A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Explore Changes in Subcutaneous Adipose Tissue and Modulation of Skin Inflammation After 12 Weeks of Treatment With Secukinumab, Compared to Placebo, and up to 52 Weeks of Treatment With Secukinumab in Adult Patients With Moderate to Severe Plaque Psoriasis
Phase: PHASE4
Conditions: Plaque Psoriasis
Sponsor: Novartis Pharmaceuticals

US Clinical Development and Medical Affairs - General Medicine 
AIN457/Secukinumab
Clinical Trial Protocol CAIN457AUS07 / NCT03055494
A randomized, double-blind, placebo-controlled, parallel-
group, multicenter study to explore changes in
subcutaneous adipose tissue and modulation of skin 
inflammation after 12 weeks of treatment with secukinumab, 
compared to placebo, and up to 52 weeks of treatment with 
secukinumab in adult patients with moderate to severe 
plaque psoriasis (ObePso-S)
Document type:
Amended Protocol Version
Version number:
v02 (Clean)
Clinical trial phase:
IV
Release date:
23-Feb-2018
Property of Novartis
Confidential
May not be used, divulged, published, or otherwise disclosed
without the consent of Novartis
Clinical Trial Protocol Template Version 3.2 (July 2016)

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Table of contents
Table of contents .................................................................................................................2
List of tables ........................................................................................................................5
List of figures ......................................................................................................................6
List of abbreviations............................................................................................................7
Glossary of terms.................................................................................................................9
Amendment 2 ....................................................................................................................10
Protocol summary..............................................................................................................11
1
Introduction .......................................................................................................................15
1.1
Background............................................................................................................15
1.2
Purpose ..................................................................................................................16
2
Study objectives and endpoints .........................................................................................17
2.1
Objectives and related endpoints...........................................................................17
3
Investigational plan ...........................................................................................................18
3.1
Study design...........................................................................................................18
3.1.1
Screening period (Screening to randomization)....................................19
3.1.2
Double-blind treatment period (Randomization to Week 12 pre-
dose)......................................................................................................19
3.1.3
Double-blind induction period (Week 12 dose through Week 15 
dose)......................................................................................................20
3.1.4
Open-label treatment period (Week 16 to Week 52) ............................20
3.1.5
Follow-up period visit 1 (F1)................................................................20
3.1.6
Control cohort of healthy volunteers sub-study....................................21
3.2
Rationale for study design .....................................................................................22
3.3
Rationale for dose/regimen, route of administration and duration of treatment....22
3.4
Rationale for choice of comparator .......................................................................22
3.5
Purpose and timing of interim analyses/design adaptations..................................23
3.6
Risks and benefits..................................................................................................23
3.6.1
Clinical trials experience in plaque psoriasis........................................23
3.6.2
Infections...............................................................................................25
3.6.3
Pre-treatment evaluation for tuberculosis .............................................26
3.6.4
Inflammatory bowel disease .................................................................26
3.6.5
Hypersensitivity reactions.....................................................................26
3.6.6
Risk of hypersensitivity in latex-sensitive Individuals .........................26
3.6.7
Vaccinations..........................................................................................26
4
Population..........................................................................................................................26

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4.1
Inclusion criteria ....................................................................................................27
4.2
Exclusion criteria...................................................................................................27
5
Treatment...........................................................................................................................29
5.1
Study treatment......................................................................................................29
5.1.1
Study drug – secukinumab....................................................................30
5.1.2
Control drug – placebo..........................................................................30
5.1.3
Additional treatment..............................................................................30
5.2
Treatment groups...................................................................................................30
5.3
Treatment assignment and randomization.............................................................31
5.3.1
Stratification..........................................................................................31
5.4
Treatment blinding.................................................................................................32
5.5
Treating the patient................................................................................................32
5.5.1
Patient numbering .................................................................................32
5.5.2
Dispensing the study drug.....................................................................33
5.5.3
Handling of study and additional treatment..........................................33
5.5.4
Instructions for prescribing and taking study treatment........................34
5.5.5
Permitted dose adjustments and interruptions of study treatment ........35
5.5.6
Rescue medication ................................................................................35
5.5.7
Concomitant treatment..........................................................................35
5.5.8
Prohibited medication ...........................................................................35
5.5.9
Emergency breaking of assigned treatment code..................................37
5.6
Study completion and discontinuation...................................................................37
5.6.1
Study completion and post-study treatment..........................................37
5.6.2
Discontinuation of study treatment .......................................................37
5.6.3
Withdrawal of informed consent...........................................................39
5.6.4
Loss to follow-up ..................................................................................39
5.6.5
Early study termination by the sponsor.................................................39
6
Visit schedule and assessments .........................................................................................40
6.1
Rescreening............................................................................................................40
6.2
Unscheduled visits.................................................................................................40
6.3
Information to be collected on screening failures..................................................46
6.4
Patient demographics/other baseline characteristics .............................................46
6.4.1
Demographics .......................................................................................46
6.4.2
Psoriasis history / Prior psoriasis therapies...........................................46
6.4.3
Smoking history ....................................................................................46
6.4.4
Alcohol use history ...............................................................................46

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6.4.5
Comorbidities – cardiovascular history ................................................47
6.4.6
Relevant medical history/current medical conditions...........................47
6.4.7
Prior and concomitant medications.......................................................47
6.4.8
Determination of tuberculosis status.....................................................47
6.4.9
Other baseline characteristics................................................................48
6.5
Treatment exposure and compliance .....................................................................48
6.6
Efficacy..................................................................................................................49
49
 
50
50
51
6.6.5
Assessment of total Body Surface Area (BSA) and Psoriasis Area 
and Severity Index (PASI) ....................................................................52
6.6.6
Appropriateness of efficacy assessments..............................................54
6.7
Safety.....................................................................................................................54
6.7.1
Physical examination ............................................................................54
6.7.2
Vital signs..............................................................................................55
6.7.3
Height and weight and waist circumference .........................................55
6.7.4
Laboratory evaluations..........................................................................55
6.7.5
Pregnancy and assessments of fertility .................................................57
6.7.6
Appropriateness of safety measurements..............................................57
6.8
Other assessments..................................................................................................57
7
Safety monitoring..............................................................................................................57
7.1
Adverse events.......................................................................................................57
7.2
Serious adverse events...........................................................................................59
7.2.1
Definition of SAE .................................................................................59
7.2.2
SAE reporting........................................................................................60
7.3
Reporting of study treatment errors including misuse/abuse ................................60
7.4
Pregnancy reporting...............................................................................................61
8
Data review and database management.............................................................................61
8.1
Site monitoring ......................................................................................................61
8.2
Data collection.......................................................................................................62
8.3
Database management and quality control............................................................62
8.4
Data Monitoring Committee..................................................................................63
8.5
Adjudication Committee........................................................................................63
9
Data analysis......................................................................................................................63

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9.1
Analysis sets ..........................................................................................................64
9.2
Patient demographics and other baseline characteristics.......................................64
9.3
Treatments .............................................................................................................64
9.4
Analysis of the primary variable(s) .......................................................................64
9.4.1
Variable(s).............................................................................................64
9.4.2
Statistical model, hypothesis, and method of analysis..........................64
9.4.3
Handling of missing values/censoring/discontinuations.......................65
9.4.4
Sensitivity analyses ...............................................................................65
9.5
Analysis of secondary variables ............................................................................65
9.5.1
Efficacy variables..................................................................................65
9.5.2
Safety variables .....................................................................................65
66
9.7
Interim analyses.....................................................................................................66
9.8
Sample size calculation..........................................................................................67
10 Ethical considerations........................................................................................................67
10.1
Regulatory and ethical compliance........................................................................67
10.2
Informed consent procedures.................................................................................67
10.3
Responsibilities of the investigator and IRB/IEC..................................................68
10.4
Publication of study protocol and results...............................................................68
10.5
Quality Control and Quality Assurance.................................................................68
11 Protocol adherence ............................................................................................................68
11.1
Protocol amendments.............................................................................................69
12 References .........................................................................................................................69
13 Appendix 1: Clinically notable laboratory values and vital signs.....................................73
14 Appendix 2: Tuberculosis screening flowchart.................................................................74
75
16 Appendix 4:  Psoriasis Area and Severity Index (PASI) and Body Surface Area 
(BSA).................................................................................................................................78
17 Appendix 5:  Sample Log Table........................................................................................79
List of tables
Table 2-1
Objectives and related endpoints ..........................................................17
Table 3-1
Clinical outcomes at Week 12 in adults with plaque psoriasis in 
Trials 1- 4 ..............................................................................................25
Table 5-1
Overview of study treatment.................................................................31
Table 5-2
Prohibited treatment..............................................................................36

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Table 6-1
Assessment schedule.............................................................................41
Table 6-2
Assessment schedule for healthy control cohort...................................45
51
Table 6-4
PASI scoring system .............................................................................52
Table 7-1 
Guidance for capturing the study treatment errors including 
misuse/abuse .........................................................................................61
Table 9-1
Sample size calculations for percentage of patients who have the 
“event”...................................................................................................67
List of figures
Figure 3-1
Study design..........................................................................................19

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List of abbreviations
AE
Adverse Event
ALT
Alanine aminotransferase
AST
Aspartate aminotransferase
BMI
Body Mass Index
CD
Cluster of differentiation
CDER
Center for Drug Evaluation and Research
CFR
US Code of Federal Regulations 
CHMP
Committee for Medicinal Products for Human Use
(e)CRF
(electronic) Case Report/Record Form
CRO
Contract Research Organization
CS
Corticosteroids
CSR
Clinical Study Report
CT
Computerized tomography
CTRD 
Clinical Trial Results Database 
CVD
Cardiovascular disease
DS&E
Drug Safety & Epidemiology
DSM
Drug Supply Management
EDC
Electronic Data Capture
EMA
European Medicines Agency
EOT
End of treatment
EU
European Union
FACS
Fluorescence-activated cell sorting
FDA
(US) Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma glutamyl transpeptidatse
Hb
Hemoglobin
HIV
Human immunodeficiency virus
hs-CRP
high sensitivity C-reactive protein
HOMA-IR
Homeostatic model assessment-insulin resistance
IB
Investigator’s Brochure
ICAM
Intercellular adhesion molecule
ICH
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IFU
Instructions for Use
IGA mod 2011
Investigator’s Global Assessment modified 2011
IL
Interleukin
IUD
Intrauterine device
i.v.
Intravenous
IRB
Institutional Review Board
IRT
Interactive Response Technology
LS
Lesional

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MedDRA
Medical dictionary for regulatory activities 
MRI
Magnetic resonance imaging
MTX
Methotrexate
OTC
Over-the-counter
PASI
Psoriasis Area and Severity Index
PC
Personal Computer
PET
Positron Emission Tomography
PMDA
Pharmaceuticals and Medical Devices Agency
PPD
Purified protein derivative
PUVA
Psoralen ultraviolet A
OC/RDC
Oracle Clinical/Remote Data Capture
PET
Positron emission tomography
PFS
Pre-filled syringe
RT-PCR
Reverse transcription - polymerase chain reaction
SAE
Serious Adverse Event
s.c.
Subcutaneous
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic pyruvate transaminase
SOP
Standard Operating Procedure
SUSAR
Suspected Unexpected Serious Adverse Reactions
TB
Tuberculosis
TCS
Topical corticosteroids
TD
Study Treatment Discontinuation
TH17
T-helper 17 (cells)
TNF
Tumor necrosis factor
UV
Ultraviolet
UVA
Ultraviolet A
UVB
Ultraviolet B
VCAM
Vascular cell adhesion molecule
WHO
World Health Organization 
WoC
Withdrawal of Consent

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Glossary of terms
Control drug
Drugs(s) 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 patient in a time unit (e.g. 100 mg 
once a day, 75 mg twice a day)
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.
Enrollment
Point/time of patient entry into the study at which informed consent must 
be obtained (e.g. prior to starting any of the procedures described in the 
protocol)
Investigational drug
The drug whose properties are being tested in the study; this definition is 
consistent with US CFR 21 Section 312.3 and is synonymous with 
“investigational new drug” or “investigational medicinal product.”
Medication number
A unique identifier on the label of each investigational drug package
Part 
A single component of a study which contains different objectives or 
populations within that single study. Common parts within a study are: a 
single dose part and a multiple dose part, or a part in patients/subjects with 
established disease and in those with newly-diagnosed disease.
Patient ID 
A unique number assigned to each patient upon signing the informed 
consent 
Period
A portion of the study which serves a specific purpose. Typical epochs are: 
screening/recruitment, wash-out, treatment, and follow-up
Randomization number
A unique identifier assigned to each randomized patient, corresponding to 
a specific treatment arm assignment
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.
Study drug/treatment
Any single drug or combination of drugs administered to the patient as part 
of the required study procedures; includes investigational drug (s), 
placebo/comparator active drug run-ins or background therapy
Variable
A measured value or assessed response that is determined in specific 
assessments and used in data analysis to evaluate the drug being tested 
in the study
Withdrawal of consent 
(WoC)
Withdrawal of consent from the study is defined as when a patient does 
not want to participate in the study any longer, and does not want any 
further visits or assessments, and does not want any further study related 
contact, and does not allow analysis of already obtained biologic material

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Amendment 2
Amendment rationale
The primary purpose of this amendment is to allow for the enrollment of healthy volunteers at 
 to act as a control cohort for the purpose of comparing skin, 
adipose tissue, 
 data/outcomes to the psoriasis patients enrolled in the 
study.  
Additionally, text related to eSource was deleted as it was not used in this study.
At the time of this amendment, all psoriasis patients have been enrolled in the study.
Changes to the protocol

List of abbreviations and Glossary of terms was updated to remove eSource

Section 3.1.6 was added for the control cohort of healthy volunteers

Table 6-2 Assessment schedule for healthy control cohort was added

Section 8 and Section 8.1 were updated to remove reference to eSource

Section 8.2 was updated to clarify that the data collection process is the same for the 
control cohort of healthy volunteers as for the psoriasis patients

Section 9.6 was updated to clarify responsibility for certain data analyses and to specify 
where those analyses will be reported 
Changes to specific sections of the protocol are shown in the track change version of the 
protocol using strike through red font for deletions and red underlined for insertions.
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.

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Protocol summary
Protocol 
number
CAIN457AUS07
Full Title
A randomized, double-blind, placebo-controlled, parallel-group, multicenter study to 
explore changes in subcutaneous adipose tissue and modulation of skin 
inflammation after 12 weeks of treatment with secukinumab, compared to placebo, 
and up to 52 weeks of treatment with secukinumab in adult patients with moderate to 
severe plaque psoriasis (ObePso-S)
Brief title
Study to explore the effect of secukinumab, compared to placebo, on fat tissue and 
skin in plaque psoriasis patients
Sponsor and 
Clinical 
Phase
Novartis Pharmaceuticals Corporation
Phase 4
Investigation 
type
Drug
Study type
Interventional
Purpose and 
rationale
Secukinumab targets interleukin 17a (IL-17a) which may play a critical role in the 
pathophysiology of psoriasis.  IL-17 is not established as a factor in excess adiposity, 
however reports suggest that obesity may be a driver for the formation of TH17 T-
cells. This study will provide a comparison of secukinumab to placebo with respect to 
skin inflammation as measured by skin exams in comparison to skin biopsies, 
adipose tissue and blood sample analyses.
Primary 
Objective(s) 
The primary objective of this study is to explore the modulation of subcutaneous 
adipose tissue and skin inflammation from baseline to Week 12 in patients with 
moderate to severe plaque psoriasis treated with secukinumab compared to placebo
Secondary 
Objectives

To explore changes in biometric measurements from baseline to Week 12 in 
patients with moderate to severe plaque psoriasis treated with secukinumab 
compared to placebo

To explore the modulation of subcutaneous adipose tissue and skin inflammation 
from baseline to Week 52 in patients with moderate to severe plaque psoriasis 
treated with secukinumab
Study design
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter 
study in approximately 75 patients with moderate to severe chronic plaque psoriasis.  

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The patients will be enrolled from approximately 15 sites within the United States.
The study consists five of periods: screening (from 1-4 weeks); a double-blind 
treatment period (12 weeks); a double-blind induction period (4 weeks); an open-
label treatment period (36 weeks); and a follow-up period (1 week).  The total study 
duration is up to 57 weeks.
At the start of the double-blind treatment period, patients are randomized in a 2:1 
ratio to one of two treatment groups – secukinumab or placebo. Randomization will 
be stratified by baseline body weight (<90 kg or ≥90 kg). At the end of the double-
blind treatment period, all patients randomized to receive placebo will be switched to 
secukinumab treatment for the remainder of the study.
Lesional (LS) 
 
will be obtained via 6 mm punch biopsy from all 
patients at three time points:  Baseline, Week 12, and Week 52.
Population
The study population will consist of approximately 75 male and female patients at 
least 18 years of age with moderate to severe plaque psoriasis who are candidates 
for systemic therapy or phototherapy.
Key Inclusion 
criteria
1.
Written informed consent must be obtained before any assessment is performed
2.
Males and females ≥18 years of age at the time of screening
3.
Clinical diagnosis of chronic plaque-type psoriasis at least 6 months prior to 
randomization as determined by patient interview of his/her medical history and 
by confirmation of diagnosis through physical examination by the investigator
4.
Moderate to severe plaque psoriasis as defined at baseline by:
o
≥10% Body Surface Area (BSA) involvement and
o
PASI total score of ≥12 and
o
IGA mod 2011 score of ≥3 (based on a scale of 0-4)
5.
Candidate for systemic therapy, defined as having psoriasis inadequately 
controlled by:
o
Topical treatment (including topical corticosteroids) and/or
o
Phototherapy and/or
o
Previous systemic therapy
Key 
Exclusion 
criteria

Forms of psoriasis other than chronic plaque psoriasis

Medication-induced or medication exacerbated psoriasis

Previous exposure to secukinumab or any other biologic drug directly targeting 
IL-17A or IL-17RA receptors

Diagnosis of other active ongoing skin diseases or skin infections (bacterial, 
fungal, or viral), or inflammatory diseases other than psoriasis that may interfere 
with the evaluation of psoriasis

History of an ongoing, chronic or recurrent infectious disease, or evidence of 
tuberculosis infection

Positive serology for human immunodeficiency virus (HIV), hepatitis B or C 
infection

Pregnant or nursing (lactating) women 

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Study 
treatment
Study drug:

Secukinumab 150 mg: 1 ml liquid  formulation in a single-use prefilled 
syringe (PFS) for subcutaneous injection
Control drug:

Placebo to secukinumab 150 mg: 1 ml liquid formulation in a single-use 
prefilled syringe (PFS) for subcutaneous injection
Efficacy 
assessments

Modulation of subcutaneous adipose tissue and skin inflammation
 

PASI: Psoriasis Area and Severity Index
Key safety 
assessments

Adverse events and serious adverse events

Laboratory assessments (e.g., hematology, clinical chemistry, hs-CRP, HbA1c, 
HOMA-IR, viral serology, serum and urine pregnancy)

Vital signs, weight, waist circumference, BMI, physical examination
Data analysis
A designated Contract Research Organization will perform the statistical analysis.
It is planned that the data from all centers that participate in this protocol will be 
combined, so that an adequate number of patients will be available for analysis.
The analysis will be conducted on all patient data at the end of Week 12, and at the 
time the trial ends at Week 53.
The following analysis sets will be used for the statistical reporting and analyses:
Randomized Set: The Randomized Set includes all randomized patients.  
Safety Set: The Safety Set includes all patients who received at least one dose of 
study medication.  Patients will be included in the analysis according to treatment 
received.
Full Analysis Set:  The Full Analysis Set comprises all patients to whom study 
medication has been assigned.  Patients inappropriately randomized (e.g., IRT was 
called in error for randomization of a screen failed patient) will be excluded from this 
analysis set.
Data will be summarized by stratum with respect to demographic and baseline 
characteristics of all patients for the Randomized Set and the Full Analysis Set.
Concomitant medications will be summarized by treatment using frequency counts 
and percentages for the Safety Set.
Efficacy, safety, and other data will be summarized for all weeks up to Week 53.
Response of psoriasis skin lesions to treatment as measured by:
a.
Response in skin histology/K16 expression to treatment  (yes, no)
b.
PASI 90 (yes, no)
The primary analysis time point will be at Week 12.
For the two primary efficacy variables at each time point (response in skin 
histology/K16 expression to treatment at Week 12, PASI 90 at Weeks 4, 8, and 12), 
95% confidence intervals for the difference between the two treatment groups with 

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respect to the percentage of patients who have the “event” will be calculated using 
the normal approximation to the binomial distribution.
For the two primary efficacy variables at Week 12 (and other time points), a patient
with a missing assessment will be considered as a non-responder.
The analysis of the primary efficacy variables will be based on the Full Analysis Set.
Cross-classification tables of response in skin histology/K16 expression to treatment 
(yes, no) 
 
 
  In addition, to assess the association 
between skin histology/K16 expression results 
, a logistic regression 
analysis will be performed and the odds ratio and 95% confidence interval for the 
odds ratio based on the fitted model will be reported.  The model will include 
response in skin histology/K16 expression as the response variable and treatment, 
body weight (<90 kg, ≥90 kg), 
. 
 
 
The assessment of safety will be based mainly on the frequency of adverse events 
and laboratory data.  Other safety data, including vital signs (weight, blood pressure, 
waist circumference, BMI), and clinical laboratory variables (glucose, insulin, hs-
CRP, HOMA-IR, HbA1c) will be summarized by stratum, as appropriate.
Analysis of safety data will be based on the Safety Set.
The table below considers total sample sizes of 75 patients (50 in secukinumab 
group and 25 in placebo group) and 99 patients (66 in secukinumab group and 33 in 
placebo group) to estimate the difference between the two groups with respect to the 
pooled estimate of the two percentages of patients who have the “event” at Week 12 
for each of the two primary efficacy variables.  The entries in the table are the 
“margin of error” (half-width of confidence interval) for a two-sided 95% confidence 
interval (Julious and Patterson, 2004; Kianifard and Islam, 2011; nQuery Advisor 
7.0).
Percentage with 
“event”
Half-width of 
confidence interval for 
n = 75
Half-width of 
confidence interval 
for n = 99
30%
25.0%
21.4%
40%
26.5%
22.7%
50%
27.0%
23.2%
60%
26.5%
22.7%
70%
25.0%
21.4%
Based on the results in the above table, it was decided that approximately 75 
randomized patients (50 in secukinumab group and 25 in placebo group) will be 
randomized in this 
 study to estimate the difference in response rates 
between the two treatment groups.
Key words
Plaque psoriasis, secukinumab, biologic, monoclonal antibody, adipose tissue, skin 
inflammation

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1
Introduction
1.1
Background
Psoriasis vulgaris is best conceptualized as a disease of focal cutaneous inflammation, but 
with associated systemic inflammation that likely results from effects of circulating cytokines 
and other inflammatory molecules that are produced at excess levels in skin lesions and 
diffuse into the circulation.  IL-17 and tumor necrosis factor (TNF) are consistently increased 
in plasma of untreated patients with moderate-to-severe psoriasis and these are decreased 
following skin improvements with a number of biologic treatments, e.g., IL-23 inhibitors or 
TNF inhibitors (Chiricozzi et al 2011).
Consequences of cytokine-driven system inflammation include: 1) activation of a set of genes 
and proteins in circulating leukocytes that increase inflammatory potential and would enable 
migration into various tissues according to chemokine gradients that may be set up; 2) 
vascular inflammation associated with large vessels as demonstrated by PET-CT imaging in 
past studies; 3) an increase in cardiovascular disease (CVD) risk; 4) inflammation in adipose 
tissue with the consequence of increased resistance to insulin signaling and metabolic 
syndrome or diabetes; and 5) inflammation in other tissues such as the gut or joints that may 
drive increased incidence of inflammatory bowel disease or psoriatic arthritis, respectively 
(Davidovici et al 2010).
Psoriasis is also associated with overt obesity in a large fraction of patients.  While IL-17 is 
not established as a factor in the formation of excess adiposity, there are reports that suggest 
obesity may be a driver for the formation of Th17 T-cells (Endo et al 2015; Luczyński et al 
2015; Reis et al 2015).  Additionally, treatment of patients with TNF antagonists can lead to 
significant weight gain, a finding that worsens the obesity problem and which mechanistically 
makes sense with inhibition of TNF signaling (Tan et al 2013; Renzo et al 2011; Gisondi et al 
2008; Saraceno et al 2008).
Therapeutic agents with different mechanisms, e.g., secukinumab, would not be expected to 
produce this negative effect of weight gain. The metabolic and inflammatory effects of IL-17 
signaling in adipose tissue are not well understood at present, but use of a directed IL-17 
antagonist has the potential to define the physiological effects of excess IL-17 signaling in this 
tissue compartment. Thus this study has the potential to establish non-negative effects (i.e., no 
weight gain) of secukinumab on adiposity, as well as pro-health consequences of blocking IL-
17 in psoriasis patients.
The present study has the dual goals of examining anti-inflammatory effects of secukinumab 
on two “systemic” tissues that lead to co-morbidity:  the vascular compartment and 
subcutaneous adipose tissue.  In both cases, treatment benefits would be related to reductions 
in inflammation in psoriasis vulgaris skin lesions.  Elements of the vascular compartment that 
affect cardiovascular disease that will be studied include endothelial cells (via microparticles), 
circulating 
leukocytes 
(via 
microparticle 
and 
full 
cell 
analysis), 
and 
inflammatory/cardiovascular risk proteins in blood plasma (Ho et al 2016).  Elements of the 
adipose tissue response include the study of overall adiposity (e.g., weight, BMI).

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Ongoing studies are using PET-CT or PET-MRI to visualize inflammation in large vessels 
during secukinumab treatment, but this imaging is based on metabolic activity of 
macrophages that are resident within the sub-endothelial space of large vessels and 
macrophage infiltration of any tissue may be relatively fixed and non-reversible, even with 
strong anti-inflammatory treatments (Mehta et al 2011; Naik et al 2015).  Researchers at 
 have found that aortic endothelial cells respond to the combination of 
TNF and IL-17 by synthesis of fractalkine, which is a chemotactic chemokine for 
“inflammatory’ 
macrophages 
that 
are 
associated 
with 
atherosclerosis 
formation.  
Macrophages with this phenotype have been identified in blood of psoriasis patients.  The 
effects of high levels of IL-17, TNF, and leukocyte trafficking across aortic endothelium will 
set-up increased microparticles (apoptotic bodies) derived from these endothelial cells in the 
blood.  A beneficial effect of IL-17 blockade on aortic inflammation can thus be measured by 
quantification of endothelial cell derived microparticles as well as expression of cytokine-
induced proteins, e.g., adhesion molecules such as ICAM-1 and VCAM, in these particles 
using flow-cytometry with appropriate antibodies to quantify levels of protein expression.
In a recent study of IL-17 inhibition with ixekizumab, researchers at 
 
were able to demonstrate that a set of IL-17 induced adhesion molecules on blood monocytes 
were reduced at the level of gene expression within two weeks of starting this antibody (Wang 
et al 2014).  The current proposal would extend this analysis to include measuring expression 
of cognate surface proteins on circulating leukocytes, including inflammatory macrophages, 
and the integration of this data with expression of cytokine-induced proteins on microparticles 
derived from endothelial cells and leukocytes.
Finally, a recent study has found that there was increased expression of IL-17 signaling
pathways in non-lesional skin of psoriasis patients (Chiricozzi et al 2016).  As a feature of this 
protocol, we would correlate anti-inflammatory effects of secukinumab in “internal” sites of 
endothelium, blood leukocytes, 
 after treatment to 
test this hypothesis.  If the concept is validated, it could have tremendous benefit for the 
design of future studies designed to prove “distant” effects of inflammatory cytokines in 
psoriasis patients on peripheral tissues.
1.2
Purpose 
Obesity has been linked to poorer long-term outcome in patients with psoriasis, with some 
evidence that weight loss may improve psoriasis (Higa-Sansone et al 2004; Naldi et al 2005; 
Wolters 2005).  In addition, one recent study showed that moderate weight loss may 
supplement pharmacologic treatment (Giscondi et al 2008).  However, what is unclear is if 
inflammatory cytokines upregulated in psoriasis patients by the TH-17 pathway are also 
contributing to the production of adipose tissue in these patients, and thereby also affecting 
the mechanism of insulin resistance.  These factors may contribute to the higher association of 
complications from insulin resistance such as dyslipidemia, hypertension, and premature heart 
disease in psoriasis patients.  Patients with moderate to severe psoriasis who undergo anti-IL-
17A treatment with secukinumab that improves the skin manifestations of psoriasis but its 
effect on adipose tissue are also of intense clinical and scientific interest.

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The purpose of this study is to explore changes in subcutaneous adipose tissue and skin 
inflammation in patients with moderate to severe plaque psoriasis treated with secukinumab 
300 mg compared to placebo at Week 12.
2
Study objectives and endpoints
2.1
Objectives and related endpoints
Table 2-1
Objectives and related endpoints
Objective(s)
Endpoint(s)
Primary Objective(s)

To explore the modulation of 
subcutaneous adipose tissue and skin 
inflammation from baseline to Week 12 
in patients with moderate to severe 
plaque psoriasis treated with 
secukinumab compared to placebo
Endpoint(s) for primary objective(s)

Response of psoriasis skin lesions to 
treatment as measured by:
a.
Response in skin histology/K16 
expression to treatment (yes, no)
b. PASI 90 (yes, no)
Secondary Objective(s)

To explore changes in biometric 
measurements from baseline to Week 12 
in patients with moderate to severe 
plaque psoriasis treated with 
secukinumab compared to placebo
Endpoint(s) for secondary objective(s)

Vital signs (blood pressure, weight, 
waist circumference, BMI), clinical 
laboratory variables (glucose, insulin, 
hs-CRP, HOMA-IR, HbA1c)

To explore the modulation of 
subcutaneous adipose tissue and skin 
inflammation from baseline to Week 52 
in patients with moderate to severe 
plaque psoriasis treated with 
secukinumab

Response of psoriasis skin lesions to 
treatment as measured by:
a.
Response in skin histology/K16 
expression to treatment (yes, no)
b. PASI 90 (yes, no)

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3
Investigational plan
3.1
Study design
This study uses a randomized, double-blind, placebo-controlled, parallel-group, multicenter 
design.  Approximately 75 moderate to severe plaque psoriasis patients from approximately 
15 sites will be randomized at Visit 2/Baseline in a 2:1 ratio to receive secukinumab 300 mg 
or placebo, respectively.  Randomization will be stratified by body weight collected at Visit 2 
(< 90 kg or ≥90 kg).
The study consists of five periods:

Screening (from 1-4 weeks);

Double-blind Treatment Period (12 weeks);

Double-blind Induction Period (4 weeks); 

Open-label Treatment Period (36 weeks); and

Follow-up Period (1 week).
A schematic of the study design is presented in Figure 3-1, while a detailed visit and 
assessment schedule can be found in Table 6-1.  An interim analysis is planned after Week 
12, which is the primary analysis time point for the study.

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Figure 3-1
Study design
3.1.1
Screening period (Screening to randomization)
The duration of the screening period will be up to four weeks.  Screening will be used to 
assess patient eligibility and to taper patients off prohibited medications and treatments.
3.1.2
Double-blind treatment period (Randomization to Week 12 pre-dose)
At the start of the Double-blind Treatment Period, eligible patients will be randomized 
via Interactive Response Technology (IRT) in a 2:1 ratio to one of two treatment arms
(secukinumab 300 mg or placebo).  Randomization will be stratified by body weight collected 
at Visit 2 (< 90 kg or ≥90 kg).
During this period, all patients will attend study visits at Baseline, Weeks 1, 2, 3, 4, 8 and 12, 
and all doses of study treatment will be self-administered at the study site.
 
Assessments for the primary efficacy variable will be performed at Week 12 prior to patients 
receiving their Week 12 dose.
All patients who discontinue from the study prematurely for any reason before the end of
the Double-blind Treatment Period should return to the study site for the performance of the 
Visit 8/Week 12 End of Treatment (EOT1) assessments. This visit should be scheduled 
approximately four weeks after the last dose of study treatment.

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3.1.3
Double-blind induction period (Week 12 dose through Week 15 dose)
All patients who complete the Double-blind Treatment Period will enter the Double-blind 
Induction Period.  The Double-blind Induction Period is defined as the Week 12 dose through 
the Week 15 dose.
During this period, patients randomized to receive placebo at Visit 2/Baseline will be 
switched over to treatment with secukinumab 300 mg weekly for four weeks at Weeks 12, 13, 
14, and 15.
Patients who were randomized to the secukinumab treatment group at Visit 2/Baseline will 
continue to self-administer secukinumab 300 mg at the Week 12 visit. In order to maintain 
the blind for the 12-week, placebo-controlled period, these patients will self-administer 
placebo injections at Weeks 13, 14, and 15.
Self-administration of the Weeks 12 and 13 doses will take place at the study site, while the 
doses at Weeks 14 and 15 will be self-administered at home.
All patients who discontinue from the study prematurely for any reason before the end of 
Double-blind Induction Period should return to the study site for the performance of the Visit 
15/Week 52 End of Treatment (EOT2) assessments.  This visit should be scheduled 
approximately four weeks after the last dose of study treatment.
3.1.4
Open-label treatment period (Week 16 to Week 52)
All patients who complete the Double-blind Induction Period will enter the Open-label 
Treatment Period.  The Open-label Treatment Period is defined as Week 16 through Week 52. 
All patients in this period will receive secukinumab 300 mg s.c. at four-week intervals 
beginning at Week 16 through Week 48 (last dose during the Open-Label Treatment Period).
Self-administration of the doses at Weeks 16, 24, 32, 40, and 48 will take place at the study 
site; the doses at Weeks 20, 28, 36, and 44 will be self-administered at home.
All patients who discontinue from the study prematurely for any reason before the end of the 
Open-label Treatment Period should return to the study site for the performance of the Visit 
15/Week 52 (EOT2) assessments. This visit should be scheduled approximately four weeks 
after the last dose of study treatment. 
3.1.5
Follow-up period visit 1 (F1)
All patients who undergo skin biopsies at Visit 15/Week 52 will return to the site 
approximately seven days later for Follow-up Visit 1 (F1) for suture removal and safety check.
Additionally, all patients who discontinue prematurely from the study and who undergo skin 
biopsies at their end of treatment visit (either Visit 8/Week 12 EOT1 or Visit 15/Week 52 
EOT2) will return to the site approximately seven days later for Follow-up Visit 1 (F1) for 
suture removal and safety check.

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3.1.6 Control cohort of healthy volunteers sub-study
Healthy volunteers will be enrolled at a single site (
) to act as a 
control cohort for the purpose of comparing skin, adipose tissue, 
 
data/outcomes to the psoriasis patients enrolled in the study.  Approximately 20 subjects
without plaque psoriasis will be enrolled into the control cohort.  These healthy volunteers 
will not receive study treatment.
Once all psoriasis patients have been randomized into the study, a listing of the requisite 
demographic and baseline characteristics (age, gender, weight, BMI) for the psoriasis study 
patients will be generated by Novartis from the clinical database and provided to The 
 through an appropriate secure channel.  This data is necessary for 
matched healthy volunteers to be recruited into the control cohort. 
The control cohort will be enrolled while the 52-week treatment period for the psoriasis 
patients is ongoing; it is planned that the sample from the last healthy volunteer will be 
collected by the time the last psoriasis subject completes Week 52/EOT visit.  
After signing informed consent, subjects in the control cohort will complete the assessments
(including safety assessments) as indicated in Table 6-2.  Visit 1 assessments may or may not 
occur on the same day.
During Visit 1, demographic and baseline characteristic data will be collected.  
 
 
  
 
 Subjects will return to the site approximately 7 
days following the Visit 1 biopsy for suture removal and safety check.
The analyses for the control cohort will be done in parallel with the psoriasis study patients, 
such that when the Week 52 data from the psoriasis patients is analyzed, the control data from 
the healthy volunteers will be available for comparison.
The control data and the psoriasis baseline and treatment data are best analyzed in a single 
batch and with a statistical model (a mixed effects model) that will consider group (control vs. 
disease), as well as treatment effects. The control data are needed to establish which baseline 
values of skin, fat, or blood measures are abnormal as a function of disease at baseline. This 
then provides the ability to determine if treatment with secukinumab normalizes baseline 
values or has effects to change inflammation that go beyond baseline disease 
characteristics. Without the control group, only a “drug effect” on the disease parameters 
could be computed without knowing whether what is modulated is part of pathogenic 
inflammation.
Inclusion criteria
Subjects in the control cohort will be judged by the investigator to be generally healthy, and 
will be generally matched to the age, gender, race, and weight/BMI composition of 
thepsoriasis study patients.  

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Exclusion criteria
Subjects fulfilling any of the following criteria are not eligible to enroll into the control cohort:

Current use of immunosuppressive medications;

Current use of anti-coagulant medications;

Use of any investigational treatment within 4 weeks prior to study enrollment, or 
within a period of 5 half-lives of the investigational treatment prior to study 
enrollment, whichever is longer;

Having a known autoimmune or inflammatory disease;

History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior 
to randomization;

Pregnant or nursing (lactating) women.
3.2
Rationale for study design
The randomized, double-blind, placebo-controlled design used in this study is aligned with the 
Phase III trials of secukinumab, and with previous studies performed in the indication of 
chronic plaque psoriasis, and is in accordance with health authority guidelines and feedback, 
including the United States Food and Drug Administration (FDA).
The study population consists of adult patients with moderate to severe plaque-type psoriasis 
who are candidates for systemic therapy or phototherapy.
The primary analysis time point of the trial is at Week 12.  This is in line with the timing of 
the primary analysis time point in the secukinumab Phase III trials, and will allow for 
assessment of efficacy at a point in time for which efficacy data from currently approved 
biologic therapies are available.  Additionally, it is unknown if modulation of adipose tissue 
by secukinumab will be detectable by the primary time point of 12 weeks.  The study design 
provides for treatment a duration of 52 weeks, which will allow for the assessment of longer-
term effects of secukinumab in adipose tissue.  For patients randomized to receive placebo at 
Visit 2/Baseline, the 52-week treatment duration allows these patients the opportunity to 
receive up to 40 weeks of treatment with secukinumab.
The study population will be described in more detail in Section 4 below.
3.3
Rationale for dose/regimen, route of administration and duration 
of treatment
The proposal to use a dose of secukinumab 300 mg administered with a weekly induction 
regimen for five weeks (at Randomization, Weeks 1, 2, 3, and 4) followed by treatment every 
four weeks thereafter (starting at Week 8) is in accordance with the current FDA-approved 
product labeling.
3.4
Rationale for choice of comparator
Due to the nature of psoriasis and the outcome measures used for this indication, a placebo 
arm is necessary to obtain reliable efficacy measurements.  Moreover, the inclusion of a 

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placebo group is in accordance with health authority guidelines and feedback (CHMP 
Psoriasis Guideline-CHMP/EWP/2454/02 2004).  The continuation of the placebo group up to 
the primary analysis time point at Week 12 is in the study design for the indication of chronic 
plaque-type psoriasis and is accepted by health authorities including the FDA, EMA and 
PMDA.
3.5
Purpose and timing of interim analyses/design adaptations
The primary analysis at Week 12 is considered an interim analysis and will be performed after 
all patients have completed the Week 12 visit and the database is locked.  As Week 12 is the 
primary analysis time point, no adjustment to the significance level of 0.05 will be made.  See 
Section 5.4 on treatment blinding for additional information.
For the purpose of developing a potential sub-study, the summary of patient demographic and 
baseline characteristics may be used.
3.6
Risks and benefits
Secukinumab is currently approved in the United States for the treatment of moderate to 
severe plaque psoriasis in adult patients who are candidates for systemic therapy or 
phototherapy.
The potential benefits of secukinumab treatment are detailed in Section 3.6.1.
The risk to patients in this trial will be minimized by compliance with the eligibility criteria 
and close clinical monitoring.
  Specifically, there is the risk of infection, 
bleeding and potentially unsatisfactory cosmetic results, e.g., due to scarring.  A skin scar is 
expected after each biopsy procedure.
All quality, non-clinical pharmacology and toxicology data, as well as the available clinical 
efficacy and safety data for secukinumab are considered sufficient to expect a positive 
benefit/risk ratio for the treatment of moderate to severe psoriasis with secukinumab.
The Investigator’s Brochure (IB) provides a more detailed review of the pre-clinical and 
clinical information on secukinumab.
3.6.1
Clinical trials experience in plaque psoriasis
Four multicenter, randomized, double-blind, placebo-controlled trials (Trials 1, 2, 3, and 4) 
enrolled 2403 subjects (691 randomized to secukinumab 300 mg, 692 to secukinumab 150 mg, 
694 to placebo, and 323 to a biologic active control) 18 years of age and older with plaque 
psoriasis who had a minimum body surface area involvement of 10%, and Psoriasis Area and 
Severity Index (PASI) score greater than or equal to 12, an Investigator Global Assessment 
modified 2011 (IGA) of at least 3, and who were candidates for phototherapy or systemic 
therapy.

Trial 1 enrolled 738 subjects (245 randomized to secukinumab 300 mg, 245 to 
secukinumab 150 mg, and 248 to placebo).  Subjects received subcutaneous treatment at 
Weeks 0, 1, 2, 3, and 4 followed by dosing every 4 weeks.  Subjects randomized to 

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secukinumab received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and 4 followed by the 
same dose every 4 weeks.  Subjects randomized to receive placebo that were non-
responders at Week 12 were then crossed over to receive secukinumab (either 300 mg or 
150 mg) at Weeks 12, 13, 14, 15, and 16 followed by the same dose every 4 weeks.  All 
subjects were followed for up to 52 weeks following first administration of study 
treatment.

Trial 2 enrolled 1306 subjects (327 randomized to secukinumab 300 mg, 327 to 
secukinumab 150 mg, 326 to placebo and 323 to a biologic active control).  Secukinumab 
and placebo data are described.  Subjects received subcutaneous treatment at Weeks 0, 1, 
2, 3, and 4 followed by dosing every 4 weeks.  Subjects randomized to secukinumab 
received 300 mg or 150 mg doses at Weeks 0, 1, 2, 3, and 4 followed by the same dose 
every 4 weeks.  Subjects randomized to receive placebo that were non-responders at Week 
12 then crossed over to receive secukinumab (either 300 mg or 150 mg) at Weeks 12, 13, 
14, 15, and 16 followed by the same dose every 4 weeks.  All subjects were followed for 
up to 52 weeks following first administration of study treatment.

Trial 3 enrolled 177 subjects (59 randomized to secukinumab 300 mg, 59 to secukinumab 
150 mg, and 59 to placebo) and assessed safety, tolerability, and usability of secukinumab 
self-administration via prefilled syringe for 12 weeks. Subjects received subcutaneous 
treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks for up to 12 
weeks total.

Trial 4 enrolled 182 subjects (60 randomized to secukinumab 300 mg, 61 to secukinumab 
150 mg, and 61 to placebo) and assessed safety, tolerability, and usability of secukinumab 
self-administration via Sensoready pen for 12 weeks. Subjects received subcutaneous 
treatment at Weeks 0, 1, 2, 3, and 4, followed by the same dose every 4 weeks for up to 12 
weeks total.
In all trials, the co-primary efficacy variables were the proportion of subjects who achieved a 
reduction in PASI score of at least 75% (PASI 75) from baseline to Week 12 and treatment 
success (clear or almost clear) on the Investigator’s Global Assessment modified 2011 (IGA 
mod 2011). Other evaluated outcomes included the proportion of subjects who achieved a 
reduction in PASI score of at least 90% (PASI 90) from baseline at Week 12, maintenance of 
efficacy to Week 52, and improvements in itching, pain and scaling at Week 12 based on the 
Psoriasis Symptom Diary©.
The PASI is a composite score that takes into consideration both the percentage of body 
surface area affected and the nature and severity of psoriatic changes within the affected 
regions (induration, erythema and scaling). 
The IGA mod 2011 is a 5-category scale 
including “0 = clear” “1 = almost clear”, “2 = mild”, “3 = moderate” or “4 = severe” 
indicating the physician’s overall assessment of the psoriasis severity focusing on induration, 
erythema and scaling. Treatment success of “clear” or “almost clear” consisted of no signs of 
psoriasis or normal to pink coloration of lesions, no thickening of the plaque and none to 
minimal focal scaling.
The results of Trials 1 - 4 are presented in Table 3-1.

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Table 3-1
Clinical outcomes at Week 12 in adults with plaque psoriasis in Trials 
1- 4
Trial 1
Trial 2
Trial 3
Trial 4
Secukinumab
300 mg
(N=245)
n (%)
Placebo
(N=248)
n (%)
Secukinumab
300 mg
(N=327)
n (%)
Placebo
(N=326)
n (%)
Secukinumab
300 mg
(N=59)
n (%)
Placebo
(N=59)
n (%)
Secukinumab
300 mg
(N=60)
n (%)
Placebo
(N=61)
n (%)
PASI 90 
response
145 (59)
3 (1)
175 (54)
5 (2)
35 (60)
0 (0)
33 (55)
0 (0)
IGA of 
clear or 
almost 
clear
160 (65)
6 (2)
202 (62)
9 (3)
40 (68)
0 (0)
44 (73)
0 (0)
Examination of age, gender, and race subgroups did not identify differences in response to 
secukinumab among these subgroups.  
PASI 90 response at Week 12 was achieved with secukinumab 300 mg and 150 mg compared 
to placebo in 59% (145/245) and 39% (95/245) versus 1% (3/248) of subjects, respectively 
(Trial 1) and 54% (175/327) and 42% (137/327) versus 2% (5/326) of subjects, respectively 
(Trial 2).  Similar results were seen in Trials 3 and 4.
With continued treatment over 52 weeks, subjects in Trial 1 who were PASI 75 responders at 
Week 12 maintained their responses in 81% (161/200) of the subjects treated with 
secukinumab 300 mg.  Trial 1 subjects who were clear or almost clear on the IGA at Week 12 
also maintained their responses in 74% (119/160) of subjects treated with secukinumab 300 
mg.  Similarly in Trial 2, PASI 75 responders maintained their responses in 84% (210/249) of 
subjects treated with secukinumab 300 mg.  Trial 2 subjects who were clear or almost clear on 
the IGA also maintained their responses in 80% (161/202) of subjects treated with 
secukinumab 300 mg.
Among the subjects who chose to participate (39%) in assessments of patient reported 
outcomes, improvements in signs and symptoms related to itching, pain, and scaling, at Week 
12 compared to placebo (Trials 1 and 2) were observed using the Psoriasis Symptom Diary©.
3.6.2
Infections
Secukinumab may increase the risk of infections.  In clinical trials, a higher rate of infections
was observed in secukinumab-treated subjects compared to placebo-treated subjects. 
In 
placebo-controlled clinical trials in patients with moderate to severe plaque psoriasis, higher
rates of common infections such as nasopharyngitis (11.4% versus 8.6%), upper respiratory
tract infection (2.5% versus 0.7%) and mucocutaneous infections with Candida (1.2% versus
0.3%) were observed with secukinumab compared with placebo.  A similar increase in risk of
infection was seen in placebo-controlled trials in patients with psoriatic arthritis and 
ankylosing spondylitis.  The incidence of some types of infections appeared to be dose-
dependent in clinical studies. Proper exclusion criteria will be applied in this study to ensure 
subject safety.

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3.6.3
Pre-treatment evaluation for tuberculosis
Evaluate subjects for tuberculosis (TB) infection prior to initiating treatment with
secukinumab.  Do not administer secukinumab to subjects with active TB infection.  Initiate
treatment of latent TB prior to administering secukinumab.  Consider anti-TB therapy prior to
initiation of secukinumab in patients with a past history of latent or active TB in whom an 
adequate course of treatment cannot be confirmed.  Patients receiving secukinumab should be 
monitored closely for signs and symptoms of active TB during and after treatment.
3.6.4
Inflammatory bowel disease
Caution should be used when prescribing secukinumab to patients with inflammatory bowel
disease. Exacerbations, in some cases serious, occurred in secukinumab-treated patients 
during clinical trials in plaque psoriasis, psoriatic arthritis and ankylosing spondylitis. In 
addition, new onset inflammatory bowel disease cases occurred in clinical trials with 
secukinumab.  In an exploratory study in 59 patients with active Crohn’s disease, there were
trends toward greater disease activity and increased adverse events in the secukinumab group 
as compared to the placebo group.  Patients who are treated with secukinumab should be 
monitored for signs and symptoms of inflammatory bowel disease.
3.6.5
Hypersensitivity reactions
Anaphylaxis and cases of urticaria occurred in secukinumab-treated subjects in the clinical 
trials.  If an anaphylactic or other serious allergic reaction occurs, administration of 
secukinumab should be discontinued immediately and appropriate therapy initiated.
3.6.6
Risk of hypersensitivity in latex-sensitive Individuals
The removable cap of the secukinumab prefilled syringe contains natural rubber latex which 
may cause an allergic reaction in latex-sensitive individuals.  The safe use of the secukinumab 
prefilled syringe in latex-sensitive individuals has not been studied.
3.6.7
Vaccinations
Prior to initiating therapy with secukinumab, consider completion of all age appropriate 
immunizations according to current immunization guidelines.  Subjects treated with 
secukinumab should not receive live vaccines.  Non-live vaccinations received during a 
course of secukinumab may not elicit an immune response sufficient to prevent disease.
4
Population
The study population will consist of male and female patients (≥18 years of age) with 
moderate to severe chronic plaque-type psoriasis that requires systemic therapy, which is 
defined as psoriasis that is inadequately controlled by topical treatments (including topical 
corticosteroids (TCS)), ultraviolet (UV) light, or systemic therapy.
The goal is to randomize a total of 75 patients in approximately 12 centers in the United 
States.  Since a 30% screen failure rate is expected, approximately 107 patients will be 
screened.

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Patients who discontinue after they have been randomized will not be replaced.
4.1
Inclusion criteria
Patients eligible for inclusion in this study must fulfill all of the following criteria:
1. Written informed consent must be obtained before any assessment is performed
2. Males and females ≥18 years of age at the time of screening
3. Clinical diagnosis of chronic plaque-type psoriasis at least 6 months prior to 
randomization as determined by patient interview of his/her medical history and by 
confirmation of diagnosis through physical examination by the investigator
4. Moderate to severe plaque psoriasis as defined at baseline by:

≥10% Body Surface Area (BSA) involvement and

PASI total score of ≥12 and

IGA mod 2011 score of ≥3 (based on a scale of 0-4)
5. Candidate for systemic therapy, defined as having psoriasis inadequately controlled by:

Topical treatment (including topical corticosteroids) and/or

Phototherapy and/or

Previous systemic therapy
4.2
Exclusion criteria
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients.
1.
Forms of diagnosed psoriasis other than chronic plaque psoriasis (e.g., erythrodermic, 
generalized or localized pustular psoriasis, or new onset guttate psoriasis)
2.
Medication-induced or medication exacerbated psoriasis (e.g., new onset or current 
exacerbation from beta-blockers, calcium channel inhibitors or lithium)
3.
Previous exposure to secukinumab or any other biologic drug directly targeting IL-17A 
or IL-17RA receptors (e.g., ixekizumab, or brodalumab)
4.
Diagnosis of other active ongoing skin diseases or skin infections (bacterial, fungal, or 
viral), or inflammatory diseases other than psoriasis that may interfere with the 
evaluation of psoriasis
5.
Ongoing use of treatments prohibited by the protocol (see Section 5.5.8, Table 5-1)
6.
Plans for administration of live vaccines during the study period or within 6 weeks 
before randomization
7.
Use of any investigational treatment within 4 weeks prior to Randomization, or within a 
period of 5 half-lives of the investigational treatment prior to Randomization, whichever 
is longer

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8.
Currently enrolled in any other clinical trial involving any investigational agent or device
9.
Patients using cholesterol-lowering medication (e.g., statins) who have not been on a 
stable dose for at least 90 days prior to randomization and who are unable to remain on a 
stable dose for the duration of the study
10. Pregnant or nursing (lactating) women
11. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during 
dosing of study treatment and for 16 weeks after stopping of study treatment.  Basic 
contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the 
patient. 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 six 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 patients on the 
study, the vasectomized male partner should be the sole partner for that patient

Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps)

Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of 
contraception or other forms of hormonal contraception that have comparable efficacy 
(failure rate <1%), for example hormone vaginal ring or transdermal hormone 
contraception or placement of an intrauterine device (IUD) or intrauterine system 
(IUS)
In cases of oral contraception use, women should have been stable on the same pill for 
a minimum of 3 months before taking study treatment.
NOTE: Women are considered post-menopausal and not of child bearing 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

surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or 
tubal ligation at least six 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 child-bearing potential.
12. Current severe progressive or uncontrolled disease which in the judgment of the 
investigator renders the patient unsuitable for the trial or puts the patient at increased risk
13. Any underlying condition (including, but not limited to metabolic, hematologic, renal, 
hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which, 
in the opinion of the investigator, significantly immunocompromises the patient and/or 
places the patient at unacceptable risk for receiving an immunomodulatory therapy
14. Presence of significant medical problems, including but not limited to the following: 
uncontrolled hypertension with measured systolic >180 mmHg and/or diastolic >95 

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mmHg; congestive heart failure (New York Heart Association [NYHA] status of class III 
or IV
15. Fasting blood glucose ≥200 mg/dL and hemoglobin A1c ≥7% at screening; fasting 
glucose ≥150 mg/dL up to 199 mg/dL will require consultation with the Medical Monitor 
to confirm eligibility
16. Total white blood cell (WBC) count <2,500/μl, or thrombocytes <100,000/μl, or 
neutrophils <1,500/μl, or hemoglobin <8.5 g/dL at screening
17. Active systemic infections during 2 weeks prior to randomization (exception: the 
common cold) or any infection that reoccurs on a regular basis
18. History of an ongoing, chronic or recurrent infectious disease, or evidence of 
tuberculosis infection as defined by a positive or indeterminate QuantiFERON TB-Gold 
test (QFT) at screening.

NOTE: Patients with a positive QFT may participate in the study if a full tuberculosis 
work up (according to local practice/guidelines) completed within 12 weeks prior to 
randomization establishes conclusively that the patient has no evidence of active 
tuberculosis.  If the presence of latent tuberculosis is established, then treatment must 
have been initiated and maintained for at least 4 weeks prior to randomization and the 
course of prophylaxis is planned to be completed.
19. Positive serology for human immunodeficiency virus (HIV), hepatitis B or C infection at 
screening
20. History of lymphoproliferative disease or any known malignancy or history of 
malignancy of any organ system within the past 5 years (except for skin Bowen’s disease, 
squamous cell carcinoma, basal cell carcinoma, actinic keratoses that have been treated, 
carcinoma in situ of the cervix, or non-invasive malignant colon polyps that have been 
removed)
21. History or evidence of ongoing alcohol or drug abuse, within the last 6 months prior to 
randomization
22. History of hypersensitivity to constituents of the study treatment and/or patients who are 
allergic to rubber or latex (the needle cap of the single-use prefilled syringe for 
secukinumab and placebo may contain natural rubber latex which may cause allergic 
reactions in latex sensitive individuals)
23. Any medical, psychiatric or other condition which, in the investigator’s opinion, would 
preclude the patient from adhering to the protocol or completing the study per protocol
24. Patients who are not able and/or not willing to self-administer secukinumab injections or 
who have no trained caregiver available to administer these injections
5
Treatment
5.1
Study treatment
All study treatments will be supplied by Novartis and will be labeled appropriately.
All doses of study treatment should be self-administered.  Self-administration of the study
treatment refers to patient self-injection or injection by a trained caregiver regardless of 

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whether dosing occurs at the study site or at home.  Instruction and training will be provided 
by site staff to patients/caregivers prior to self-injection.
All doses of study treatment that are administered at the study site should be performed after 
all study assessments for the visit have been completed.
5.1.1
Study drug – secukinumab

Secukinumab 150 mg: 1 ml liquid  formulation in a single-use prefilled syringe (PFS)
Secukinumab for subcutaneous (s.c.) injection is provided in a PFS containing 150 mg 
secukinumab. Each secukinumab 300 mg dose is given as two s.c. injections of 150 mg.
5.1.2
Control drug – placebo

Placebo to secukinumab 150 mg: 1 ml liquid formulation in a single-use prefilled syringe 
(PFS)
Placebo to secukinumab 150 mg for s.c. injection is provided in a matching PFS. Each PFS
contains a mixture of inactive excipients, matching the composition of the secukinumab 150
mg dose. Each placebo dose is given as two s.c. injections of placebo to secukinumab 150 mg.
5.1.3
Additional treatment
No additional treatment beyond the study drug and control drug are included in this trial.
5.2
Treatment groups
At Visit 2/Baseline, eligible patients will be randomized to one of the following two treatment 
groups in a ratio of 2:1:
Secukinumab group

Patients (or trained caregivers) will administer a dose of secukinumab 300 mg s.c. (two 
injections of the 150 mg PFS) once weekly for five weeks (at Baseline, Weeks 1, 2, 3, and 
4), followed by dosing every four weeks, starting at Week 8 through Week 48.  In order to 
maintain the blinding for the 12-week, placebo-controlled period, two injections of the 
placebo PFS will be administered at Weeks 13, 14, and 15 during the Double-blind 
Induction Period.
Placebo group

Patients (or trained caregivers) will administer a dose of placebo s.c. (two injections of the 
placebo PFS) once weekly for five weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by 
a dose after four weeks at Week 8. 

Beginning at Visit 8/Week 12, all patients in the placebo group will be switched to 
treatment with secukinumab 300 mg s.c.  Patients will receive a dose of secukinumab 300 
mg s.c. (two injections of the 150 mg PFS) once weekly for five weeks (at Weeks 12, 13, 
14, 15, and 16) followed by dosing every four weeks starting at Week 20 through Week 
48.
The treatment groups and dosing frequency are also described in Table 5-1 below.

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Table 5-1
Overview of study treatment
Treatment group
DB Treatment Period 
(Rand – Wk 12 pre-dose)
DB Induction Period
(Wk 12 – Wk 15 )
OL Treatment Period 
(Wk 16 – Wk 52)
Secukinumab 300 mg 
2x s.c. secukinumab 150 
mg injection at BSL, Wks 
1, 2, 3, 4 and 8
2x s.c. secukinumab 150 
mg injection at  Wk 12
2x s.c. PBO injection at 
Wks 13, 14 and 15
2x s.c. secukinumab 
150 mg injection at 
four-week intervals 
from Wks 16 - 48
Placebo (PBO)
2x s.c. PBO injection at 
BSL, Wks 1, 2, 3, 4 and 8
2x s.c. secukinumab 150 
mg injection at Wks 12, 
13, 14, and 15
2x s.c. secukinumab 
150 mg injection at 
four-week intervals 
from Wks 16 – 48
DB = Double-blind; OL = Open-label; PBO = placebo; BSL = Baseline; Wk = Week
5.3
Treatment assignment and randomization
At Visit 2/Baseline, all eligible patients will be randomized via Interactive Response 
Technology (IRT) to one of the two treatment groups. The investigator or his/her delegate 
will contact the IRT after confirming that the patient fulfills all the inclusion/exclusion criteria.
The IRT will assign a randomization number to the patient, which will be used to link the 
patient to a treatment arm and will specify a unique medication number for the first package 
of study treatment to be dispensed to the patient.
The randomization number will not be 
communicated to the caller.
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from patients and investigator staff. A 
patient randomization list will be produced by the IRT provider using a validated system that 
automates the random assignment of patient numbers to randomization numbers. These 
randomization numbers are linked to the different treatment groups, which in turn are linked 
to medication numbers. A separate medication list will be produced by or under the 
responsibility of Novartis Drug Supply Management using a validated system that automates 
the random assignment of medication numbers to boxes containing the study treatment. 
The randomization scheme for patients will be reviewed and approved by a member of the 
Novartis Biometrics group.
5.3.1
Stratification
Randomization will be stratified by body weight.  The stratification ensures balanced 
allocation of patients to treatment groups within the weight strata.  The strata will be “body 
weight <90 kg” or “body weight ≥90 kg”.
Stratification by body weight will occur at Visit 2/Baseline.  The body weight collected at 
Visit 2 will be used for the stratification.

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5.4
Treatment blinding
Patients, investigators/site staff, persons performing assessments, and Novartis study 
personnel will remain blinded to individual treatment assignment from the time of
randomization until the final database lock at Week 53, using the following methods:
1. Randomization data will be kept strictly confidential until the time of unblinding, and will 
not be accessible by anyone else involved in the study with the following exceptions:

specific vendors whose role in trial conduct requires their unblinding (e.g., IRT)

Drug Supply Management (DSM);
2. The identity of secukinumab and placebo prefilled syringes (PFS) will be concealed by
identical packaging, labeling, schedule of administration, and appearance.
At the Week 12 primary analysis time point, there will be a database lock after all patients 
have completed the Week 12 visit.  At that time, only the statistician and programmer(s) from 
the designated CRO will be unblinded in order to perform the analysis.  Results from the 
analyses of all data through Week 12, including the data for the primary efficacy variable, will 
be reported.  For publication purposes, summary results from the Week 12 primary analysis 
time point may be shared with the health care community, however individual patient-level 
data will remain blinded until the end of the trial.
Unblinding will only occur in the case of patient emergencies (see Section 5.5.9), at the time 
of the primary analysis (Week 12) for designated CRO personnel only, and at the conclusion 
of the study.
A full analysis of all data collected up to Week 53 will be performed when all patients have 
completed Follow-up Visit 1/Week 53.
5.5
Treating the patient
Sponsor qualified medical personnel will be readily available to advise on trial-related 
medical questions or problems.
5.5.1
Patient numbering
Each patient is uniquely identified by a Patient Number which is composed by the site number 
assigned by Novartis and a sequential number assigned by the investigator.  Once assigned to 
a patient, the Patient Number will not be reused. 
Upon signing the informed consent form, the patient is assigned the next sequential number 
by the investigator.  The investigator or his/her staff will contact the IRT and provide the 
requested identifying information for the patient to register them into the IRT.  The site must 
select the CRF book with a matching Patient Number from the EDC system to enter data. 
If the patient fails to be treated for any reason, the IRT system must be notified that the patient
was not treated.  The reason for not being treated will be entered on the Screening Study 
Disposition eCRF.

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5.5.2
Dispensing the study drug
Each study site will be supplied by Novartis with secukinumab and placebo treatment in 
packaging of identical appearance.
The study drug packaging has a 2-part label.  A unique medication number is printed on each 
part of this label which corresponds to one of the two treatment groups.  Investigator staff will 
identify the study drug package(s) to dispense to the patient by contacting the IRT and 
obtaining the medication number(s).  Immediately before dispensing the package to the 
patient, investigator staff will detach the outer part of the label from the packaging and affix it 
to the source document (Drug Label Form) for that patient.
IRT will assign secukinumab or placebo at each visit from Randomization to Week 48.  All 
boxes of study treatment assigned by the IRT will be recorded/databased in the IRT system.
5.5.3
Handling of study and additional treatment
5.5.3.1
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 
designees 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.  For any syringe with a technical issue, a description of the issue must be
communicated to Novartis Quality Assurance, and the syringe may be required to be 
returned to Novartis for further assessment.  In the event a technical issue with a syringe is 
identified, site staff should contact their monitor for guidance on the reporting and returns 
process.
The prefilled syringes (150 mg secukinumab or placebo) sealed in their outer box must be
stored in a locked refrigerator between 2° to 8°C (36° to 46°F) and must be carefully
controlled in accordance with regulations governing investigational medicinal products and
local regulations.  Study treatment should not be frozen.  All temperature excursions 
(either below or above the required, specified temperature range) must be reported to Novartis 
for review and assessment of impact on the study treatment.  In the event of a temperature 
excursion, site staff should contact their monitor for guidance on the reporting process.
Medication labels will be in English and will comply with US legal requirements.  They will 
include storage conditions for the study treatment but no information about the patient 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 trial.  Patients will be 
asked to return all used/unused study treatment and packaging to the study site.
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator will return all used and unused study treatment, packaging, drug labels, and a 
copy of the completed drug accountability log to the Novartis or responsible CRO monitor, or 
to the Novartis or responsible CRO address provided in the investigator folder at each site.

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5.5.3.2
Handling of additional treatment
Not applicable.
5.5.4
Instructions for prescribing and taking study treatment
All doses of study treatment that are administered at the study site should be performed after 
all study assessments for the visit have been completed.  The first study treatment 
administration will occur at V i s i t  2 / B a s e l i n e after inclusion/exclusion criteria has
been confirmed and all scheduled assessments have been performed.
The prefilled syringes will be provided by the site staff to the patient, who will then self-
inject the study treatment.  Site staff should remove the assigned study treatment from the 
refrigerator and allow the syringes to reach room temperature in their unopened box 
(approximately 15-30 minutes) before self-injection by the patient.
Detailed instructions on the self-administration of the study treatment will be described in the 
Instructions For Use (IFU), a copy of which will be provided to each patient. At the
Baseline visit, the patient will be instructed by the site staff (using the IFU) on how to self-
inject with the PFS.  Patients will be asked to raise any questions if they have any.
Starting at Visit 3/Week 1, patients will be asked to refer to the IFU and to proceed with self-
injection of the study treatment at the study site under the supervision of site staff.
Patients must inject the study treatment into the appropriate body site (thighs, abdomen, 
upper outer arm).  Study treatment should not be injected into areas where the skin is tender,
bruised, red, scaly or hard, or in an area of skin affected by psoriasis.  Areas with scars or
stretch marks should be avoided.  As possible throughout the trial, the injection site should 
be rotated from visit to visit.
All self-injections during the Double-blind Treatment Period will take place at the study
site; during the Double-blind Induction and Open-label Treatment Periods, self-injections will 
occur both at the study site and at home (refer to Table 6-1).
Used study treatment syringes should be disposed immediately after use in a sharps container.
The investigator must promote compliance by instructing the patient to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the patient’s 
safety and the validity of the study.  The patient must also be instructed to contact the 
investigator if he/she is unable for any reason to take the study treatment as prescribed.
Study treatment administration at home
If the patient or caregiver is not able/confident to perform home administration, the patient
will be allowed to return to the site for administration of the medication.  During those visits, 
no additional assessments will be required.
Patients will be instructed to contact the investigator/site staff prior to self-administration at 
home if they are experiencing any AE/SAEs or have any concerns.  Additionally, site staff 
will contact patients via telephone at the time of scheduled at-home dosing to check 
compliance and to ensure completion of the dosing log.

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Patients will be provided with the following items to facilitate the at-home injections of study 
treatment:  an insulated bag with cool gel packs to transport the study treatment from the site to 
the patient’s home; alcohol swabs and gauze pads; a sharps container for immediate disposal of 
the used syringes; a copy of the IFU; and a paper Self-administration Log to record the dates 
and times of the at-home doses.
5.5.5
Permitted dose adjustments and interruptions of study treatment
Study treatment dose adjustments are not permitted.
Study treatment interruption is permitted if, in the opinion of the investigator, a subject is 
deemed to be placed at a safety risk unless dosing is temporarily interrupted. In such cases 
study treatment should be interrupted only during the time that this risk is present and ongoing. 
Study treatment can be started again at the next scheduled visit after resolution of the safety 
risk.
5.5.6
Rescue medication
Use of rescue medication is not permitted during the study. 
5.5.7
Concomitant treatment
The investigator must instruct the patient to notify study staff about any new medications 
he/she takes after the patient was enrolled into the study. All medications, procedures and 
significant non-drug therapies (including physical therapy and blood transfusions) 
administered after the patient was enrolled into the study must be recorded in the Prior and 
Concomitant Medications eCRF or the Surgical and Medical Procedures eCRF as appropriate.
Each concomitant drug or therapy/procedure must be individually assessed against all
exclusion criteria/prohibited medication. If in doubt the investigator should contact the study 
Medical Monitor before randomizing a patient or allowing a new medication or 
therapy/procedure to be started.
5.5.8
Prohibited medication
Use of the treatments displayed in Table 5-2 is NOT allowed for any indication after the 
start of study treatment; the use of these treatments could confound the efficacy of the 
study drug. Wash-out periods for these treatments are provided in Table 5-2. If the use of
any of these treatments is required, then the patient must NOT be randomized into the study.
The i nvestigator/qualified site staff must instruct the patient to notify them about any new 
treatments he/she initiates during the study. All prohibited medications and significant
non-drug therapies administered after the patient starts study treatment must be listed on
the eCRF.
If a prohibited treatment listed in Table 5-2 is used after the start of study treatment, the
patient must discontinue use of the prohibited treatment if he/she wishes to continue in the
study.
If, in the investigator’s clinical judgment, the patient’s use of a prohibited treatment
presents an undue safety risk for the patient, the patient must discontinue study treatment; if a

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patient receives a live virus vaccination during the study, the patient must discontinue study
treatment (see Section 5.6.2).
Table 5-2
Prohibited treatment
Prior Therapy (Before Visit 2/Baseline)
Prohibited Treatments1,2
Washout Period
(before Randomization)
Secukinumab
No prior use allowed
Any biologic drug directly targeting IL-17 or the IL-17 receptor
(e.g., ixekizumab or brodalumab)
No prior use allowed
Alefacept, briakinumab, efalizumab, ustekinumab
24 weeks
Biological immunomodulating agents other than above
(e.g., adalimumab, infliximab, etanercept)
12 weeks
Other systemic immunomodulating treatments3 [e.g., MTX,
cyclosporine A, corticosteroids (oral, i.v., transdermal)3, 
cyclophosphamide]
4 weeks
Other systemic psoriasis treatments (e.g., retinoid, fumarates)
4 weeks
Photo chemotherapy (e.g., PUVA)
4 weeks
Phototherapy (e.g., UVA, UVB)
2 weeks
Medicated psoriasis shampoo (including OTC)
2 weeks
Topical treatment that is likely to impact signs and symptoms of 
psoriasis (e.g., vitamin D analogues, pimecrolimus, retinoids, 
salicylvaseline, salicylic acid, lactic acid, tacrolimus, tar, urea,
α-hydroxy or fruit acids)
2 weeks
Topical Corticosteroids (TCS) any potency on areas of 
psoriasis
2 weeks
Live virus vaccines
6 weeks
An investigational treatment or participation in any 
interventional trial
4 weeks or 5 half-lives
(whichever is longer)
Any other treatment known to worsen psoriasis (e.g., beta-
blockers, calcium channel blockers)
Stable dose for at least 4 weeks prior 
to randomization
Cholesterol-lowering medication (e.g., statins)
Stable dose for ≥90 days prior to 
randomization and remain stable for 
duration of the study
Concomitant Therapy with TCS (after Visit 2/Baseline)
Topical Corticosteroids (TCS)
Concomitant Use
TCS on areas of psoriasis (including scalp)
Hydrocortisone 2.5% cream is 
allowed on face and intertriginous 
areas; medicated OTC shampoos are 
allowed for the scalp 
TCS mild to moderate potency used for up to 7 consecutive 
days per event for an indication other than psoriasis and on 
areas not affected by psoriasis
Allowed during the study

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1 If the prohibited treatment was used during the study for any indication, the patient must discontinue use of the 
prohibited treatment if he/she wishes to continue in the study.
2 In case of undue safety risk for the patient as determined by the investigator, the patient should discontinue 
study treatment. If the patient receives a live virus vaccination during the study, the patient must discontinue 
study treatment.
3 Inhaled CS with only a topical effect (e.g., to treat asthma) are not considered “systemic immunomodulating
treatments” and are therefore acceptable as concomitant medication.
5.5.9
Emergency breaking of assigned treatment code
Emergency code breaks must only be undertaken when it is required to in order to treat the 
patient safely. Most often, study treatment discontinuation and knowledge of the possible 
treatment assignments are sufficient to treat a study patient who presents with an emergency 
condition. Emergency treatment code breaks are performed using the IRT. When the 
investigator contacts the system to break a treatment code for a patient, he/she must provide 
the requested patient identifying information and confirm the necessity to break the treatment 
code for the patient. The investigator will then receive details of the investigational drug 
treatment for the specified patient and a fax or email confirming this information. The system 
will automatically inform the Novartis monitor for the site and the Study Team that the code 
has been broken.
It is the investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT at any time in case of emergency. The investigator will provide:

protocol number

study drug name (if available)

patient number
In addition, oral and written information to the patient must be provided on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable, to ensure that un-
blinding can be performed at any time. 
Study treatment must be discontinued after emergency unblinding.
The appropriate personnel from the study site and Novartis will assess whether study 
treatment should be discontinued for any patient whose treatment code has been broken 
inadvertently for any reason
5.6
Study completion and discontinuation 
5.6.1
Study completion and post-study treatment
A patient will be considered to have completed the study when (s)he has completed the last 
visit planned in the protocol.
Continuing care should be provided by the investigator and/or referring physician based on 
patient availability for follow-up.
5.6.2
Discontinuation of study treatment
Discontinuation of study treatment for a patient occurs when study treatment is stopped earlier 
than the protocol planned duration, and can be initiated by either the patient or the investigator.

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Patients may voluntarily discontinue study treatment for any reason at any time.
The investigator must discontinue study treatment for a given patient if, on balance, he/she 
believes that continuation would negatively impact the risk/benefit of trial participation.
Study treatment must be discontinued under the following circumstances: 

Patient decision

Pregnancy (see Section 6.7.5 and Section 7.4)

AEs that in the judgment of the investigator/qualified site staff, taking into account the 
patient’s overall status prevent the patient from continuing study treatment

Any laboratory abnormalities that in the judgment of the investigator, taking into 
consideration the patient’s overall status, prevents the patient from continuing 
participation in the study

Ongoing use of prohibited treatment, use of a prohibited treatment that results in an undue
safety risk for the patient as per the investigator’s clinical judgment, or receipt of a live 
virus vaccine during the study (as detailed in Section 5.5.8)

Any situation in which study participation might result in a safety risk to the patient

Emergency unblinding
The investigator/site staff must contact the IRT to register the patient’s discontinuation from 
study treatment.
If study drug discontinuation occurs because treatment code has been broken, please refer to
Section 5.5.9.
5.6.2.1
End of treatment visit
Patients who discontinue study treatment should return to the study site for an end of 
treatment visit. The end of treatment visit should be scheduled to occur approximately four (4) 
weeks after the patient’s last dose of study treatment.  Discontinuation during:

Double-blind Treatment Period: For patients who discontinue study treatment 
prematurely before the end of the Double-blind Treatment Period, the Visit 8/Week 12 
(EOT1) assessments should be performed.  
 
 
 
 

Double-blind Induction or Open-label Treatment Periods: For patients who 
discontinue study treatment prematurely before the end of the Double-blind Induction or 
Open-label Treatment Periods, the Visit 15/Week 52 (EOT2) visit should be performed.
 
 
 
Assessments scheduled to be performed during the appropriate end of treatment visit per
Table 6-1 should be completed and recorded in the eCRF. The investigator must determine

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the primary reason for the patient’s premature study discontinuation and record this 
information on the eCRF.
5.6.3
Withdrawal of informed consent
Patients may voluntarily withdraw consent to participate in the study for any reason at any 
time.  Withdrawal of consent from the study is defined as when a patient:

Does not want to participate in the study anymore
and

Does not want any further visits or assessments
and

Does not want any further study related contacts
and

Does not allow analysis of already obtained biologic material.
In this situation, the investigator must make every effort (e.g. telephone, e-mail, letter) to 
determine the primary reason for the patient’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 patient 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 patient’s study withdrawal should be made as detailed in Table 6-
1.
5.6.4
Loss to follow-up
For patients 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 patient, e.g. dates of 
telephone calls, registered letters, etc. A patient cannot be considered as lost to follow-up 
until the time point of his/her scheduled end of study visit has passed.
5.6.5
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, or 
for regulatory or medical reasons (including slow enrollment). Should this be necessary, the 
patient must be seen as soon as possible and treated as a prematurely withdrawn patient. 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 patient’s interests. The investigator 
will be responsible for informing the Institutional Review Board/Independent Ethics 
Committee (IRBs/IECs) of the early termination of the trial.

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6
Visit schedule and assessments
Table 6-1 lists all of the assessments and indicates with an “X” when the assessments are 
performed.  An “S” indicates the data for that assessment reside in the source documents at 
the site.
Patients must be seen for all visits on the designated day per the original planned 
visit schedule or as close as possible to it. Every effort should be made to respect the
time frame for all visits, particularly the Week 12 and Week 52 visits.
6.1
Rescreening
Rescreening may be allowed under certain conditions.  Requests from the investigator/site 
staff to rescreen patients will be handled on a case-by-case basis with Medical Monitor 
approval required before proceeding with the rescreening.  Rescreening cannot be done if a 
patient was previously randomized into the study.
If a patient rescreens for the study, the patient must sign a new ICF and be issued a new
patient number prior to any screening assessments being conducted under the new patient
number.  The date of the new informed consent signature must be entered on the Informed 
consent eCRF to correspond to the new patient number. 
For rescreening, all screening assessments must be performed per protocol, except for the
tuberculosis (TB) work up (if applicable). If the date of the TB work up is less than 12
weeks from the projected randomization date, then it is not required that the TB work up be
repeated; however, the rescreened patient MUST repeat the QuantiFERON test performed by
the central laboratory.
6.2
Unscheduled visits
Patients may be seen at any time for an unscheduled visit, e.g., if they experience
deterioration of psoriasis or suspected AEs. 
The assessments performed at an 
unscheduled visit are at the discretion of the investigator/qualified site staff.  During
an unscheduled visit, study treatment will not be administered.

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Table 6-1
Assessment schedule
Period
SCR
Double-blind Treatment Period
Double-blind 
Induction 
Period
Open-label Treatment Period
F-up
Unscheduled 
Visit2
Notes
Visit
1
2
3
4
5
6
7
8/
EOT1
9
10
11
12
13
14
15/
EOT2
F11
Week
-4 to BL
BL
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
53
Assessment Day
≤-28 to BL
1
8
15
22
29
57
85
92
99
106
113
141
169
197
225
253
281
309
337
365
372
Obtain informed 
consent
X
Demographics
X
See Section 6.4.1
Inclusion/exclusion 
criteria
X
X
See Section 4.1
and Section 4.2
Smoking and 
alcohol history
X
See Section 6.4.3
and Section 6.4.4
Psoriasis medical 
history/ prior
psoriasis therapies
X
See Section 6.4.2
Cardiovascular 
medical history
X
See Section 6.4.5
Other medical 
history/ current 
medical conditions
X
See Section 6.4.6
Prior/concomitant 
medications /
Surgical and 
medical procedures
Update as necessary
See Section 6.4.7
(s)AE assessment 
Update as necessary
See Section 7
Physical 
examination
S
S
S
S
S
S
See Section 6.7.1
Height
X
See Section 6.7.3
Weight
X
X
X
X
X
X
X
X
X
X
X
X
See Section 6.7.3
Waist 
circumference
X
X
X
X
See Section 6.7.3

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Period
SCR
Double-blind Treatment Period
Double-blind 
Induction 
Period
Open-label Treatment Period
F-up
Unscheduled 
Visit2
Notes
Visit
1
2
3
4
5
6
7
8/
EOT1
9
10
11
12
13
14
15/
EOT2
F11
Week
-4 to BL
BL
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
53
Assessment Day
≤-28 to BL
1
8
15
22
29
57
85
92
99
106
113
141
169
197
225
253
281
309
337
365
372
BMI calculation
X
X
X
X
See Section 6.7.3; 
calculated in 
eCRF
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
See Section 6.7.2
Lab analysis: 
Hematology3
X
X
X
X
X
See Section 
6.7.4.1
Lab analysis: 
Clinical chemistry3
X
X
X
X
X
See Section 
6.7.4.2
hs-CRP3
X
X
X
X
X
See Section 
6.7.4.3
HbA1c3
X
X
X
X
X
X
See Section 
6.7.4.4
Fasting labs: 
plasma glucose, 
insulin, lipids3
X
X
X
X
X
X
See Section 
6.7.4.5
HOMA-IR 
calculation
X
X
X
X
See Section 
6.7.4.5; calculated 
and reported by 
central lab
Serology lab 
analysis: HIV, Hep 
B and Hep C3
X
X
See Section 
6.7.4.6
QuantiFERON® 
TB-Gold 
In-Tube test3
X
X
See Section 6.4.8
Serum pregnancy 
test3
X
X
See Section 6.7.5
Urine pregnancy 
test (local)
X
X
X
X
See Section 6.7.5

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Period
SCR
Double-blind Treatment Period
Double-blind 
Induction 
Period
Open-label Treatment Period
F-up
Unscheduled 
Visit2
Notes
Visit
1
2
3
4
5
6
7
8/
EOT1
9
10
11
12
13
14
15/
EOT2
F11
Week
-4 to BL
BL
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
53
Assessment Day
≤-28 to BL
1
8
15
22
29
57
85
92
99
106
113
141
169
197
225
253
281
309
337
365
372
PASI
X
X
X
X
X
X
X
X
X
X
X
X
See Section 6.6.5
Alcohol and 
tobacco use 
assessments
X
X
X
See Section 6.4.3
and Section 6.4.4
Randomization via 
IRT
S
See Section 5.3
Patient self-
administration of 
study treatment at 
site
X
X
X
X
X
X
X
X
X
X
X
X
X
See Section 5.5.4
Dispense study 
treatment to patient
for at-home dosing
S
S
S
S
S
See Section 5.5.4

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Period
SCR
Double-blind Treatment Period
Double-blind 
Induction 
Period
Open-label Treatment Period
F-up
Unscheduled 
Visit2
Notes
Visit
1
2
3
4
5
6
7
8/
EOT1
9
10
11
12
13
14
15/
EOT2
F11
Week
-4 to BL
BL
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
53
Assessment Day
≤-28 to BL
1
8
15
22
29
57
85
92
99
106
113
141
169
197
225
253
281
309
337
365
372
Patient self-
administration of 
study treatment at 
home and 
completion of Self-
Administration Log
X
X
X
X
X
X
See Section 5.5.4
and Section 6.5
At-home Dosing 
Phone Reminder 
S
S
S
S
S
S
See Section 6.5
Check Self-
Administration Log 
and returned 
used/unused study 
treatment and 
packaging
S
S
S
S
S
See Section 6.5
(S)AE = (serious) adverse event; BL = Baseline; BMI = body mass index; FACS = fluorescence activated cell sorting; F-up = Follow-up Period; hs-CRP = high 
sensitivity C-reactive protein; HIV = human immunodeficiency virus; HOMA-IR = homeostatic model assessment of insulin resistance; IRT = interactive 
response technology; 
; SCR = Screening; TB = tuberculosis; 
Weeks in dark/grey columns: At these weeks, patients are expected to self-administer the study treatment at home.  If the patient or caregiver cannot 
administer the drug at home, then the patient may return to the site for study treatment administration.
X = assessment to be recorded on clinical data base; S = assessment to be recorded in source documentation only
1.
Patients who undergo skin biopsies at Visit 15/Week 52 will return to the site for completion of Visit F1; additionally, all patients who discontinue prematurely from 
the study and who undergo skin biopsies at their end of treatment visit (either Visit 8/EOT1 or Visit 15/EOT2) will return to the site for completion of Visit F1
2.
Unscheduled Visit:  assessment(s) performed at an unscheduled visit are at the investigator’s discretion
3.
Samples will be analyzed by a central laboratory

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Table 6-2
Assessment schedule for healthy control cohort
Visit
1/EOT1
F2
Notes
Obtain informed consent
X
Demographics
X
See Section 6.4.1
Inclusion/exclusion criteria
S
See Section 3.1.6
Smoking and alcohol history
X
See Section 6.4.3 and Section 6.4.4
Cardiovascular medical history
X
See Section 6.4.5
Other medical history/ current medical 
conditions
X
See Section 6.4.6
Prior/concomitant medications / 
Surgical and medical procedures
X
See Section 6.4.7
(s)AE assessment
X
X
See Section 7
Height
X
See Section 6.7.3
Weight
X
See Section 6.7.3
Waist circumference
X
See Section 6.7.3
BMI calculation
X
See Section 6.7.3; calculated in eCRF
Vital signs
X
See Section 6.7.2
Lab analysis: Hematology2
X
See Section 6.7.4.1
Lab analysis: Clinical chemistry2
X
See Section 6.7.4.2
hs-CRP2
X
See Section 6.7.4.3
HbA1c2
X
See Section 6.7.4.4
Fasting labs: plasma glucose, insulin, 
lipids2
X
See Section 6.7.4.5
HOMA-IR calculation
X
See Section 6.7.4.5; calculated and reported by central lab
Urine pregnancy test (local)
X
See Section 6.7.5
(S)AE = (serious) adverse event; BMI = body mass index; FACS = fluorescence activated cell sorting; 
F2 = Follow-up Visit 2; hs-CRP = high sensitivity C-reactive protein; HOMA-IR = homeostatic model 
assessment of insulin resistance; 
 
X = assessment to be recorded on clinical data base; S = assessment to be recorded in source documentation 
only
1.
Visit 1 assessments may or may not occur on the same day, however all assessments should be 
performed and completed within 7 calendar days of the informed consent date
2.
Samples will be analyzed by a central laboratory
 

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6.3
Information to be collected on screening failures
All patients who sign the informed consent but discontinue prior to randomization at Visit 
2/Baseline are considered to be screen failures.
If a patient discontinues prior to randomization, the IRT provider must be notified, and the 
reason for the patient not being randomized will be entered on the Screening Phase
Disposition eCRF. The Screening Visit Date, the Demography eCRF, the Informed Consent 
eCRF, the Inclusion/Exclusion eCRF, and the Subject Re-screening eCRF must be completed. 
The Adverse Event eCRF should be completed for any SAEs that occurred during the
screening period.  Adverse events that are not SAEs will be followed by the investigator
and collected only in the source data.  The Withdrawal of Consent eCRF must be completed 
if consent was withdrawn during the screening period before the patient was randomized.
6.4
Patient demographics/other baseline characteristics
All baseline assessments will be performed prior to the first study treatment administration.
6.4.1
Demographics
Patient demographic data will be collected at Visit 1/Screening.  Data to be collected on all
patients include: date of birth, patient initials, age, sex, race, ethnicity, and child-bearing 
potential (for females only).
6.4.2
Psoriasis history / Prior psoriasis therapies
Disease history will be collected at Visit 1/Screening. The information to be collected and 
entered in the Psoriasis History eCRF and Prior Psoriasis Therapy eCRF includes the 
following:

start date of plaque psoriasis;

previous psoriasis treatments (including previous use of biologic therapies, as well as 
phototherapy and/or photo chemotherapy), duration of exposure, and the reason for 
discontinuation of each therapy;

presence of psoriatic arthritis and the date of first diagnosis (by a physician).
6.4.3
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.
Current tobacco use will be assessed throughout the duration of the study as the scheduled 
visits as indicated in Table 6-1.
6.4.4
Alcohol use history
The current and/or previous use of alcohol will be recorded. This includes the estimated 
number of alcoholic drinks consumed on average per day, and the date alcohol was last 
consumed.

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Current alcohol use will be assessed throughout the duration of the study at the scheduled
visits as indicated in Table 6-1.
6.4.5
Comorbidities – cardiovascular history
Information pertaining to cardiovascular medical history assessed prior to randomization 
should be reported on the Cardiovascular History eCRF.
6.4.6
Relevant medical history/current medical conditions
Relevant medical history and current medical conditions prior to providing informed consent 
(not including psoriasis or psoriatic arthritis) will be recorded in the Medical History eCRF.
Whenever possible, diagnoses and not symptoms will be recorded.
Significant findings that are observed after the patient has signed the informed consent form 
and that meet the definition of an AE must be recorded in the AE eCRF. Investigators will
have the discretion to record abnormal test findings on the Medical History eCRF when in
their judgment, the test abnormality occurred prior to the informed consent signature.
6.4.7
Prior and concomitant medications
Concomitant medications and prior medications taken over the six (6) months preceding study 
enrollment will be captured in the Prior and Concomitant Medication eCRF at the screening 
visit, and updated at Visit 2/Baseline.
6.4.8
Determination of tuberculosis status
Determination of tuberculosis (TB) status will be required before administration of study 
treatment. TB status must be determined by medical history, signs, symptoms, and TB
testing (QuantiFERON-TB Gold assay). Any significant findings will be recorded in the
appropriate eCRF(s), as necessary.
If the QuantiFERON-TB Gold Assay test is positive or indeterminate, a TB workup should
be performed as defined by local guidelines to determine the patient’s TB status.
6.4.8.1
QuantiFERON TB-Gold In-Tube assay
A QuantiFERON® TB-Gold In-Tube assay will be performed to assess the TB status at 
screening for all patients. This test will only be used to determine patient’s eligibility for the 
trial. The test will be used to screen the patient population for latent tuberculosis infection 
(Doherty, Van Vorhees and Lebwohl 2008).
This blood-based assay is specific for Mycobacterium tuberculosis and is not influenced by 
previous Bacillus Calmette-Guérin vaccination or exposure to other Mycobacteria species.
This test, in contrast to the purified protein derivative (PPD) skin test, is also insensitive to a 
booster effect since the patient is not exposed to the vaccine.
The assay measures the 
production of interferon-gamma and presents it relative to a negative and a positive control 
sample (Manuel and Kumar 2008).

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The QuantiFERON®-TB Gold assay test will be supplied by the central laboratory. Details on 
the collection, shipment of samples and reporting of results by the central laboratory are 
provided in the Laboratory Manual.
The results of a TB workup for a patient with a positive or indeterminate test must be
recorded in the eCRF.

If the test result is negative, the patient may be randomized

If the test result is positive, the investigator should perform a TB workup for the test result
as per local procedures.

Patients positive for latent TB per workup may be randomized to the study if sufficient
treatment has been initiated according to local routine clinical practice and will be
maintained for the prescribed duration.

Patients positive for active TB per workup are not eligible for the study.

Patients negative for TB per workup (no signs of latent or active TB) may be 
randomized to the study.

If the test result is indeterminate, it is recommended to repeat the test once. The 
investigator may decide to skip the repetition of the test and proceed directly to the workup
(however this is not recommended). If a TB workup was conducted prior to screening,
results from the workup can be used to assess eligibility if the workup was conducted
within 12 weeks prior to randomization.

If the second test is negative, the patient may be randomized.

If the second test is positive or indeterminate, the investigator should perform a TB 
workup as per local guidelines. The patient will not be eligible for randomization if: 
“active tuberculosis is present”, or if “latent tuberculosis is present” and is untreated as
per local guidelines.
Refer to Section 14 Appendix 2 to see a schematic of the tuberculosis screening 
process and patient eligibility with respect to TB testing.
6.4.9
Other baseline characteristics
Baseline characteristic data to be collected on all patients include (see also Table 6-1):

vital signs, hematology, clinical chemistry, viral serology (HIV, Hepatitis B and Hepatitis 
C), serum pregnancy, height, weight; BMI, HOMA-IR, hs-CRP, HbA1c, PASI, 
 
.
6.5
Treatment exposure and compliance
All administered doses of secukinumab or placebo will be recorded on the Dosage
Administration Record eCRF.  Compliance will be assessed at each visit by Novartis and 
CRO study personnel using the Dosage Administration Record eCRF, medication numbers,
Drug Label Form information, empty medication boxes/outer packaging brought back to site
by patient, and information collected by IRT.
Patients will be provided with a Self-Administration Log at Visit 8/Week 12 to record the date 
and time of all at-home study treatment administrations during the Double-blind Induction 
and Open-label Treatment Periods. Patients will be instructed to return to the study site at 

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each scheduled visit with their completed Self-Administration Log, where the dosing 
information will be transcribed by site staff into the Dosage Administration Record eCRF.
Patients will also be instructed to return all used/unused study treatment and packaging to the 
study site at each visit as part of the compliance check. The patient’s Self-Administration Log 
will be retained in the patient’s source documents. 
The investigator/qualified site staff should promote compliance by instructing patients to 
attend the study visits as scheduled, to take the study treatments exactly as prescribed, and by 
reiterating that compliance is necessary for patient safety and the validity of the study.
Additionally, site staff will contact patients via telephone at the time of scheduled at-
home dosing to check compliance and to ensure completion of the Self-Administration 
Log.  Likewise, patients should be instructed to contact the investigator/qualified site staff
if he/she is unable for any reason to attend a study visit as scheduled, or if he/she is unable 
for any reason to take the study treatment at home as prescribed.
6.6
Efficacy
Primary efficacy variables are response of psoriasis skin lesions to treatment as measured by:

Response in skin histology/K16 expression to treatment (yes, no)

PASI 90 (yes, no). 
The primary analysis time point will be at Week 12.
Results for the data collected from the assessments in Section 6.6.2 and Section 6.6.3 below 
will be included as a separate appendix to the Clinical Study Report (CSR).

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6.6.5
Assessment of total Body Surface Area (BSA) and Psoriasis Area and 
Severity Index (PASI)
The investigator or trained qualified designee will complete the PASI assessment at scheduled 
visits as indicated in Table 6-1.  Whenever possible, the same evaluator should perform this
assessment at all study visits for a given patient.
The total BSA affected by plaque psoriasis will be estimated by the investigator/trained 
qualified designee from the percentages of areas affected, including head, trunk, upper limbs
and lower limbs (see below for full details of the PASI assessment).  The following
calculations will be done electronically:  each reported percentage will be multiplied by its
respective body region corresponding factor (head=0.1, trunk=0.3, upper limbs=0.2, lower
limbs=0.4).  The resulting four percentages will be added up to estimate the total BSA
affected by plaque psoriasis.
A PASI score (Fredriksson and Pettersson 1978, Weisman et al 2003, Gottlieb et al 2005) will 
be derived as indicated in Table 6-4.  The head, trunk, upper limbs and lower limbs are 
assessed separately by the investigator/trained qualified designee for erythema, thickening
(plaque elevation, induration), and scaling (desquamation).  The average degree of severity of
each sign in each of the four body regions is assigned a score of 0-4.  The area covered by
lesions on each body region is estimated as a percentage of the total area of that particular 
body region.  The following practical details help the assessment:
1. The neck is assessed as part of the head
2. The axillae and groin are assessed as part of the trunk
3. The buttocks are assessed as part of the lower limbs
4. When scoring the severity of erythema, scales should not be removed.
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the body surface area, respectively, the PASI score is calculated 
electronically within the eCRF using the following formula:
PASI = 0.1(EH+IH+DH)AH + 0.2(EU+IU+DU)AU+ 0.3(ET+IT+DT)AT + 0.4(EL+IL+DL)AL
The keys for the letters are provided in Table 6-4.
PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a 
theoretic maximum of 72.0.
The baseline value for analysis of the PASI is collected at Visit 2/Baseline.  A copy of the 
PASI worksheet is provided in Section 16 Appendix 4.
Table 6-4
PASI scoring system
Body region
Erythema (E)
Thickening -
plaque elevation, 
induration (I)
Scaling –
desquamation 
(D)
Area score –
based on true 
area % (A)*
Head (H)†
0=none
0=none
0=none
0=no involvement
1=slight
1=slight
1=slight
1=>0-<10%
2=moderate
2=moderate
2=moderate
2=10-<30%
3=severe
3=severe
3=severe
3=30-<50%

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Body region
Erythema (E)
Thickening -
plaque elevation, 
induration (I)
Scaling –
desquamation 
(D)
Area score –
based on true 
area % (A)*
4=very severe
4=very severe
4=very severe
4=50-<70%
5=70-<90%
6=90-100%
Trunk (T)‡
0=none
0=none
0=none
0=no involvement
1=slight
1=slight
1=slight
1=>0-<10%
2=moderate
2=moderate
2=moderate
2=10-<30%
3=severe
3=severe
3=severe
3=30-<50%
4=very severe
4=very severe
4=very severe
4=50-<70%
5=70-<90%
6=90-100%
Upper
0=none
0=none
0=none
0=no involvement
limbs (U)
1=slight
1=slight
1=slight
1=>0-<10%
2=moderate
2=moderate
2=moderate
2=10-<30%
3=severe
3=severe
3=severe
3=30-<50%
4=very severe
4=very severe
4=very severe
4=50-<70%
5=70-<90%
6=90-100%
Lower
0=none
0=none
0=none
0=no involvement
limbs (L)§
1=slight
1=slight
1=slight
1=>0-<10%
2=moderate
2=moderate
2=moderate
2=10-<30%
3=severe
3=severe
3=severe
3=30-<50%
4=very severe
4=very severe
4=very severe
4=50-<70%
5=70-<90%
6=90-100%
*Percentage (not score) of body region (not whole body) affected will be entered in the eCRF
†Neck is assessed as part of the Head (H) body region
‡Axillae and groin are assessed as part of the Trunk (T) body region
§Buttocks are assessed as part of the Lower limbs (L) body region
Definitions of efficacy variables based on PASI
The following definitions will be used in this study based on the CHMP guidelines for 
psoriasis (CHMP/EWP/2454/02 2004):

 

PASI 90 response: patients achieving ≥90% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 90 responders


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6.6.6
Appropriateness of efficacy assessments
Determining the response of skin to psoriasis treatment, by using combined genetic studies 
including microarray technology with histopathology over the course of anti-TNF alpha 
treatment (etanercept) and anti-IL-17A (ixekizumab) treatment has been used previously and 
are well established methodology (Zaba et al 2007; Zaba et al 2009; Wang et al 2014).
 
 
Flow cytometry has been used to measure T-cell activation for skin diseases such as atopic 
dermatitis and psoriasis (Czarnowicki et al 2015).
The PASI is a standard and validated measurement for chronic plaque psoriasis.
 
 
6.7
Safety
All blood draws and safety assessments must be performed prior to study treatment
administration.  Appropriate safety assessments (e.g., evaluation of AEs and SAEs including 
injection site reactions) should be repeated after dosing with study treatment.
6.7.1
Physical examination
The physical examination, including general appearance, will be performed at the scheduled 
study visits as indicated in Table 6-1.
The physical examination is performed by a professionally trained physician or health 
professional licensed to perform physical examinations, and listed on FDA Form 1572. 
If indicated, based on medical history and/or symptoms, additional exams will be
performed at the discretion of the investigator.
If possible, assessments for an individual patient should be performed by the same member of 
the study site staff throughout the study.
Information for all physical examinations must be included in the source documentation at the 
study site.  Significant findings that are present prior to the patient signing informed consent 
must be included in the Medical History eCRF.  Significant findings made after the signing
of the informed consent which meet the definition of an AE (see Section 7) must be recorded
on the AE eCRF.

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6.7.2
Vital signs
Vital signs will be performed at the scheduled study visits as indicated in Table 6-1.  Vital 
signs include blood pressure (BP) and pulse measurements. BP will be measured using a 
standard sphygmomanometer with an appropriate sized cuff.
All clothing that covers the location of the cuff placement is to be removed by the patient.  
The patient should be asked to sit comfortably with the back supported and legs uncrossed; 
the arm should be supported so that the middle of the cuff is level with the right atrium (mid-
point of the sternum).  The patient should be instructed not to talk and relax as much as 
possible while the measurement is being taken.  The measurement should be taken after the 
patient has been in a seated position and has been resting for 5 minutes (Pickering et al 2005).  
Every effort should be made to use the same arm for the patient for all vital signs assessments 
and where possible, the same person performing the assessment.
Normal blood pressure will be defined as a systolic pressure of 90 to <120 mmHg, and a 
diastolic blood pressure of 60 to <80 mmHg under the measurement conditions outlined 
above. Notable blood pressure 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 (Chobanian et al 2003).
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 rates are a rate below 60 bpm 
(bradycardia) or above 100 bpm (tachycardia).
Whether action needs to be taken to address notable vital signs values will be decided by the 
investigator, taking into account the overall status of the patient. No specific action is pre-
defined as part of the study protocol.
6.7.3
Height and weight and waist circumference
The measurements will be performed at scheduled visits as indicated in Table 6-1.
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram (kg) in indoor 
clothing, but without shoes) will be measured. The body weight recorded at Visit 2/Baseline 
will be used to stratify randomization at Visit 2.
Waist circumference to the nearest centimeter (cm) will be measured using a tape measure.  
Starting at the top of the hip bone, bring the tape measure all the way around so that it is level 
with the belly button.  Make sure the tape measure is not too tight and that it is straight.  The 
patient should be instructed not to hold their breath during the measurement.
Body Mass Index (BMI) will be calculated within the eCRF.
6.7.4
Laboratory evaluations
Laboratory evaluations will be performed at the scheduled study visits as indicated in Table 6-
1.

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A central laboratory will be used for analysis of all specimens unless noted otherwise. 
Details on the collections, shipment of samples and reporting of results by the central
laboratory are provided to investigators in the Laboratory Manual.
Refer to the Laboratory Manual for identification of laboratory reference ranges, and notable 
values.
Whether or not any action needs to be taken to address notable laboratory values will be 
determined by the investigator/qualified site staff, taking into account the overall status of the
patient.  No specific action is pre-defined within this study protocol.
6.7.4.1
Hematology
Hematology assessments will be performed at the scheduled visits as indicated in Table 6-1
and include: hemoglobin, hematocrit, red blood cell count, white blood cell count with 
differential (neutrophils including bands, lymphocytes, monocytes, eosinophils, basophils)
and platelet count.
6.7.4.2
Clinical chemistry
Serum chemistry panel will be performed at the scheduled visits as indicated in Table 6-1 and 
includes: urea, creatinine, total bilirubin, alanine transaminase (ALT)/serum glutamic 
pyruvate transaminase (SGPT), aspartate transaminase (AST)/serum glutamic oxaloacetic
transaminase (SGOT), gamma glutamyl transpeptidatse (GGT), and alkaline phosphatase.
6.7.4.3
High-sensitivity C-reactive protein
High-sensitivity C-reactive protein (hs-CRP) will be measured by the central laboratory at the 
scheduled visits as indicated in Table 6-1.
6.7.4.4
Hemoglobin A1c
Hemoglobin A1c (HbA1c) will be measured by the central laboratory at the scheduled visits 
as indicated in Table 6-1.
6.7.4.5
  Fasting laboratory evaluations and HOMA-IR
Fasting (minimum 8 hour duration with water ad libitum) laboratory tests will be performed at 
scheduled visits as indicated in Table 6-1 and will include:

plasma glucose

insulin

lipids
Homeostatic model assessment of insulin resistance (HOMA-IR) values will be reported by 
the central laboratory at the scheduled visits as indicated in Table 6-1.
6.7.4.6
Viral serology
Viral serology will be performed at screening and will include:

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
Hepatitis screening: Hepatitis B surface antigen (HBsAg); Hepatitis C virus antibody 
(HCVAb)

HIV screening: HIV 1/2
6.7.5
Pregnancy and assessments of fertility
All pre-menopausal women who are not surgically sterile will have a serum β-hCG test
performed at screening (Visit 1). 
All women of childbearing potential will also have a urine pregnancy test performed locally at 
Visit 2/Baseline. Visit 8/Week 12, and Visit 15/Week 52.
Any woman with a confirmed positive pregnancy test during screening is not eligible for 
randomization.
A positive urine pregnancy test during the study requires immediate interruption of study 
treatment until serum β-hCG is performed and found to be negative. If the serum β-hCG test 
is positive, the patient must be discontinued from the study as described in Section 5.6.2.
6.7.6
Appropriateness of safety measurements
The safety assessments selected for this study are reliable and standard measures for a 
biologic immunomodulating agent in adult patients with psoriasis.
6.8
Other assessments
No additional tests will be performed on patients entered into this study.
7
Safety monitoring
7.1
Adverse events
An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or 
clinical investigation patient after providing written informed consent for participation in the 
study until the end of study visit. Therefore, an AE may or may not be temporally or causally 
associated with the use of a medicinal (investigational) product.
In addition, all reports of intentional misuse and abuse of the product are also considered an 
adverse event irrespective if a clinical event has occurred.
The occurrence of adverse events must be sought by non-directive questioning of the patient
at each visit during the study.
Adverse events also may be detected when they are 
volunteered by the patient during or between visits or through physical examination findings, 
laboratory test findings, or other assessments.
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria:

they induce clinical signs or symptoms, 

they are considered clinically significant, 

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
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 which are considered to be non-typical in a patient 
with underlying disease. Investigators have the responsibility for managing the safety of 
individual patients and identifying adverse events. Alert ranges for laboratory and other test 
abnormalities are included in Section 13 Appendix 1.
Adverse events must be recorded in the Adverse Events CRF under the signs, symptoms or 
diagnosis associated with them, accompanied by the following information:

the severity grade

mild: usually transient in nature and generally not interfering with normal activities

moderate: sufficiently discomforting to interfere with normal activities

severe: prevents normal activities

its relationship to the study treatment

Yes

No

its duration (start and end dates) or if the event is ongoing, an outcome of not 
recovered/not resolved must be reported

whether it constitutes a serious adverse event (SAE - see Section 7.2 for definition of SAE) 
and which seriousness criteria have been met

action taken regarding study treatment 
All adverse events must be treated appropriately. Treatment may include one or more of 
the following: 

no action taken (e.g. further observation only) 

study treatment dosage increased/reduced

study treatment interrupted/withdrawn

concomitant medication

non-drug therapy given 

patient hospitalized/patient’s hospitalization prolonged (see Section 7.2 for definition of 
SAE)

its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown)
Once an adverse event is detected, it must be followed until its resolution or until it is judged 
to be permanent, and assessment must be made at each visit (or more frequently, if necessary) 
of any changes in severity, the suspected relationship to the study drug, the interventions 
required to treat it, and the outcome.
Worsening of psoriasis in this study is evaluated via the use of the PASI 
and is not expected to be captured as an AE in the eCRF.  Exceptions include 
cases where:  a) a new type of psoriasis is diagnosed, e.g. guttate psoriasis, or b) the 
worsening of psoriasis is so severe that a qualitatively different status is reached.

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Information about common side effects already known about the investigational drug can be 
found in the Investigator Brochure (IB). This information will be included in the patient
informed consent and should be discussed with the patient during the study as needed. Any 
new information regarding the safety profile of the medicinal product 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 has then to be discussed with the patient.
The investigator must also instruct each patient to report any new adverse event (beyond the 
protocol observation period) that the patient, or the patient’s personal physician, believes 
might reasonably be related to study treatment. This information must be recorded in the 
investigator’s source documents; however, if the AE meets the criteria of an SAE, it must be 
reported to Novartis.
7.2
Serious adverse events
7.2.1
Definition of SAE
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)]
undesirable sign(s), symptom(s) or medical conditions(s)) which meets any one of the 
following criteria:

is fatal or life-threatening 

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:

routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (specify what this includes)

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

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 

social reasons and respite care in the absence of any deterioration in the patient’s 
general condition

is medically significant, e.g. defined as an event that jeopardizes the patient or may 
require medical or surgical intervention.
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.
Life-threatening in the context of a SAE refers to a reaction in which the patient was 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 Annex IV, ICH-E2D Guideline).
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 

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patient or might require intervention to prevent one of the other outcomes listed above.
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 (please refer to Annex IV, ICH-E2D Guideline).
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
7.2.2
SAE reporting
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 30 days after the last study visit must be reported to 
Novartis safety within 24 hours of learning of its occurrence. Any SAEs experienced after the 
30 day period after the last study visit should only be reported to Novartis safety if the 
investigator suspects a causal relationship to study treatment. 
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 to 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.
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form; all applicable sections of the form must be completed in order to provide a clinically 
thorough report. The investigator must assess the relationship of each SAE to study treatment, 
complete the SAE Report Form in English, and submit the completed form within 24 hours to 
Novartis.
Detailed instructions regarding the submission process and requirements for 
signature are to be found in the investigator folder provided to each site. 
Follow-up information is submitted as instructed in the investigator folder.
Each re-
occurrence, complication, or progression of the original event must be reported as a follow-up 
to that event regardless of when it occurs. The follow-up information should describe 
whether the event has resolved or continues, if and how it was treated, whether the blind was 
broken or not, and whether the patient continued or withdrew from study participation.
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert 
(new occurrence) and is thought to be related to the study treatment, a Drug Safety and 
Epidemiology Department associate 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.
7.3
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, patient or 
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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 collected in 
the Dose Administration Record eCRF irrespective of whether or not associated with an 
AE/SAE, and reported to Safety only if associated with an SAE. Misuse or abuse will be 
collected and reported in the safety database irrespective of it being associated with an 
AE/SAE.
Table 7-1 
Guidance for capturing the study treatment errors including 
misuse/abuse
Treatment error 
type
Document in Dose 
Administration (DAR) 
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
7.4
Pregnancy reporting
To ensure patient 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 must be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the local Novartis Drug Safety and Epidemiology Department. Pregnancy 
follow-up should be recorded on the same form and should include an assessment of the 
possible relationship to the study treatment.
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on an SAE form.
8
Data review and database management
8.1
Site monitoring
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and data capture requirements 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 patient records, the accuracy of data capture / data entry, the 
adherence to the protocol and to Good Clinical Practice, the progress of enrollment, and to 
ensure that study treatment is being stored, dispensed, and accounted for according to 

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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 CRA organization. Additionally, a central analytics organization may analyze data 
and identify risks and trends for site operational parameters, and provide reports to Novartis 
Clinical Teams to assist with trial oversight.
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on eCRFs must be traceable to these source documents in the 
patient's file. The investigator must also keep the original informed consent form signed by 
the patient (a signed copy is given to the patient).
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 all 
primary variables. 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 patients will be disclosed.
8.2
Data collection
The trial (including the control cohort of healthy volunteers) will be conducted in a fully 
validated Data Capture system which conforms to US CRF 21 Part 11 requirements. 
Investigator site staff will not be given access to the system until they have been trained. 
Designated investigator staff will enter the data required by the protocol into the Data Capture 
system. Automatic validation programs within the system check for data discrepancies in the 
CRFs and by generating appropriate error messages, allow the data to be confirmed or 
corrected by the investigator staff. The investigator staff must certify that the data entered are 
complete and accurate. After database lock, the investigator will receive copies of the patient 
data for archiving at the investigational site.
Designated investigator staff will enter the data required by the protocol into the OC/RDC 
system. Designated investigator site staff will not be given access to the system until they 
have been trained. 
Automatic validation procedures within the system check for data discrepancies during and 
after data entry and, by generating appropriate error messages, allow the data to be confirmed 
or corrected online by the designated investigator site staff. The Investigator must certify that 
the data entered into the electronic Case Report Forms are complete and accurate. After 
database lock, the investigator will receive copies of the patient data for archiving at the 
investigational site.
8.3
Database management and quality control
Novartis staff [or CRO working on behalf of Novartis] review the data entered into the CRFs 
by investigational staff for completeness and accuracy and instruct the site personnel to make 
any required corrections or additions. Queries are sent to the investigational site using an 

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electronic data query. Designated investigator site staff is required to respond to the query 
and confirm or correct the data. If the electronic query system is not used, a paper Data Query 
Form will be faxed to the site. Site personnel will complete and sign the faxed copy and fax it 
back to Novartis staff that will make the correction to the database. The signed copy of the 
Data Query Form is kept at the investigator site.
Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system. 
Concomitant procedures, non-drug therapies and adverse events 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 drug(s) dispensed to the patient and all dosage 
changes will be tracked using an Interactive Response Technology (IRT). The system will be 
supplied by a vendor, who will also manage the IRT database. The database will be sent 
electronically to Novartis (or a designated CRO).
Each occurrence of a code break via IRT 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. 
The occurrence of relevant protocol deviations will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 
locked and the treatment codes will be unblinded and made available for data analysis. Any 
changes to the database after that time can only be made after written agreement by Novartis 
Development management.
8.4
Data Monitoring Committee
Not required.
8.5
Adjudication Committee
Not required.
9
Data analysis
A designated Contract Research Organization will perform the statistical analysis.
It is planned that the data from all centers that participate in this protocol will be combined, so 
that an adequate number of patients will be available for analysis.
The analysis will be conducted on all patient data at the end of Week 12 and at the time the 
trial ends at Week 53. Any data analysis carried out independently by the investigator should 
be submitted to Novartis before publication or presentation.
Efficacy, safety, and other data will be summarized for all weeks up to Week 53.  For 
continuous variables, summary statistics (mean, standard deviation, median, 25th and 75th 
percentiles, interquartile range, minimum, and maximum) at each time point and for change 

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from baseline to each time point will be reported by treatment group.  For discrete variables, 
frequency counts and percentages at each time point will be reported by treatment group.
Primary 
 efficacy variables will be summarized for lesional 
 
samples.
9.1
Analysis sets 
The following analysis sets will be used for the statistical reporting and analyses:
Randomized Set: The Randomized Set includes all randomized patients.  
Safety Set: The Safety Set includes all patients who received at least one dose of study 
medication.  Patients will be included in the analysis according to treatment received.
Full Analysis Set:  The Full Analysis Set comprises all patients to whom study medication has 
been assigned.  Patients inappropriately randomized (e.g., IRT was called in error for 
randomization of a screen failed patient) will be excluded from this analysis set.  Following 
the intent-to-treat principle, patients will be analyzed according to the treatment they were 
assigned to at randomization.
9.2
Patient demographics and other baseline characteristics
Data will be summarized by stratum with respect to demographic and baseline characteristics 
of all patients for the Randomized Set and the Full Analysis Set.
9.3
Treatments
The number of patients and the length of time (in days) exposed to each treatment will be 
summarized for the Safety Set.
Concomitant medications will be summarized by treatment using frequency counts and 
percentages for the Safety Set.
Any condition entered as medical history or current medical condition at baseline will be 
coded using the MedDRA dictionary for the Safety Set. They will be summarized by system 
organ class and preferred term of the MedDRA dictionary.
9.4
Analysis of the primary variable(s)
9.4.1
Variable(s)
Response of psoriasis skin lesions to treatment as measured by:
a. Response in skin histology/K16 expression to treatment (yes, no)
b. PASI 90 (yes, no) 
The primary analysis time point will be at Week 12.
9.4.2
Statistical model, hypothesis, and method of analysis
For the two primary efficacy variables at each time point (response in skin histology/K16 
expression to treatment at Week 12, PASI 90 at Weeks 4, 8, and 12), 95% confidence interval 

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for the difference between the two treatment groups with respect to the percentage of patients 
who have the “event” will be calculated using the normal approximation to the binomial 
distribution.
The primary analysis of the primary efficacy variables will be based on the Full Analysis Set.
9.4.3
Handling of missing values/censoring/discontinuations
For the two primary efficacy variables at Week 12 (and other time points), a patient with a 
missing assessment will be considered as a non-responder.
9.4.4
Sensitivity analyses
The two primary efficacy variables will be analyzed at each time point for the Full Analysis 
Set using a logistic regression model with treatment and body weight (<90 kg, ≥90 kg) as 
explanatory variables (Stokes, Davis, and Koch, 2012).  The odds ratios and 95% confidence 
intervals for the odds ratios based on the fitted model will be reported.
Estimates of differences between the two proportions within each stratum will be calculated 
and examined for meaningful treatment-by-stratum interaction.
9.5
Analysis of secondary variables
9.5.1
Efficacy variables
The secondary efficacy objective (i.e., explore the modulation of subcutaneous adipose tissue
and skin inflammation from baseline to Week 52) will be assessed using the same two 
primary efficacy variables, but measured at Week 52.
9.5.2
Safety variables
The assessment of safety will be based mainly on the frequency of adverse events and 
laboratory data.  Other safety data, including vital signs (blood pressure, weight, waist 
circumference, BMI), and clinical laboratory variables (glucose, insulin, hs-CRP, HOMA-IR, 
HbA1c) will be summarized by stratum, as appropriate.
Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of patients having any adverse event, having an adverse event in each body system 
and having each individual adverse event.  Any other information collected (e.g., severity or 
relatedness to study medication) will be listed, as appropriate.
Adverse events and serious adverse events up to and including Week 12 visit will be included 
in the database for the analysis at the primary analysis time point (Week 12).  All Adverse 
events and serious adverse events will be included in the final database analysis (Week 53).
Laboratory variables and other safety variables will be summarized, as appropriate.
Analysis of safety data will be based on the Safety Set.

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9.7
Interim analyses
The database of this study will be locked twice, first after the end of double-blind treatment 
period (Week 12) and again at the end of the follow-up period (Week 53).  Data analyses will 
follow each database lock.  The main analysis for the primary objective will be done at Week 
12.  As Week 12 analysis considered primary and no specific hypothesis is pre-identified for 
testing, adjustment of significance level due to this interim analysis is irrelevant.
In addition, after all patients complete their baseline visit, the demographic and baseline 
characteristics may be summarized to help design new studies.

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9.8
Sample size calculation
The table below considers total sample sizes of 75 patients (50 in secukinumab group and 25 
in placebo group) and 99 patients (66 in secukinumab group and 33 in placebo group) to 
estimate the difference between the two groups with respect to the pooled estimate of the two 
percentages of patients who have the “event” at Week 12 for each of the two primary efficacy
variables.  The entries in the table are the “margin of error” (half-width of confidence interval) 
for a two-sided 95% confidence interval (Julious and Patterson, 2004; Kianifard and Islam, 
2011; nQuery Advisor 7.0).  
Table 9-1
Sample size calculations for percentage of patients who have the 
“event”
Percentage with “event”
Half-width of confidence 
interval for n = 75
Half-width of confidence 
interval for n = 99
30%
25.0%
21.4%
40%
26.5%
22.7%
50%
27.0%
23.2%
60%
26.5%
22.7%
70%
25.0%
21.4%
Based on the results in the above table, it was decided that approximately 75 randomized 
patients (50 in secukinumab group and 25 in placebo group) will be randomized in this 
exploratory study to estimate the difference in response rates between the two treatment 
groups.  
10
Ethical considerations
10.1
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 
Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in 
the Declaration of Helsinki.
10.2
Informed consent procedures
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if applicable after 
such consent has been provided by a legally acceptable representative(s) of the patient. In 
cases where the patient’s representative gives consent, the patient must be informed about the 
study to the extent possible given his/her understanding. If the patient is capable of doing so, 
he/she must indicate assent by personally signing and dating the written informed consent 
document or a separate assent form. 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 patient’s source documents. 

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Novartis will provide to investigators in a separate document a proposed informed consent 
form that complies with the ICH GCP guideline and regulatory requirements and is 
considered appropriate for this study. Any changes to the proposed consent form suggested 
by the investigator must be agreed to by Novartis before submission to the IRB/IEC, and a 
copy of the approved version must be provided to the Novartis or CRO monitor after IRB/IEC 
approval.
10.3
Responsibilities of the investigator and IRB/IEC
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion 
from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial 
protocol, written informed consent form, consent form updates, patient recruitment 
procedures (e.g., advertisements) and any other written information to be provided to patients.
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.
10.4
Publication of study protocol and results
The key design elements of this protocol will be posted in a publicly accessible database such 
as clinicaltrials.gov. In addition, upon study completion and finalization of the study report 
the results of this trial will be either submitted for publication and/or posted in a publicly 
accessible database of clinical trial results.
10.5
Quality Control and Quality Assurance
Novartis maintains a robust Quality Management (QM) system that includes all activities 
involved in quality assurance and quality control, including the assignment of roles and 
responsibilities, the reporting of results, and the documentation of actions and escalation of 
issues identified during the review of quality metrics, incidents, audits and inspections.
Audits of investigator sites, vendors, and Novartis systems are performed by Novartis Pharma 
Auditing and Compliance Quality Assurance, a group independent from those involved in 
conducting, monitoring or performing quality control of the clinical trial. 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.
11
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 patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances is an 

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investigator allowed to collect additional data or conduct any additional procedures for any 
research-related purpose involving any investigational drugs under the protocol.
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. 
11.1
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 intended to eliminate an apparent immediate 
hazard to patients 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 patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 7 Safety Monitoring must be followed.
12
References
References are available upon request
Chiricozzi, A., Guttman-Yassky, E., Suárez-Fariñas, M., Nograles, K., Tian, S., Cardinale, I., 
Chimenti, S. and Krueger, J. (2011). Integrative Responses to IL-17 and TNF-α in Human 
Keratinocytes Account for Key Inflammatory Pathogenic Circuits in Psoriasis. Journal of 
Investigative Dermatology, 131(3), pp.677-687.
Chiricozzi, A., Suárez-Fariñas, M., Fuentes-Duculan, J., Cueto, I., Li, K., Tian, S., 
Brodmerkel, C. and Krueger, J. (2016). Increased expression of interleukin-17 pathway genes 
in nonlesional skin of moderate-to-severe psoriasis vulgaris. Br J Dermatol, 174(1), pp.136-
145.
Chobanian, A., Bakris, G., Black, H., Cushman, W., Green, L., Izzo, J., Jones, D., Materson, 
B., Oparil, S., Wright, J. and Roccella, E. (2003). Seventh Report of the Joint National 
Committee for human medicinal products (CHMP), European Agency for the Evaluation of 
Medicinal Products (2004)] Guideline on Clinical Investigation of Medicinal Products 
Indicated for the Treatment of Psoriasis. EMEA, London.
Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. 
Hypertension, 42(6), pp.1206-1252.
Czarnowicki, T., Esaki, H., Gonzalez, J., Malajian, D., Shemer, A., Noda, S., Talasila, S., 
Berry, A., Gray, J., Becker, L., Estrada, Y., Xu, H., Zheng, X., Suárez-Fariñas, M., Krueger, J., 
Paller, A. and Guttman-Yassky, E. (2015). Early pediatric atopic dermatitis shows only a 
cutaneous lymphocyte antigen (CLA)+ TH2/TH1 cell imbalance, whereas adults acquire 
CLA+ TH22/TC22 cell subsets. Journal of Allergy and Clinical Immunology, 136(4), pp.941-
951.e3.

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Davidovici, B., Sattar, N., Jörg, P., Puig, L., Emery, P., Barker, J., van de Kerkhof, P., Ståhle, 
M., Nestle, F., Girolomoni, G. and Krueger, J. (2010). Psoriasis and Systemic Inflammatory 
Diseases: Potential Mechanistic Links between Skin Disease and Co-Morbid Conditions. 
Journal of Investigative Dermatology, 130(7), pp.1785-1796.
Doherty, S., Van Voorhees, A., Lebwohl, M., Korman, N., Young, M. and Hsu, S. (2008). 
National Psoriasis Foundation consensus statement on screening for latent tuberculosis 
infection in patients with psoriasis treated with systemic and biologic agents. Journal of the 
American Academy of Dermatology, 59(2), pp.209-217.
Endo, Y., Asou, H., Matsugae, N., Hirahara, K., Shinoda, K., Tumes, D., Tokuyama, H., 
Yokote, K. and Nakayama, T. (2015). Obesity Drives Th17 Cell Differentiation by Inducing 
the Lipid Metabolic Kinase, ACC1. Cell Reports, 12(6), pp.1042-1055.
Fredriksson, T. and Pettersson, U. (1978). Severe Psoriasis – Oral Therapy with a New 
Retinoid. Dermatology, 157(4), pp.238-244.
Gisondi, P., Cotena, C., Tessari, G. and Girolomoni, G. (2008). Anti–tumour necrosis factor-α 
therapy increases body weight in patients with chronic plaque psoriasis: a retrospective cohort 
study. Journal of the European Academy of Dermatology and Venereology, 22(3), pp.341-344.
Gottlieb, A., Griffiths, C., Ho, V., Lahfa, M., Mrowietz, U., Murrell, D., Ortonne, J., Todd, G., 
Cherill, R., Marks, I., Emady-Azar, S. and Paul, C. (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), pp.1219-1227.
Higa-Sansone, G., Szomstein, S., Soto, F., Brasecsco, O., Cohen, C. and Rosenthal, R. (2004). 
Psoriasis Remission after Laparoscopic Roux-En-Y Gastric Bypass for Morbid Obesity. 
Obesity Surgery, 14(8), pp.1132-1134.
Ho JC., Lee CH. and Lin SH. (2016). No significant reduction of circulating endothelial-
derived and platelet-derived microparticles in patients with psoriasis successfully treated with 
anti-IL-12/23. Biomed Res Int, 2016:2016, pp.1-6.
Julious, S. and Patterson, S. (2004). Sample sizes for estimation in clinical research. 
Pharmaceut. Statist., 3(3), pp.213-215.
Kianifard, F. and Islam, M. (2011). A guide to the design and analysis of small clinical studies. 
Pharmaceut. Statist., 10(4), pp.363-368.
Łuczyński, W., Grubczak, K., Moniuszko, M., Głowińska-Olszewska, B. and Bossowski, A. 
(2015). Elevated levels of Th17 cells in children with central obesity. Scandinavian Journal of 
Clinical and Laboratory Investigation, 75(7), pp.595-601.
Manuel, O. and Kumar, D. (2008). QuantiFERON ® -TB Gold assay for the diagnosis of 
latent tuberculosis infection. Expert Review of Molecular Diagnostics, 8(3), pp.247-256.
Mehta, N. (2011). Systemic and Vascular Inflammation in Patients With Moderate to Severe 
Psoriasis as Measured by [18F]-Fluorodeoxyglucose Positron Emission Tomography –
Computed Tomography (FDG-PET/CT). Arch Dermatol, 147(9), p.1031.
Naik, H., Natarajan, B., Stansky, E., Ahlman, M., Teague, H., Salahuddin, T., Ng, Q., Joshi, 
A., Krishnamoorthy, P., Dave, J., Rose, S., Doveikis, J., Playford, M., Prussick, R., Ehrlich, 
A., Kaplan, M., Lockshin, B., Gelfand, J. and Mehta, N. (2015). Severity of Psoriasis 
Associates With Aortic Vascular Inflammation Detected by FDG PET/CT and Neutrophil 

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Activation in a Prospective Observational StudySignificance. Arterioscler Thromb Vasc Biol, 
35(12), pp.2667-2676.
Naldi, L., Chatenoud, L., Linder, D., Belloni Fortina, A., Peserico, A., Virgili, A., Bruni, P., 
Ingordo, V., Scocco, G., Solaroli, C., Schena, D., Barba, A., Di Landro, A., Pezzarossa, E., 
Arcangeli, F., Gianni, C., Betti, R., Carli, P., Farris, A., Barabino, G. and Vecchia, C. (2005). 
Cigarette Smoking, Body Mass Index, and Stressful Life Events as Risk Factors for Psoriasis: 
Results from an Italian Case–Control Study. Journal of Investigative Dermatology, 125(1), 
pp.61-67.
Pickering, T., Hall, J., Appel L., Falkner, B., Graves, J., Hill, M., Jones, D., Kurtz, D., Sheps, 
S., Roccella, E. (2005). Recommendations for blood pressure measurement in humans and 
experimental animals: Part 1: Blood pressure measurement in humans. Circulation, 111, 
pp.697-716.
Reis, B., Lee, K., Fanok, M., Mascaraque, C., Amoury, M., Cohn, L., Rogoz, A., Dallner, O., 
Moraes-Vieira, P., Domingos, A. and Mucida, D. (2015). Leptin Receptor Signaling in T 
Cells Is Required for Th17 Differentiation. The Journal of Immunology, 194(11), pp.5253-
5260.
Renzo, L., Saraceno, R., Schipani, C., Rizzo, M., Bianchi, A., Noce, A., Esposito, M., Tiberti, 
S., Chimenti, S. and De Lorenzo, A. (2011). Prospective assessment of body weight and body 
composition changes in patients with psoriasis receiving anti-TNF-α treatment. Dermatologic 
Therapy, 24(4), pp.446-451.
 
 
Saraceno, R., Schipani, C., Mazzotta, A., Esposito, M., Direnzo, L., Delorenzo, A. and 
Chimenti, S. (2008). Effect of anti-tumor necrosis factor-α therapies on body mass index in 
patients with psoriasis. Pharmacological Research, 57(4), pp.290-295.
Stokes, M., Davis, C. and Koch, G. (2012). Categorical data analysis using the SAS system, 
third edition. Cary, NC: SAS Institute.
Tan, E., Baker, C. and Foley, P. (2013). Weight gain and tumour necrosis factor-alpha 
inhibitors in patients with psoriasis. Australasian Journal of Dermatology, 54(4), pp.259-263.
Wang, C., Suárez-Fariñas, M., Nograles, K., Mimoso, C., Shrom, D., Dow, E., Heffernan, M., 
Hoffman, R. and Krueger, J. (2014). IL-17 Induces Inflammation-Associated Gene Products 
in Blood Monocytes, and Treatment with Ixekizumab Reduces Their Expression in Psoriasis 
Patient Blood. Journal of Investigative Dermatology, 134(12), pp.2990-2993.
Weisman, S., Pollack, C. and Gottschalk, R. (2003). Psoriasis disease severity measures: 
comparing efficacy of treatments for severe psoriasis. Journal of Dermatological Treatment, 
14(3), pp.158-165.
Wolters, M. (2005). Diet and psoriasis: experimental data and clinical evidence. Br J 
Dermatol, 153(4), pp.706-714.
Zaba LC, Cardinale I, Gilleaudeau P, et al. (2007). Amelioration of epidermal hyperplasia by 
TNF inhibition is associated with reduced Th17 responses. J Exp Med; 204:3183–3194.

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Zaba LC, Krueger JG, Lowes MA (2009) Resident and "inflammatory" dendritic cells in 
human skin. J Invest Dermatol; 129:302–308.

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13
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 Section 6.7.2.
No specific action is pre-defined within this protocol to respond to specific notable laboratory
o r  v i t a l  s i g n s  values. It will be decided by the investigator/qualified site staff
whether and which specific action needs to be taken to respond to any notable values, taking 
into account the overall status of the patient.
Liver function and related variables
ALT (SGPT)
> 3 x Upper Limit of Normal (ULN)
AST (SGOT)
> 3 x ULN
Total bilirubin
> 1.5 x ULN
Alkaline phosphatase
> 2 x ULN
Renal function
Creatinine (serum)
> 1.5 x ULN
Hematology variables
Hemoglobin
≥ 2.0 g/dL decrease from baseline
Platelet count
< Lower Limit of Normal (LLN)
White blood cell
< 0.8 x LLN
Neutrophils
< 0.9 x LLN
Eosinophils
> 1.1 x ULN
Lymphocytes:
> 1.1 x ULN

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Appendix 2: Tuberculosis screening flowchart

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Appendix 4:  Psoriasis Area and Severity Index (PASI) and 
Body Surface Area (BSA)

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Appendix 5:  Sample Log Table
Sample log time schedule for sampling for 
 adipose tissue, 

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Week
Visit 
No.
Time Point
Blood - 
Microparticles 
& Leukocytes 
(FACS - 
ambient)
Blood - 
Microparticles 
& Leukocytes 
(FACS - 
ambient)
Blood - 
Microparticles 
& Leukocytes 
(FACS - frozen)
Blood - 
Microparticles 
& Leukocytes 
(FACS - frozen)
Sample #
Screening
1
Weeks -4 to Baseline
Baseline
2
predose
10 mL
601
10 mL
605
Week 1 (Day 8)
3
Week 2 (Day 15)
4
Week 3 (Day 22)
5
Week 4 (Day 29)
6
predose
Week 8 (Day 57)
7
Week 12 (Day 85)
8
predose
10 mL
602
10 mL
606
Week 13 (Day 92)
9
Week 16 (Day 113)
10
Week 24 (Day 169)
11
predose
10 mL
603
10 mL
607
Week 32 (Day 225)
12
Week 40 (Day 281)
13
Week 48 (Day 337)
14
Week 52 (Day 365)
15
10 mL
604
10 mL
608
Week 53 (Day 372)
Total mL:
40
40
Consolidated total mL: 147.5

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