A 16-week Randomized, Open-label, Multicenter Study to Assess the Superiority of Secukinumab Over Guselkumab in the Complete Treatment of Ustekinumab Resistant Psoriatic Plaques
Phase: PHASE2
Conditions: Chronic Plaque-type Psoriasis
Sponsor: Novartis Pharmaceuticals

Global Medical Affairs - General Medicine
AIN457/secukinumab
Clinical Study Protocol CAIN457A2403 / NCT03553823
A 16-week randomized, open-label, multicenter study to 
assess the superiority of secukinumab over guselkumab in 
the complete treatment of ustekinumab-resistant psoriatic 
plaques – ARROW
Document type:
Clinical Study Protocol
EUDRACT number:
2018-001048-70
Version number:
00 (Original Protocol)
Clinical study phase:
2a
Release date:
22-May-2018
Property of Novartis
Confidential
May not be used, divulged, published, or otherwise disclosed
without the consent of Novartis
Clinical Study Protocol Template Version 1.0 (01-Dec-2017)

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Table of contents
Table of contents .................................................................................................................2
List of tables ........................................................................................................................5
List of figures ......................................................................................................................5
List of abbreviations............................................................................................................6
Glossary of terms.................................................................................................................7
Protocol summary................................................................................................................9
1
Introduction .......................................................................................................................12
1.1
Background............................................................................................................12
1.2
Purpose ..................................................................................................................13
2
Objectives and endpoints...................................................................................................14
3
Study design ......................................................................................................................14
4
Rationale............................................................................................................................15
4.1
Rationale for study design .....................................................................................15
4.2
Rationale for dose/regimen and duration of treatment ..........................................16
4.3
Rationale for choice of comparator .......................................................................16
4.4
Purpose and timing of interim analyses/design adaptations..................................16
4.5
Risks and benefits..................................................................................................16
4.5.1
Risks......................................................................................................16
4.5.2
Benefits .................................................................................................18
5
Population..........................................................................................................................18
5.1
Inclusion criteria ....................................................................................................18
5.2
Exclusion criteria...................................................................................................18
6
Treatment...........................................................................................................................21
6.1
Study treatment......................................................................................................21
6.1.1
Investigational and control drugs..........................................................21
6.1.2
Additional study treatments ..................................................................21
6.1.3
Treatment arms......................................................................................21
6.1.4
Treatment duration................................................................................21
6.2
Other treatments.....................................................................................................21
6.2.1
Concomitant therapy.............................................................................22
6.2.2
Prohibited medication ...........................................................................22
6.3
Subject numbering, treatment assignment, randomization....................................23
6.3.1
Subject numbering ................................................................................23
6.3.2
Treatment assignment, randomization ..................................................23
6.4
Treatment blinding.................................................................................................23

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6.5
Dose escalation and dose modification..................................................................23
6.6
Additional treatment guidance...............................................................................23
6.6.1
Treatment compliance...........................................................................23
6.7
Preparation and dispensation.................................................................................24
6.7.1
Handling of study treatment and additional treatment..........................24
6.7.2
Instruction for prescribing and taking study treatment .........................24
7
Informed consent procedures ............................................................................................25
8
Visit schedule and assessments .........................................................................................26
8.1
Screening ...............................................................................................................28
8.1.1
Information to be collected on screening failures.................................28
8.2
Subject demographics/other baseline characteristics.............................................29
8.2.1
Smoking history ....................................................................................29
8.2.2
Relevant medical history/current medical conditions...........................29
8.2.3
Prior and concomitant medications.......................................................29
8.2.4
Determination of tuberculosis status.....................................................29
8.3
Efficacy..................................................................................................................30
8.3.1
Total clinical score ................................................................................30
31
8.3.3
Skin biopsies .........................................................................................31
8.3.4
Microscopic morphology of the skin plaque.........................................31
8.3.5
Infiltrating immune cells in the skin plaque..........................................32
8.3.6
Composition of the inflammatory infiltrate in the skin plaque.............32
32
32
32
32
36
8.4
Safety.....................................................................................................................36
8.4.1
Laboratory evaluations..........................................................................37
8.4.2
Electrocardiogram.................................................................................38
8.4.3
Pregnancy..............................................................................................38
8.4.4
Appropriateness of safety measurements..............................................39
8.5
Additional assessments..........................................................................................39
39
40
40
9
Study discontinuation and completion ..............................................................................40

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9.1
Discontinuation......................................................................................................40
9.1.1
Discontinuation of study treatment .......................................................40
9.1.2
Withdrawal of informed consent...........................................................41
9.1.3
Lost to follow up...................................................................................42
9.1.4
Early study termination by the Sponsor................................................42
9.2
Study completion and post-study treatment ..........................................................42
10 Safety monitoring and reporting........................................................................................43
10.1
Definition of adverse events and reporting requirements......................................43
10.1.1
Adverse events ......................................................................................43
10.1.2
Serious adverse events ..........................................................................44
10.1.3
Serious adverse event reporting ............................................................45
10.1.4
Pregnancy reporting ..............................................................................46
10.1.5
Reporting of study treatment errors including misuse/abuse................46
10.2
Additional safety monitoring.................................................................................46
11 Data collection and database management........................................................................47
11.1
Data collection.......................................................................................................47
11.2
Database management and quality control............................................................47
11.3
Site monitoring ......................................................................................................48
12 Data analysis and statistical methods ................................................................................48
12.1
Analysis sets ..........................................................................................................49
12.2
Subject demographics and other baseline characteristics......................................49
12.2.1
Demographics and baseline characteristics...........................................49
12.2.2
Medical history......................................................................................49
12.3
Treatments .............................................................................................................49
12.3.1
Study treatments....................................................................................49
12.3.2
Prior and concomitant treatments..........................................................49
12.4
Analysis of the primary endpoint ..........................................................................49
12.4.1
Definition of primary endpoint .............................................................49
12.4.2
Statistical model, hypothesis, and method of analysis..........................50
12.4.3
Handling of missing values/censoring/discontinuations.......................50
12.4.4
Sensitivity and supportive analyses ......................................................50
12.5
Analysis of secondary endpoints ...........................................................................50
12.6
Analysis of exploratory endpoints.........................................................................50
12.7
Safety analysis .......................................................................................................51
12.8
Interim analyses.....................................................................................................52
12.9
Sample size calculation..........................................................................................52
12.9.1
Primary endpoint...................................................................................52

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13 Ethical considerations and administrative procedures ......................................................53
13.1
Regulatory and ethical compliance........................................................................53
13.2
Responsibilities of the Investigator and IRB/IEC .................................................53
13.3
Publication of study protocol and results...............................................................54
13.4
Quality control and quality assurance....................................................................54
14 Protocol adherence ............................................................................................................54
14.1
Protocol amendments.............................................................................................55
15 References .........................................................................................................................55
16 Appendices ........................................................................................................................58
16.1
Appendix 1: Clinically notable laboratory values and vital signs .........................58
16.2
Appendix 2.............................................................................................................59
16.2.1
Skin type classification scale ................................................................59
List of tables
Table 2-1
Objectives and related endpoints ..........................................................14
Table 6-1
Investigational and control drug............................................................21
Table 6-2
Prohibited medication ...........................................................................22
Table 6-3
Study treatment administration schedule ..............................................25
Table 8-1
Assessment schedule.............................................................................27
Table 8-2
Assessments of total clinical score........................................................31
34
35
Table 8-5
Physical assessments.............................................................................36
Table 8-6
Laboratory assessments.........................................................................37
Table 10-1
Guidance for capturing the study treatment errors including 
misuse/abuse .........................................................................................46
Table 12-1
Exact 95% confidence intervals for P1 and P2, the corresponding 
difference P1-P2, and the estimated power of the Fisher’s exact test 
for different P1 and P2 values...............................................................53
List of figures
Figure 1-1
Central role of IL-17A in psoriasis .......................................................12
Figure 3-1
Study design..........................................................................................15

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List of abbreviations
AE
adverse event
BSA
body surface area
CMO&PS
office and patient safety 
CRO
contract research organization
CTCAE
common terminology criteria of adverse events 
ECG
electrocardiogram
eCRF
electronic case report form 
EDC
electronic data capture 
FAS
full analysis set
GCP
good clinical practice
hCG
human chorionic gonadotropin 
IB
investigator’s brochure
IEC
independent ethics committee
IF
immunofluorescence
IHC
immunohistochemical
IRB
institutional review board
NIRT
Novartis interactive response technology
LLN
lower limit of normal 
 
 
PASI
psoriasis area and severity index
QFT
QuantiFERON TB-gold test in-tube assay 
SAE
serious adverse event
TB
tuberculosis
TCS
total clinical score 
TNFα
tumor necrosis factor alpha 
ULN
upper limit of normal 

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Glossary of terms
Assessment
A procedure used to generate data required by the study
Biologic samples
A biological specimen including, for example, blood (plasma, serum), 
tissue, urine, 
 etc. taken from a study subject 
Cohort
A specific group of subjects fulfilling certain criteria and generally treated at 
the same time
Control drug
A study drug (active or placebo) used as a comparator to reduce 
assessment bias, preserve blinding of investigational drug, assess internal 
study validity, and/or evaluate comparative effects of the investigational 
drug
Dosage
Dose of the study treatment given to the subject in a time unit 
Electronic data capture 
(EDC)
Electronic data capture (EDC) is the electronic acquisition of clinical study 
data using data collection systems, such as Web-based applications, 
interactive voice response systems and clinical laboratory interfaces. EDC 
includes the use of Electronic Case Report Forms (eCRFs) which are used 
to capture data transcribed from paper source forms used at the point of 
care.
End of the clinical study
The end of the clinical study is defined as the last visit of the last subject or 
at a later point in time as defined by the protocol. 
Enrollment
Point/time of subject entry into the study at which informed consent must 
be obtained 
Investigational 
drug/treatment
The drug whose properties are being tested in the study
Medication number
A unique identifier on the label of medication kits
Mis-randomized 
subjects
Mis-randomized subjects are those who were not qualified for 
randomization and who did not take study treatment, but have been 
inadvertently randomized into the study
Other treatment
Treatment that may be needed/allowed during the conduct of the study 
(concomitant or rescue therapy)
Period
The subdivisions of the study design (e.g. Screening, Treatment, 
Follow-up) which are described in the Protocol. Periods define the study 
phases and will be used in clinical study database setup and eventually in 
analysis
Personal data
Subject information collected by the Investigator that is transferred to 
Novartis for the purpose of the clinical study. This data includes subject 
identifier information, study information, and biological samples. 
Premature subject 
withdrawal
Point/time when the subject exits from the study prior to the planned 
completion of all study drug administration and/or assessments; at this time 
all study drug administration is discontinued and no further assessments 
are planned
Randomization number
A unique identifier assigned to each randomized subject
Screen failure
A subject who did not meet one or more criteria that were required for 
participation in the study
Source data/document
Source data refers to the initial record, document, or primary location from
where data comes. The data source can be a database, a dataset, a 
spreadsheet or even hard-coded data, such as paper or eSource.

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Start of the clinical study
The start of the clinical study is defined as the signature of the informed 
consent by the first subject.
Study treatment
Any single drug or intervention administered to the subject as part of the 
required study procedures.
Study treatment 
discontinuation
When the subject permanently stops taking any of the study drug(s) prior to 
the defined study treatment completion date (if any) for any reason; may or 
may not also be the point/time of study discontinuation 
Subject
A study participant (can be a healthy volunteer or a patient)
Subject number
A unique number assigned to each subject upon signing the informed 
consent. This number is the definitive, unique identifier for the subject and 
should be used to identify the subject throughout the study for all data 
collected, sample labels, etc.
Treatment arm/group
A treatment arm/group defines the dose and regimen or the combination, 
and may consist of 1 or more cohorts.
Variable
A measured value or assessed response that is determined from specific 
assessments and used in data analysis to evaluate the drug being tested in 
the study
Withdrawal of study 
consent 
Withdrawal of consent from the study occurs only when the subject does 
not want to participate in the study any longer, and does not allow any 
further collection of personal data.

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Protocol summary
Protocol number
CAIN457A2403
Full title
A 16-week randomized, open-label, multicenter study to assess the 
superiority of secukinumab over guselkumab in the complete treatment of
ustekinumab-resistant psoriatic plaques – ARROW
Brief title 
Comparison of secukinumab versus guselkumab in clearing psoriatic 
plaques refractory to ustekinumab
Sponsor and clinical 
phase
Novartis Pharma AG 
Clinical Phase 2a
Investigation type
Drug
Study type
Interventional 
Purpose and rationale
The aim of this study is to assess the superiority of direct IL-17A inhibition 
with secukinumab as compared with the selective inhibition of IL-23 with 
guselkumab (p19 subunit blocker) in controlling inflammation in psoriatic 
plaques that remain active despite treatment with the non-selective IL-23 
inhibitor ustekinumab (blocker of p40 subunit, shared by IL-12 and IL-23). 
Primary objective 
To assess the superiority of secukinumab over guselkumab in controlling 
clinical activity in psoriatic plaques resistant to treatment with 
ustekinumab. 
Secondary objectives
Not applicable. 
Exploratory 
objectives
 
2. To compare the effect of secukinumab versus guselkumab on the 
microscopic morphology of the skin plaque
3. To compare the effect of secukinumab versus guselkumab on the 
number of IL-17A and IL-23R positive immune cells infiltrating the skin 
plaque
4. To compare the effects of secukinumab versus guselkumab on the 
composition of inflammatory infiltrate in the skin plaque
 
 
 
 
 
 
 
 
Study design
This is a 16-week, randomized, open-label, parallel-group, active-control, 
Phase 2a study comparing secukinumab 300 mg s.c. versus guselkumab 
100 mg s.c. in subjects with plaque psoriasis who had an inadequate 
response to ustekinumab. 
Population
The study population will consist of a total of 40 male and female subjects 
aged 18 years or older, who have chronic plaque-type psoriasis 
considered inadequately controlled after treatment with ustekinumab. 

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Key inclusion criteria
1. Signed informed consent must be obtained prior to participation in the 
study 
2. Men or women ≥18 years of age at the time of consent 
3. Chronic plaque-type psoriasis considered inadequately controlled after 
treatment with ustekinumab according to the following criteria: 
o
ustekinumab administered at a dose equal or higher than that on 
the label for at least 24 weeks. The last administration must be at 
least 12 weeks before randomization 
o
absolute psoriasis area and severity index (PASI) score of 1-10 at 
Screening 
4. Presence of at least 1 refractory skin plaque, defined by a total clinical 
score (TCS) of at least 6 and severity score of at least 2 or 3 
(moderate) for each individual item, with an area ≥10 cm2 at 
Screening and Baseline (Day 1)
Key exclusion criteria
1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, 
erythrodermic, and guttate psoriasis) at Screening or Baseline 
2. Drug-induced psoriasis (i.e., new onset or current exacerbation from 
beta-blockers, calcium channel inhibitors or lithium) at Screening or 
Baseline
3. Previous treatment with more than one tumor necrosis factor alpha 
(TNFα) inhibitors or with IL-17A (including secukinumab), IL-17R or 
IL-23 (including guselkumab) inhibitors 
Study treatment
Secukinumab 300 mg s.c and guselkumab 100 mg s.c
Efficacy assessments

Total clinical score 

Microscopic morphology of the skin plaque

Infiltrating immune cells in the skin plaque

Composition of the inflammatory infiltrate in the skin plaque 
 
 
 
Other assessments
Safety:

Physical examination

Vital signs

Height and weight

Laboratory evaluations (hematology, clinical chemistry, 
urinalysis)

Pregnancy test 

Electrocardiogram (ECG)

Adverse events (AEs) and serious adverse events (SAEs)
Additional:
 
 

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Data analysis
The number (%) of subjects of subjects whose plaque achieves “clear” or 
“almost clear” status (TCS = 0-2) by Week 16 treatment with 
secukinumab or guselkumab (i.e., responders) will be provided based on 
the full analysis set (FAS) together with the 95% confidence interval using 
the exact method for the difference in proportions of responders in each 
arm. 
Furthermore, a 1-sided Fisher’s exact test for the difference in the 
proportions of responders in the secukinumab (P1) and gesulkumab (P2)
arms, H0: P1-P2 ≤ 0 versus H1: P1-P2 > 0 at a Type I error rate of 0.05 
will be performed. 
Subjects who discontinue between Week 4 and Week 16 will be required 
to complete the End-of-study Visit assessments. The plaque status based 
on the TCS at the End-of-study Visit will be used for the primary endpoint 
assessment i.e., the last observation carried forward approach will be 
applied.
Keywords
Plaque psoriasis, secukinumab, guselkumab, 

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1
Introduction
1.1
Background
Interleukin17-A (IL-17A) is a key effector cytokine of skin and joint inflammation in 
psoriasis (Keijsers et al 2014, Lowes et al 2013). It stimulates keratinocytes to release 
inflammatory molecules that mediate skin damage and recruit neutrophils, monocytes, Th17
cells and other cell types sustaining the inflammatory response through a positive chemotactic 
feedback loop (Keijsers et al 2014, Reich et al 2015, Hawkes et al 2017). Moreover, IL-17A 
mediates tissue damage in joints and atherosclerotic plaques (Keijsers et al 2014, Paulissen et 
al 2013, Cornelissen et al 2013). 
The central role of IL-17A is also related to its synergistic activity with many different 
upstream cytokines and tissue-related factors involved in skin and joint inflammation such as 
IL-6 (Ogura et al 2008), TNFα (Noack and Miossec 2017, Bosteen et al 2014, Johansen et al 
2016), IL-22 (Murakami et al 2011, Dixon et al 2016, Tohyama et al 2009), IFNγ (Simanski 
et al 2013), BMP-2 (Croes et al 2016), LCN2 (Hau et al 2016), and LL37 (Chen et al 2013), 
establishing self-reinforcing cycles orchestrated by IL-17A itself. 
It has been recently shown in patients with plaque psoriasis that after 52 weeks of treatment 
with the IL-17A inhibitor secukinumab, the mRNA levels of upstream cytokines along the 
T17 pathway – including IL-23, IL-12, IL-17A, IL-17F, IL-22, and IL-26 – decreased to the 
level of healthy controls (Lebwohl et al 2017). 
IL-17A production in response to IL-23 is dependent on the presence of the IL-23 receptor in 
both T17 and innate immune cells (Figure 1-1). However, additional inflammatory cytokines 
can promote IL-23-independent production of IL-17A in subsets of innate cell populations 
(Sofen et al 2014, Patel et al 2012). For example, innate immune cells expressing the T-cell 
receptor (TCR, e.g., γδ-T cells) can be activated by direct ligation of TCR or pattern 
recognition receptors (PRR) (Housseau et al 2016) and iNKT cells can be activated by IL-18 
or α-GalCer, in turn releasing IL-17A (Cua and Tato 2010, Yoshiga et al 2008). 
Figure 1-1
Central role of IL-17A in psoriasis

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The availability of biologic drugs in clinical practice gives the unique opportunity to assess 
the effect of direct blocking of single cytokines in human psoriasis, thus exploring in-vivo
their role in the pathogenesis of the underlying disorder. Anti-TNFα, anti-IL-12/IL-23p40 and 
anti-IL-23p19 agents all block the development program of T17 cells (Keijsers et al 2014). 
These drugs have shown various degrees of efficacy in controlling inflammation in plaque 
psoriasis and psoriatic arthritis. 
It has been recently shown that inadequate response to IL-12/23 inhibition with ustekinumab 
in psoriatic plaques is related to the persistence of IL-17A produced independently from IL-23 
by innate immune cells (Jack et al 2017). Innate immune cells seem to play a prominent role 
in inducing inflammation in difficult-to-treat areas (namely nails, scalp, palm and soles) and 
joints (Keijsers et al 2014, Paulissen et al 2013, Cornelissen et al 2013, Bissonette et al 2014, 
Appel et al 2011). This is consistent with the observation of a suboptimal efficacy of 
ustekinumab in palmoplantar psoriasis (Bissonette et al 2014) and in axial spondyloarthritis, 
suggesting disconnect regarding the importance of IL-23 in the skin versus difficult to treat 
areas and joints. 
In addition, it has been shown that the selective inhibition of IL-23 through p19 blockers 
(guselkumab) is associated with persistence of significant amounts of IL-17A at the site of 
inflammation and in circulation (Sofen et al 2014). This is possibly due to IL-23-independent 
release of IL-17A by innate immune cells in the skin and in circulation. 
Jack et al (2017) have recently observed that patients treated with ustekinumab can present 
discrete refractory active plaques despite a good response on other skin locations. They have 
shown in biopsies of those active plaques the persistence of IL-17A and human β-defensin-2 
(hBD2) at the same levels as in plaques from untreated patients. They also showed that IL-23 
levels are highly increased in those plaques but not the IL-23 receptor on infiltrating immune 
cells. Infiltrating cells in those plaques consisted of IL-17A+ T lymphocytes (same levels as 
untreated plaques) and IL-17A+ cells other than T lymphocytes. Those alternative cells were 
not further characterized, but the authors postulated that they may include mast cells or innate 
lymphoid type 3 immune cells (Mashiko et al 2015, Villanova et al 2014). Taken together, 
these data suggest that psoriatic plaques refractory to ustekinumab are infiltrated with non-
T17 cells (likely innate immune cells) which actively produce IL-17A independently of IL-23. 
Considering that direct targeting of IL-17A allows inhibition of the activity of this cytokine 
irrespective of its cellular source, possibly overcoming the issue of IL-23-independent IL-17A 
release, we hypothesize that secukinumab may be more effective than the selective IL-23p19 
inhibitor guselkumab in clearing inflammation in inadequate responders (see Inclusion 
criterion 5.1) to ustekinumab since under those conditions IL-17A appears to be produced in 
an IL-23-independent manner. 
1.2
Purpose
The aim of this study is to assess the superiority of direct IL-17A inhibition with secukinumab 
as compared with the selective inhibition of IL-23 with guselkumab (p19 subunit blocker) in 
controlling inflammation in psoriatic plaques that remain active despite treatment with the 
non-selective IL-23 inhibitor ustekinumab (blocker of p40 subunit, shared by IL-12 and 
IL-23). 

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Data from this study will help describe which immune cells may drive IL-17A-mediated 
inflammation that escapes control from IL-12/23p40 inhibition in plaque psoriasis. 
2
Objectives and endpoints
Table 2-1
Objectives and related endpoints 
Objectives
Endpoints
Primary objective
Endpoint for primary objective 
To assess the superiority of secukinumab 
over guselkumab in controlling clinical 
activity in psoriatic plaques resistant to 
treatment with ustekinumab 
Proportion of subjects whose plaque achieves “clear” or “almost 
clear” status (TCS = 0-2, see Section 8.3.1) by 16 weeks of 
treatment with secukinumab or guselkumab
Exploratory objectives
Endpoints for exploratory objectives
 
 
 
2.
To compare the effect of secukinumab 
versus guselkumab on the 
microscopic morphology of the skin 
plaque
2. Change from Baseline to Week 16 in epidermal thickness and 
in the number of Ki-67 and K16 positive cells of lesional skin 
biopsies and difference from the Baseline non-lesional skin 
biopsy (Section 8.3.4) 
3.
To compare the effect of secukinumab 
versus guselkumab on the number of 
IL-17A and IL-23R positive immune 
cells infiltrating the skin plaque
3. Change from Baseline to Week 16 in the number of 
infiltrating cells expressing IL-17A and IL-23R of lesional 
skin biopsies and difference from the Baseline non-lesional 
skin biopsy (Section 8.3.5) 
4.
To compare the effects of 
secukinumab versus guselkumab on 
the composition of inflammatory 
infiltrate in the skin plaque
4.
Change from Baseline to Week 16 in the number of different 
immune cell types in the inflammatory infiltrate of lesional 
skin biopsies and difference from the Baseline non-lesional 
skin biopsy (Section 8.3.6) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3
Study design
This is a 16-week, randomized, open-label, parallel-group, active-control, Phase 2a study 
comparing secukinumab 300 mg s.c. versus guselkumab 100 mg s.c. in subjects with plaque 
psoriasis who had an inadequate response to ustekinumab (see Inclusion criterion 5.1). 

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Inadequate responders are defined as subjects who, after treatment with ustekinumab at a dose 
equal or higher than that on the label for at least 24 weeks, present a PASI of 1-10 and one or 
more refractory skin plaques, defined by a TCS of at least 6 and an area ≥10 cm2 at Baseline. 
At Baseline (Day 1), subjects will be randomized to treatment with secukinumab or 
guselkumab in a 1:1 ratio. Secukinumab will be self-administered as two 150-mg s.c. 
injections at Baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 12 inclusive. 
Guselkumab will be self-administered as 100-mg s.c. injections at Baseline, Weeks 4, and 12. 
The initiation of study treatment at Baseline should not happen earlier than 12 weeks after the 
last administration of ustekinumab. 
Forty subjects will be enrolled and treated for 16 weeks. Additional unscheduled visits can be 
called by the Investigators according to their own judgement and personal clinical experience. 
At Baseline, two 6-mm punch biopsies will be taken from all the subjects, one from the 
identified active plaque (TCS ≥6) and one from never-lesional skin. At the End-of-study Visit, 
one biopsy will be taken from the same area of the active plaque sampled at Baseline. 
Whenever possible, biopsies should be taken from the trunk to avoid scars in exposed body 
areas. 
 
 
The duration of enrollment is expected to be 6 months. The design of the study is outlined in 
Figure 3-1. 
Figure 3-1
Study design 
4
Rationale
4.1
Rationale for study design
Due to the nature of the treatments given, the study will be open label. 
In order to ensure full integrity of clinical and molecular observations, the assessment of all 
endpoints (primary and exploratory) will be performed by blinded independent clinicians, and 
pathologists/researchers. 

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4.2
Rationale for dose/regimen and duration of treatment
Secukinumab 300 mg s.c. and the dose regimen with an initial weekly induction at Baseline, 
Weeks 1, 2, 3, 4 and then every 4 weeks until Week 12 inclusive is based on the approved 
product label in the United States of America and the European Union. 
4.3
Rationale for choice of comparator
The comparator treatment is guselkumab, the first selective IL-23p19 inhibitor that has been 
approved for use in clinical practice. The dose regimen is based on the approved product label 
in the United States of America and the European Union. 
4.4
Purpose and timing of interim analyses/design adaptations
Not applicable. 
4.5
Risks and benefits
4.5.1
Risks 
The risk to subjects in this study may be minimized by compliance with the eligibility criteria 
and study procedures, as well as close clinical monitoring, and minimal study duration.
Women of childbearing potential and sexually active males must be informed that taking the 
study treatment may involve unknown risks to the fetus if pregnancy were to occur during the 
study, and agree that in order to participate in the study they must adhere to the contraception 
requirements outlined in the exclusion criteria. If there is any question that the subject will not 
reliably comply, they must not be entered or continue in the study.
The potential risks for subjects participating in this study are listed below. 
4.5.1.1
Risks associated with the administration of secukinumab
The safety data from the completed and ongoing studies including AEs and SAEs, laboratory 
parameters and immunogenicity demonstrate a favorable safety profile. Observed risks 
included infections, in particular of the upper respiratory tract, neutropenia and 
hypersensitivity reactions that can be seen with the administration of foreign proteins. Most of 
the infections were non-serious, mild to moderate in severity, clinically easy to manage and 
did not lead to treatment discontinuation. Cases of neutropenia were uncommon, generally 
mild to moderate and transient, and did not lead to treatment discontinuation, and only a few 
cases were temporally associated with non-serious infections. 
Subjects with pre-existing malignancies within the past 5 years are generally excluded from 
studies with secukinumab, although there is no scientific basis to suggest that secukinumab 
would increase the risk for malignancies. Indeed, the majority of the preclinical data available 
in the literature suggest that blocking IL-17A may actually prevent tumor growth
(Fabre et al 2016). 

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4.5.1.2
Risks associated with the administration of guselkumab 
The following side effects have been reported for guselkumab in the approved product label, 
all usually mild or moderate.
Very common (may affect more than 1 in 10 people): 
Upper respiratory infections. 
Common (may affect up to 1 in 10 people):
Headache, arthralgia, diarrhea, gastroenteritis, redness at the injection site, hives, fungal 
infection of the skin (e.g., athlete’s foot), herpes simplex infections. 
Uncommon (may affect up to 1 in 100 people):
Pain at the injection site. 
4.5.1.3
Risks associated with the skin biopsy procedure
A skin biopsy is a routine procedure as part of the diagnostic practice in all dermatology 
clinics, which may cause bleeding and infections. Subjects may experience bruising, swelling, 
pain in the area, scarring and fainting caused by a drop in blood pressure. They may also have 
an allergic response from the anesthetic agent used for the procedure. 
Wound healing after the procedure may be compromised in subjects who are smokers or take 
steroids. 
 
 
 
 
 
 
 
 
 
 
 
 
4.5.1.5
Other risks
Problems or side effects that are not currently known could also occur. 
The procedures done at each visit are standard medical procedures. Blood samples will be 
taken. The risks of taking blood may include fainting, pain and/or bruising. Rarely, there may 

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be a small blood clot or infection where the needle punctures the skin. The blood pressure cuff 
may also cause discomfort or bruising of the upper arm. 
4.5.2
Benefits 
The potential benefits of an intervention with secukinumab may result in quick clearance of 
psoriatic plaques. Secukinumab has also been shown to be efficacious in clearing 
inflammation from nails, palms of the hands, soles of the feet, and joints. Subjects may 
benefit from 16 weeks of treatment that has been proven to be safe and effective. 
Subjects randomized to treatment with guselkumab may also benefit from a reduction in 
psoriasis severity. Guselkumab can improve the condition of the skin and appearance of nails 
and reduce symptoms, such as scaling, shedding, flaking, itching, pain and burning.
All quality, non-clinical pharmacology and toxicology data, as well as the available clinical 
efficacy and safety data, are considered sufficient to expect a positive benefit/risk ratio for the 
treatment of the study subjects. 
5
Population
The study population will consist of a total of 40 male and female subjects aged 18 years or 
older, who have chronic plaque-type psoriasis considered inadequately controlled after 
treatment with ustekinumab. 
5.1
Inclusion criteria
Subjects eligible for inclusion in this study must meet all of the following criteria:
1. Signed informed consent must be obtained prior to participation in the study
2. Men or women ≥18 years of age at the time of consent 
3. Chronic plaque-type psoriasis considered inadequately controlled after treatment with 
ustekinumab according to the following criteria: 
o
ustekinumab administered at a dose equal or higher than that on the label for at least 
24 weeks. The last administration must be at least 12 weeks before randomization
o
absolute PASI score of 1-10 at Screening 
4. Presence of at least 1 refractory skin plaque, defined by a TCS of at least 6 and severity 
score of at least 2 or 3 (moderate) for each individual item, with an area ≥10 cm2 at 
Screening and Baseline
5.2
Exclusion criteria
Subjects meeting any of the following criteria are not eligible for inclusion in this study.
1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic, and 
guttate psoriasis) at Screening or Baseline
2. Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, 
calcium channel inhibitors or lithium) at Screening or Baseline
3. Previous treatment with more than one TNFα inhibitor or with IL-17A (including 
secukinumab), IL-17R or IL-23 (including guselkumab) inhibitors 

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4. Use of other investigational drugs within 4 weeks before enrolment, or within a period of 
5 half-lives of enrollment/initiation of the study treatment, whichever is longer 
5. Ongoing use of prohibited treatments (see Section 6.2.2) 
6. Known immunosuppression (e.g., AIDS) at Screening or Baseline
7. History of an ongoing, chronic, or recurrent infectious disease, or evidence of tuberculosis 
(TB) infection as defined by a positive QuantiFERON TB-Gold test In-Tube assay (QFT) 
at Screening. Subjects with a positive or indeterminate QFT test may participate in the 
study if a full tuberculosis workup (according to local practice/guidelines) is completed 
within 12 weeks prior to randomization and conclusively establishes that the subject has 
no evidence of active tuberculosis. If presence of latent tuberculosis is established, then 
treatment must have been initiated and maintained according to local guidelines prior to 
randomization (see Section 8.2.4)
8. History of hepatitis B, hepatitis C, or HIV infection 
9. History of congestive heart failure (NYHA functional classification ≥III) at Screening or 
Baseline 
10. Uncontrolled hypertension (systolic ≥160 mmHg, diastolic ≥95 mmHg) 
11. History of hypersensitivity to any of the study treatments or its excipients or to any human 
or humanized biological agents (antibody or soluble receptor) at Screening including 
reactions to local anesthetics required to perform skin biopsy 
12. History or evidence of ongoing alcohol or drug abuse, within the last 6 months before 
Baseline
13. Any live vaccines (including nasal-spray flu vaccine) starting from 6 weeks prior to initial 
treatment administration and during the study period 
14. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive human 
chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL) 
Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during the 
study or longer if required by locally-approved prescribing information (e.g., 20 weeks in 
the European Union and countries where applicable for secukinumab). Effective 
contraception methods include: 
total abstinence (when this is in line with the preferred and usual lifestyle of the 
subject). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception 
female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy) total hysterectomy or tubal ligation at least 6 weeks before taking study 
treatment. In case of oophorectomy alone, only when the reproductive status of the 
woman has been confirmed by follow up hormone level assessment 
male sterilization (at least 6 months prior to Screening). For female subjects on the 
study, the vasectomized male partner should be the sole partner for that subject
barrier methods of contraception: condom or occlusive cap (diaphragm or 
cervical/vault caps). For countries where applicable, the use of spermicidal 
foam/gel/film/cream/vaginal suppository will be allowed 

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use of oral (estrogen and progesterone), injected, or implanted hormonal methods of 
contraception or placement of an intrauterine device or intrauterine system or other 
forms of hormonal contraception that have comparable efficacy (failure rate < 1%), for 
example hormone vaginal ring or transdermal hormone contraception 
In case of use of oral contraception, women should have been stable on the same pill for a 
minimum of 12 weeks before taking study treatment. 
Women are considered post-menopausal and not of childbearing potential if they have 
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile 
(e.g., age appropriate history of vasomotor symptoms) or have had surgical bilateral 
oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at 
least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status 
of the woman has been confirmed by follow-up hormone level assessment is she 
considered not of childbearing potential.
If local regulations deviate from the contraception methods listed above to prevent 
pregnancy, local regulations apply and will be described in the informed consent form.
15. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system treated or untreated within the past 5 years, regardless of whether 
there is evidence of local recurrence or metastases (except for skin Bowen’s disease, or 
basal cell carcinoma or actinic keratosis that have been treated with no evidence of 
recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-invasive malignant 
colon polyps that have been removed) 
16. Underlying conditions (including, but not limited to metabolic, hematologic, renal, hepatic, 
pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the 
opinion of the Investigator significantly immunocompromise the subject and/or places the 
subject at unacceptable risk for receiving an immunomodulatory therapy. In addition, 
current severe progressive or uncontrolled diseases which render the subject unsuitable for 
the study or put the subject at increased risk, including any medical or psychiatric 
condition which, in the Investigator’s opinion, would preclude the participant from 
adhering to the protocol or completing the study per protocol 
17. Inability or unwillingness to undergo study procedures, including venipunctures and skin 
biopsy 
No additional exclusions may be applied by the Investigator in order to ensure that the study 
population will be representative of all eligible subjects. 

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6
Treatment
6.1
Study treatment
6.1.1
Investigational and control drugs
Table 6-1
Investigational and control drug 
Investigational/ 
control drug
(name and strength)
Pharmaceutical 
dosage form
Route of 
administration
Supply type
Sponsor 
(global or 
local)
Secukinumab 300 mg
Solution for 
injection in pre-filled 
syringe
s.c use
Open label 
subject packs; 
pre-filled 
syringes
Sponsor 
global 
Guselkumab 100 mg
Solution for 
injection in pre-filled 
syringe
s.c use
Open label 
subject packs; 
pre-filled 
syringes
Sponsor 
global 
6.1.2
Additional study treatments
No other treatment beyond investigational drug and control drug are included in this study.
6.1.3
Treatment arms
At Baseline, subjects will be randomized to one of the 2 treatment arms in a 1:1 ratio 
(Figure 3-1). 
Secukinumab treatment arm: 20 subjects with plaque psoriasis with an inadequate response 
to ustekinumab will self-administer 300 mg secukinumab as two 150-mg s.c. injections at 
Baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 12 inclusive. 
Guselkumab treatment arm: 20 subjects with plaque psoriasis with an inadequate response 
to ustekinumab will self-administer guselkumab as 100-mg s.c. injections at Baseline, 
Weeks 4, and 12. 
The initiation of secukinumab and guselkumab should not happen earlier than 12 weeks from 
the last administration of ustekinumab. 
6.1.4
Treatment duration
The planned duration of treatment is 16 weeks.
6.2
Other treatments
No additional treatment is included in this study. 

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6.2.1
Concomitant therapy
All medications, procedures and significant non-drug therapies (including physical therapy 
and blood transfusions) administered after the subject is enrolled in the study must be 
recorded on the appropriate eCRF.
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt, the Investigator should contact the Novartis medical monitor before 
randomizing a subject or allowing a new medication to be started. If the subject is already 
enrolled, contact Novartis to determine if the subject should continue participation in the 
study.
6.2.2
Prohibited medication
Use of topical pharmaceutically active treatment will not be allowed for the entire duration of 
the study, with the exception of mild topical treatments applied to the face, scalp, and/or 
genitoanal area. 
Use of the treatments displayed in Table 6-2 prior to study start (period specified in the table) 
or after study start will not be allowed.
Table 6-2
Prohibited medication
Prohibited treatments 
Prohibition period 
before Baseline a
Any biologic drug directly targeting IL-17 or any IL-17 receptor or IL-
23 (e.g., secukinumab, brodalumab, ixekizumab, guselkumab, 
risankizumab)
No prior use allowed
TNFα inhibitors (if more than one have been used)
Prior use of one inhibitor 
allowed. None allowed after 
Baseline
Any biological immunomodulatory agent other than the above listed 
(e.g., alefacept, briakinumab, efalizumab) 
6 months
Other systemic immunomodulatory treatments b (e.g., methotrexate, 
cyclosporine A, glucocorticosteroids, cyclophosphamide) and any 
treatment for psoriatic arthritis, except for NSAIDs
4 weeks
Other systemic psoriasis treatments (e.g., retinoids, fumarates, 
apremilast)
4 weeks
Photo-chemotherapy (e.g., psoralen plus UVA)
4 weeks
Phototherapy (e.g., UVA, UVB)
2 weeks
Live virus vaccinations 
6 weeks
Any investigational treatment or participation in any interventional 
study
4 weeks or 5 half-lives
(whichever is longer) 
a) In case of undue safety risk for the subjects, they should discontinue study treatment at the 
discretion of the Investigator or qualified site staff. If subjects treated with secukinumab receive a live 
virus vaccination during the study, they must discontinue study treatment 
b) Inhalational steroids with only a topical effect (e.g., to treat asthma) are not considered systemic
immunomodulatory treatments and are therefore acceptable 

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NSAID = nonsteroidal anti-inflammatory drug, UVA = ultraviolet light A, UVB = ultraviolet light B
6.3
Subject numbering, treatment assignment, randomization
6.3.1
Subject numbering
Each subject will be identified in the study by a subject number, which is assigned when the 
subject is first enrolled for screening and is retained as the primary identifier for the subjects
throughout their entire participation in the study. The subject number consists of the study site 
number (assigned by Novartis to the study site) with a sequential subject number suffixed to it, 
so that each subject is numbered uniquely across the entire database. Upon signing the 
informed consent form, the subject is assigned to the next sequential subject number available.
6.3.2
Treatment assignment, randomization
At the Baseline Visit, all eligible subjects will be randomized to one of the treatment arms via 
the Novartis Interactive Response Technology (NIRT). After confirming that the subject 
fulfills all the inclusion/exclusion criteria, the Investigator or delegate will contact the NIRT
and randomize the subject. The NIRT will assign a randomization number to the subject and 
allocate the subject to a treatment arm. The treatment allocation will be confirmed in the 
NIRT and communicated to the Investigator or designee, who will dispense the medication 
accordingly. 
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased from subjects and Investigator staff. A subject 
randomization list will be produced by the NIRT provider using a validated system that 
automates the random assignment of subject numbers to randomization numbers. These 
randomization numbers are linked to the different treatment arms.
The randomization scheme for subjects will be reviewed and approved by a member of the 
Randomization Office.
6.4
Treatment blinding
Treatment will be open to subjects, Investigator staff, and the clinical trial team. 
The assessment of all efficacy endpoints (primary and exploratory) will be performed by 
blinded independent clinicians, and pathologists/researchers. 
6.5
Dose escalation and dose modification
Dose adjustments and/or interruptions are not permitted.
6.6
Additional treatment guidance
6.6.1
Treatment compliance
All doses of study treatment administered will be recorded on the appropriate Dosage 
Administration Record eCRF page. Subject compliance with study treatment should be 
assessed by qualified study site personnel at each study visit using the study kits and 
documentation regarding study treatment dispensation and administration. 

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Compliance will also be assessed continuously by Novartis study personnel during the 
conduct of the study using medication kits and the corresponding documentation. Study 
treatment doses and the corresponding dates of self-administration at home should be 
documented in a self-administration log. Subjects will be required to return the 
self-administration log as well as all dispensed study treatment at every visit for a compliance 
check. 
The Investigator must promote compliance by instructing the subjects to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the subject’s 
safety and the validity of the study. The subject must also be instructed to contact the 
Investigator if he/she is unable for any reason to take the study treatment as prescribed. 
6.7
Preparation and dispensation
Each study site will be supplied with study drug in packaging as described under 
investigational and control drugs section.
6.7.1
Handling of study treatment and additional treatment
6.7.1.1
Handling of study treatment
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only the Investigator and 
designated site personnel have access. Upon receipt, all study treatment must be stored 
according to the instructions specified on the labels. Clinical supplies are to be dispensed only 
in accordance with the protocol. Technical complaints are to be reported to the respective 
Novartis Country Organization Quality Assurance.
Medication labels will be in the local language and comply with the legal requirements of 
each country. They will include storage conditions for the study treatment but no information 
about the subject except for the medication number.
The Investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
monitors during site visits or remotely and at the completion of the study. Subjects will be 
asked to return all unused study treatment and packaging at the end of the study or at the time 
of discontinuation of study treatment.
At the conclusion of the study, and as appropriate during the course of the study, the 
Investigator will return all unused study treatment, packaging, drug labels, and a copy of the 
completed drug accountability log to the Novartis monitor or to the Novartis address provided 
in the Investigator folder at each site.
6.7.2
Instruction for prescribing and taking study treatment
Study treatments will be administered subcutaneously throughout the study (Table 6-3). The 
first dose will be administered under supervision at the study site. Self-administration at home 
will be allowed from the second dose or when the subject, after being instructed and trained, 
is qualified to self-inject at the discretion of the Investigator. 

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Study treatments must be injected in never-lesional areas of the skin to one of the following 
body regions: front of thighs, or lower abdomen (but not the area 2 centimeters around the 
navel). Investigator/qualified site staff can also inject in the outer upper arms. Study treatment 
should not be injected into areas where the skin is tender, bruised, red, scaly or hard, and areas 
with scars or stretch marks should be avoided. As far as possible, the injection site should be 
changed from administration to administration throughout the study. 
Detailed instructions on the self-administration of the study treatment will be described in the 
instructions for use and provided to each subject. 
Subjects will be asked to return all used and unused medication and packaging at each 
scheduled study visit.
Secukinumab 300 mg s.c.
Secukinumab will be administered at Baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until 
Week 12 inclusive. After Week 4 (the last weekly administration of secukinumab), the 
subjects will be contacted by the Investigator or staff and be reminded to start the 
self-administration every 4 weeks instead of every week until Week 12. 
Guselkumab 100 mg s.c. 
Guselkumab will be administered subcutaneously at Baseline, Weeks 4, and 12. 
Table 6-3
Study treatment administration schedule
Treatment
Baseline
Week 1
Week 2
Week 3
Week 4
Week 8
Week 12
Secukinumab
X
X
X
X
X
X
X
Guselkumab
X
X
X
7
Informed consent procedures
Eligible subjects may only be included in the study after providing (witnessed, where required 
by law or regulation), Institutional Review Board/Independent Ethics Committee 
(IRB/IEC)-approved informed consent.
If applicable, in cases where the subject’s representative gives consent (if allowed according 
to local requirements), the subjects must be informed about the study to the extent possible 
given their understanding. If the subjects are capable of doing so, they must indicate 
agreement by personally signing and dating the written informed consent document.
Informed consent must be obtained before conducting any study-specific procedures (e.g., all 
of the procedures described in the protocol). The process of obtaining informed consent must 
be documented in the subject source documents.
Novartis will provide to Investigators in a separate document a proposed informed consent 
form that complies with the ICH Good Clinical Practice (GCP) guidelines and regulatory 
requirements and is considered appropriate for this study. Any changes to the proposed 
consent form suggested by the Investigator must be agreed by Novartis before submission to 
the IRB/IEC.

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Information about common side effects already known about the investigational drug can be 
found in the Investigator’s Brochure (IB). This information will be included in the subject 
informed consent and should be discussed with the subject during the study as needed. Any 
new information regarding the safety profile of the investigational drug that is identified 
between IB updates will be communicated as appropriate, for example, via an Investigator
notification or an aggregate safety finding. New information might require an update to the 
informed consent and then must be discussed with the subject.
Women of childbearing potential must be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirements.
Male subjects must be informed that if a female partner becomes pregnant while he is enrolled 
in the study, contact with the female partner will be attempted to request her consent to collect 
pregnancy outcome information.
 
 
 
 
 
A copy of the approved version of all consent forms must be provided to Novartis after 
IRB/IEC approval.
8
Visit schedule and assessments
Assessment schedule (Table 8-1) lists all of the assessments when they are performed. All 
data obtained from these assessments must be supported in the subject’s source 
documentation.
Subjects should be seen for all visits/assessments as outlined in the assessment schedule or as 
close to the designated day/time as possible. Missed or rescheduled visits should not lead to 
automatic discontinuation. Subjects who prematurely discontinue the study for any reason 
should be scheduled for a visit as soon as possible, at which time all of the assessments listed 
for the final visit will be performed. At this final visit, all dispensed investigational product 
should be reconciled, and the AEs and concomitant medications recorded on the eCRF.

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Table 8-1
Assessment schedule
Visit name
Screening
Baseline
End of study
Unscheduled
Visit number
1
2
3
-
Week
-4 to -1
-
16
-
Day
-28 to -1
1
112
-
Informed consent
X
Inclusion/exclusion criteria 
X
X
Pregnancy test 2
X
X
Randomization via NIRT
X
Physical examination
X
X
X
X
Smoking history
X
Medical history
X
Relevant family history
X
Demography
X
Psoriasis medical and treatment 
history
X
QFT
X
Skin type
X
Body temperature (°C)
X
X
Height (cm)
X
Weight (Kg)
X
X
X
Vital signs
X
X
X
Electrocardiogram 
X
Laboratory assessments
X
X
Adverse events 3
X
X
X 
X
Drug administration record
X
X 
X
Concomitant medications
X
X
X 
X
TCS of target plaque
X
X
X
X
Skin biopsies
6
X
X
Information on study completion 
X 
Baseline Visit (Visit 2) should be conducted within 28 days of the Screening Visit (Visit 1). 

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Unscheduled visits can be decided by the Investigators according to their own clinical judgment and 
practice. 
End-of-study assessments (Visit 3) should be conducted only on subjects who complete 4 to 16 weeks 
of treatment. There will be a ± 2-day window for Visit 3 (Week 16) 
 
2) Performed on serum for women of childbearing potential 
3) SAEs collected up to 30 days after the last administration of study treatment 
 
6) At Baseline, two 6-mm punch biopsies will be taken, one from the identified active plaque (TCS ≥6) 
and one from never-lesional skin. At the End-of-study Visit, one biopsy will be taken from the same 
area of the plaque sampled at Baseline. Biopsies should be sampled from the trunk whenever possible 
to avoid scars in exposed areas of the body 
8.1
Screening
Subject’s eligibility for the study will be assessed at the Screening Visit (Day -28 to Day -1 
before Baseline) and at the Baseline Visit (see Table 8-1).
Subjects who fail screening for any reason may be rescreened. There will be no restriction on 
the number of times a potential subject may be rescreened or on how much time must pass 
from the date of screen failure and the date of rescreening. Subjects who are rescreened must 
sign a new informed consent form and be issued a new subject number before any 
study-related assessment is performed or any data for the Screening Visit are collected for the 
subject under the new subject number. 
The Investigator or qualified site staff will record all rescreenings on the Rescreening eCRF 
page and any applicable screening numbers the subject was issued prior to the current 
screening number. The date of the new informed consent signature must be entered on the 
Informed Consent eCRF page to correspond with the new screening subject number. 
The Withdrawal of Consent eCRF page must be completed if consent was withdrawn during 
the Screening Visit before the subject was randomized. 
8.1.1
Information to be collected on screening failures
Subjects who sign an informed consent form and subsequently are found to be ineligible prior 
to randomization will be considered screen failures. The reason for screen failure should be 
recorded on the appropriate eCRF page. The demographic information, informed consent, and 
inclusion/exclusion pages must also be completed for screen failures. No other data will be 
entered into the clinical database for screen failures, unless the subject experienced an SAE 
during the Screening Visit (see Section 10.1.3 for reporting details). If the subject fails to be 
randomized, the NIRT must be notified within 2 days.
Subjects who are randomized and fail to start treatment, e.g., randomized in error, will be 
considered early terminators. The reason for early termination should be recorded on the 
appropriate eCRF page. 

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8.2
Subject demographics/other baseline characteristics
Subject demographics and baseline characteristics will be collected at the Screening Visit. 
Data to be collected on all subjects include: date of birth, age, sex, race, ethnicity, height, 
weight, and skin type (see Section 16.2.1). 
8.2.1
Smoking history
The current and/or previous use of tobacco products will be recorded, as well as the estimated 
number of pack-years based on the approximate consumption per year. Non-smokers will be 
advised to not start smoking during the study. 
8.2.2
Relevant medical history/current medical conditions 
Relevant medical history and current medical conditions, not including psoriasis or psoriatic 
arthritis, prior to signing of the informed consent will be recorded in the Medical History 
eCRF page. Whenever possible, diagnoses and not symptoms will be recorded. 
Subjects with inflammatory bowel disease will be eligible for the study but should be closely 
followed when randomized to secukinumab. 
Significant findings that are observed after the subject has signed the informed consent form 
and that meet the definition of an AE must be recorded in the Adverse Event eCRF page. 
8.2.2.1
Psoriasis medical and treatment history 
Disease history will be collected at the Screening Visit. The information to be collected and 
entered in the Psoriasis History eCRF page and Prior Psoriasis Therapies eCRF page will 
include the following: 
1. Date of first diagnosis of plaque psoriasis 
2. Previous treatments of psoriasis (including previous use of biologic therapies, as well as 
phototherapy and/or photo-chemotherapy) and the reason for discontinuation of each 
therapy 
3. Presence of psoriatic arthritis or ankylosing spondylitis (including questions on signs and 
symptoms captured in the eCRF) and the date of the first diagnosis by a physician 
8.2.3
Prior and concomitant medications 
Concomitant medications and prior medications taken within the 6 months preceding study 
enrollment will be captured at the Screening Visit, and updated at the Baseline Visit or 
subsequent visits. 
8.2.4
Determination of tuberculosis status 
Determination of TB status will be required at the Screening Visit and should be performed as 
defined by local guidelines. Tuberculosis status must be determined by medical history, signs, 
symptoms, and TB testing (QFT). 
Any significant findings will be recorded in the Tuberculosis Assessment eCRF page and the 
Medical History eCRF page, as necessary. 

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8.2.4.1
QuantiFERON TB-Gold In-Tube assay
This test will only be used to screen the subject population for latent TB infection
(Doherty et al 2008) and determine subject’s eligibility for the study.
This blood-based assay is specific for Mycobacterium tuberculosis and is not influenced by 
previous bacillus Calmette-Guerin vaccination or exposure to other Mycobacteria species. In 
contrast to the purified protein derivative skin test, it is also insensitive to a booster effect, 
since the subject is not exposed to the vaccine. The assay measures the production of 
interferon-gamma and presents it relative to negative and positive control samples
(Manuel and Kumar 2008). 
The QFT will be supplied by the central laboratory. Details on the collection, shipment of 
samples and reporting of results by the central laboratory will be provided to Investigators in 
the laboratory manual. 
1. If the test result is negative, the subject may be randomized 
2. If the test result is positive, the Investigator should perform workup as per local guidelines 
(if a TB workup was conducted prior to the screening of the subject, results of the workup 
can be used to assess eligibility if the workup was conducted within 12 weeks prior to 
Randomization)
a.
subjects positive for active TB per workup are not eligible for the study
b.
subjects diagnosed with latent TB per workup may be randomized to the study if 
sufficient treatment has been initiated according to local routine clinical practice or 
guidelines and will be maintained for the prescribed duration
3. If the test result is indeterminate, it is recommended to repeat the test once
a.
if the second test is negative, the subject may be randomized
b.
if the second test is positive or indeterminate, the investigator should perform workup 
as per local guidelines (if a TB workup was conducted prior to the screening of the 
subject, results of the workup can be used to assess eligibility if the workup was 
conducted within 12 weeks prior to Randomization)
o
subjects positive for active TB per workup are not eligible for the study
o
subjects diagnosed with latent TB per workup may be randomized to the study if 
sufficient treatment has been initiated according to local routine clinical practice 
or guidelines and will be maintained for the prescribed duration 
8.3
Efficacy
8.3.1
Total clinical score 
The TCS will be assessed at all study visits as indicated in Table 8-1. At Baseline, it should be 
performed before the first administration of study treatment. 
The TCS for each plaque will be determined (ideally by the same evaluator) as the sum of 
3 scores: erythema (0-3), scaling (0-3) and infiltration (0-3) rated according to their severity 
as shown in Table 8-2. The TCS can range from 0 (all signs absent) to 9 (all signs severe).

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Table 8-2
Assessments of total clinical score 
Score
Intensity
Erythema
Scaling
Infiltration
0
No evidence
Normal skin color
No scaling
No infiltration
0.5
Doubtful or very 
mild
1.0
Mild
Pink/light red
Slight roughness, 
mainly fine scales 
Slight definite 
infiltration
1.5
Mild to moderate
2.0
Moderate
Red 
Coarse scaling
Moderate infiltration
2.5
Moderate to severe
3.0
Severe 
Intense red
Coarse, thick scales
Very marked 
infiltration
8.3.3
Skin biopsies
At Baseline, two 6-mm punch biopsies will be taken, one from the identified active plaque 
(TCS ≥6) and one from never-lesional skin. At the End-of-study Visit, one biopsy will be 
taken from the same area of the active plaque sampled at Baseline.
After collection, biopsies will be transported within 24 hours to the laboratory for further 
processing using a Novartis delegated service provider. 
Laboratory manuals will be provided with detailed information on sample collection, handling, 
and shipment. The sample collection date and exact time must be entered on the Sample 
Collection eCRF page. 
8.3.4
Microscopic morphology of the skin plaque
General histopathology of the skin will be assessed by hematoxylin and eosin staining and 
epidermal proliferation and differentiation by immunohistochemical (IHC) staining of Ki-67 
and keratin-16 positive nuclei. The quantification of positive cells will be performed at X 200 
magnification and calculated per mm of skin length. 

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8.3.5
Infiltrating immune cells in the skin plaque
The number of infiltrating cells expressing IL-17A and IL-23R will be assessed by 
single-staining IF using IHC and immunofluorescence (IF) if needed, and will be counted per 
mm of skin length. 
8.3.6
Composition of the inflammatory infiltrate in the skin plaque
Single or double staining (IHC/IF) will be used to identify different cell types in the immune 
infiltrate according to the following markers: T-cells (CD3, CD8); neutrophils (elastase); 
mastocytes (tryptase); dendritic cells (CD11c); macrophages (CD163); NK cells (CD56); 
NKT cells (CD3, CD56); T-resident memory cells (CD49, CD103). The number of cells per 
cell type will be counted per mm of skin length. 

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8.4
Safety
Safety assessments are specified in Table 8-5 and Table 8-6. For details on AE collection and 
reporting, refer to the AE section.
Table 8-5
Physical assessments
Assessment
Specification
Physical 
examination
A complete physical examination will include the inspection of general appearance, 
skin, neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, 
lymph nodes, and extremities, and the vascular and neurological systems. If 
indicated based on medical history and/or symptoms, rectum, external genitalia, 
breast, and pelvic will be examined. 
In particular, will include recognition of enthesitis, dactylitis, and the patterns of joint, 
or nail involvement. 
Information for all physical examinations must be included in the source 
documentation at the study site. Significant findings that are present prior to signing 
the informed consent must be included in the Medical History eCRF page. Significant 
findings made after the first administration of investigational drug, which meet the 
definition of an AE must be recorded on the Adverse Event eCRF page.
Vital signs
Vital signs include measurements of blood pressure and pulse. After the subject has 
been sitting for 5 minutes, with the back supported and both feet placed on the floor, 
systolic and diastolic blood pressures will be measured 3 times using an automated 
validated device, e.g., OMRON, with an appropriately sized cuff. The repeat-sitting 
measurements will be made at 1-2 minute intervals and the mean of the 
3 measurements will be used. If the available cuff sizes are not large enough for the 
subject’s arm circumference, a sphygmomanometer with an appropriately sized cuff 
may be used. 
If possible, assessments should be performed by the same study site staff member 
throughout the study. 

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Assessment
Specification
Normal blood pressure will be defined as systolic pressure of 90 to < 120 mmHg, 
and diastolic blood pressure of 60 to < 80 mmHg under the measurement conditions 
outlined above. Notable blood pressure findings will be hypertension (systolic blood 
pressure of ≥140 mmHg and/or diastolic blood pressure of ≥90 mmHg) or 
hypotension (systolic blood pressure of < 90 mmHg and/or a diastolic blood pressure 
of < 60 mmHg). A blood pressure indicative of prehypertension (systolic blood 
pressure of 120 to < 140 mmHg and/or diastolic blood pressure of 80 to < 90 mmHg) 
will not be regarded as notable (Whelton et al 2017).
A normal pulse rate will be defined as a rate of 60 to 100 beats per minute (bpm) 
under the measurement conditions outlined above. Notable pulse rate will be a rate 
below 60 bpm (bradycardia) or above 100 bpm (tachycardia).
Whether action needs to be taken to address notable vital signs will be decided by 
the Investigator, taking into account the overall status of the subject. No specific 
action is foreseen as part of the study protocol. 
Height and 
weight
Height in cm and body weight (to the nearest 0.1 Kg in indoor clothing, but without 
shoes) will be measured.
8.4.1
Laboratory evaluations
A central laboratory will be used for the analysis of all specimens collected. Details on the 
collection, shipment of samples and reporting of results by the central laboratory will be 
provided to Investigators in the laboratory manual. 
Clinically notable laboratory findings are defined in Appendix 1.
Table 8-6
Laboratory assessments
Test category
Test name
Hematology
Hemoglobin, hematocrit, red blood cell count, white blood cell count with 
differential, and platelet count will be quantified.
Chemistry
Blood urea, creatinine, total bilirubin, alkaline phosphatase, international 
normalized ratio, sodium, potassium, chloride, calcium, phosphorous, total protein, 
albumin, uric acid, and lipid panel will be quantified.
Urinalysis
The central laboratory will provide dipsticks to the sites for local analysis of urine. 
Dipstick analysis will measure specific gravity, albumin, protein, glucose and blood. 
Microscopy and white blood cell count and red blood cell count sediments will be 
assessed in case of an abnormal dipstick test. Only samples with abnormal 
dipstick will be assessed by the central laboratory and the results provided in 
loaded data.
Study sites should record the results in the source documentation.
Additional tests
Pregnancy test
A serum β-hCG test will be performed to all pre-menopausal women as shown in
Table 8-1. 
Any woman with a confirmed positive pregnancy test (hCG > 5 mIU/mL) during 
Screening will not be eligible for randomization. 
Women of childbearing potential should use an effective method of contraception 
while on treatment, or longer if required by locally-approved prescribing information 
(e.g., 20 weeks after the last dose in the EU and countries where applicable for 
secukinumab).

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8.4.2
Electrocardiogram
At the Screening Visit, an ECG must be recorded after 10 minutes rest in the supine position 
to ensure a stable baseline. The preferred sequence of cardiovascular data collection at is ECG 
first, followed by vital signs, and blood sampling for laboratory assessments. The Fridericia 
QT correction formula (QTcF) should be used for clinical decisions. 
If the ECG findings are clinically relevant and would prevent the subject from participating in 
the study (taking into account the subject’s overall status and the medication profile), the 
subject should be recorded as a screen failure, should not be enrolled and should not receive 
treatment. 
Single 12-lead ECGs will be collected. The original ECGs, appropriately signed, should be 
collected and archived at the study site. 
Each ECG tracing must be labelled with study number, subject initials, subject number, date 
and time, and filed in the study site source documents. Clinically significant ECG findings at 
Baseline must be discussed with the Sponsor before administration of study treatment. 
For any ECGs with subject safety concerns, 2 additional ECGs must be performed to confirm 
the safety finding and copies forwarded to the central ECG laboratory for assessment. A 
monitoring or review process should be in place for clinically significant ECG findings 
throughout the study and especially at Baseline before administration of study treatment.
Any identifier details must be redacted e.g., subject initials, date of birth.
In the event that a clinically significant ECG abnormality is identified at the site (e.g., severe 
arrhythmia, conduction abnormality of QTcF > 500 ms), a copy of the assessment is sent to 
the core laboratory for expedited review if applicable, and the ECG is repeated to confirm the 
diagnosis. If the subject is hemodynamically compromised, the Investigator or a medically 
qualified person must initiate appropriate safety procedures without delay (for example 
cardioversion).
Clinically significant abnormalities must be recorded on the eCRF as either medical 
history/current medical conditions or AEs as appropriate.
8.4.3
Pregnancy 
All pre-menopausal women who are not surgically sterile will have pregnancy testing. 
Additional pregnancy testing might be performed if requested by local requirements.
Medical documentation of oophorectomy, hysterectomy, or tubal ligation must be retained as 
source documents. Subsequent hormone level assessment to confirm the woman is not of 
childbearing potential must also be available as source documentation in the following cases:
1. Surgical bilateral oophorectomy without a hysterectomy
2. Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile
In the absence of the above medical documentation, follicle-stimulating hormone testing is 
required of any female subject, regardless of reported reproductive/menopausal status at 
Screening/Baseline.

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8.4.4
Appropriateness of safety measurements
The safety assessments selected are standard for this indication/subject population.
8.5
Additional assessments

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9
Study discontinuation and completion
9.1
Discontinuation
9.1.1
Discontinuation of study treatment
Discontinuation of study treatment for a subject occurs when study treatment is stopped 
earlier than the protocol planned duration, and can be initiated by either the subject or the 
Investigator.
The Investigator must discontinue study treatment for a given subject if, he/she believes that 
continuation would negatively impact the subject’s well-being.
Study treatment must be discontinued under the following circumstances:

subject decision 

pregnancy 

use of prohibited treatment as per recommendations in the prohibited treatment section 

any situation in which study participation might result in a safety risk to the subject 

any laboratory abnormalities that in the judgment of the Investigator, taking into 
consideration the subject’s overall status, prevents the subject from continuing 
participation in the study 

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If discontinuation of study treatment occurs, the Investigator should make a reasonable effort 
to understand the primary reason for the subject’s premature discontinuation of study 
treatment and record this information.
Subjects who discontinue study treatment or who decide they do not wish to participate in the 
study further should NOT be considered withdrawn from the study UNLESS they withdraw
their consent (see Section 9.1.2). Where possible, they should return for the assessments 
indicated in the assessment schedule. If they fail to return for these assessments for unknown 
reasons, every effort (e.g., telephone, e-mail, or letter) should be made to contact the 
subject/pre-designated contact as specified in the lost to follow-up section. This contact 
should preferably be done according to the study visit schedule.
If the subject cannot or is unwilling to attend any visit(s), the site staff should maintain regular 
telephone contact with the subject, or with a person pre-designated by the subject. This 
telephone contact should preferably be done according to the study visit schedule.
After study treatment discontinuation, at a minimum, in abbreviated visits, the following data 
should be collected at study site visits or via telephone/email contact:

new/concomitant treatments

adverse events/SAEs 
The Investigator must also contact the NIRT to register the subject’s discontinuation from 
study treatment.
9.1.2
Withdrawal of informed consent
Subjects may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent occurs only when a subject:

does not want to participate in the study anymore
and

does not allow further collection of personal data 
In this situation, the Investigator should make a reasonable effort (e.g., telephone, e-mail, or 
letter) to understand the primary reason for the subject’s decision to withdraw his/her consent 
and record this information.
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing.
Further attempts to contact the subject are not allowed unless safety findings require 
communicating or follow up.
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the subject’s study withdrawal should be made as detailed in the 
assessment table.
Novartis will continue to retain and use collected study information (including any data 
resulting from the analysis of subject’s samples until the time of withdrawal) according to 
applicable law.

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For US and Japan: all biological samples not yet analyzed at the time of withdrawal may still 
be used for further testing/analysis in accordance with the terms of this protocol and of the 
informed consent form. 
For EU and rest of the world: all biological samples not yet analyzed at the time of 
withdrawal will no longer be used unless permitted by applicable law. They will be stored 
according to applicable legal requirements. 
9.1.3
Lost to follow up
For subjects whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the Investigator must show “due diligence” by 
documenting in the source documents steps taken to contact the subject, e.g., dates of 
telephone calls, registered letters, etc. A subject should not be considered as lost to follow up 
until due diligence has been completed or until the end of the study.
9.1.4
Early study termination by the Sponsor
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit/risk assessment of participating in the study, practical reasons (including 
slow enrollment), or for regulatory or medical reasons. In taking the decision to terminate, 
Novartis will always consider the subject welfare and safety. Should early termination be 
necessary, subjects must be seen as soon as possible (provide instruction for contacting the 
subject, when the subject should stop taking drug, when the subject should come for a final 
visit) and treated as a prematurely withdrawn subject. The Investigator may be informed of 
additional procedures to be followed in order to ensure that adequate consideration is given to 
the protection of the subject’s interests. The Investigator or sponsor depending on the local 
regulation will be responsible for informing IRBs/IECs of the early termination of the study.
9.2
Study completion and post-study treatment
Study completion is defined as when the last subject finishes their End-of-study Visit, and any 
repeat assessments associated with this visit have been documented and followed up 
appropriately by the Investigator, or in the event of an early study termination decision, the 
date of that decision (e.g., each subject will be required to complete the study in its entirety 
and thereafter no further study treatment will be made available to them).
All randomized and/or treated subjects should have a safety follow up conducted 30 days after 
the last administration of study treatment. This will be performed at Week 16 for subjects who 
complete the study [last administration received at Week 12]. The information collected is 
kept as source documentation. All SAEs reported during this period must be reported as 
described in Section 10.1.3. Attempts to contact the subject should be recorded in the source 
documentation.

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10
Safety monitoring and reporting
10.1
Definition of adverse events and reporting requirements
10.1.1
Adverse events
An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign 
[including abnormal laboratory findings], symptom or disease) in a subject or clinical 
investigation subject after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product.
The Investigator has the responsibility for managing the safety of individual subject and 
identifying AEs.
Novartis qualified medical personnel will be readily available to advise on study related 
medical questions or problems.
The occurrence of AEs must be sought by non-directive questioning of the subject at each 
visit during the study. Adverse events also may be detected when they are volunteered by the 
subject during or between visits or through physical examination findings, laboratory test 
findings, or other assessments.
Adverse events must be recorded under the signs, symptoms or diagnosis associated with 
them, accompanied by the following information (as far as possible, if the event is serious 
refer to Section 10.1.2):
1. The Common Toxicity Criteria (CTC) AE grade (version 4.03 or higher). Adverse events 
will be assessed and graded according to the Common Terminology Criteria for Adverse 
Events (CTCAE) version 
2. Its relationship to the study treatment. If the event is due to lack of efficacy or progression 
of underlying illness (i.e., progression of the study indication) the assessment of causality 
will usually be ‘Not suspected’. The rationale for this guidance is that the symptoms of a 
lack of efficacy or progression of underlying illness are not caused by the trial drug, they 
happen in spite of its administration and/or both lack of efficacy and progression of 
underlying disease can only be evaluated meaningfully by an analysis of cohorts, not on a 
single subject
3. Its duration (start and end dates) or if the event is ongoing, an outcome of not 
recovered/not resolved must be reported.
4. Whether it constitutes a SAE (see Section 10.1.2) for definition of SAE) and which 
seriousness criteria have been met
5. Action taken regarding with study treatment.
All AEs must be treated appropriately. Treatment may include one or more of the following:

dose not changed

dose reduced/increased

drug interrupted/withdrawn
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Conditions that were already present at the time of informed consent should be recorded in 
medical history of the subject.
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible, rather than individual underlying signs and symptoms.
Adverse event monitoring should be continued for at least 30 days following the last dose of 
study treatment.
Information about adverse drug reactions for the investigational drug can be found in the IB.
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria:

they induce clinical signs or symptoms

they are considered clinically significant

they require therapy
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
Baseline or the previous visit, or values that are considered to be non-typical in subjects with 
the underlying disease. 
10.1.2
Serious adverse events
An SAE is defined as any AE (appearance of or worsening of any pre-existing one) 
undesirable sign, symptom or medical conditions that meets any one of the following criteria:

fatal

life-threatening
Life-threatening in the context of a SAE refers to a reaction in which the subject is at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to the ICH-E2D Guidelines).

results in persistent or significant disability/incapacity

constitutes a congenital anomaly/birth defect

requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
a.
routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (including psoriasis and psoriatic arthritis)
b. elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent
c. social reasons and respite care in the absence of any deterioration in the subject’s 
general condition
d. treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission

is medically significant, e.g., defined as an event that jeopardizes the subject or may 
require medical or surgical intervention to prevent one of the outcomes listed above

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Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalization but might jeopardize the 
subject or might require intervention to prevent one of the other outcomes listed above. Such 
events should be considered as “medically significant”. Examples of such events are intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization or development of dependency or abuse. 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
All reports of intentional misuse and abuse of the product are also considered SAEs
irrespective if a clinical event has occurred.
10.1.3
Serious adverse event reporting
To ensure subject safety, every SAE, regardless of causality, occurring after the subject has 
provided informed consent and until 30 days following the last administration of study 
treatment must be reported to Novartis Safety within 24 hours of learning of its occurrence. 
Detailed instructions regarding the submission process and requirements are to be found in the 
Investigator folder provided to each study site.
Serious adverse events occurring after the subject has provided informed consent until the 
time the subject is deemed a Screen Failure must be reported to Novartis. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow up of the original episode 
within 24 hours of the Investigator receiving the follow-up information. An SAE occurring at 
a different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event.
If the SAE is not previously documented in the IB or Package Insert (new occurrence) and is 
thought to be related to the study treatment, an associate from the Novartis Chief Medical 
Office and Patient Safety (CMO&PS) Department may urgently require further information 
from the Investigator for health authority reporting. Novartis may need to issue an 
Investigator Notification (IN) to inform all Investigators involved in any study with the same 
study treatment that this SAE has been reported.
Suspected unexpected serious adverse reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with EU Guidance 
2011/C 172/01 or as per national regulatory requirements in participating countries.
Any SAEs experienced after the 30-day period following the last administration of study 
treatment should only be reported to Novartis Safety if the Investigator suspects a causal 
relationship to study treatment.

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10.1.4
Pregnancy reporting
Pregnancies
To ensure subject safety, each pregnancy occurring after signing the informed consent must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should 
be followed up to determine outcome, including spontaneous or voluntary termination, details 
of the birth, and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications.
Pregnancy should be recorded and reported by the Investigator to the CMO&PS. Pregnancy 
follow up should be recorded on the same form and should include an assessment of the 
possible relationship to study treatment any pregnancy outcome. Any SAE experienced during 
pregnancy must be reported.
10.1.5
Reporting of study treatment errors including misuse/abuse
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, subject or 
consumer (EMA definition).
Misuse refers to situations where the medicinal product is intentionally and inappropriately 
used not in accordance with the protocol.
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects.
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate eCRF irrespective of whether or not associated with an AE/SAE and reported 
to Novartis Safety only if associated with an SAE. Misuse or abuse will be collected and 
reported in the safety database as SAEs within 24 hours of Investigator’s awareness (Table 
10-1).
Table 10-1
Guidance for capturing the study treatment errors including 
misuse/abuse
Treatment error type
Document in dosing
eCRF (Yes/No)
Document in AE 
eCRF
Complete SAE form
Unintentional study 
treatment error
Yes
Only if associated 
with an AE
Only if associated with an 
SAE
Misuse/Abuse
Yes
Yes
Yes, even if not associated 
with a SAE
For more information on AE and SAE definition and reporting requirements, please see the, 
respective sections.
10.2
Additional safety monitoring 
Not applicable. 

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11
Data collection and database management
11.1
Data collection
Designated Investigator staff will enter the data required by the protocol into the eCRF. The 
eCRFs have been built using fully validated secure web-enabled software that conforms to 
21 CFR Part 11 requirements, Investigator site staff will not be given access to the EDC 
system until they have been trained. Automatic validation programs check for data 
discrepancies in the eCRFs, and allow modification and/or verification of the entered data by 
the Investigator staff.
The Investigator/designee is responsible for assuring that the data (recorded on eCRFs) 
(entered into eCRF) is complete, accurate, and that entry and updates are performed in a 
timely manner. The Investigator must certify that the data entered are complete and accurate. 
After final database lock, the Investigator will receive copies of the subject data for archiving 
at the study site.
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification. 
11.2
Database management and quality control
Novartis personnel (or designated contract research organization [CRO]) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the study site via the EDC system. Designated Investigator site 
staff is required to respond promptly to queries and to make any necessary changes to the data.
Concomitant treatments and prior medications entered into the database will be coded using 
the WHO Drug Reference List, which employs the Anatomical Therapeutic Chemical 
classification system. Medical history/current medical conditions and AEs will be coded using 
the Medical dictionary for regulatory activities (MedDRA) terminology.
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated CRO). 
Randomization codes and data about all study treatments dispensed to the subject and all 
dosage changes will be tracked using an NIRT system. The randomization list will be 
generated by a vendor who will transfer it after the RRS has been approved. Later this will be 
uploaded into the NIRT system.
Each occurrence of a code break via NIRT will be reported to the clinical team and monitor. 
The code break functionality will remain available until study shut down or upon request of 
Novartis.
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked. Any changes to the database after that time can only 
be made after written agreement by Novartis development management.

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11.3
Site monitoring
Before study initiation, at a site initiation visit or at an Investigator’s meeting, a 
Novartis/delegated CRO representative will review the protocol and data capture requirements 
(i.e., eCRFs) with the Investigators and their staff. During the study, Novartis employs several 
methods of ensuring protocol and GCP compliance and the quality/integrity of the sites’ data. 
The field monitor will visit the site to check the completeness of subject records, the accuracy 
of data capture/data entry, the adherence to the protocol and to GCP, the progress of 
enrollment, and to ensure that study treatment is being stored, dispensed, and accounted for 
according to specifications. Key study personnel must be available to assist the field monitor 
during these visits. Continuous remote monitoring of each site’s data may be performed by a 
centralized Novartis/delegated CRO. Additionally, a central analytics organization may 
analyze data & identify risks & trends for site operational parameters, and provide reports to 
Novartis clinical teams to assist with study oversight.
The Investigator must maintain source documents for each subject in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, ECGs, and the results of any other tests or assessments. All 
information on eCRFs must be traceable to these source documents in the subject’s file. The 
Investigator must also keep the original informed consent form signed by the subject (a signed 
copy is given to the subject).
The Investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the data capture and/or data entry. Novartis monitoring standards 
require full verification for the presence of informed consent, adherence to the 
inclusion/exclusion criteria, documentation of SAEs, and of data that will be used for the 
primary endpoint. Additional checks of the consistency of the source data with the eCRFs are 
performed according to the study-specific monitoring plan. No information in source 
documents about the identity of the subjects will be disclosed.
12
Data analysis and statistical methods
All analyses will be performed by Novartis or a designated CRO. Any data analysis carried 
out independently by the Investigator should be submitted to Novartis before publication or 
presentation.
Continuous variables will be summarized by number of subjects, mean, standard deviation, 
minimum, median, and maximum. For selected parameters, 25th and 75th percentiles will also 
be presented. Categorical variables will be summarized by frequencies and percentages.
In addition to the statistical methods outlined below, further details and any additional 
exploratory analyses that may be performed will be described in the Statistical Analysis Plan. 
The last available assessment on or before the start date of study treatment (i.e., secukinumab 
or guselkumab) is taken as the baseline assessment. 

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12.1
Analysis sets
The following analysis sets will be used in this study: 
The FAS comprises all subjects to whom study treatment has been assigned by randomization. 
According to the intent-to-treat principle, subjects will be analyzed according to the treatment 
they have been assigned to during the randomization procedure. 
The Safety Set includes all subjects who receive at least one dose of study treatment. Subjects 
will be analyzed according to the study treatment received.
12.2
Subject demographics and other baseline characteristics
12.2.1
Demographics and baseline characteristics 
Demographic and other baseline data including disease characteristics will be listed and 
summarized descriptively by treatment arm for the FAS. 
12.2.2
Medical history 
Relevant medical histories and current medical conditions at Screening will be listed and 
summarized by system organ class and preferred term for each treatment arm for the FAS.
12.3
Treatments
The Safety Set will be used for the analyses below. 
12.3.1
Study treatments
The duration of exposure to secukinumab and guselkumab (in weeks), will be summarized by 
means of descriptive statistics. In addition, the number and percentage of subjects with 
cumulative exposure levels (e.g., any exposure, ≤ 1 week, ≤2 weeks, ≤ 3 weeks, ≤ 4 weeks, 
≤8 weeks, etc.) will be presented. 
The number of subjects with dose adjustments (reductions, interruption, or permanent 
discontinuation) and the reasons thereof will be summarized. All dosing data will be listed. 
12.3.2
Prior and concomitant treatments
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be listed and summarized according to the Anatomical Therapeutic 
Chemical (ATC) classification system by treatment arm. 
12.4
Analysis of the primary endpoint
12.4.1
Definition of primary endpoint
The primary objective is to assess the superiority of secukinumab over guselkumab in 
controlling clinical activity in psoriatic plaques resistant to treatment with ustekinumab.
The primary endpoint is the proportion of subjects whose plaque achieves “clear” or “almost 
clear” status (TCS = 0-2) by 16 weeks of treatment with secukinumab or guselkumab. 

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12.4.2
Statistical model, hypothesis, and method of analysis
The number (%) of subjects whose plaques achieve “clear” or “almost clear” status 
(TCS = 0-2) at Week 16 (i.e., responders) will be provided based on the FAS together with the 
95% confidence interval using the exact method for the difference in proportions of 
responders in each arm.
Furthermore, a 1-sided Fisher’s exact test for the difference in the proportions of responders 
in the secukinumab (P1) and gesulkumab (P2) arms, H0: P1-P2 = 0 versus H1: P1-P2 > 0 at a 
Type I error rate of 0.05 will be performed.
12.4.3
Handling of missing values/censoring/discontinuations
Subjects who discontinue between Week 4 and Week 16, will be required to complete the 
End-of-study Visit assessments as shown in Table 8-1. The plaque status based on the TCS at 
the End-of-study Visit will be used for the primary endpoint assessment i.e., the last 
observation carried forward approach will be applied. Subjects discontinued before Week 4 
will be treated as failures.
12.4.4
Sensitivity and supportive analyses
Analysis of the primary endpoint as observed i.e., without missing data imputation (as 
described in Section 12.4.3) will be performed as a sensitivity analysis for the primary 
endpoint.
12.5
Analysis of secondary endpoints
Not applicable. 
12.6
Analysis of exploratory endpoints
The following exploratory endpoints will be analyzed: 
 
2. Change from Baseline to Week 16 in epidermal thickness and in the number of Ki-67 and 
K16 positive cells of lesional skin biopsies and difference from the Baseline non-lesional 
skin biopsy (Section 8.3.4) will be provided based on the FAS. Box plots and bar plots 
will also be provided 
3. Change from Baseline to Week 16 in the number of infiltrating cells expressing IL 17A 
and IL-23R of lesional skin biopsies and difference from the Baseline non-lesional skin 
biopsy (Section 8.3.5) will be provided based on the FAS 
4. Change from Baseline to Week 16 in the number of different immune cell types in the 
inflammatory infiltrate of lesional skin biopsies and difference from the Baseline 
non-lesional skin biopsy (Section 8.3.6) will be provided based on the FAS
 

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 Values below the lower limit of quantification and above 
the upper limit of quantification will be flagged.
12.7
Safety analysis 
The Safety Set will be used for all safety analyses. All summary tables and listings will be 
presented by treatment arm. 
Safety summary tables will include only data from the on-treatment period (from first 
administration of study treatment to 30 days after the last administration of study treatment) 
with the exception of baseline data which will also be summarized where appropriate. 
Adverse events
All information obtained on AEs will be displayed by treatment arm.
Summary tables for AEs will include only AEs that started or worsened during the 
on-treatment period, the treatment-emergent AEs (TEAEs). 
The incidence of TEAEs will be summarized by system organ class and/or preferred term, 
severity based on the Common Terminology Criteria of Adverse Events (CTCAE) grades, 
type of AE and relation to study treatment. 
Serious adverse events, AEs leading to discontinuation, and AEs leading to dose adjustment 
during the on-treatment period will be tabulated.
All on-treatment deaths will be summarized. 
All AEs and SAEs will be listed. 
A subject with multiple AEs within a primary SOC will only be counted once towards the 
total of the primary SOC.

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Clinical laboratory evaluations
Grading of laboratory values will be assigned programmatically as per the CTCAE 
version 4.03. The calculation of CTCAE grades will be based on the observed laboratory 
values only, clinical assessments will not be taken into account. 
CTCAE Grade 0 will be assigned for all non-missing values not graded as 1 or higher.
Grade 5 will not be used. For laboratory tests where grades are not defined by CTCAE 
version 4.03, results will be categorized as low/normal/high based on laboratory normal 
ranges. 
The following summaries will be generated separately for key hematology and biochemistry 
laboratory tests:

shift tables comparing baseline to the worst on-treatment value. Each subject will be 
counted only once for the worst grade observed post-baseline.

for laboratory tests where grades are not defined shift tables using the low/normal/high/ 
(low and high) classification to compare baseline to the worst on-treatment value will be 
used. 
In addition to the above-mentioned tables and listings, other exploratory analyses, for example 
summary tables, figures plotting time course of raw or change in laboratory tests over time or 
box plots might be specified in the Statistical Analysis Plan. Listings will be provided for all 
data.
Other safety evaluations
Data on ECG, vital sign, height, and weight will be summarized descriptively, listed and 
flagged as appropriate. Any significant findings will be documented as AEs and reported as 
such.
12.8
Interim analyses
Not applicable.
12.9
Sample size calculation 
12.9.1
Primary endpoint
A total of 40 subjects will be enrolled in this study i.e., 20 subjects per treatment arm. Based 
on the feedback from dermatologists with experience in prescribing biologic treatments for 
psoriasis (there is no historical data in the literature), the response rates to treatment are 
assumed to be 35% for guselkumab and 75% for secukinumab. 
Table 12-1 presents the 95% exact confidence interval for different P1 (proportion of 
responders in the secukinumab arm) and P2 (proportion of responders in the guselkumab arm) 
and their corresponding difference P1-P2, together with the estimated power of a 1-sided 
Fisher’s exact test at the target 1-sided Type I error rate of 5%. 
For the favorable P1 = 0.75 and P2 = 0.35 values, the Fisher’s exact test at the target Type I 
error of 5% will correctly reject H0: P1-P2 ≤ 0 with the power of 0.72%. 

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Table 12-1
Exact 95% confidence intervals for P1 and P2, the corresponding 
difference P1-P2, and the estimated power of the Fisher’s exact test 
for different P1 and P2 values
Proportion 
(number) of 
responders in 
the 
secukinumab 
arm at 
Week 16:
P1
Proportion 
(number) of 
responders in 
the 
guselkumab 
arm at 
Week 16:
P2
95% exact 
confidence 
interval for 
P1
95% exact 
confidence 
interval for 
P2
95% exact 
confidence 
interval for 
P1-P2
Power of a 
1-sided 
Fisher’s 
exact test: 
H1: 
P1-P2 > 0
0.60 (12)
0.20 (4)
(0.36, 0.80)
(0.05, 0.43)
(0.10, 0.66)
75%
0.65 (13)
0.25 (5)
(0.40, 0.84)
(0.08, 0.49)
(0.06, 0.66)
72%
0.70 (14)
0.30 (6)
(0.45, 0.88)
(0.11, 0.54)
(0.09, 0.64)
71%
0.75 (15)
0.30 (6)
(0.50, 0.91)
(0.11, 0.54)
(0.13, 0.70)
82%
0.75 (15)
0.35 (7)
(0.50, 0.91)
(0.15, 0.59)
(0.06, 0.66)
72%
0.75 (15)
0.40 (8)
(0.50, 0.91)
(0.19, 0.63)
(0.01, 0.62)
61%
0.80 (16)
0.40 (8)
(0.56, 0.94)
(0.19, 0.63)
(0.10, 0.66)
75%
13
Ethical considerations and administrative procedures
13.1
Regulatory and ethical compliance
This clinical study was designed and shall be implemented, executed and reported in 
accordance with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with 
applicable local regulations (including European Directive 2001/20/EC, US CFR 21), and 
with the ethical principles laid down in the Declaration of Helsinki.
13.2
Responsibilities of the Investigator and IRB/IEC
Before initiating a study, the Investigator/institution must obtain approval/favorable opinion 
from the IRB/IEC for the study protocol, written informed consent form, consent form 
updates, subject recruitment procedures (e.g., advertisements) and any other written 
information to be provided to subjects. Prior to study start, the Investigator is required to sign 
a protocol signature page confirming his/her agreement to conduct the study in accordance 
with these documents and all of the instructions and procedures found in this protocol and to 
give access to all relevant data and records to Novartis monitors, auditors, Novartis Quality 
Assurance representatives, designated agents of Novartis, IRBs/IECs, and regulatory 
authorities as required. If an inspection of the clinical site is requested by a regulatory 
authority, the Investigator must inform Novartis immediately that this request has been made.

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13.3
Publication of study protocol and results
The protocol will be registered in a publicly accessible database such as clinicalstudys.gov 
and as required in EudraCT. In addition, after study completion (e.g., defined as last patient 
last visit) and finalization of the study report the results of this study will be submitted for 
publication and posted in a publicly accessible database of clinical study results, such as the 
Novartis clinical study results website and all required Health Authority websites (e.g., 
Clinicalstudys.gov, EudraCT etc.).
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the study
Investigator meetings. 
13.4
Quality control and quality assurance
Novartis maintains a robust Quality Management System that includes all activities involved 
in quality assurance and quality control, to ensure compliance with written Standard 
Operating Procedures as well as applicable global/local GCP regulations and ICH Guidelines.
Audits of Investigator sites, vendors, and Novartis systems are performed by auditors, 
independent from those involved in conducting, monitoring or performing quality control of 
the clinical study. The clinical audit process uses a knowledge/risk based approach.
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal SOPs, and are performed according to written Novartis processes. 
14
Protocol adherence
This protocol defines the study objectives, the study procedures and the data to be collected 
on study participants. Additional assessments required to ensure safety of subjects should be 
administered as deemed necessary on a case by case basis. Under no circumstances including 
incidental collection is an Investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the Investigator shall immediately disclose it to 
Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants.
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
Investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis
and approved by the IRB/IEC and health authorities, where required, it cannot be 
implemented.

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14.1
Protocol amendments
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation.
Only amendments that are required for subject safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified.
Notwithstanding the need for approval of formal protocol amendments, the Investigator is 
expected to take any immediate action required for the safety of any subject included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis 
should be notified of this action and the IRB/IEC at the study site should be informed 
according to local regulations.
15
References
References are available upon request
Appel H, Maier R, Wu P et al (2011) Analysis of IL-17(+) cells in facet joints of patients with
spondyloarthritis suggests that the innate immune pathway might be of greater relevance than 
the Th17-mediated adaptive immune response. Arthritis Res Ther; 13(3):R95 
Bissonnette R, Nigen S, Langley RG et al (2014) Increased expression of IL-17A and limited 
involvement of IL-23 in patients with palmo-plantar (PP) pustular psoriasis or PP pustulosis; 
results from a randomised controlled trial. J Eur Acad Dermatol Venereol; 28(10):1298-305 
Bosteen MH, Tritsaris K, Hansen AJ et al (2014) IL-17A potentiates TNFα-induced secretion 
from human endothelial cells and alters barrier functions controlling neutrophils rights of 
passage. Pflugers Arch; 466(5):961-72 
Chen X, Takai T, Xie Y et al (2013) Human antimicrobial peptide LL-37 modulates 
proinflammatory responses induced by cytokine milieus and double-stranded RNA in human 
keratinocytes. Biochem Biophys Res Commun;433(4):532-7 
Cornelissen F, Asmawidjaja PS, Mus AM et al (2013) IL-23 dependent and independent 
stages of experimental arthritis: no clinical effect of therapeutic IL-23p19 inhibition in 
collagen-induced arthritis. PLoS One;8(2):e57553 
Croes M, Öner FC, van Neerven D et al (2016) Proinflammatory T cells and IL-17 stimulate 
osteoblast differentiation. Bone;84:262-70 
Cua DJ, Tato CM (2010) Innate IL-17-producing cells: the sentinels of the immune system. 
Nat Rev Immunol; 10(7):479-89 
Dixon BR, Radin JN, Piazuelo MB et al (2016) IL-17a and IL-22 Induce Expression of 
Antimicrobials in Gastrointestinal Epithelial Cells and May Contribute to Epithelial Cell 
Defense against Helicobacter pylori. PLoS One; 11(2):e0148514 

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Doherty SD, Van Voohes A, Lebwohl MG et al (2008) National Psoriasis Foundation 
consensus statement on screening for latent tuberculosis infection in patients with psoriasis 
treated with systemic and biologic agents. J Am Acad Dermatol; 59(2): 209-17 
Fabre J, Giustiniani J, Garbar C et al (2016) Targeting the tumor microenvironment: The 
protumor effects of IL-17 related to cancer type. Int. J. Mol. Sci.; 17(9): 1433
 
 
Gottlieb AB, Griffiths CE, Ho VC (2005) Oral pimecrolimus in the treatment of moderate to 
severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding 
trial. Br J Dermatol; 152(6):1219-27 
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inflammation by augmenting T-helper 17 response. J Dermatol; 43(7):785-94 
Hawkes JE, Chan TC, Krueger JG (2017) Psoriasis pathogenesis and the development of 
novel targeted immune therapies. J Allergy Clin Immunol; 140(3):645-53 
Housseau F, Wu S, Wick EC et al (2016) Redundant Innate and Adaptive Sources of IL17 
Production Drive Colon Tumorigenesis. Cancer Res; 76(8):2115-24 
Jack C, Mashiko S, Arbour N et al (2017) Persistence of interleukin (IL)-17A+ T lymphocytes 
and IL-17A expression in treatment-resistant psoriatic plaques despite ustekinumab therapy. 
Br J Dermatol; 177(1):267-270 
Johansen C, Bertelsen T, Ljungberg C et al (2016) Characterization of TNF-α- and 
IL-17A-mediated synergistic induction of DEFB4 gene expression in human keratinocytes
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Keijsers RR, Joosten I, van Erp PE et al (2014) Cellular sources of IL-17 in psoriasis: a 
paradigm shift? Exp Dermatol; 23(11):799-803 
 
Lebwohl M, Iversen L, Eidsmo L et al (2017) Long-term psoriasis control following 
secukinumab discontinuation indicates disease modification of moderate to severe psoriasis: 
clinical and mechanistic results. P1747 at the EADV2017 congress 
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amplified by keratinocyte responses. Trends Immunol;34(4);174-81
Manuel O, Kumar D (2008) QuantiFERON-TB gold assay for the diagnosis of latent 
tuberculosis infection. Expert Rev Mol Diagn; 8(3):247-56 
Mashiko S, Bouguermouh S, Rubio M et al (2015) Human mast cells are major IL-22 
producers in patients with psoriasis and atopic dermatitis. J Allergy Clin Immunol; 136:351–9 

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Murakami M, Hagforsen E, Morhenn V et al (2011) Patients with palmoplantar pustulosis 
have increased IL-17 and IL-22 levels both in the lesion and serum. Exp Dermatol; 
20(10):845-7 
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Immunopathol;39(4):365-383 
Ogura H, Murakami M, Okuyama Y et al (2008) Interleukin-17 promotes autoimmunity by 
triggering a positive-feedback loop via interleukin-6 induction. Immunity; 29(4):628-36 
Patel DD, Lee DM, Kolbinger F et al (2013) Effect of IL-17A blockade with secukinumab in 
autoimmune diseases. Ann Rheum Dis; 72 Suppl 2:ii116-23 
Paulissen SM, van Hamburg JP, Davelaar N et al (2013) Synovial fibroblasts directly induce 
Th17 pathogenicity via the cyclooxygenase/prostaglandin E2 pathway, independent of IL-23. 
J Immunol; 191(3):1364-72 
Reich K, Papp KA, Matheson RT et al (2015) Evidence that a neutrophil-keratinocyte 
crosstalk is an early target of IL-17A inhibition in psoriasis. Exp Dermatol; 24(7):529-35 
Simanski M, Rademacher F, Schröder L et al (2013) IL-17A and IFN-γ synergistically induce 
RNase 7 expression via STAT3 in primary keratinocytes. PLoS One; 8(3):e59531 
Sofen H, Smith S, Matheson RT et al (2014) Guselkumab (an IL-23-specific mAb) 
demonstrates clinical and molecular response in patients with moderate-to-severe psoriasis. J 
Allergy Clin Immunol; 133(4):1032-40 
Tohyama M, Hanakawa Y, Shirakata Y et al (2009) IL-17 and IL-22 mediate IL-20 subfamily 
cytokine production in cultured keratinocytes via increased IL-22 receptor expression. Eur J 
Immunol; 39(10):2779-88 
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skin and blood demonstrates increase of NKp44+ ILC3 in psoriasis. J Invest Dermatol; 
134(4):984-91 
Whelton PK, Carey RM, Aronow WS et al (2017) 
ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the
prevention, detection, evaluation, and management of high blood pressure in adults: a report 
of the American College of Cardiology/American Heart Association Task Force on clinical 
practice guidelines. J Am Coll Cardiol; S0735-1097(17):41519-1 
Yoshiga Y, Goto D, Segawa S et al (2008) Invariant NKT cells produce IL-17 through 
IL-23-dependent and -independent pathways with potential modulation of Th17 response in 
collagen-induced arthritis. Int J Mol Med; 22(3):369-74 

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16
Appendices
16.1
Appendix 1: Clinically notable laboratory values and vital signs
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. Notable values for blood pressure and pulse are presented in Table 8-5. 
Liver function and related variables 
Total bilirubin:
> 2 x upper limit of normal (ULN)
Alkaline phosphatase:
> 2.5 x ULN
Renal function and electrolyte variables
Creatinine (serum):
> 1.5 x ULN
Potassium: 
> 6 mmol/L or < 3 mmol/L
Sodium: 
> 160 mmol/L or < 115 mmol/L
Urinalysis variable 
Protein urine dipstick: 
2+ (100 mg/dL) 
Hematology variables 
Hemoglobin:
≥ 20 g/L decrease from Baseline 
Platelet count:
< lower limit of normal (LLN)
White blood cell count:
< 0.8 x LLN
Neutrophils:
< 0.9 x LLN
Eosinophils:
> 1.1 x ULN
Lymphocytes:
> 1.1 x ULN

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16.2
Appendix 2
16.2.1
Skin type classification scale