a DLQI score of 0 or 1 at Week 56 
• The change from baseline in DLQI score at Week 56 
• The proportion of subjects with a DLQI score 0 or 1 at Week 32 who maintain response 
at Week 56 
The proportion of responding 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. 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 56 value and the change from the 
baseline value will be displayed. 
Exploratory statistical analyses for PASI 75 responder treatment arms at Week 32: 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 56 per treatment arm and for the difference between the two arms. 
Exploratory statistical analyses (also including analyses of time to DLQI 0/1 response) will 
be performed as described in SAP section 13.4.1. 
 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2). 
14.4.3.6 
Endpoints related to ss-IGA 
Other secondary endpoints related to ss-IGA are: 
• The proportion of subjects achieving an ss-IGA score of absence of disease (0) at Week 
56 in randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at baseline 
The proportion of responding 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. 
Exploratory statistical analyses for PASI 75 responder treatment arms at Week 32: 
The chi-square test will be used to compare the proportion of subjects responding to 
treatment. Two-sided 95% confidence intervals will be calculated for the response rate at 
Week 56 per treatment arm and for the difference between the two arms. 
Additional exploratory statistical analyses will be performed as described in SAP section 
13.4.1. 
In addition, the proportion of subjects achieving an ss-IGA score of absence of disease (0) 
or very mild disease (1) at Week 56 will be analyzed analogously. 
 
 
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14.4.3.7 
Endpoints related to SF-36 
Other secondary endpoints related to SF-36 are: 
• The change from baseline in the physical and mental component summary scores of 
SF-36 at Week 56 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 56 value and the change from the 
baseline value will displayed. 
Exploratory statistical analyses for PASI 75 responder treatment arms at Week 32: 
Exploratory statistical evaluation of the change from baseline will be based on an analysis 
of covariance model (ANCOVA) with the fixed effect factor for treatment group and the 
baseline value as covariate (see SAP section 13.4.2). 
 
14.4.4 
Other Efficacy Assessments 
In addition to the efficacy analyses described above all efficacy data related to PASI, DLQI, 
PSSD, IGA, ss-IGA, and SF-36 at all scheduled study visits during the active treatment 
period from Week 0 until Week 56 will be summarized descriptively without any 
imputation of missing data (‘observed cases analysis’; see SAP section 13.1.6). For binary 
endpoints summary results using nonresponder imputation will also be provided. 
 
 
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14.4.5 
Additional Efficacy Analyses 
Furthermore, the following additional efficacy analyses for the endpoints PASI 75/90/100 
response, PASI ≤ 1, PASI ≤ 3, DLQI score 0 or 1, PSSD sign score, and PSSD symptom 
score will be performed: 
• 
Analyses of Efficacy for GUSresp/non-resp-GUS (Week 0 to Week 56) vs. FAE (Week 0 to 
Week 32) 
Item  
Specification 
Treatment Groups 
GUSresp/non-resp-GUS vs. FAE 
Treatment Periods 
• 
GUSresp/non-resp-GUS: Week 0 to Week 56 
• 
FAE: Week 0 to Week 32 
Analysis set 
Safety Analysis Set Week 24 Analysis 
Baseline 
Week 0 
Endpoints 
PASI 75/90/100 Response, PASI≤1, ≤3, 
DLQI Score 0 or 1, PSSD Sum Scores 
Observed Cases Analyses  
Yes 
Missing Data Imputation 
at Week 4, 16, 24, 32, 40, 48, 56 
• 
Binary Endpoint: NRI, MI, LOCF 
• 
Continuous Endpoint: MI, LOCF 
Subgroups 
No 
Statistical Analysis 
Descriptive 
Tables 
Yes 
Figures 
Yes 
 
 
 
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• 
Analyses of Efficacy for GUSresp -GUS (Week 32 to Week 56) vs. FAEresp-FAE (Week 32 
to Week 56) 
Item  
Specification 
Treatment Groups 
GUSresp-GUS vs. FAEresp-FAE 
Treatment Period 
Week 32 to Week 56 
Analysis set 
Study Part IIb Analysis Set 
Baseline 
Week 0 
Endpoints 
PASI 75/90/100 Response, PASI≤1, ≤3, 
DLQI Score 0 or 1, PSSD Sum Scores 
Observed Cases Analyses  
Yes 
Missing Data Imputation 
at Week 36, 40, 44, 48, 56 
• 
Binary Endpoint: NRI, LOCF 
• 
Continuous Endpoint:  LOCF 
Subgroups 
No 
Statistical Analysis 
Descriptive, Exploratory Inferential 
Tables 
Yes 
Figures 
Yes 
 
 
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• 
Analyses of Efficacy for FAEnon-resp-GUS (Week 32 to Week 56) ('Switcher' Analysis) 
Item  
Specification 
Treatment Group 
FAEnon-resp-GUS ('Switcher') 
Treatment Period 
Week 32 to Week 56 
Analysis set 
Study Part IIb Analysis Set 
Baseline 
Week 0 AND Week 32 
Endpoints 
PASI 75/90/100 Response, PASI≤1, ≤3, 
DLQI Score 0 or 1, PSSD Sum Scores 
Observed Cases Analyses  
Yes 
Missing Data Imputation 
at Week 36, 40, 44, 48, 56 
• 
Binary Endpoint: NRI, LOCF 
• 
Continuous Endpoint:  LOCF 
Subgroups 
No 
Statistical Analysis 
Descriptive 
Tables 
Yes 
Figures 
Yes 
 
 
 
 
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• 
Analyses of Efficacy for GUS Starter vs. FAE Starter 
Item  
Specification 
Treatment Group 
GUS Starter vs. FAE Starter 
Treatment Period 
only Week 56 
Analysis set 
Safety Analysis Set Week 24 Analysis 
Baseline 
Week 0 
Endpoints 
PASI 75/90/100 Response, PASI≤1, ≤3, 
DLQI Score 0 or 1, PSSD Sum Scores 
Observed Cases Analyses  
Yes 
Missing Data Imputation 
at Week 56 
• 
Binary Endpoint: NRI, MI, LOCF 
• 
Continuous Endpoint: MI, LOCF 
Subgroups 
No 
Statistical Analysis 
Descriptive 
Tables 
Yes 
Figures 
Yes 
 
 
 
 
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14.5  Analysis of Safety 
Safety data, including but not limited to, adverse events (AEs), serious adverse events 
(SAEs), infections, serious infections, mortality, changes in laboratory assessments, and 
changes in vital signs will be summarized using descriptive statistics. All safety analyses to 
compare guselkumab vs. FAE will be performed for all treated subjects ('Study Part IIb 
analysis set') in the four treatment arms. 
 
14.5.1 
Extent of Exposure  
Extent of exposure will be defined as the total number of days from Week 32 to Week 56 
(for all patients still under treatment) or to study discontinuation. 
Descriptive summary statistics and frequency tables (using appropriate categories) will be 
provided for the extent of exposure.  
In addition, extent of exposure from Week 0 to Week 56 for the PASI 75 responder 
treatment arms will be analyzed analogously. 
 
14.5.2 
Adverse Events 
Adverse events data will be processed in the statistical analysis after coding according to 
the MedDRA dictionary version 19.1. All reported AEs with onset date during the active 
treatment period from Week 32 through Week 56 or the safety follow-up period from 
Week 56 through Week 64 (i.e., treatment emergent AEs) will be included in the analysis. 
In case of early treatment discontinuation before Week 56 all reported AEs with onset date 
during the safety follow-up period until Week 64 (i.e., treatment emergent AEs) will be 
included in the analysis. AEs reported after Week 64 will NOT be considered in the 
analysis. 
 
14.5.2.1 
Definitions 
The following definitions will be applied in the present study 
Crude Incidence Rate 
Where percentages of subjects are reported in summary tables, incidences provide 
information on the proportion of subjects experiencing adverse events in relation to the 
total number of subjects exposed, i.e., if not otherwise specified, the crude incidence rate 
will be used.  
The crude incidence rate is defined as the number of subjects experiencing a certain 
event, divided by the number of subjects exposed to study treatment, regardless of 
duration of use: 
 
exposed
 
patients
 
of
number 
events
 
adverse
 with 
patients
 
of
number 
 *
100
 
rate
 
incidence
 
Crude
=
 
 
Treatment Emergent Adverse Events 
Treatment emergent adverse events (TEAEs) are those AEs that occurred during the 
active treatment period from Week 32 to Week 56 or the safety follow-up period from 
Week 56 through Week 64 or those AEs that were present before Week 32 but worsened 
in severity after the Week 32. AEs reported after Week 64 will NOT be considered in the 
present analysis.  
In case of early treatment discontinuation before Week 56 all reported AEs with onset date 
during the safety follow-up period until Week 64 will be included in the analyses. Thus, 
identification of TEAEs (distinguished by subjects who completed or discontinued the 
treatment period until Week 56) will be performed as follows: 
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• 
TEAE for Completer:  Date of Week 32 ≤ Start Date of AE ≤ Date of Week 64 
• 
TEAE for Non-Completer: Date of Week 32 ≤ Start Date of AE ≤ Date of Final 
Study Visit 
AEs which are not classified as TEAEs will be considered as not treatment emergent 
adverse events (NTEAEs). 
 
14.5.2.2 
Analyses 
Overview of adverse events 
For summary presentation of the overall adverse event experience overview tables will be 
provided for AEs and SAEs including the following information: 
Adverse events: 
• 
n (%) of subjects with AEs *) 
• 
n (%) of subjects with NTEAEs *) 
• 
n (%) of subjects with TEAEs *) 
• 
n (%) of subjects with TEAEs by highest causality to study medication 
• 
n (%) of subjects with TEAEs by worst severity 
• 
n (%) of subjects with TEAEs leading to dose modification *) 
• 
n (%) of subjects with TEAEs leading to permanent stop of study medication *) 
Serious Adverse events: 
• 
n (%) of subjects with SAEs *) 
• 
n (%) of subjects with NTESAEs *) 
• 
n (%) of subjects with TESAEs *) 
• 
n (%) of subjects with TESAEs leading to death *) 
• 
n (%) of subjects with TESAEs by highest causality to study medication 
• 
n (%) of subjects with TESAEs by worst severity 
• 
n (%) of subjects with TESAEs leading to permanent stop of study medication *) 
*) the number of events (i.e., number of coded preferred terms) will also be given. 
TEAEs/TESAEs leading to dose modification will be defined as all events with 'Action taken 
with study treatment' is not equal to 'DOSE NOT CHANGED'. 
In addition, the number of TEAEs will be displayed for the following investigator’s ratings: 
• 
severity  
• 
seriousness 
• 
causality 
• 
action taken 
• 
outcome 
 
 
 
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Detailed display of adverse events 
For a more detailed display, adverse events will be presented in summary tables, listing 
these events in code form according to the preferred term. These tables will show the 
number of subjects per group presenting an adverse event and the incidence of its 
occurrence. Adverse events will be grouped by primary SOC (System Organ Class) and will 
be stratified additionally by highest causality to study treatment (not related, doubtful, 
possible, probable, or very likely) and by worst severity (mild, moderate, or severe). The 
incidence of adverse events will be presented by decreasing order of frequency at 
preferred term level within the primary SOC. 
The following tables will be provided for the detailed display of adverse events: 
Adverse events: 
• 
TEAEs by primary SOC and preferred term *) 
• 
TEAEs by primary SOC and preferred term stratified by highest causality 
• 
TEAEs by primary SOC and preferred term stratified by worst severity 
 thereof 
o 
Drug related TEAEs 
o 
Not drug related TEAEs 
• 
TEAEs leading to permanent stop of study medication by primary SOC and 
preferred term *) 
Serious Adverse events: 
• 
TESAEs by primary SOC and preferred term *) 
• 
TESAEs by primary SOC and preferred term stratified by highest causality 
• 
TESAEs by primary SOC and preferred term stratified by worst severity 
• 
TESAEs leading to permanent stop of study medication by primary SOC and 
preferred term *) 
• 
TESAEs leading to death by primary SOC and preferred term *) 
Not treatment emergent adverse events: 
• 
NTEAEs by primary SOC and preferred term *) 
*) These tables will show additionally the number of events (i.e., number of coded preferred terms). 
Summary tabulation of TEAEs and TESAEs by primary SOC and preferred term will also be 
provided for the following types of adverse events: 
• 
injection site reactions (according to the tick box in the e-CRF) 
• 
infections (according to the tick box in the e-CRF) 
o 
thereof, infections treated with oral or parenteral antibiotics 
• 
adverse events of psoriasis (adverse events of psoriasis include any event of 
erythrodermic psoriasis, pustular psoriasis, guttate psoriasis, inverse psoriasis, 
palmo-plantar psoriasis and worsening or exacerbation of psoriasis; final allocation 
will be performed after blinded data review). 
Note that the summary tables will provide the number of subjects per event (i.e., coded as 
preferred term) and will also provide the number of events for certain tables. 
 
 
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For calculation of the number of subjects per event each preferred term will be counted 
only once per subject and will be linked to the primary SOC. A subject may contribute with 
more than one different adverse event (at preferred term level); however, a subject with 
more than one occurrence of the same adverse event (at preferred term level) is displayed 
and counted only once for this event in the tables. 
Tables that are stratified by the severity of adverse events will summarize the worst 
severity per subject and preferred term.  
Tables that are stratified by the relationship of adverse events will summarize the highest 
relationship per subject and preferred term. 
For presentation of drug related/ not drug related adverse events the following categories 
will be used: 
• 
drug related   
=  
very likely, probable, possible 
• 
not drug related  
=  
doubtful, not related 
For summarization of severity of drug related TEAEs, events with a causality assessment 
of 'doubtful/not related' will be excluded and the worst severity will be tabulated as 
described above. Summarization of severity of not drug related TEAEs will be performed 
likewise. 
 
 
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Analyses of adverse events per treatment week 
The rate of TEAEs/TESAEs of special interest per subject per week for the treatment 
periods Week 0-32, and Week 32-64 will be estimated using Poisson regression. Tabulated 
summaries will also display 95% CIs for the respective rates.  
The following TEAEs/TESAEs of special interest are planned to be analysed: 
• 
infections (according to the tick box in the e-CRF)  
• 
SOC ' INFECTIONS AND INFESTATIONS' 
• 
SOC 'GASTROINTESTINAL DISORDERS' 
• 
MACEs (major adverse cardiac events) 
• 
Neoplasm 
• 
Flushing 
The final allocation of TEAEs/TESAEs of special interest will be performed after review of 
data from a locked data base. The planned analyses for the TEAEs/TESAEs of special 
interest are detailed below:  
• 
Analyses of TEAEs/TESAEs of special interest from Week 0 to Week 32 
Item  
Specification 
Treatment Group 
GUS Starter vs. FAE Starter 
Treatment Period 
Week 0 to Week 32 
Analysis set 
Safety Analysis Set Week 24 Analysis 
 
• 
Analyses of TEAEs/TESAEs of special interest from Week 32 to Week 64 
 a) subjects treated with GUS from W32 vs. subjects treated with FAE from W32 
Item  
Specification 
Treatment Group 
GUSresp-GUS + GUSnon-resp-GUS + FAEnon-resp-GUS 
vs. FAEresp - FAE 
Treatment Period 
Week 32 to Week 64 
Analysis set 
Study Part IIb Analysis Set 
 
 
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 b) all subjects treated with GUS-GUS vs. subjects on FAE-FAE vs. FAE-GUS 
Item  
Specification 
Treatment Group 
GUSresp-GUS + GUSnon-resp-GUS vs. FAEnon-resp-GUS 
vs. FAEresp - FAE 
Treatment Period 
Week 32 to Week 64 
Analysis set 
Study Part IIb Analysis Set 
 c) single comparison of all 4 treatment groups 
Item  
Specification 
Treatment Group 
GUSresp-GUS vs. GUSnon-resp-GUS vs. FAEnon-resp-GUS 
vs. FAEresp - FAE 
Treatment Period 
Week 32 to Week 64 
Analysis set 
Study Part IIb Analysis Set 
 
Analyses of adverse events from Week 0 to Week 64 
Summary tables for TEAEs/TESAEs by primary SOC and preferred term in all subjects 
treated with GUS-GUS vs. subjects on FAE-FAE will also be provided for all reported AEs 
with onset date during the active treatment period from Week 0 through Week 56 or the 
respective safety follow-up period in case of early treatment discontinuation. The safety 
analysis set of the Week 24 analysis will be used for these analyses.  
 
Listings 
All adverse events (AEs) and serious adverse events (SAEs) will be listed in the individual 
subject data listings by treatment group in Study Part IIb, study center and subject 
number including all information documented on the respective form of the eCRF. 
Separate listings of subjects with the following AEs will be provided: SAEs, SAEs leading to 
death, AEs of severe intensity, AEs leading to permanent discontinuation of study 
medication. 
Verbatim description of the adverse event reported by the investigator, MedDRA preferred 
terms and primary SOCs (system organ class) for all adverse events will be contained in 
the data listings. Non-treatment emergent adverse events will be flagged in the respective 
listings. 
 
 
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14.5.3 
Clinical Laboratory Tests 
Laboratory data will be summarized by type of laboratory test within the time period from 
Week 32 to Week 64. Reference ranges will be used in the summary of laboratory data. 
Descriptive statistics will be calculated for each laboratory item at each scheduled time. 
Changes from baseline results will be presented in pre- versus post-treatment cross-
tabulations (with classes for below, within, and above normal ranges).  
Results of tuberculosis testing, serology, urine pregnancy testing and local urinalysis 
(glucose, protein) will be displayed in frequency tables providing the number and 
percentage of subjects per category (i.e., negative or positive) at each scheduled time. 
The results of all laboratory tests will be provided in individual subject data listings 
including the reference ranges. Abnormal values will be identified by flagging all values 
below and above the reference range. 
A listing of subjects with any laboratory results outside the reference ranges will be 
provided.  
For the lymphocyte count the following subjects will be listed and summarized in a 
frequency table:  
• 
lowest lymphocyte count < 500/µl 
• 
500/µl ≤ lowest lymphocyte count <700/µl  
• 
700/µl ≤ lowest lymphocyte count < lower limit of normal range 
Graphical presentation of quantitative laboratory data will be given by means of box plots. 
 
 
 
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14.5.4 
Vital Signs 
Descriptive statistics of pulse and blood pressure (systolic and diastolic) values within the 
time period from Week 32 to Week 64 and changes from baseline will be summarized at 
each scheduled time. Subjects reporting vital signs findings beyond clinically important 
limits will be identified using the following criteria.  
Criteria for Identifying Potentially Clinically Significant Vital Signs Findings 
Variable (units) 
Criterion Valuea 
Change from Baseline 
Systolic Blood Pressure (mmHg) 
 
>200 
 
<80 
Increase of >40 
Decrease of >40 
Diastolic Blood Pressure (mmHg) 
 
>120 
 
<40 
Increase of >30 
Decrease of >30 
Heart Rate (bpm) 
 
>110 
 
<40 
 
In order to be identified as an abnormality of potential clinical importance, a value would need to 
meet the criterion value or also represent a change of at least the magnitude noted in the change 
column. 
Vital signs values of potentially clinically significant importance will be analyzed by 
providing the number and percentages of subjects with values of potential clinical 
importance per scheduled study visit, overall during the study and with first occurrence 
after baseline. 
 
14.5.5 
Physical Examination 
Physical examination findings within the time period from Week 32 to Week 64 will be 
tabulated by the body systems given in the eCRF at each scheduled time. Moreover, 
abnormal findings with first occurrence after baseline reported during the treatment phase 
and follow-up phase will be presented. Details on abnormal findings in verbatim terms will 
be displayed in individual subject data listings. 
 
14.5.6 
Body Weight 
For body weight absolute values within the time period from Week 32 to Week 64 and 
changes from baseline values will be presented by descriptive statistics at each scheduled 
time. 
 
14.5.7 
Early Detection of Active Tuberculosis 
Categorical data on early detection of active tuberculosis will be presented in a frequency 
table providing the number and percentage of subjects per category at each scheduled 
time within the time period from Week 32 to Week 64. 
 
 
 
 
 
 
 
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14.6 Analysis of MedDRA Codes 
Previous / concomitant diseases (including indications for use of concomitant and other 
medications) and adverse events will be coded with version 19.1 of the MedDRA-
dictionary. 
In general, tabulation will be displayed by preferred term and primary SOC. 
 
14.7 Analysis of WHO Drug Dictionary Codes 
The use of concomitant and other medications will be coded using the WHO Drug 
Dictionary (version 2016/1). Medications will be tabulated by preferred name (i.e., the 
decode of the code which results when SEQ1 and SEQ2 are set to 01 and 001, respectively 
(usually resulting in a decode close to the generic drug name)) and they will be grouped 
by level 2 of the Anatomical Therapeutic Chemical (ATC) code. Codes being linked to more 
than one ATC code at this level will be assigned to one primary ATC code by medical data 
analysts. 
 
 
 
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15.0 Changes to Planned Analyses 
This statistical analysis plan includes the following relevant changes to the planned 
analyses which are described in the clinical study protocol. 
• 
A per-protocol analysis will be performed for the PASI 90, PASI 75, and DLQI 0/1 
response rates (see SAP section 11.0). 
• 
No treatment failure imputation rules will be applied (see to SAP section 13.1.5 and 
CSP section 11.4) 
 
• 
The following additional efficacy endpoints will be defined and used for the 
statistical analyses: 
o 
The proportion of subjects achieving a 75%/90%/100% improvement of 
their psoriasis according to the PASI at Week 56 (PASI 75/90/100 response) 
compared to baseline 
o 
The change from baseline in the signs and symptoms aggregate scores of 
the PSSD at Week 56 
o 
The change from baseline in the individual scale scores for itch, pain and 
scaling of PSSD components at Week 56 
o 
The proportion of subjects achieving an absolute PASI score ≤1, 2, ≤3, ≤5 
at Week 56 
o 
The proportion of subjects achieving an IGA score of cleared (0) at Week 56 
o 
The proportion of subjects achieving an IGA score of cleared (0) or  
minimal (1) at Week 56 
o 
The change from baseline of body surface area (BSA) psoriatic involvement 
at Week 56 
o 
The change from baseline in DLQI score at Week 56 
o 
The proportion of subjects achieving an ss-IGA score of absence of  
disease (0) at Week 56 in randomized subjects with scalp psoriasis and an 
ss-IGA score ≥2 at baseline 
o 
The proportion of subjects achieving an ss-IGA score of absence of  
disease (0) or very mild disease (1) at Week 56 in randomized subjects with 
scalp psoriasis and an ss-IGA score ≥2 at baseline 
o 
The change from baseline in the physical and mental component summary 
scores of SF-36 at Week 56 
Any major changes to this plan after sign-off of the latest final version will be specified in 
the clinical study report. 
 
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16.0 Tabulation 
16.1  General 
The statistical output will be prepared in American English. No separate statistical report 
will be written. 
 
16.2 Format of Data Displays 
The layout of all tables, listings and figures will be drafted by acromion GmbH when 
providing the first draft tables, listings and figures on final data. No sponsor or other 
requirements for layout specifications have to be followed. 
 
The SAS outputs will be post-processed within Microsoft Word®. SAS tables and listings 
will be integrated into Microsoft Word® using the SAS Monospace 8 points font. 
 
Separate appendices will be provided for tables, listings, and figures. For each appendix a 
corresponding table of contents will be generated. All pages within one appendix will be 
numbered consecutively. Tables, listings and figures generally should be self-explaining. 
Abbreviations will be described in the footnote if necessary. 
 
16.2.1 
Tables 
SAS summary tables will be produced using a landscape page. The maximum number of 
lines per page will be pagesize = 40 and the number of characters in one line will be 
linesize = 140.  
 
16.2.2 
Listings  
SAS subject data listings will be produced using a landscape page. The maximum number 
of lines per page will be pagesize = 40 and the number of characters in one line will be 
linesize = 140.  
 
Data listings will be created for groups of variables which logically belong together (e.g. 
demographic variables) and will be sorted by treatment group, center, subject and visit (if 
applicable). 
 
 
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16.2.3 
Figures  
Figures will be created using the following graphical SAS options, if not otherwise 
specified: 
 
 
GOPTIONS  
    RESET   = ALL  
    NOBORDER 
    KEYMAP = WINANSI  
    DEVMAP = WINANSI  
    DEV       = EMF 
    TARGET = WINPRTC  
    GUNIT   = CM  
    CTEXT   = BLACK  
    FTEXT   = 'Arial/bold'  
    HTEXT   = 0.5 CM  
    LFACTOR= 1  
    HSIZE   = 6 IN  
    VSIZE   = 5 IN; 
 
Variables may be presented in the following graphical formats, if applicable: 
 
Box plot 
Box plots summarize the data by a box reaching from the 1st to the 3rd quartile. The 
median is displayed inside this box by a horizontal line. Above the box a vertical line 
indicates the region from the 3rd quartile to the max. value below the upper fence ; below 
the box a vertical line indicates the region from the 1st quartile to the min. value above the 
lower fence. The upper fence lies 1.5 interquartile-ranges above the 3rd quartile, the lower 
fence lies 1.5 interquartile ranges below the 1st quartile. Values outside the fences are 
displayed by a distinct marker. 
A graphical presentation is given below: 
 
 
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Bar chart 
A bar chart displays a categorical variable. A sample display is provided below. 
 
 
 
16.3  Data Format 
Unless otherwise specified, percentage values will be printed with one digit to the right of 
the decimal point. 
In general, minima and maxima will be quoted to the number of decimal places as 
recorded in the eCRF; means, standard deviations and medians will be quoted to one 
further decimal place. 
All p-values will be given by four digits to the right of the decimal point. Verbatim terms 
documented in the eCRFs will be presented as entered in the clinical data base. 
0
10
20
30
40
50
25
35
45
55
% 
AGE 
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17.0 References 
Study Documents: 
Document 
Version, Date 
Protocol / Amendments 
Version 2.0, 25-APR-2017 
eCRF 
Version 2.0, 08-JUN-2017 
Data Management Plan 
Version 1.0, 09-DEC-2016 
Data Validation Plan 
Version 1.0, 09-DEC-2016 
Statistical Analysis Plan 
- Week 24 Analysis 
Version 1.0, 10-JUL-2017 
SOPs and Guidelines acromion: 
Document 
Title, Date 
acromion SOP BM04 
Statistical Analysis Plans, Oct-2016 
acromion SOP BM05 
Determination of Availability of Data for Analysis, Oct-2016 
acromion SOP BM06 
Generation and Release of Blinded Randomization Code, Oct-
2016 
acromion SOP BM07 
Programming of Derived Data Sets, Oct-2016 
acromion SOP BM08  
Programming of SAS Data Displays, Oct-2016 
acromion SOP BM11  
Documentation and Project Close-Out, Oct-2016 
acromion Guideline 
BM01  
SAS Programming Guideline, Oct-2016 
acromion Guideline 
BM02  
Biometrics Naming Conventions for SAS Datasets and SAS 
Programs, Oct-2016 
Other Documents: 
Document 
Title, Date 
ICH Guideline E 9 
Statistical Principles for Clinical Trials, final approval 1998 
 
 
 
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18.0 Appendices 
18.1  Table of Contents for Data Displays 
The tables, subject data listings and figures will be provided using the following numbering 
system, which will be updated after start of programming the data displays.  
All summary tables will start with the one-character identifier for the displayed analysis 
set followed by the one-digit identifier for the displayed analysis chapter as listed below. 
Identifier for displayed analysis set: 
• 
A: Study Part IIb analysis set 
• 
B: Study Part IIb per-protocol analysis set 
• 
C: Study Part I safety analysis set  
 
Identifier for displayed analysis chapter: 
• 
1: Study subjects 
• 
2: Demographics and other baseline characteristics 
• 
3: Treatment compliance 
• 
4: Analysis of efficacy 
• 
5: Analysis of safety 
Data displays will be provided for the following analysis sets: 
 
Chapter 
No. 
Chapter Title 
Analysis set 
1 
Study subjects 
• A: Study Part IIb analysis set 
2 
Demographic and other baseline 
characteristics 
• A: Study Part IIb analysis set 
3 
Treatment compliance 
• A: Study Part IIb analysis set 
4 
Analysis of efficacy 
• A: Study Part IIb analysis set 
• B: Study Part IIb per-protocol 
analysis set 
• C: Study Part I safety analysis 
Set  
5 
Analysis of safety 
• A: Study Part IIb analysis set 
• C: Study Part I safety analysis 
Set 
All individual subject data listings will start with the one-digit identifier for the displayed 
chapter analogously as for the summary tables. Data displays and subject data listings will 
be provided in separate appendices and pages will be numbered for each appendix 
separately starting with page no. 1. 
 
 
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18.1.1 
Tables 
Study Subjects, Prefix A 
No. 
Analysis Chapter 
1.1 
Disposition of subjects 
1.2 
Discontinuation of study treatment 
1.3 
Protocol deviations 
1.4 
Analysis sets 
 
Demographic and Other Baseline Characteristics, Prefix A 
No. 
Analysis Chapter 
2.1 
Demographics  
2.2 
Medical history 
2.3 
Diagnosis of Psoriasis 
2.4 
Previous Psoriasis Therapy 
2.5 
Substance Use 
2.6 
Physical Examination 
2.7 
Tuberculosis Evaluation 
2.8 
Chest Radiograph Result 
2.9 
Concomitant Medication and Therapy 
2.10 
Shampoo and Moisturizer 
 
Treatment Compliance, Prefix A 
No. 
Analysis Chapter 
3.1 
Visit windows 
3.2 
Study medication 
 
Analysis of Efficacy, Prefix A, B, C 
No. 
Analysis Chapter 
 
- Other Secondary Endpoints - 
4.1 
PASI 90% Response 
4.2.1 
PASI 75% Response 
4.2.2 
DLQI 0/1 Response 
4.3.1 
Other Endpoints related to PASI  
4.3.2 
Endpoints related to PSSD 
4.3.3 
Endpoints related to IGA 
4.3.4 
Endpoints related to BSA 
4.3.5 
Other Endpoints related to DLQI 
4.3.6 
Endpoints related to ss-IGA 
4.3.7 
Endpoints related to SF-36 
 
- Other Efficacy Assessments - 
4.4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, BSA, ss-IGA, SF-36) 
4.5 
Additional Efficacy Analyses (PASI, DLQI, PSSD) 
 
Analysis of Safety, Prefix A, C 
No. 
Analysis Chapter 
5.1 
Extent of Exposure 
5.2 
Adverse Events  
5.3 
Clinical Laboratory Tests 
5.4 
Vital Signs 
5.5 
Physical Examination 
5.6  
Body Weight 
5.7 
Early Detection of Active Tuberculosis 
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18.1.2 
Listings 
Study Subjects  
No. 
Analysis Chapter 
1.1 
Disposition of subjects 
1.2 
Discontinuation of study treatment  
1.3 
Protocol deviations 
1.4 
Analysis sets 
 
Demographic and Other Baseline Characteristics 
No. 
Analysis Chapter 
2.1 
Demographics 
2.2 
Medical history 
2.3 
Diagnosis of Psoriasis 
2.4 
Previous Psoriasis Therapy 
2.5 
Substance Use 
2.6 
Physical Examination 
2.7 
Tuberculosis Evaluation 
2.8 
Chest Radiograph Result 
2.9 
Concomitant Medication and Therapy 
2.10 
Shampoo and Moisturizer 
 
Treatment Compliance 
No. 
Analysis Chapter 
3.1 
Visit windows 
3.2 
Study medication 
 
Analysis of Efficacy 
No. 
Analysis Chapter 
 
- Other Secondary Endpoints - 
4.1 
PASI 90% Response 
4.2.1 
PASI 75% Response 
4.2.2 
DLQI 0/1 Response 
4.3.1 
Other Endpoints related to PASI 
4.3.2 
Endpoints related to PSSD 
4.3.3 
Endpoints related to IGA 
4.3.4 
Endpoints related to BSA 
4.3.5 
Other Endpoints related to DLQI 
4.3.6 
Endpoints related to ss-IGA 
4.3.7 
Endpoints related to SF-36 
 
- Other Efficacy Assessments - 
4.4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, BSA, ss-IGA, SF-36) 
 
Analysis of Safety 
No. 
Analysis Chapter 
5.1 
Extent of Exposure 
5.2 
Adverse Events  
5.3 
Clinical Laboratory Tests 
5.4 
Vital Signs 
5.5 
Physical Examination 
5.6  
Body Weight 
5.7 
Early Detection of Active Tuberculosis 
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18.1.3 
Figures 
Analysis of Efficacy, Prefix A, B, C 
No. 
Analysis Chapter 
Type of Figure 
 
- Other Secondary Endpoints - 
 
1 
PASI 90% Response 
Bar Chart, 
Survival Graph 
2.1 
PASI 75% Response 
Bar Chart, 
Survival Graph 
2.2 
DLQI 0/1 Response 
Bar Chart, 
Survival Graph 
3.1 
Other Endpoints related to PASI 
Bar Chart,  
Survival Graph 
3.2 
Endpoints related to PSSD 
Box Plot 
3.3 
Endpoints related to IGA 
Bar Chart 
3.4 
Endpoints related to BSA 
Box Plot 
3.5 
Other Endpoints related to DLQI 
Bar Chart 
3.6 
Endpoints related to ss-IGA 
Bar Chart 
3.7 
Endpoints related to SF-36 
Box Plot 
 
- Other Efficacy Assessments - 
 
4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, 
BSA, ss-IGA, SF-36) 
Bar Chart,  
Box Plot 
 
- Additional Efficacy Analyses - 
 
5 
Additional Efficacy Analyses (PASI, DLQI, PSSD) 
Bar Chart,  
Box Plot 
 
 
Analysis of Safety, Prefix A 
No. 
Analysis Chapter 
Type of Figure 
5 
Clinical Laboratory Tests 
Box Plot 
6 
Vital Signs 
Box Plot 
7 
Body Weight 
Box Plot 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Polaris_SAP_W100_V1.0_09May2019 
 
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. 
Statistical Analysis Plan 
 
Multicenter, randomized, open-label, efficacy assessor-blinded, active 
comparator-controlled phase 3b study to compare the efficacy of 
guselkumab to fumaric acid esters (Fumaderm® initial/ Fumaderm®) for 
adult patients with moderate to severe plaque psoriasis who are 
candidates for and naive to systemic treatment 
POLARIS 
- Study Part III: Week 100 Analysis - 
 
Study Code 
CNTO1959PSO3008 
EudraCT Number 
2016-002135-15 
Development phase 
Phase 3b 
Study Design 
randomized, open-label, efficacy assessor-
blinded, single country, multicenter, 
active-comparator-controlled 
Sponsor 
Janssen-Cilag GmbH, Neuss 
Johnson & Johnson Platz 1, 
41470 Neuss, Germany 
Contract Research Organization 
acromion GmbH 
Europaallee 27 – 29 
50226 Frechen, Germany 
Version No., Date 
Final Version 1.0, 09-May-2019 
 
 
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Table of Contents 
1.0 
Signatures .................................................................................... 4 
2.0 
List of Abbreviations .................................................................... 5 
3.0 
Introduction ................................................................................. 6 
4.0 
Responsibilities ............................................................................ 7 
5.0 
Software Utilized .......................................................................... 7 
6.0 
Coding Systems Utilized ............................................................... 7 
7.0 
Study Objectives and Hypotheses ................................................ 8 
7.1 
Objectives ................................................................................................. 8 
7.2 
Hypotheses ............................................................................................... 8 
8.0 
Study Endpoints ........................................................................... 9 
9.0 
Study Design .............................................................................. 10 
9.1 
Overview ................................................................................................. 10 
9.2 
Sample Size Determination ........................................................................ 14 
9.3 
Randomization and Blinding ....................................................................... 15 
10.0 
Study Schedule........................................................................... 16 
11.0 
Analysis Sets .............................................................................. 26 
11.1 
Definition of Analysis Sets ......................................................................... 26 
11.2 
Protocol Deviations ................................................................................... 26 
11.3 
Screening Failures .................................................................................... 26 
12.0 
Definition and Calculation of Efficacy Endpoints ......................... 27 
12.1 
Involved Body Surface Area (BSA%) ........................................................... 27 
12.2 
Investigator's Global Assessment (IGA) ....................................................... 27 
12.3 
Scalp Specific Investigator's Global Assessment (ss-IGA) .............................. 27 
12.4 
Psoriasis Area and Severity Index (PASI) .................................................... 28 
12.5 
Dermatology Life Quality Index (DLQI) ....................................................... 28 
12.6 
Psoriasis Symptom and Sign Diary (PSSD) .................................................. 29 
12.7 
Short Form Health Survey (SF-36) ............................................................. 30 
13.0 
Statistical Methodology .............................................................. 31 
13.1 
Data Handling Rules ................................................................................. 31 
13.1.1 Baseline and Post-baseline Points in Time of Interest .................................... 31 
13.1.2 Definition of Within- and Between-Group Differences .................................... 32 
13.1.3 Visit Windows .......................................................................................... 32 
13.1.4 Treatment Failure Criteria .......................................................................... 32 
13.1.5 Treatment Failure Rules ............................................................................ 32 
13.1.6 Handling of Missing Values ........................................................................ 33 
13.1.7 Data Transformations ............................................................................... 33 
13.2 
Descriptive Statistics ................................................................................ 33 
13.2.1 Dichotomous and Categorical Variables ....................................................... 33 
13.2.2 Continuous and Quasi-Continuous Variables ................................................ 33 
13.2.3 Graphical Presentations ............................................................................. 34 
13.3 
Confirmatory Statistics .............................................................................. 34 
13.4 
Exploratory Statistics ................................................................................ 34 
13.4.1 Binary Endpoints ...................................................................................... 34 
13.4.2 Continuous Endpoints ............................................................................... 34 
13.5 
Adjustment for Covariates ......................................................................... 34 
13.6 
Main, Interim, and Final Analyses ............................................................... 35 
13.7 
Multi-center Data ..................................................................................... 35 
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13.8 
Subgroup Analyses ................................................................................... 36 
13.9 
Sensitivity Analyses .................................................................................. 36 
14.0 
Statistical Analyses .................................................................... 37 
14.1 
Study Subjects ......................................................................................... 37 
14.1.1 Disposition of Subjects .............................................................................. 37 
14.1.2 Discontinuation of Study ........................................................................... 38 
14.1.3 Protocol Deviations ................................................................................... 38 
14.1.4 Analysis Sets ........................................................................................... 38 
14.2 
Demographic and Other Baseline Characteristics .......................................... 39 
14.2.1 Demographics .......................................................................................... 39 
14.2.2 Medical History ........................................................................................ 39 
14.2.3 Diagnosis of Psoriasis ................................................................................ 39 
14.2.4 Previous Psoriasis Therapy ........................................................................ 39 
14.2.5 Substance Use ......................................................................................... 39 
14.2.6 Physical Examination ................................................................................ 39 
14.2.7 Tuberculosis Evaluation ............................................................................. 39 
14.2.8 Chest Radiograph Result ........................................................................... 39 
14.2.9 Concomitant Medication and Therapy .......................................................... 40 
14.2.10 Shampoo and Moisturizer .......................................................................... 40 
14.2.11 Planned Next Psoriasis Therapy .................................................................. 40 
14.3 
Treatment Compliance .............................................................................. 41 
14.3.1 Visit Windows .......................................................................................... 41 
14.3.2 Study Medication ...................................................................................... 41 
14.4 
Analysis of Efficacy ................................................................................... 42 
14.4.1 Primary Endpoint ...................................................................................... 43 
14.4.2 Major Secondary Endpoints ....................................................................... 43 
14.4.3 Other Secondary Endpoints ....................................................................... 43 
14.4.4 Other Efficacy Assessments ....................................................................... 45 
14.5 
Analysis of Safety ..................................................................................... 46 
14.5.1 Extent of Exposure ................................................................................... 46 
14.5.2 Adverse Drug Reactions/Death ................................................................... 46 
14.5.3 Clinical Laboratory Tests ........................................................................... 49 
14.5.4 Vital Signs ............................................................................................... 49 
14.5.5 Physical Examination ................................................................................ 49 
14.5.6 Body Weight ............................................................................................ 49 
14.5.7 Early Detection of Active Tuberculosis ......................................................... 49 
14.6 
Analysis of MedDRA Codes ......................................................................... 50 
14.7 
Analysis of WHO Drug Dictionary Codes ...................................................... 50 
15.0 
Changes to Planned Analyses ..................................................... 51 
16.0 
Tabulation .................................................................................. 52 
16.1 
General ................................................................................................... 52 
16.2 
Format of Data Displays ............................................................................ 52 
16.2.1 Tables ..................................................................................................... 52 
16.2.2 Listings ................................................................................................... 52 
16.2.3 Figures .................................................................................................... 53 
16.3 
Data Format ............................................................................................ 54 
17.0 
References ................................................................................. 55 
18.0 
Appendices ................................................................................. 56 
18.1 
Table of Contents for Data Displays ............................................................ 56 
18.1.1 Tables ..................................................................................................... 57 
18.1.2 Listings ................................................................................................... 58 
18.1.3 Figures .................................................................................................... 59 
 
 
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Polaris_SAP_W100_V1.0_09May2019 
 
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2.0 
List of Abbreviations 
 
ADR 
Adverse Drug Reaction 
ANCOVA 
Analysis of Covariance 
BSA 
Body Surface Area 
CRF 
Case Report Form(s)  
CSP 
Clinical Study Protocol 
DLQI 
Dermatology Life Quality Index 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
e.g. 
example given 
FAE 
Fumaric Acid Esters 
FSV 
Final Study Visit 
HBV/ HCV 
Hepatitis B virus/ Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
HTA 
Health Technology Assessment 
ICH 
International Council on Harmonization 
i.e. 
that is 
IGA 
Investigator´s Global Assessment 
IL 
Interleukin 
LOCF 
Last Observation Carried Forward 
MCS 
Mental Component Summary 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
Methotrexate 
PASI 
Psoriasis Area and Severity Index 
PCS 
Physical Component Summary 
PRO 
Patient-Reported Outcome(s)  
PSSD 
Psoriasis Symptom and Sign Diary 
SADR 
Serious Adverse Drug Reaction 
SAP 
Statistical Analysis Plan 
SC 
subcutaneous 
SF-36 
Short Form (36-item) health survey 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
ss 
scalp-specific 
TB 
tuberculosis 
TES 
Time and Events Schedule 
 
 
 
 
 
 
 
 
 
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3.0 
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 and the relevant acromion 
SOPs and/or guidelines. This plan describes the statistical analyses planned to be performed 
for the Week 100 analysis (Study Part III) of Janssen-Cilag GmbH Clinical Study Protocol 
CNTO1959PSO3008 and should be read in conjunction with the statistical analysis plans for 
the Week 24 and week 64 analysis, the protocol amendments INT-1 and INT-2 to the CSP 
and the electronic Case Report Form (eCRF).  
An overview about all planned analyses is given in Section 13.6. The Week 100 analysis 
summarizes the study data in Study Part III from Week 64 until Week 100 (Study Part III: 
follow-up extension period). All statistical analyses will be descriptive and exploratory. 
Statistical analyses of study data until Week 64 have been laid out in separate SAPs. 
Confirmatory analyses for the primary endpoint and the major secondary endpoints were 
already performed at the Week 24 analysis as described in the statistical analysis plan for 
Week 24 (Final 1.0, 10-July-2017). Evaluations on health technology assessment (HTA) 
were also specified in this SAP. No separate HTA SAP was provided. Exploratory and 
descriptive analyses for the secondary endpoints at Week 32 and Week 56 were already 
performed at the Week 64 analysis and are described in the respective statistical analysis 
plans (Study Part IIa: Final 1.0, 15-Aug-2018; Study Part IIb: Final 1.0, 29-Aug-2018). The 
Week 100 analysis (Study Part III) will be performed after all subjects have completed the 
Week 100 visit, lost their response prior to Week 100, or have terminated the study 
prematurely. Data base lock for the Week 100 analysis will be after the Final Study Visit 
(FSV) /Week 100 visit data are ready for statistical analysis (ie, clean data). 
This SAP is the core document for all statistical programming planned to be performed for 
the Week 100 analysis (Study Part III) and is based on the following study documents to 
protocol no. CNTO1959PSO3008: 
Document 
Version, Date 
Protocol / Amendments 
Version 1.0, 03-AUG-2016 
 
Protocol Amendment INT-1, Version 2.0, 25-APR-2017 
 
Protocol Amendment INT-2, Version 3.0, 25-JAN-2018 
eCRF 
Version 2.0, 08-JUN-2017 
Data Management Plan 
Version 1.0, 09-DEC-2016 
Data Validation Plan 
Version 1.0, 09-DEC-2016 
Statistical Analysis Plan - Week 
24 Analysis (Study Part I) 
Version 1.0, 10-JUL-2017 
Statistical Analysis Plan - Week 
32 Analysis (Study Part IIa) 
Version 1.0, 15-AUG-2018 
Statistical Analysis Plan - Week 
64 Analysis (Study Part IIb) 
Version 1.0, 29-AUG-2018 
 
 
Note: In the following text the term 'Week 100' always includes the Final Study Visit Part 
III (FSV) according to the documentation in the eCRF (i.e. Week 100 = Week 100 /FSV) 
even if the study was completed before W100 (i.e., subjects meet the definition of loss of 
response). 
 
 
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4.0 
Responsibilities 
The responsibilities for the biometrical tasks at acromion GmbH are assigned as follows: 
Name 
Function 
Task 
Statistician 
Statistical Programming and Analysis 
Statistician 
Statistical Programming and Analysis 
Statistical Programmer 
Statistical Programming and Analysis 
Statistical Programmer 
Statistical Programming and Analysis 
Medical Data Analyst 
Medical Data Review and Coding 
5.0 
Software Utilized 
The statistical analysis and generation of tables, patient data listings and figures will be 
performed using the SAS® software package version 9.4 under the Microsoft Windows® 7 
operating system at the computer facilities of acromion GmbH. Additional analyses 
regarding health technology assessment (HTA) may be performed by or under the 
responsibility of Janssen-Cilag GmbH. 
 
6.0 
Coding Systems Utilized 
The MedDRA-dictionary version 19.1 is used for coding of prior and concomitant diseases 
and for coding of adverse events. The following items are coded. 
eCRF Module 
Item 
SDTM Domain/ Variable 
Name 
Medical History of Interest 
Medical History Term 
MH/MHTERM 
Previous Phototherapy 
Type of Phototherapy 
MH/MHTERM 
Concomitant Medication 
Indication 
CM/CMIND 
Concomitant Therapy 
Indication 
CM/CMIND 
Concomitant Therapy 
Therapy 
CM/CMTRT 
(S)AE  
Term 
AE/AETERM 
Prior and concomitant medications are coded according to the WHO terminology using the 
2016/1 version of the WHO-Drug Dictionary. The following items are coded. 
eCRF Module 
Item 
SDTM Domain/ Variable 
Name 
Previous Topical Therapy 
Medication/Therapy 
MH/MHTERM 
Concomitant Medication  
Compound 
CM/CMTRT 
Details are specified in the Data Management Plan. 
 
 
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7.0 
Study Objectives and Hypotheses 
7.1 
Objectives 
Primary Objectives 
The primary objectives of the study are 
• 
to compare the efficacy of guselkumab to fumaric acid esters (FAE) in systemic 
treatment-naïve subjects with moderate to severe plaque-type psoriasis. 
• 
to assess the safety and tolerability of guselkumab in systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis. 
Secondary Objectives 
The secondary objectives of the study are 
• 
in Study Parts I and II: to compare improvement of health-related quality of life 
(QOL) and other patient-reported outcomes (PRO) when systemic treatment-naïve 
subjects with moderate to severe plaque-type psoriasis are treated with guselkumab 
compared to FAE. 
• 
in Study Part II: to compare sustainability of response to treatment when systemic 
treatment naïve subjects with moderate to severe plaque-type psoriasis are treated 
with guselkumab compared to FAE. 
• 
in Study Part III (guselkumab withdrawal): to investigate the maintenance of 
response in subjects withdrawn from study treatment, and to explore prediction 
parameters of disease modification. 
 
7.2 
Hypotheses 
The primary hypothesis of this study is that guselkumab treatment is superior to FAE 
(Fumaderm® initial/Fumaderm®) treatment as assessed by the proportion of subjects 
achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are: 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a PASI 75 response at Week 24 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a DLQI score of 0 or 1 at Week 24. 
If the primary hypothesis is accepted, the study will be considered positive. 
 
 
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8.0 
Study Endpoints 
This section provides a description of all study endpoints as pre-specified in the CSP 
(Protocol Amendment INT-2) for the Week 24, the Week 64, and the Week 100 analyses.  
Primary Endpoint 
The primary endpoint is the proportion of subjects achieving at least a 90% improvement 
of their psoriasis according to the Psoriasis Area and Severity Index (PASI 90 response) at 
Week 24. 
Secondary Endpoints 
The major secondary endpoints are: 
• 
The proportion of subjects achieving at least a 75% improvement of their psoriasis 
according to the PASI (PASI 75 response) at Week 24  
• 
The proportion of subjects achieving a DLQI score of 0 or 1 at Week 24. 
Other secondary endpoints are: 
• 
The proportion of subjects achieving a 100% improvement of their psoriasis according to 
the PASI (PASI 100 response) at Week 24  
• 
The change from baseline in the signs and symptoms aggregate scores of the PSSD at 
Week 24 
• 
The change from baseline in the individual scale scores for itch, pain and scaling of PSSD 
components at Week 24 
• 
The proportion of subjects achieving an absolute PASI score ≤1 at Week 24 
• 
The proportion of subjects achieving an IGA score of cleared (0) at Week 24 
• 
The change from baseline of body surface area (BSA) psoriatic involvement at Week 24  
• 
The change from baseline in DLQI score at Week 24 
• 
The proportion of subjects achieving an ss-IGA score of absence of disease (0) at Week 
24 in randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at baseline 
• 
The change from baseline in the physical and mental component summary scores of SF-
36 at Week 24 
• 
Maintenance of response.  
− 
Proportion of subjects with a  
- PASI 75 response at Week 32 who maintain response at Week 56 
- PASI 90 response at Week 32 who maintain response at Week 56 
- DLQI score 0 or 1 at Week 32 who maintain response at Week 56 
− 
Proportion of subjects with a  
- PASI 75 response (compared to baseline) at Week 56 
- PASI 90 response (compared to baseline) at Week 56 
- PASI 100 response (compared to baseline) at Week 56 
- DLQI score 0 or 1 at Week 56 
− 
Proportion of subjects with a  
- PASI 75 response (compared to baseline) at Week 32 
- PASI 90 response (compared to baseline) at Week 32 
- PASI 100 response (compared to baseline) at Week 32 
- DLQI score 0 or 1 at Week 32 
− 
Maintenance of response after guselkumab withdrawal. Proportion of subjects of the 
guselkumab group (GUS-GUS and FAE-GUS) with a   
− 
PASI 90 response at Week 56 who maintain response at Week 100 (PASI ≤5) 
− 
Time to loss of response (PASI >5) from Week 56 after guselkumab withdrawal at 
Week 100 
• 
Safety and tolerability data will be summarized using descriptive statistics 
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Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
Polaris_SAP_W100_V1.0_09May2019 
 
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9.0 
Study Design 
This section provides a description of the study design as defined in the CSP (Protocol 
Amendment INT-2) for the Week 100 analysis. 
The description is written in future tense according to the wording in the CSP, even though 
some of the planned actions, analyses and procedures have been carried out meanwhile. 
Note: References to 'Section' always refer to the respective section in the CSP (Protocol 
Amendment INT-2). 
9.1 
Overview 
This is a randomized, open-label, efficacy assessor-blinded, single country, multicenter, 
active comparator-controlled phase 3b study of guselkumab in adult subjects with moderate 
to severe plaque-type psoriasis who have not yet received any systemic therapy. The study 
will be performed at about 30 to 45 sites in Germany. 
This study will have a 3-week screening phase, a 56-week treatment phase and a safety 
follow-up phase until Week 64, followed by a follow-up extension phase after withdrawal of 
guselkumab until loss of response or until Week 100 at the latest (as shown in Figure 1). 
The maximum duration of a subject’s participation in this study will be 103 weeks. With 
protocol Amendments INT-1 and INT-2, the study will be split into three parts (Study Part 
I, II and III): 
Study Part I (Core Study)—Week 0 through Week 24: 
Subjects will be randomized in a 1:1 ratio to either the study drug (guselkumab) or to the 
active comparator (FAE). Efficacy of treatment will be assessed before any tests, procedures 
or other evaluations, first by the subject him/herself (1st DLQI, 2nd PSSD 7-day version, 
and 3rd SF-36), and subsequently, in Study Part I and II, by a blinded efficacy assessor 
(BSA%, IGA, ss-IGA, and PASI). Preferably the same efficacy assessor continues evaluation 
of the disease in Study Part III, but efficacy assessments are no longer blinded. 
A subject will be considered to have completed Study Part I if he or she has completed 
assessments at Week 24 of the open-label phase. For subjects who discontinue study 
treatment or withdraw from study participation in Study Part I or who do not enter Study 
Part II, a safety follow-up visit (Study Part I) will be performed at Week 32 or 12 weeks 
after the last treatment (whatever comes first). For subjects enrolled in Study Part I only, 
maximum duration of study participation will be 35 weeks. 
Study Part II (Extension, Continuation/Switch of Study Treatment)—Week 24 
through Week 56 
Subjects may enter the study extension at Week 24 only when the ICF for Study Part II was 
signed before or at Week 24, study treatment was not terminated prior to Week 24 and no 
protocol-prohibited medication/therapy was started. Study Part II is subdivided in two 
treatment periods: 
• 
Part IIa – Week 24 through Week 32: All subjects who enter Study Part II will 
continue their assigned treatment (guselkumab or FAE) from Week 24 through Week 
32. Study Part IIa is considered completed when the subject has completed 
assessments at Week 32. 
• 
Part IIb – Week 32 through Week 56: Following Week 32, subjects with PASI 75 
response will continue assigned treatment (guselkumab or FAE). For PASI 75 non-
responders at Week 32 the following options will be available: 
− Guselkumab group: Subjects may continue guselkumab treatment, if the 
investigator considers therapy medically appropriate.  
 
 
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− FAE group: Subjects will switch to guselkumab unless barred by safety reasons 
(based on lab values ≥Week 28). Subjects who terminate FAE treatment prior to 
Week 32 cannot continue study treatment but will enter safety follow-up per 
protocol. 
A subject will be considered to have completed Study Part II if he or she has completed 
assessments at Week 56 of the open-label phase. For subjects who discontinue study 
treatment or withdraw from study participation in Study Part II, final study assessments are 
obtained and a final safety follow-up visit (Study Part II) is completed at Week 64 or 12 
weeks after last treatment.  
For subjects completing Study Part II, and not entering Study Part III, maximum duration 
of study participation in this study will be 67 weeks including a 3-week screening phase. 
Study Part III (Follow-up extension, guselkumab withdrawal, no study 
treatment)—Week 64 through Week 100 
Subjects who received guselkumab in Study Part II (subjects who started guselkumab 
treatment at Week 0 or switched from FAE to guselkumab treatment in Week 32), had no 
psoriatic arthritis diagnosed at baseline and achieved a PASI 90 response at end of Study 
Part II (Week 56) may enter follow-up extension at Week 64. To be eligible for follow-up 
extension subjects must have signed ICF for Study Part III before or at Week 64, must not 
have started a new psoriasis treatment (including commercially available guselkumab 
therapy) or started any other protocol-prohibited medication/therapy. In Study Part III, 
subjects are withdrawn from guselkumab treatment and will be followed until loss of 
response (defined as an increase in absolute PASI >5), but until Week 100 at the latest, 
which is almost 1 year after the last guselkumab treatment at visit Week 52.  
All other subjects may not enter Study Part III and complete the study at Week 64. 
Efficacy assessments will be performed first by the subject him/herself, and subsequently 
by an efficacy assessor. Preferably, in Study Part III the same efficacy assessor as in Study 
Parts I and II continues evaluation of the disease, but efficacy assessments are no longer 
blinded. 
A subject will be considered to have completed Study Part I or Study Part II if he or she has 
completed assessments at Week 24 and Week 56, respectively. A subject will be considered 
to have completed Study Part III if he or she has completed assessments at Week 100 or 
completed final assessments after loss of response. The maximum duration of a subject’s 
participation will be 103 weeks including a 3-week screening phase. 
Safety Follow-up Phase 
• 
Safety FUP (Part I) – Week 24 through Week 32 
For subjects who complete study treatment at Week 24 a final safety follow-up visit is 
completed at Week 32.  
• 
Safety Follow-up (Part II) – Week 56 through Week 64 
All ongoing subjects complete the safety follow-up until Week 64. For subjects who 
complete study treatment at Week 56 a final safety follow-up visit is completed at 
Week 64. For subjects entering Study Part III, the safety follow-up visit will be 
conducted and subjects will continue as described below. 
• 
Safety Follow-up after discontinuation/withdrawal – 12 weeks after last 
treatment 
For subjects who discontinue study treatment or withdraw from study participation, 
final study assessments are obtained and a final safety follow-up visit is completed 12 
weeks after the last treatment.  
 
 
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The efficacy of treatment will be assessed before any tests, procedures or other evaluations, 
first by the subject him/herself (1st DLQI, 2nd PSSD 7-day version, and 3rd SF-36), and 
subsequently, in Study Part I and II, by a blinded efficacy assessor (BSA%, IGA, ss-IGA, 
and PASI). Preferably, the same efficacy assessor continues evaluation of these outcome 
parameters in Study Part III, but efficacy assessments are no longer blinded. 
Safety evaluations will include the monitoring of adverse events (including injection site and 
allergic reactions), physical examinations, measurement of body weight, vital sign 
measurement, clinical laboratory testing (HBV, HCV, HIV, hematology, chemistry), 
concomitant medication review, tuberculosis test and evaluation, urinalysis and pregnancy 
testing.  
The confirmatory analysis will be conducted after the primary endpoint at Week 24 is 
reached including subjects who have completed the Week 24 visit and subjects who have 
terminated the study prematurely (Section 11.3). The second and third statistical analyses 
will be performed after Week 64 and after Week 100 (see Section 11). 
A subject will be considered to have completed Study Part I or Study Part II if he or she has 
completed assessments at Week 24 and Week 56, respectively. A subject will be considered 
to have completed Study Part III if he or she has completed assessments at Week 100 or 
completed final assessments after loss of response. The maximum duration of a subject’s 
participation will be 103 weeks including a 3-week screening phase. 
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 transferred to the sponsor (or designee) 
after completion of the final subject visit at that site, in the time specified in the Clinical Trial 
Agreement. The overall duration of the study is expected to be approximately 30 months 
(start in December 2016, stop in July 2019). 
The estimated frequency and timing of the study visits are summarized in the ‘Time and 
Events Schedule’ (TES). 
 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W100_V1.0_09May2019 
 
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Figure 1: Schematic Overview of the Study 
 
 
 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W100_V1.0_09May2019 
 
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9.2 
 Sample Size Determination 
As described in the CSP, the primary hypothesis of this study is that guselkumab treatment 
is superior to FAE (Fumaderm® initial/ Fumaderm®) treatment as assessed by the proportion 
of subjects achieving a PASI 90 response at Week 24. 
The major secondary hypotheses are:  
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a PASI 75 response at Week 24. 
• 
Guselkumab treatment is superior to FAE as assessed by the proportion of subjects 
achieving a DLQI score of 0 or 1 at Week 24. 
In order to control the overall experiment wise type 1 error rate, the primary endpoint and 
the two major secondary endpoints will be tested in a fixed sequence as a-priori ordered 
hypotheses. That is, the first major secondary endpoint will be tested only if the primary 
endpoint is positive (i.e., p <0.05), and the second major secondary endpoint will be tested 
only if the first major secondary endpoint is positive (i.e., p <0.05). Due to the testing of 
ordered hypotheses, no adjustment of the significance level with respect to the threefold 
test procedure is required. 
The assumptions for the sample size and power calculations using the threefold test 
procedure were based on guselkumab phase 2 data and unpublished data from the German 
PsoBest Registry and are as follows: PASI 90 responder rates for guselkumab and FAE in 
Week 24 are assumed to be 60% and 25%, respectively. PASI 75 responder rates are 
assumed to be 80% and 45%, respectively. DLQI responder rates are assumed to be 60% 
and 30%, respectively. 
Based on these assumptions, with a total of 114 subjects planned to be randomized in a 1:1 
ratio to guselkumab (n = 57) and to FAE (n = 57), superiority of guselkumab vs. FAE can 
be demonstrated at a 5% significance level (two-sided) with power of at least 90% for each 
test of the threefold test procedure as displayed in the table below. 
Table 1: Power to detect a treatment effect on expected proportions of subjects 
achieving the primary and the major secondary endpoints 
Order of 
testing 
Endpoint in  
Week 24 
Guselkumab 
(% responder) 
FAE 
(% responder) 
Power 
1 
PASI 90 
60 
25 
97% 
2 
PASI 75 
80 
45 
98% 
3 
DLQI 0/1 
60 
30 
90% 
type 1 error rate alpha 5% (two-sided) 
sequential testing with a-priori ordered hypotheses (only proceed with testing, if p <0.05)  
sample size n = 114 with 1:1 ratio guselkumab (n = 57) and FAE (n = 57) 
two group chi-square test; nQuery Advisor® Release 7.0 
 
 
 
 
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CNTO1959 (guselkumab) 
 
Polaris_SAP_W100_V1.0_09May2019 
 
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9.3 
 Randomization and Blinding 
Procedures for Randomization  
Central randomization is implemented in this study as described in Section 5 of the CSP. 
Subjects will be randomly assigned to 1 of 2 treatment groups (1:1 ratio) based on a 
computer-generated randomization schedule prepared before the study by or under the 
supervision of the sponsor. The randomization will be balanced by using randomly permuted 
blocks. The interactive web-based eCRF will assign a unique treatment code, which will 
dictate the treatment assignment at baseline visit of the subject. The investigator will not 
be provided with randomization codes. The randomization codes will be stored invisible for 
the investigator in a separate, blind part of the EDC (Electronic Data Capture) system.  
Blinding 
As this is an open study, blinding procedures for the treatment are not applicable. However, 
a blinded efficacy evaluator will assess effectiveness of treatment as described in Section 
9.2.3 of the CSP. 
 
 
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10.0 Study Schedule 
An overview of the study procedures is displayed in the following time and events schedule of the CSP. References to 'Section' always refer 
to the respective section in the CSP. 
Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section Fehler! Verweisquelle 
konnte nicht gefunden werden. 
Study Proceduresb 
Screening/Administrative 
Informed consent I 
(Study Part I) 
X 
 
 
 
 
 
 
 
 
 
 
Must be signed before first study-related activity 
Informed consent II 
(Study Part II) 
------------------------------------------------------------------------------X 
 
 
ICF addendum for Study Part II to be signed at 
Week 24 at the latest 
Medical history and 
demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/ 
exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
Minimum criteria for the availability of 
documentation supporting the eligibility criteria 
are described in protocol, Section 4; check 
clinical status again before first dose of study 
medication 
Study Drug Administration 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
All baseline study procedures and evaluations are 
to be completed before randomization 
Study drug 
administration 
 
   Xc-------------------------------------------------------------------…  
 
All study procedures and evaluations are to be 
completed before study drug administration 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before administration of study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
c: Subjects randomized to guselkumab will get guselkumab 100 mg on site at Weeks 0, 4, 12 and then every 8 weeks. Subjects randomized to FAEs will start with Fumaderm® 
initial regimen (0-0-1) at the day of the baseline visit; thereafter, FAE doses will be increased to find the optimal Fumaderm® dose for each subject as described in Section 
6.  
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CNTO1959 (guselkumab) 
Polaris_SAP_W100_V1.0_09May2019 
 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section Fehler! Verweisquelle 
konnte nicht gefunden werden. 
Study Proceduresb 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit: for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section Fehler! Verweisquelle konnte 
nicht gefunden werden. 
Safety Assessments 
Physical examination  
X 
x 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X  
X 
 
Tuberculosis evaluation 
X 
X 
   X--------------------------------------------------------… 
X 
X 
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 
(Section 9.3) 
Chest radiograph 
X 
 
 
 
 
 
 
 
 
 
 
Taken within 3 months before the first 
administration of study drug and read by a 
qualified radiologist 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Women of childbearing potential must have a 
negative 
urine 
pregnancy 
test 
before 
randomization and at all study visits (prior to 
administration of study drug). 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
Weight 
 
X 
 
 
 
 
 
 
X 
X 
X 
 
Concomitant therapy 
      X--------------------------------------------------------------------------… 
X 
X 
 
Adverse events 
      X--------------------------------------------------------------------------… 
X 
X 
 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section Fehler! Verweisquelle 
konnte nicht gefunden werden. 
Study Proceduresb 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section Fehler! Verweisquelle konnte 
nicht gefunden werden. 
Efficacy Assessments 
DLQI 
X 
X 
 
X  
X 
 
X 
 
X 
 
X 
 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd 
SF-36; should be performed before any tests, 
procedures or other evaluations (PASI, IGA, ss-
IGA, BSA) for that visit; completion of the 
baseline 
PROs 
has 
to 
be 
done 
before 
randomization 
PSSD (7d) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
SF-36 
 
X 
 
 
X 
 
X 
 
X 
 
X 
IGAd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
PASId 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
ss-IGAd,e 
 
X 
 
 
X 
 
X 
 
X 
 
X 
BSA%d 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
d: Dermatological evaluation of the subjects will be done by a blinded assessor starting with the Baseline visit; assessments will be done before any study related procedure 
will take place 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section Fehler! Verweisquelle konnte 
nicht gefunden werden. 
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Phase 
Screen-
inga 
Active Treatment 
Safety FUP 
(Final study 
visit Part I)h1 
ETVh2 
Notes 
Week max. –3 
0 
2 
4 
8 
12 
16 
20 
24 
≤32 
 
All visits should occur within ±7 days of the 
scheduled visit, Section Fehler! Verweisquelle 
konnte nicht gefunden werden. 
Study Proceduresb 
Clinical Laboratory Assessment 
Tuberculosis testf 
X 
 
 
 
 
 
 
 
 
 
 
 
Hepatitis B and C 
Serologies 
X 
 
 
 
 
 
 
 
 
 
 
 
HIV antibody test 
X 
 
 
 
 
 
 
 
 
 
 
 
Hematologyg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Laboratory tests are listed in Section 9.3 
Chemistryg 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urinalysis by dipstick: glucose and protein; if 
there are signs of proteins and/or glucose on urine 
test strip, the urine sample must be analyzed 
centrally; here, protein and glucose levels must 
not exceed trace levels, eg, ≤ +; one re-test 
(central urine analysis) is allowed. 
a: To occur within 3 weeks prior to Week 0 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
f: The QuantiFERON-TB Gold Plus test will generally be performed by the central laboratory; however, if available, test results from local laboratory can be accepted 
g: All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled; fasting is not necessary; details will be 
provided in the Laboratory Manual 
h1: Safety Follow-up/Final Study Visit Part I (≤Week 32): only for subjects who do not enter Study Part II. Visit is completed at Week 32 or 12 weeks after last treatment 
(whatever comes first). 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section Fehler! Verweisquelle konnte 
nicht gefunden werden. 
 
 
 
 
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Phase 
Active Treatment 
Safety FUP 
(Final Study visit 
Part II)h3 
ETVh2 
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the scheduled 
visit, Section 7 
Study Proceduresb 
Study Drug Administration 
Study drug administration 
…---------Xi--------------------------------------------------X 
 
 
Subjects may enter the study extension at Week 24 
when ICF for Study Part II was signed, study 
treatment was not terminated and no protocol-
prohibited medication/therapy was started. 
Safety Assessments 
Physical examination  
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
Vital signs 
X 
X 
  
X 
 
X 
 
X 
X  
X 
Tuberculosis evaluation 
……----------------------------------------------------------X 
X 
X 
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 (Section 9.3) 
Urine pregnancy test 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Weight 
 
 
 
 
 
 
 
 
X 
X 
 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section Fehler! Verweisquelle konnte 
nicht gefunden werden.. 
h3: Safety Follow-up/Final Study Visit Study Part II (≤Week 64): For subjects who complete Study Part II or discontinue study treatment or withdraw from study 
participation in Study Part II. Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
i: Week 24 to Week 32 (Study Part IIa): subjects continue assigned treatments through Week 32. Subjects treated with 100 mg SC guselkumab continue q8w (ie, at Week 
28). Subjects treated with FAE continue Fumaderm® tablets (individual dosing according to local SmPC) until Week 32. 
Week 32 to Week 56 (Study Part IIb): Treatment decision based on PASI assessment at Week 32 and safety assessment (≥Week 28): 
- PASI 75 responders at Week 32: subject continues assigned therapy. Subjects in the guselkumab group continue 100 mg guselkumab SC at Weeks 36, 44, 52. 
Subjects in the FAE group continue Fumaderm® treatment (individual dosing according to local SmPC) until Week 56. 
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Phase 
Active Treatment 
Safety FUP 
(Final Study visit 
Part II)h3 
ETVh2 
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the scheduled 
visit, Section 7 
Study Proceduresb 
- PASI 75 non-responders at Week 32: subjects in the FAE group may switch to guselkumab treatment unless barred by safety reasons (see treatment criteria Section 
4.4). In case of safety concerns (based on lab values of Week ≥28), assessment can be repeated before Week 32. Subjects will receive guselkumab SC at Weeks 32, 
36, 44 and Week 52. Non-responders in the guselkumab group may continue guselkumab (continuation of therapy is at the investigator’s discretion). 
Safety Assessments (continued) 
Concomitant therapy 
…----------------------------------------------------------X 
X 
X 
 
Adverse events 
    …----------------------------------------------------------X 
X 
X 
 
Efficacy Assessments 
DLQI 
X 
X 
X* 
X  
 
X 
 
X 
 
X 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd SF-
36; should be performed before any tests, procedures 
or other evaluations (PASI, IGA, ss-IGA, BSA) for 
that visit. 
*ONLY applicable for subjects who switched to 
guselkumab at Week 32  
PSSD (7d) 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
SF-36 
 
X 
 
 
 
 
 
X 
 
X 
IGAd 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
PASId 
X 
X 
X* 
X 
 
X 
 
X 
 
X 
ss-IGAd,e 
 
X 
X* 
X 
 
X 
 
X 
 
X 
BSA%d 
 
X 
 
 
 
 
 
X 
 
X 
 
Study Proceduresb  
 
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
d: Dermatological evaluation of the subjects will be done by a blinded assessor as in Study Part I; assessments will be done before any study related procedure will take 
place 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section Fehler! Verweisquelle konnte 
nicht gefunden werden.. 
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Phase 
Active Treatment 
Safety FUP 
(Final Study visit 
Part II)h3 
ETVh2 
Notes 
Week 
28 
32 
36 
40 
44 
48 
52 
56 
≤64 
 
All visits should occur within ±7 days of the scheduled 
visit, Section 7 
Study Proceduresb 
h3: Safety Follow-up/Final Study Visit Study Part II ≤Week 64: For subjects who complete Study Part II or discontinue study treatment or withdraw from study participation 
in Study Part II. Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
Clinical Laboratory Assessment 
Hematologyg 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X 
Laboratory tests are listed in Section 9.3 
∆  NOT applicable for subjects continuing gusel-
kumab treatment since beginning of the study 
(Week 0) 
Chemistryg 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X∆ 
X 
X 
Urinalysis 
X 
Xβ  
X 
Xβ  
X 
Xβ  
X 
Xβ  
X 
X 
Urinalysis by dipstick: glucose and protein; if there are 
signs of proteins and/or glucose on urine test strip, the 
urine sample must be analyzed centrally; here, protein 
and glucose levels must not exceed trace levels, eg, 
≤+; one re-test (central urine analysis) is allowed. 
β  ONLY applicable for subjects treated with FAE 
  
b: All study procedures and evaluations are to be completed before the subject administers study drug. For assessments on subjects who discontinue administration of study 
treatments, see Section 10.2 
g: All blood samples must be collected before study drug administration at visits when a study drug administration is scheduled; fasting is not necessary; details will be 
provided in the Laboratory Manual 
h2: Early Termination Visit; for subjects who discontinue study treatment or withdraw from study participation before end of treatment, every effort should be made to 
conduct the final assessments (Early Termination Visit) and to conduct the post-treatment assessments (Safety Follow-up), see Section Fehler! Verweisquelle konnte 
nicht gefunden werden.. 
h3: Safety Follow-up/Final Study Visit Study Part II ≤Week 64: For subjects who complete Study Part II or discontinue study treatment or withdraw from study participation 
in Study Part II. Safety FUP Part II visit is completed at Week 64 or 12 weeks after last treatment (whatever comes first). 
 
 
 
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Study Part II 
Study Part III 
 
Phase 
Active 
treatment 
Safety FUP / 
FSV Part II 
Guselkumab withdrawal 
FSVj  
Part III Notes 
Week 
52 
56 
≤64 
64 
76 
88 
≤100 
After visit Week 64, all visits should occur within ±14 days of the scheduled 
visit, see Section Fehler! Verweisquelle konnte nicht gefunden werden. 
Study Procedures 
Administrative 
Informed consent III  
…-----------------------X 
 
 
ICF addendum for Study Part III signed at W64 at the latest (before efficacy 
assessments) 
Eligibility criteria 
for Study Part III 
…-----------------------X 
 
 
Criteria include: subject treated with Gus in Study Part II (ie, last application at 
W52), no PsA diagnosis at baseline, PASI 90 response at W56, no start of new 
psoriasis treatment including commercially available guselkumab or any other 
prohibited treatment/therapy before W64; details see Section Fehler! 
Verweisquelle konnte nicht gefunden werden.  
Study Drug Administration 
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Study Part II 
Study Part III 
 
Phase 
Active 
treatment 
Safety FUP / 
FSV Part II 
Guselkumab withdrawal 
FSVj  
Part III Notes 
Week 
52 
56 
≤64 
64 
76 
88 
≤100 
After visit Week 64, all visits should occur within ±14 days of the scheduled 
visit, see Section Fehler! Verweisquelle konnte nicht gefunden werden. 
Study Procedures 
Guselkumab 
 
X 
 
Not allowed for subjects participating in Study Part III 
Last study drug application at W52. Subjects may start a commercially available 
topical psoriasis treatment at Week 64 or later at the investigator’s discretion; 
topical corticosteroids class IV (alone or in combination) and phototherapy are 
prohibited 
Safety Assessments 
Concomitant therapy 
X, see Table 2 
X---------psoriasis therapy------------X 
In case any prohibited therapy is applied (for psoriasis or any other indication) 
the subject is withdrawn from study participation. Prohibited therapy is recorded 
at the end of study participation (FSV Part III). If already known, planned next 
psoriasis therapy is recorded at the end of study, 
Physical examination  
X, see Table 2 
 
X 
X 
X 
 
Vital signs 
X, see Table 2 
 
X 
X 
X 
 
Weight 
X, see Table 2 
 
 
 
Adverse Events/ 
ADRs 
(S)AEs, see Table 2 
 
(S)ADRs and death -- X 
During Study Part III, Adverse Drug Reactions (ADRs) and deaths are recorded 
until FSV. Details see Section Fehler! Verweisquelle konnte nicht gefunden 
werden. 
Clinical Laboratory 
Assessments 
X, see Table 2 
 
 
No lab assessments during Study Part III 
FSV=final study visit 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
j: FSV Study Part III ≤ Week 100; FSV is done at loss of response (defined as an increase in absolute PASI >5), upon withdrawal from study participation or at Week 100 
at the latest.  
 
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Study Part II 
Study Part III 
 
Phase 
Active 
treatment 
Safety FUP / 
FSV Part II 
Guselkumab withdrawal 
FSVj  
Part III Notes 
Week 
52 
56 
≤64 
64 
76 
88 
≤100 
After visit Week 64, all visits should occur within ±14 days of the scheduled 
visit, see Section Fehler! Verweisquelle konnte nicht gefunden werden. 
Study Procedures 
Efficacy Assessments 
DLQI 
 
X 
X 
X 
X 
Order of assessments: 1st DLQI, 2nd PSSD, 3rd SF-36; should be performed 
before any other evaluations (PASI, IGA, ss-IGA, BSA) for that visit 
PSSD (7d) 
 
X 
X 
X 
X 
SF-36 
 
X 
X 
X 
X 
IGA 
 
X 
X 
X 
X 
As only subjects treated with guselkumab may enter follow-up extension phase, 
efficacy assessments are not blinded during Study Part III. However, it is 
recommended to have the efficacy assessments done by the same assessor as in 
Study Parts I and II. 
PASIj 
 
X 
X 
X 
X 
ss-IGAe 
 
X 
X 
X 
X 
BSA% 
 
X 
X 
X 
X 
e: To be performed only for those subjects with a corresponding diagnosis at baseline (Week 0) 
j: FSV Study Part III ≤Week 100: FSV is done at loss of response (defined as an increase in absolute PASI >5), upon withdrawal from study participation or at Week 100 
at the latest. FSV should also be performed for subjects who withdraw from study participation. 
 
 
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11.0 Analysis Sets 
If not otherwise specified, the following study groups will be analyzed in Study Part III.  
o 
GUSwithdrawal: PASI 90 responder GUS 'overall' withdrawal group (FAE-
GUSwithdrawal + GUS-GUSwithdrawal) 
o 
FAE-GUSwithdrawal: PASI 90 responder FAE-GUS 'switcher' withdrawal group 
o 
GUS-GUSwithdrawal: PASI 90 responder GUS-GUS 'non-switcher' withdrawal 
group 
11.1 
Definition of Analysis Sets 
The following analysis data sets will be defined: 
• 
Study Part III Analysis Set 
The Study Part III analysis set is defined as the set of all subjects receiving guselkumab 
treatment in Study Part IIb and who were eligible to enter Study Part III and who were 
withdrawn from study treatment. 
• 
Study Part III Per-Protocol Analysis Set 
The Study Part III per-protocol analysis set will consist of all subjects in the Study Part 
III 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. 
Data on study subjects, demographic and baseline characteristics, as well as all efficacy and 
safety analyses will be analyzed for the Study Part III analysis set. A per-protocol analysis 
using the Study Part III per-protocol analysis set will not be performed because of the low 
number of subjects with major protocol deviations. 
11.2 
Protocol Deviations 
The determination of evaluability of subjects, especially in cases of protocol deviations, 
withdrawals or drop-outs and the assignment of subjects to the planned analysis sets will 
be performed according to the requirements of the study protocol. Minor and major and 
potentially major protocol deviations that can be expected based on the prescriptions in the 
protocol were defined by Janssen-Cilag GmbH during the trial set up period and adapted 
during the study conduct. A detailed description of major and potentially major protocol 
deviation criteria is included in a separate document. 
Data on subjects who had a major protocol deviation will be documented continuously by 
Janssen-Cilag GmbH in a Clinical Trial Management System during the trial period. Final 
data on major protocol deviations regarding the Week 100 analysis of Study Part III will be 
transferred to the data management department of acromion GmbH as Excel spreadsheets 
and will be further processed for statistical analysis. 
 
11.3 
Screening Failures 
Not applicable for the present analysis. 
 
 
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12.0 Definition and Calculation of Efficacy Endpoints 
The following sections provide a detailed description of the definition and the planned 
calculation of the efficacy endpoints as defined in the CSP. The same applies also for 
additional endpoints not defined in the CSP. 
 
12.1 
Involved 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).  
 
12.2 
Investigator's Global Assessment (IGA) 
The Investigator’s Global Assessment (IGA) documents the investigator’s assessment of the 
subject’s psoriasis at a given time. Overall lesions are graded for induration, erythema, and 
scaling. The subject’s psoriasis is assessed as cleared (0), minimal (1), mild (2), moderate 
(3), or severe (4). 
The efficacy endpoint related to the IGA score is defined below: 
IGA cleared responder 
Subjects who achieve an IGA score of cleared (0) will be considered IGA cleared responders. 
 
12.3 
Scalp Specific Investigator's Global Assessment (ss-IGA) 
The scalp-specific (ss-)IGA instrument is used to evaluate the disease severity of scalp 
psoriasis. The lesions are assessed in terms of the clinical signs of redness, thickness, and 
scaliness which are scored as: absence of disease (0), very mild disease (1), mild disease 
(2), moderate disease (3), and severe disease (4). 
The analyses for ss-IGA will be based on subjects randomized at Week 0 with baseline ss-
IGA score ≥2.  
ss-IGA absence of disease responder 
Subjects with an ss-IGA score ≥2 at baseline who achieve ss-IGA score of absence of disease 
(0) will be considered ss-IGA absence of disease responders. 
 
 
 
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12.4 
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. 
Maintenance of response after guselkumab withdrawal  
• 
Proportion of subjects with a PASI 90 response at Week 56 who maintain response 
at Week 100 (defined as an absolute PASI ≤5) 
• 
Time to loss of response (defined as an absolute PASI >5) from Week 56 after 
guselkumab withdrawal at Week 100 
The time to loss of response from Week 56 after guselkumab withdrawal at Week 100 will 
be calculated as time from Week 56 to first onset of loss of response. In the absence of 
documented loss of response the time will be censored at the date of Week 100 or the date 
of discontinuation in case of early discontinuation. 
12.5 
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 (e.g., not all 10 answers in the DLQI questionnaire 
were available) the following rules will be applied: 
• 
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. 
• 
If two or more questions are left unanswered the questionnaire will not be scored. 
• 
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. 
. 
 
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12.6 
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 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) 
• 
Symptom score includes itch (Q1), pain (Q11), stinging (Q10), burning (Q9) and skin 
tightness (Q4). 
• 
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) 
• 
Sign score includes skin dryness (Q2), cracking (Q3), scaling (Q5), shedding or 
flaking (Q6), redness (Q7) and bleeding (Q8). 
• 
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. 
 
 
 
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12.7 
Short Form Health Survey (SF-36) 
The Short Form Health Survey (SF-36) is a 36-item questionnaire used for subjects’ self-
assessment of health-related quality of life, consisting of the following 8 dimensions: 1) 
limitations in physical functioning due to health problems, 2) limitations in usual role 
activities due to physical health problems, 3) bodily pain, 4) general mental health 
(psychological distress and well-being), 5) limitations in usual role activities due to personal 
or emotional problems, 6) limitations in social functioning due to physical or mental health 
problems, 7) vitality (energy and fatigue), and 8) general health perception.  
A physical component summary (PCS) score and a mental component summary (MCS) score 
can be derived. The concepts measured by the SF-36 are not specific to age, disease or 
treatment group, allowing comparison of relative burden of different diseases and the 
relative benefit of different treatments. The estimated completion time will be 10 minutes. 
Each of these 8 scales (domains) is scored from 0 to 100 with higher scores indicating better 
health. Based on the scale scores, the summary scores, PCS and MCS, will be derived. These 
summary scores are also scaled with higher scores indicating better health. 
The QualityMetric Health Outcomes™ Scoring Software 5.0 offered by QualityMetric 
Incorporated will be used to score the SF-36. The Software is designed to provide users with 
standard scoring methods in an easy-to-use way. By using this Software, users will have 
the confidence that the data they obtain on their SF form are scored in accordance with 
standards set by the developers of the SF tools. The Software also provides evaluation of 
data quality and applies methods for missing data recovery. The PCS score can be calculated 
when seven scale scores are available and the Physical Functioning scale is not missing. The 
MCS score can be calculated when at least seven scale scores are available and the Mental 
Health scale is not missing. 
 
A more detailed description of the scoring procedure is provided in the User's Guide of 
QualityMetric Health Outcomes™ Scoring Software 5.0 (see especially Appendix F). 
 
 
 
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13.0 Statistical Methodology 
The present Week 100 analysis summarizes the study data in Study Part III from Week 64 
until Week 100. All statistical analyses will be descriptive and exploratory only. 
The biometrical evaluation will be carried out by acromion GmbH under the authority of the 
sponsor. Statistical programming and analyses will be performed using the statistical 
software system SAS®. 
The following sections provide a more detailed description of the planned statistical 
methodology. 
13.1 
Data Handling Rules 
13.1.1 
Baseline and Post-baseline Points in Time of Interest 
Baseline Definition 
• All Endpoints: The values of the Week 56 visit will be used as baseline values, as 
applicable. 
Definition of Post-baseline Points in Time of Interest 
The primary point in time for efficacy assessment will be the Week 100 visit (= the study 
visit 100 weeks after randomization) or the Final Study Visit Part III after loss of response. 
Secondary points in time for efficacy assessment will be the study visits scheduled at Week 
64, at Week 76, and at Week 88 during the follow-up extension phase. Handling of missing 
values is described in SAP section 13.1.6. 
The safety analysis will cover the time period from Week 64 through Week 100.  
 
 
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13.1.2 
Definition of Within- and Between-Group Differences 
Within-group differences for continuous endpoints will be computed as differences of the 
post-baseline visits as compared to the baseline visit (Week 56), if applicable: 
• 
post-baseline visit minus baseline visit 
 
 
The following between-group differences will be calculated, if applicable: 
• 
FAE-GUSwithdrawal - GUS-GUSwithdrawal 
 
 
13.1.3 
Visit Windows 
Nominal visits (i.e., visits as recorded in the eCRF) will be used for all by-visit analyses in 
the study. The study visits scheduled post randomization should occur at the times 
delineated in the Time and Events Schedule. No visit windows will be defined and used for 
analysis. 
13.1.4 
Treatment Failure Criteria 
Not applicable. 
 
13.1.5 
Treatment Failure Rules 
No treatment failure rules will be applied.  
 
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13.1.6 
Handling of Missing Values 
All available data will be included in the analyses and will be summarized descriptively as 
far as possible. If not otherwise specified, there will be no substitution of missing data, i.e., 
missing data will not be replaced, missing data will be handled as ‘missing’ in the statistical 
evaluation (‘observed cases analysis’). 
Missing data for the efficacy endpoints at key visits Week 64, 76, 88 and 100 will be handled 
as follows for all exploratory inferential statistical analyses. 
Missing data imputation for the efficacy endpoints at Week 64, 76, 88 and 100: 
1. Nonresponder imputation (NRI) will be applied for binary endpoints 
o 
i.e., subjects with missing data at Week 64/76/88/100 will be considered non-
responders at Week 64/76/88/100. 
2. Last observation carried forward (LOCF) will be applied for continuous endpoints 
o 
i.e., in subjects with missing data at Week 64/76/88/100 the last available 
observation after Week 64 will be calculated and used for analysis for 
continuous response variables at Week 64/76/88/100. 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. 
Sensitivity analyses with respect to the handling of missing values at Week 100 are 
described in SAP section 13.9. 
 
13.1.7 
Data Transformations 
No data transformations (e.g. square root, logarithmic) to confirm basic statistical 
assumptions will be performed. All variables will be used in the analysis as reported. 
 
13.2 
Descriptive Statistics 
13.2.1 
Dichotomous and Categorical Variables 
Categorical data will be presented in frequency tables using counts and percentages. 
Percentages will be based on the total number of subjects in the respective analysis set 
(i.e., missing values will be included in percentage calculation). Besides presentation of 
absolute values cross tabulation vs. baseline by study visit will be provided, if appropriate. 
 
13.2.2 
Continuous and Quasi-Continuous Variables 
Standard descriptive summary statistics will be calculated for continuous and quasi-
continuous variables: arithmetic mean, standard deviation, minimum value, lower quartile, 
median, upper quartile, maximum value, number of non-missing values. Besides 
presentation of absolute values tabulation for differences to baseline by study visit will be 
provided, if appropriate. 
 
 
 
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13.2.3 
Graphical Presentations 
Graphical presentation of pertinent data will be given by means of box plots, bar charts, and 
survival graphs, as appropriate. Additional forms of graphical presentations may be 
specified. Descriptions of graphical presentations are included in the appendix of this 
document. 
 
13.3 
Confirmatory Statistics 
Not applicable for the present Week 100 analysis (Study Part III). The confirmatory analysis 
is described in the SAP for the Week 24 analysis (Final 1.0, 10-July-2017). 
 
13.4 
Exploratory Statistics 
Exploratory statistical analyses will be performed for the endpoints listed under 'other 
secondary endpoints' relevant for Study Part III at Week 100, and at Week 64, at Week 76, 
and at Week 88. All confidence intervals and p-values will be calculated two-sided and will 
be interpreted in the exploratory sense only.  
 
13.4.1 
Binary Endpoints 
For binary endpoints counts and percentage of subjects with 95% confidence intervals (95% 
CIs) using normal approximation will be provided. 
A two-sided chi-square test will be used to compare the FAE-GUSwithdrawal vs GUS-GUSwithdrawal 
with respect to the following endpoint: 
• The proportion of subjects with a PASI 90 response at Week 56 who maintain response 
(PASI ≤5) at Week 100 
The time to loss of response from Week 56 after guselkumab withdrawal at Week 100 will 
be calculated as time from Week 56 to first onset of loss of response (defined as an absolute 
PASI >5). In the absence of documented loss of response the time will be censored at the 
date of Week 100 or the date of discontinuation in case of early discontinuation. 
The time-to-event analysis will be performed using Kaplan-Meier product limit method. A 
summary table will provide the number of subjects analyzed, the 25%, 50% (median), and 
75% quantiles time-to-event with 95% confidence intervals (CI). The survival curve will also 
be displayed graphically. The time-to-event analysis will be performed on the observed 
cases only (i.e., missing data will not be replaced for the time-to-event analysis). 
 
13.4.2 
Continuous Endpoints 
For the change from baseline of continuous endpoints 95% confidence intervals (95% CIs) 
using normal approximation will be provided. 
 
13.5 
Adjustment for Covariates 
Not applicable.  
 
 
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13.6 
Main, Interim, and Final Analyses 
The following analyses are planned to be performed. 
1. Main Analysis (Confirmatory Week 24 Analysis) 
The confirmatory main analysis was performed at the end of Study Part I, i.e., after all 
subjects had completed their visit at 24 weeks after randomization or discontinued 
earlier. This analysis, described in a separate SAP (‘SAP Week 24’, final version 1.0, 10-
July-2017), included the confirmatory analysis of the primary endpoint and the major 
secondary endpoints as well as all other exploratory predefined efficacy and safety 
analyses until Week 24. The results of the analysis are described in the Clinical Study 
Report Week 24, dated 14.05.2018. 
2. Interim Analysis (Exploratory Week 64 Analysis)  
No confirmatory analysis is planned to be performed. The (exploratory) interim analysis 
will be performed at the end of Study Part II, i.e. after all subjects had completed their 
visits at 64 weeks after randomization or discontinued earlier. The Week 64 analysis will 
be split into 2 parts, the Week 32 analysis and the Week 64 analysis. 
- 
The Week 32 analysis, described in a separate SAP (‘SAP Week 32’), summarizes the 
study data until Week 32 (Study Part IIa; continuation of assigned treatment from 
Week 24 through Week 32). All statistical analyses will be descriptive and exploratory 
only for the predefined efficacy and safety analyses until Week 32.  
- 
The Week 64 analysis, described in a separate SAP (‘SAP Week 64’), summarizes the 
study data until Week 64 (Study Part IIb). The analysis will include all efficacy 
measures until Week 56 and safety measures until the Week 64 safety visit.  
The results of the analysis are described in the Clinical Study Report Week 32, dated 
15.03.2019 and in the Clinical Study Report Week 64, dated 07.05.2019 
3. Final Analysis (Exploratory Week 100 Analysis) 
No confirmatory analysis is planned to be performed. The (exploratory) final analysis will 
be performed at the end of Study Part III, i.e. after all subjects had completed their 
visits at 100 weeks after randomization or completed earlier (i.e., subjects meet the 
definition of loss of response) or discontinued earlier. 
13.7 
Multi-center Data 
Analyses with respect to the results of the individual centers will not be performed. 
 
 
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13.8 
 Subgroup Analyses 
The following subgroup analyses are planned to be performed to evaluate consistency over 
demographics and baseline disease characteristics: 
Analyses set:  
• 
GUSwithdrawal group of the Study Part III analysis set 
Endpoints:  
• 
PASI 90 response at Week 56 who maintain response at Week 100 (PASI ≤5) 
• 
Time to loss of response (PASI >5) from Week 56 after guselkumab withdrawal at 
Week 100 
Subgroups: 
• 
Gender 
o 
male 
o 
female 
• 
Age at baseline Week 0 in years 
o 
≤35 
o 
> 35 
• 
PASI at baseline Week 0 
o 
< 20 
o 
≥ 20 
• 
Duration of disease in years 
o 
≤ 5 
o 
≤ 10 
o 
> 10 - ≤18 
o 
> 18 
• 
BMI at baseline Week 0 
o 
18.5 - < 25 
o 
≥ 25 - < 30 
o 
≥ 30 
• 
PASI 100 
o 
at Week 24 
o 
at Week 56 
Subgroup analyses for the efficacy endpoints will be performed using the imputation rules 
of missing values at Week 100 as specified in SAP section 13.1.6. 
13.9 
Sensitivity Analyses 
An 'observed cases analysis' for all binary and continuous endpoints without substitution of 
missing data will be used (see SAP section 13.1.6). 
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14.0 Statistical Analyses 
A table of contents of planned data displays is provided in section 18.1 of this document. 
The following sections are intended to provide more details of the planned analyses. In 
addition, mock tables were created and were used as template for statistical programming 
at the Week 24 analysis. The mock tables will be used analogously at the present Week 100 
analysis of Study Part III. 
Data will be appropriately summarized and analyzed using tabulation and graphs with 
respect to demographic/baseline characteristics and efficacy/safety observations and 
measurements. Standard descriptive summary statistics (i.e., n, arithmetic mean, standard 
deviation, median, minimum/maximum value, quartiles) will be calculated for continuous 
variables. Categorical data will be presented in frequency tables using counts and 
percentages. In general, summary tables will be displayed for the total sample in the 
respective analysis set. Additional classification variables or statistical analyses on 
subgroups are explicitly mentioned in the following text. Individual subject data listings will 
be presented parameter wise and will be sorted by treatment group (in Study Parts I and 
II), center, subject number and study visit, if applicable. 
14.1 
Study Subjects 
Unless otherwise specified, data on study subjects will be analyzed based on data from all 
subjects who entered Study Part III ('Study Part III analysis set').  
14.1.1 
Disposition of Subjects 
The overview of subject disposition from Week 0 to Week 32, from Week 32 to Week 56, 
and from Week 64 to Week 100 will provide the respective frequency counts and 
percentages regarding the following subjects: 
• 
Treatment phase from Week 0 until Week 32 
o 
Subjects who were enrolled (i.e., signed informed consent Part I) 
o 
Subjects who were randomized 
o 
Subjects who were treated 
o 
Subjects with premature discontinuation of study treatment until Week 24 
o 
Subjects who completed the treatment phase until Week 24 
o 
Subject who entered Study Part II (i.e., signed informed consent Part II) 
o 
Subjects with premature discontinuation of study treatment until Week 32 
o 
Subjects who completed the treatment phase until Week 32 
• 
Treatment phase from Week 32 to Week 56 
o 
Subjects who were treated 
o 
Subjects with premature discontinuation of study treatment until Week 56 
o 
Subjects who completed the treatment phase until Week 56 
• 
Follow-up extension phase from Week 64 to Week 100 
o 
Subjects who were enrolled (i.e., signed informed consent Part III) 
o 
Subjects with premature discontinuation until Week 100 
o 
Subjects who completed the follow-up extension phase until Week 100 or due 
to loss of response 
 
Subjects who completed the follow-up extension phase until Week 100 
 
Subjects who completed the follow-up extension phase due to loss of 
response 
 
 
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The table will also include the total number of study sites and the dates of the entry of the 
first subject and the last visit of the last subject. A flow diagram (according to the CONSORT 
statement) giving an overview of subject disposition will also be provided in the clinical 
study report. 
In addition, the number and percentage of treated/observed subjects continuing and 
attending by study visit will be displayed in a separate table. Subjects will be counted as 
continuing at the time of visit whether they attend the visit or not. Only those subjects that 
prematurely discontinued before the visit will not be counted as attending.  
14.1.2 
Discontinuation of Study 
The number and percentage of subjects who discontinued the Study Part III prematurely 
within the time period from Week 64 to Week 100 will be tabulated for each reason of 
premature discontinuation (including tabulation of specifications for category 'other'). 
Moreover, the number of subjects not included in Study Part III will be given. Categorical 
data on the planned next psoriasis therapy and the planned start will be summarized in a 
frequency table providing the number and percentages of subjects within each category. 
 
14.1.3 
Protocol Deviations 
In general, the following list of major protocol deviations may have the potential to impact 
subjects’ rights, safety or well-being, or the integrity and/or result of the clinical trial. 
Subjects with major protocol deviations will be summarized by category for all subjects in 
Study Part III. 
• 
Developed withdrawal criteria but not withdrawn 
• 
Entered but did not satisfy criteria 
• 
Received a disallowed concomitant treatment 
• 
Received wrong treatment or incorrect dose 
• 
Other 
The summary table will provide the number of subjects per major protocol deviation and 
will also provide the number of major protocol deviations in Study Part III. 
 
14.1.4 
Analysis Sets 
The number and percentage of subjects included in each analysis set, together with a 
breakdown of the reasons for exclusion for non-evaluable subjects, will be provided. 
 
 
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14.2  Demographic and Other Baseline Characteristics 
Generally, assessments made at the screening visit and the baseline visit will be 
summarized. These assessments will include demographic characteristics and other 
parameters (such as medical history, diagnosis of psoriasis, concomitant diseases, and 
concomitant medication). Summary tables will be provided by means of descriptive statistics 
and frequency tables, where appropriate. Demographic and other baseline characteristics 
will be analyzed based on data from all enrolled subjects in Study Part III ('Study Part III 
analysis set'). 
 
14.2.1 
Demographics 
Age (categorized), gender, and race will be presented in a frequency table. Age group 
categories will be chosen as < 45; ≥ 45 - < 65; ≥ 65years. Descriptive summary statistics 
will be calculated for age, body height, body weight and body mass index (BMI).  
Tables for demographic data will also be stratified by gender. Age and gender distribution 
will be presented in a bar chart. 
Note: Age is documented as 'age at date of informed consent signature' at the screening visit. Body 
height and body weight data will be taken from the vital signs eCRF form at the Week 0 visit. BMI will 
be calculated as body weight in kg / body height in m². 
14.2.2 
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 terminology as described in SAP section 14.6. Summary 
tabulation will also consider whether the disease is ongoing or not at screening visit. 
14.2.3 
Diagnosis of Psoriasis 
The time from date of initial diagnosis of psoriasis to date of screening visit will be calculated 
and will be displayed by descriptive statistics. If the day is unknown the day will be set to 
day = 1. If the month is unknown the month will be set to month = July. 
14.2.4 
Previous Psoriasis Therapy 
No statistical analysis will be performed.  
14.2.5 
Substance Use  
No statistical analysis will be performed.  
14.2.6 
Physical Examination 
No statistical analysis will be performed.  
14.2.7 
Tuberculosis Evaluation 
No statistical analysis will be performed.  
14.2.8 
Chest Radiograph Result 
No statistical analysis will be performed.  
 
 
 
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14.2.9 
Concomitant Medication and Therapy 
Only topical psoriasis medication/therapy and prohibited medication (if applicable) should 
be documented. Other medication/therapy should not be documented in Study Part III. 
Analyses of concomitant medication and therapy will consider the data recorded within the 
time period from Week 64 to Week 100. Analyses may also be performed for subjects with 
and without loss of PASI response. 
Concomitant Medication 
The number and percentage of subjects with use of concomitant medication from Week 64 
to Week 100 will be displayed in WHO-DD terminology as described in SAP section 14.7. 
Concomitant medication will be identified from the Concomitant Medication form of the 
eCRF. 
The number and percentage of subjects with indication for concomitant medication from 
Week 64 to Week 100 will be displayed in MedDRA terminology as described in SAP section 
14.6. 
Concomitant Therapy 
The number and percentage of subjects with use of concomitant therapy from Week 64 to 
Week 100 will be displayed in MedDRA terminology as described in SAP section 14.6. 
Concomitant therapy will be identified from the Concomitant Therapy form of the eCRF. 
The number and percentage of subjects with indication for concomitant therapy from Week 
64 to Week 100 will be displayed in MedDRA terminology as described in SAP section 14.6. 
 
14.2.10 
Shampoo and Moisturizer 
The number and percentage of subjects with use of shampoo or moisturizer from Week 64 
to Week 100 will be displayed in a frequency table. 
 
14.2.11 
Planned Next Psoriasis Therapy 
The number and percentage of subjects with planned next psoriasis therapy will be tabulated 
by type and planned start of therapy 
 
 
 
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14.3  Treatment Compliance 
Calculation of treatment compliance is not applicable because no study treatment was 
provided in Study Part III. Analyses of visit windows will be based on data from all enrolled 
subjects in Study Part III ('Study Part III analysis set').  
14.3.1 
Visit Windows 
The number of days between the scheduled study visits and the baseline visit will be 
calculated using the reported visit dates per scheduled study visit and will be displayed by 
summary descriptive statistics from Week 64 to Week 100. 
 
14.3.2 
Study Medication 
Not applicable because no study treatment was provided. 
 
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14.4  Analysis of Efficacy 
All efficacy analyses will be performed for all enrolled subjects in Study Part III ('Study Part 
III analysis set').  
All statistical analyses will be descriptive and exploratory only for the predefined efficacy 
analyses from Week 56 through Week 100. 
Handling of missing values, exploratory statistics, subgroup analyses, and sensitivity 
analyses will be performed as described in detail in the following sections of this SAP: 
SAP Section No. 
Topic 
13.1.6 
Handling of missing values 
13.4.1 
Exploratory statistics - binary endpoints 
13.4.2 
Exploratory statistics - continuous endpoints 
13.8 
Subgroup analyses 
13.9 
Sensitivity analyses 
Data at the scheduled points Week 64, Week 76 and Week 88 during the follow-up extension 
period will be analyzed analogously to the Week 100 data. However, no subgroup or 
sensitivity analyses will be performed for these points in time. 
 
 
 
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14.4.1 
Primary Endpoint 
Not applicable for the present analysis. The confirmatory statistical analysis was already 
performed at the Week 24 analysis. 
 
14.4.2 
Major Secondary Endpoints 
14.4.2.1 
Endpoint related to PASI 
Not applicable for the present analysis. The confirmatory statistical analysis was already 
performed at the Week 24 analysis. 
 
14.4.2.2 
Endpoint related to DLQI 
Not applicable for the present analysis. The confirmatory statistical analysis was already 
performed at the Week 24 analysis. 
 
14.4.3 
Other Secondary Endpoints 
The following sections provide a description of the planned statistical analyses of the other 
secondary endpoints as reported in the CSP and as well as of additional endpoints for Study 
Part III not explicitly stated in the CSP (see SAP section 15.0). 
 
14.4.3.1 
Endpoints related to PASI 
Other secondary endpoints related to PASI are: 
• The proportion of subjects achieving an absolute PASI score ≤1, ≤2, ≤3 at Week 100 
• The proportion of subjects with a PASI 90 response at Week 56 who maintain response 
(PASI ≤5) at Week 100 
• The proportion of subjects with a PASI 90 response at Week 56 who maintain PASI 90 
response at Week 100 
• Time to loss of response (PASI >5) from Week 56 after guselkumab withdrawal  
The proportion of responding 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. The time to loss of response will be analyzed using Kaplan-Meier product limit 
method. 
Exploratory statistical analyses will be performed as described in SAP section 13.4.1. 
 
 
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14.4.3.2 
Endpoints related to PSSD 
Other secondary endpoints related to PSSD are: 
• The change from baseline (Week 56) in the signs and symptoms aggregate scores of the 
PSSD at Week 100 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 100 value and the change from the 
baseline value will be displayed. 
Exploratory statistical analyses will be performed as described in SAP section 13.4.2. 
 
14.4.3.3 
Endpoints related to IGA 
Other secondary endpoints related to IGA are: 
• The proportion of subjects achieving an IGA score of cleared (0) at Week 100. 
The proportion of responding 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.  
Additional exploratory statistical analyses will be performed as described in SAP section 
13.4.1. 
In addition, the proportion of subjects achieving an IGA score of cleared (0) or minimal (1) 
at Week 100 will be analyzed analogously. 
 
14.4.3.4 
Endpoints related to BSA 
Other secondary endpoints related to BSA are: 
• The change from baseline (Week 56) of body surface area (BSA) psoriatic involvement 
at Week 100 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 100 value and the change from the 
baseline value will be displayed. 
Exploratory statistical analyses will be performed as described in SAP section 13.4.2. 
 
14.4.3.5 
Endpoints related to DLQI 
Other secondary endpoints related to DLQI are: 
• The proportion of subjects achieving a DLQI score of 0 or 1 at Week 100 
• The change from baseline in DLQI score at Week 100 
• The proportion of subjects with a DLQI score 0 or 1 at Week 56 who maintain response 
at Week 100 
The proportion of responding 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. 
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The change from Week 56 will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The Week 56 value, the Week 100 value and the change from the 
Week 56 value will be displayed. 
Additional exploratory statistical analyses will be performed as described in SAP sections 
13.4.1 and 13.4.2. 
 
14.4.3.6 
Endpoints related to ss-IGA 
Other secondary endpoints related to ss-IGA are: 
• The proportion of subjects achieving an ss-IGA score of absence of disease (0) at Week 
100 in randomized subjects with scalp psoriasis and an ss-IGA score ≥2 at baseline 
The proportion of responding 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. 
Exploratory statistical analyses will be performed as described in SAP section 13.4.1. 
In addition, the proportion of subjects achieving an ss-IGA score of absence of disease (0) 
or very mild disease (1) at Week 100 will be analyzed analogously. 
 
14.4.3.7 
Endpoints related to SF-36 
Other secondary endpoints related to SF-36 are: 
• The change from baseline (Week 56) in the physical and mental component summary 
scores of SF-36 at Week 100 
The change from baseline will be summarized by descriptive statistics using appropriate 
tabulation and box plots. The baseline value, the Week 100 value and the change from the 
baseline value will displayed. 
Exploratory statistical analyses will be performed as described in SAP section 13.4.2. 
 
14.4.4 
Other Efficacy Assessments 
In addition to the efficacy analyses described above all efficacy data related to PASI, DLQI, 
PSSD, IGA, ss-IGA, and SF-36 at Week 56 and all scheduled study visits during the follow-
up extension period from Week 64 until Week 100 will be summarized descriptively without 
any imputation of missing data (‘observed cases analysis’; see SAP section 13.1.6). For 
binary endpoints summary results using nonresponder imputation will also be provided. 
 
 
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14.5  Analysis of Safety 
All safety analyses will be performed for all enrolled subjects in Study Part III ('Study Part 
III analysis set'). 
14.5.1 
Extent of Exposure  
Not applicable because no study treatment was administered. 
 
14.5.2 
Adverse Drug Reactions/Death 
During Study Part III, only Adverse Drug Reactions (ADRs) and deaths (regardless of 
causality) should be recorded until the final study visit. ADRs will be processed in the 
statistical analysis after coding according to the MedDRA dictionary version 19.1. Deaths 
were not reported during Study Part III. 
All reported ADRs (i.e. those ADRs with an onset date during the follow-up extension period 
from Week 64 through Week 100 and those ADRs that were present before Week 64 but 
were ongoing at Week 64) will be included in the analysis. In addition, analyses will be 
perfomed for those ADRs that were present before Week 64 but were ongoing at Week 65. 
 
14.5.2.1 
Definitions 
The following definitions will be applied for the analysis of Study Part III. 
Crude Incidence Rate 
Where percentages of subjects are reported in summary tables, incidences provide 
information on the proportion of subjects experiencing ADRs in relation to the total number 
of subjects enrolled in Study Part III, i.e., if not otherwise specified, the crude incidence 
rate will be used.  
The crude incidence rate is defined as the number of subjects experiencing a certain ADR, 
divided by the number of subjects enrolled in Study Part III, regardless of duration of 
observation: 
 
enrolled
 
patients
 
of
number 
ADRs
 
 with
patients
 
of
number 
 *
100
 
rate
 
incidence
 
Crude
=
 
 
Adverse Drug Reactions 
ADRs are those AEs with causality 'very likely', 'probable', or 'possible' that occurred during 
the follow-up extension period from Week 64 to Week 100 or those ADRs that were present 
before Week 64 but were ongoing at Week 64. 
 
 
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14.5.2.2 
Analyses 
Overview of Deaths from Week 64 to Week 100 
A frequency table with n (%) of subjects who died will be provided. 
Overview of ADRs from Week 64 to Week 100 
For summary presentation of the overall ADRs experience overview, tables will be provided 
for ADRs and serious ADRs (SADRs) including the following information: 
ADRs: 
• 
n (%) of subjects with ADRs *) 
SADRs: 
• 
n (%) of subjects with SADRs *) 
• 
n (%) of subjects with SADRs leading to death *) 
*) the number of events (i.e., number of coded preferred terms) will also be given. 
In addition, the number of ADRs will be displayed for the following investigator’s ratings: 
• 
severity  
• 
seriousness 
• 
causality 
• 
action taken 
• 
outcome 
 
 
 
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Detailed display of ADRs from Week 64 to Week 100 
For a more detailed display, (S)ADRs will be presented in summary tables, listing these 
events in code form according to the preferred term. These tables will show the number of 
subjects presenting an (S)ADR and the incidence of its occurrence. (S)ADRs will be grouped 
by primary SOC (System Organ Class) and will be stratified additionally by highest causality 
to study treatment (possible, probable, or very likely) and by worst severity (mild, 
moderate, or severe). The incidence of (S)ADRs will be presented by decreasing order of 
frequency at preferred term level within the primary SOC. 
The following tables will be provided for the detailed display of (S)ADRs: 
ADRs: 
• 
ADRs by primary SOC and preferred term *) 
SADRs: 
• 
SADRs by primary SOC and preferred term *) 
• 
SADRs leading to death by primary SOC and preferred term *) 
*) These tables will show additionally the number of events (i.e., number of coded preferred terms). 
Note that the summary tables will provide the number of subjects per event (i.e., coded as 
preferred term) and will also provide the number of events for certain tables. 
For calculation of the number of subjects per event each preferred term will be counted only 
once per subject and will be linked to the primary SOC. A subject may contribute with more 
than one different (S)ADR (at preferred term level); however, a subject with more than one 
occurrence of the same (S)ADR (at preferred term level) is displayed and counted only once 
for this event in the tables. 
Tables that are stratified by the severity of (S)ADRs will summarize the worst severity per 
subject and preferred term.  
Tables that are stratified by the relationship of (S)ADRs will summarize the highest 
relationship per subject and preferred term. 
 
Analyses of ADRs present before Week 64 but ongoing at Week 64. 
Summary tables for (S)ADRs that were present before Week 64 but were ongoing at Week 
64 will be provided by primary SOC and preferred term. 
 
Listings 
All ADRs and death will be listed in the individual subject data listings by study center and 
subject number including all information documented on the respective form of the eCRF. 
Separate listings of subjects with the following ADRs will be provided: SADRs, SADRs leading 
to death, ADRs of severe intensity. 
Verbatim description of the (S)ADR reported by the investigator, MedDRA preferred terms 
and primary SOCs (system organ class) for all (S)ADRs will be contained in the data listings.  
 
 
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14.5.3 
Clinical Laboratory Tests 
No lab assessments were performed during Study Part III. 
 
14.5.4 
Vital Signs 
Descriptive statistics of pulse and blood pressure (systolic and diastolic) values within the 
time period from Week 64 to Week 100 and changes from baseline (Week 56) will be 
summarized at each scheduled time. 
 
 
14.5.5 
Physical Examination 
Physical examination findings within the time period from Week 64 to Week 100 will be 
tabulated by the body systems given in the eCRF at each scheduled time. Moreover, 
abnormal findings with first occurrence after baseline reported during the treatment phase 
and follow-up phase will be presented. Details on abnormal findings in verbatim terms will 
be displayed in individual subject data listings. 
 
14.5.6 
Body Weight 
No body weight measurements were performed during Study Part III. 
 
14.5.7 
Early Detection of Active Tuberculosis 
Categorical data on early detection of active tuberculosis will be presented in a frequency 
table providing the number and percentage of subjects per category at each scheduled time 
within the time period from Week 64 to Week 100. 
 
 
 
 
 
 
 
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14.6 Analysis of MedDRA Codes 
Previous / concomitant diseases (including indications for use of concomitant and other 
medications) and (S)ADRs will be coded with version 19.1 of the MedDRA-dictionary. 
In general, tabulation will be displayed by preferred term and primary SOC. 
 
14.7 Analysis of WHO Drug Dictionary Codes 
The use of concomitant and other medications will be coded using the WHO Drug Dictionary 
(version 2016/1). Medications will be tabulated by preferred name (i.e., the decode of the 
code which results when SEQ1 and SEQ2 are set to 01 and 001, respectively (usually 
resulting in a decode close to the generic drug name)) and they will be grouped by level 2 
of the Anatomical Therapeutic Chemical (ATC) code. Codes being linked to more than one 
ATC code at this level will be assigned to one primary ATC code by medical data analysts. 
 
 
 
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15.0 Changes to Planned Analyses 
This statistical analysis plan includes the following relevant changes to the planned analyses 
of Study Part III which are described in the clinical study protocol. 
• 
No treatment failure imputation rules will be applied (see to SAP section 13.1.5 and 
CSP section 11.4) 
• 
The following additional efficacy endpoints will be defined and used for the statistical 
analyses of Study Part III: 
o 
The change from baseline in the signs and symptoms aggregate scores of the 
PSSD at Week 100 
o 
The proportion of subjects achieving an absolute PASI score ≤1, ≤2, ≤3 at 
Week 100 
o 
The proportion of subjects with a PASI 90 response at Week 56 who maintain 
PASI 90 response at Week 100 
o 
The proportion of subjects achieving an IGA score of cleared (0) at Week 100 
o 
The proportion of subjects achieving an IGA score of cleared (0) or  
minimal (1) at Week 100 
o 
The change from baseline of body surface area (BSA) psoriatic involvement 
at Week 100 
o 
The change from baseline in DLQI score at Week 100 
o 
The proportion of subjects achieving an ss-IGA score of absence of  
disease (0) at Week 100 in randomized subjects with scalp psoriasis and an 
ss-IGA score ≥2 at baseline 
o 
The proportion of subjects achieving an ss-IGA score of absence of  
disease (0) or very mild disease (1) at Week 100 in randomized subjects with 
scalp psoriasis and an ss-IGA score ≥2 at baseline 
o 
The change from baseline in the physical and mental component summary 
scores of SF-36 at Week 100 
Any major changes to this plan after sign-off of the latest final version will be specified in 
the clinical study report. 
 
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16.0 Tabulation 
16.1  General 
The statistical output will be prepared in American English. No separate statistical report will 
be written. 
 
16.2  Format of Data Displays 
The layout of all tables, listings and figures will be drafted by acromion GmbH when 
providing the first draft tables, listings and figures on final data. No sponsor or other 
requirements for layout specifications have to be followed. 
 
The SAS outputs will be post-processed within Microsoft Word®. SAS tables and listings will 
be integrated into Microsoft Word® using the SAS Monospace 8 points font. 
 
Separate appendices will be provided for tables, listings, and figures. For each appendix a 
corresponding table of contents will be generated. All pages within one appendix will be 
numbered consecutively. Tables, listings and figures generally should be self-explaining. 
Abbreviations will be described in the footnote if necessary. 
 
16.2.1 
Tables 
SAS summary tables will be produced using a landscape page. The maximum number of 
lines per page will be pagesize = 40 and the number of characters in one line will be linesize 
= 140.  
 
16.2.2 
Listings  
SAS subject data listings will be produced using a landscape page. The maximum number 
of lines per page will be pagesize = 40 and the number of characters in one line will be 
linesize = 140.  
 
Data listings will be created for groups of variables which logically belong together (e.g. 
demographic variables) and will be by treatment group (in Study Parts I and II),, center, 
subject and visit (if applicable). 
 
 
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16.2.3 
Figures  
Figures will be created using the following graphical SAS options, if not otherwise specified: 
 
 
GOPTIONS  
    RESET   = ALL  
    NOBORDER 
    KEYMAP = WINANSI  
    DEVMAP = WINANSI  
    DEV       = EMF 
    TARGET = WINPRTC  
    GUNIT   = CM  
    CTEXT   = BLACK  
    FTEXT   = 'Arial/bold'  
    HTEXT   = 0.5 CM  
    LFACTOR= 1  
    HSIZE   = 6 IN  
    VSIZE   = 5 IN; 
 
Variables may be presented in the following graphical formats, if applicable: 
 
Box plot 
Box plots summarize the data by a box reaching from the 1st to the 3rd quartile. The median 
is displayed inside this box by a horizontal line. Above the box a vertical line indicates the 
region from the 3rd quartile to the max. value below the upper fence ; below the box a 
vertical line indicates the region from the 1st quartile to the min. value above the lower 
fence. The upper fence lies 1.5 interquartile-ranges above the 3rd quartile, the lower fence 
lies 1.5 interquartile ranges below the 1st quartile. Values outside the fences are displayed 
by a distinct marker. 
A graphical presentation is given below: 
 
 
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Bar chart 
A bar chart displays a categorical variable. A sample display is provided below. 
 
 
Survival Graph 
A survival graph displays the survival distribution functions according to Kaplan-Meier. A 
sample display is provided below. 
 
 
 
 
16.3  Data Format 
Unless otherwise specified, percentage values will be printed with one digit to the right of 
the decimal point. 
In general, minima and maxima will be quoted to the number of decimal places as recorded 
in the eCRF; means, standard deviations and medians will be quoted to one further decimal 
place. 
All p-values will be given by four digits to the right of the decimal point. Verbatim terms 
documented in the eCRFs will be presented as entered in the clinical data base. 
0
10
20
30
40
50
25
35
45
55
%
AGE
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17.0 References 
Study Documents: 
Document 
Version, Date 
Protocol / Amendments 
Version 1.0, 03-AUG-2016 
 
Protocol Amendment INT-1, Version 2.0, 25-APR-2017 
 
Protocol Amendment INT-2, Version 3.0, 25-JAN-2018 
eCRF 
Version 2.0, 08-JUN-2017 
Data Management Plan 
Version 1.0, 09-DEC-2016 
Data Validation Plan 
Version 1.0, 09-DEC-2016 
Statistical Analysis Plan 
– Week 24 Analysis 
(Study Part I) 
Version 1.0, 10-JUL-2017 
Statistical Analysis Plan 
– Week 32 Analysis 
(Study Part IIa) 
Version 1.0, 15-AUG-2018 
Statistical Analysis Plan 
– Week 64 Analysis 
(Study Part IIb) 
Version 1.0, 29-AUG-2018 
SOPs and Guidelines acromion: 
Document 
Title, Date 
acromion SOP BM04 
Statistical Analysis Plans, Oct-2016 
acromion SOP BM05 
Determination of Availability of Data for Analysis, Oct-2016 
acromion SOP BM06 
Generation and Release of Blinded Randomization Code, Oct-
2016 
acromion SOP BM07 
Programming of Derived Data Sets, Oct-2016 
acromion SOP BM08  
Programming of SAS Data Displays, Oct-2016 
acromion SOP BM11  
Documentation and Project Close-Out, Oct-2016 
acromion Guideline 
BM01  
SAS Programming Guideline, Oct-2016 
acromion Guideline 
BM02  
Biometrics Naming Conventions for SAS Datasets and SAS 
Programs, Oct-2016 
Other Documents: 
Document 
Title, Date 
ICH Guideline E 9 
Statistical Principles for Clinical Trials, final approval 1998 
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CNTO1959 (guselkumab) 
 
 
Polaris_SAP_W100_V1.0_09May2019 
 
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18.0 Appendices 
18.1  Table of Contents for Data Displays 
The tables, subject data listings and figures will be provided using the following numbering 
system, which will be updated after start of programming the data displays.  
All summary tables will start with the one-character identifier for the displayed analysis set 
followed by the one-digit identifier for the displayed analysis chapter as listed below. 
Identifier for displayed analysis set: 
• 
A: Study Part III analysis set 
 
Identifier for displayed analysis chapter: 
• 
1: Study subjects 
• 
2: Demographics and other baseline characteristics 
• 
3: Treatment compliance 
• 
4: Analysis of efficacy 
• 
5: Analysis of safety 
Data displays will be provided for the following analysis sets: 
 
Chapter 
No. 
Chapter Title 
Analysis set 
1 
Study subjects 
• A: Study Part III analysis set 
2 
Demographic and other baseline 
characteristics 
• A: Study Part III analysis set 
3 
Treatment compliance 
• A: Study Part III analysis set 
4 
Analysis of efficacy 
• A: Study Part III analysis set 
5 
Analysis of safety 
• A: Study Part III analysis set 
All individual subject data listings will start with the one-digit identifier for the displayed 
chapter analogously as for the summary tables. Data displays and subject data listings will 
be provided in separate appendices and pages will be numbered for each appendix 
separately starting with page no. 1. 
 
 
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CNTO1959 (guselkumab) 
 
 
Polaris_SAP_W100_V1.0_09May2019 
 
Page 57 of 59 
18.1.1 
Tables 
Study Subjects, Prefix A 
No. 
Analysis Chapter 
1.1 
Disposition of subjects 
1.2 
Discontinuation of study 
1.3 
Protocol deviations 
1.4 
Analysis sets 
 
Demographic and Other Baseline Characteristics, Prefix A 
No. 
Analysis Chapter 
2.1 
Demographics  
2.2 
Medical history 
2.3 
Diagnosis of Psoriasis 
2.4 
Previous Psoriasis Therapy 
2.5 
Substance Use 
2.6 
Physical Examination 
2.7 
Tuberculosis Evaluation 
2.8 
Chest Radiograph Result 
2.9 
Concomitant Medication and Therapy 
2.10 
Shampoo and Moisturizer 
2.11 
Planned next Psoriasis Therapy 
 
Treatment Compliance, Prefix A 
No. 
Analysis Chapter 
3.1 
Visit windows 
 
Analysis of Efficacy, Prefix A 
No. 
Analysis Chapter 
 
- Other Secondary Endpoints - 
4.1 
PASI 90 Response 
4.2.1 
PASI 75 Response 
4.2.2 
DLQI 0/1 Response 
4.3.1 
Other Endpoints related to PASI  
4.3.2 
Endpoints related to PSSD 
4.3.3 
Endpoints related to IGA 
4.3.4 
Endpoints related to BSA 
4.3.5 
Other Endpoints related to DLQI 
4.3.6 
Endpoints related to ss-IGA 
4.3.7 
Endpoints related to SF-36 
 
- Other Efficacy Assessments - 
4.4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, BSA, ss-IGA, SF-36) 
4.5 
Additional Efficacy Analyses (PASI, DLQI, PSSD) 
 
Analysis of Safety, Prefix A 
No. 
Analysis Chapter 
5.1 
Extent of Exposure 
5.2 
Adverse Events  
5.3 
Physical Examination 
5.4  
Body Weight 
5.5 
Early Detection of Active Tuberculosis 
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Polaris_SAP_W100_V1.0_09May2019 
 
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18.1.2 
Listings 
Study Subjects  
No. 
Analysis Chapter 
1.1 
Disposition of subjects 
1.2 
Discontinuation of study  
1.3 
Protocol deviations 
1.4 
Analysis sets 
 
Demographic and Other Baseline Characteristics 
No. 
Analysis Chapter 
2.1 
Demographics 
2.2 
Medical history 
2.3 
Diagnosis of Psoriasis 
2.4 
Previous Psoriasis Therapy 
2.5 
Substance Use 
2.6 
Physical Examination 
2.7 
Tuberculosis Evaluation 
2.8 
Chest Radiograph Result 
2.9 
Concomitant Medication and Therapy 
2.10 
Shampoo and Moisturizer 
2.11 
Planned next Psoriasis Therapy 
 
Treatment Compliance 
No. 
Analysis Chapter 
3.1 
Visit windows 
 
Analysis of Efficacy 
No. 
Analysis Chapter 
 
- Other Secondary Endpoints - 
4.1 
PASI 90 Response 
4.2.1 
PASI 75 Response 
4.2.2 
DLQI 0/1 Response 
4.3.1 
Other Endpoints related to PASI 
4.3.2 
Endpoints related to PSSD 
4.3.3 
Endpoints related to IGA 
4.3.4 
Endpoints related to BSA 
4.3.5 
Other Endpoints related to DLQI 
4.3.6 
Endpoints related to ss-IGA 
4.3.7 
Endpoints related to SF-36 
 
- Other Efficacy Assessments - 
4.4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, BSA, ss-IGA, SF-36) 
 
Analysis of Safety 
No. 
Analysis Chapter 
5.1 
Extent of Exposure 
5.2 
Adverse Events  
5.3 
Vital Signs 
5.4 
Physical Examination 
5.5 
Early Detection of Active Tuberculosis 
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Janssen-Cilag GmbH 
CNTO1959 (guselkumab) 
 
 
Polaris_SAP_W100_V1.0_09May2019 
 
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18.1.3 
Figures 
Analysis of Efficacy, Prefix A 
No. 
Analysis Chapter 
Type of Figure 
 
- Other Secondary Endpoints - 
 
1 
PASI 90 Response 
Bar Chart, 
Survival Graph 
2.1 
PASI 75 Response 
Bar Chart, 
Survival Graph 
2.2 
DLQI 0/1 Response 
Bar Chart, 
Survival Graph 
3.1 
Other Endpoints related to PASI 
Bar Chart,  
Survival Graph 
3.2 
Endpoints related to PSSD 
Box Plot 
3.3 
Endpoints related to IGA 
Bar Chart 
3.4 
Endpoints related to BSA 
Box Plot 
3.5 
Other Endpoints related to DLQI 
Bar Chart 
3.6 
Endpoints related to ss-IGA 
Bar Chart 
3.7 
Endpoints related to SF-36 
Box Plot 
 
- Other Efficacy Assessments - 
 
4 
Other Efficacy Assessments (PASI, DLQI, PSSD, IGA, 
BSA, ss-IGA, SF-36) 
Bar Chart,  
Box Plot 
 
 
Analysis of Safety, Prefix A 
No. 
Analysis Chapter 
Type of Figure 
5 
Vital Signs 
Box Plot 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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