Clinical trial NCT02690701
Conditions: Chronic Plaque Psoriasis
Keywords: psoriasis plaque psoriasis secukinumab AIN457 biologic monoclonal antibody aortic vascular inflammation
Sponsor: Novartis Pharmaceuticals
Start date: 2016-02-10; Completion date: 2018-02-19
Enrollment: 91 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study evaluated the effect of secukinumab compared to placebo on aortic vascular inflammation in adult patients who have moderate to severe plaque psoriasis that is poorly controlled by current psoriasis treatments.

Detailed description:

Arms: arm 1: Eligible patients received secukinumab 300 mg once weekly at Baseline, Weeks 1, 2, 3 and 4 followed by monthly dosing starting at Week 8 through Week 48 inclusive arm 2: Eligible patients received placebo doses once weekly at Baseline, Weeks 1, 2, 3 and 4 followed by a dose after four weeks at Week 8.

Beginning with the Week 12 dose, participants were switched to treatment with secukinumab 300 mg and were dosed once weekly at Weeks 12, 13, 14, 15 and 16 followed by monthly dosing through Week 48 inclusive.
Interventions: intervention 1: Secukinumab 300 mg intervention 2: Placebo
Intervention descriptions: intervention 1: Secukinumab 300 mg was provided in 1 mL prefilled syringes of 150 mg. Each dose of 300 mg secukinumab consisted of two secukinumab 150 mg injections once weekly for 5 weeks (Baseline, Weeks 1, 2, 3 and 4), followed by dosing every four weeks starting at Week 8 through Week 48 inclusive.

The patients (or caregivers) self-injected each dose at the study site under the supervision of site personnel when injections occurred on days of study visits.

The injections not occurring on days of study visits were done by the patients (or caregivers) at home. intervention 2: Placebo was provided in 1 mL prefilled syringe. Each placebo dose consisted of two placebo injections once weekly for five weeks (Baseline, Weeks 1, 2, 3, 4), then after four weeks at Week 8. At Week 12, patients were switched to receive 300 mg secukinumab once weekly for five weeks (Weeks 12, 13, 14, 15, 16) followed by monthly dosing through Week 48 inclusive.

The patients (or caregivers) self-injected each dose at the study site under the supervision of site personnel when injections occured on days of study visits.

The injections not occurring on days of study visits were done by the patients (or caregivers) at home.

Protocol documents:
Prot_000.pdf: 
US Clinical Development and Medical Affairs - General Medicine
AIN457/Secukinumab
Clinical Trial Protocol CAIN457AUS02 / NCT02690701
A randomized, double-blind, placebo-controlled, parallel-
group, multicenter study to evaluate the effect of 
secukinumab on aortic vascular inflammation and 
cardiometabolic biomarkers after 12 weeks of treatment, 
compared to placebo, and up to 52 weeks of treatment with 
secukinumab in adult subjects with moderate to severe 
chronic plaque-type psoriasis
Document type:
Amended Protocol Version
Version number:
v03 (Clean)
Development phase:
IV
Release date:
27-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 2.0, November, 2013


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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 3 ....................................................................................................................10
Protocol summary..............................................................................................................11
1
Introduction .......................................................................................................................17
1.1
Background............................................................................................................17
1.2
Purpose ..................................................................................................................18
2
Study objectives.................................................................................................................18
2.1
Primary objective(s)...............................................................................................18
2.2
Secondary objectives .............................................................................................18
18
3
Investigational plan ...........................................................................................................19
3.1
Study design...........................................................................................................19
3.1.1
Screening period (Screening to randomization)....................................19
3.1.2
Double-blind treatment period (Randomization through Week 12 pre-
dose)......................................................................................................20
3.1.3
Double-blind induction period (Week 12 dose through Week 15 dose)21
3.1.4
Open-label treatment period (Week 16 through Week 52)...................21
3.2
Rationale of study design.......................................................................................22
3.3
Rationale of dose/regimen, route of administration and duration of treatment.....23
3.4
Rationale for choice of comparator .......................................................................23
3.5
Purpose and timing of interim analyses/design adaptations..................................23
3.6
Risks and benefits..................................................................................................23
4
Population..........................................................................................................................27
4.1
Inclusion criteria ....................................................................................................27
4.2
Exclusion criteria...................................................................................................28
5
Treatment...........................................................................................................................31
5.1
Protocol requested treatment .................................................................................31
5.1.1
Study treatment .....................................................................................31


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5.1.2
Additional study treatment....................................................................31
5.2
Treatment groups...................................................................................................31
5.3
Treatment Assignment, randomization..................................................................32
5.4
Treatment blinding.................................................................................................33
5.5
Treating the subject................................................................................................34
5.5.1
Subject numbering ................................................................................34
5.5.2
Dispensing the study treatment.............................................................34
5.5.3
Handling of study treatment..................................................................34
5.5.4
Instructions for prescribing and taking study treatment........................35
5.5.5
Permitted dose adjustments and interruptions of study treatment ........36
5.5.6
Rescue medication ................................................................................36
5.5.7
Concomitant treatment..........................................................................37
5.5.8
Prohibited Treatment.............................................................................37
5.5.9
Discontinuation of study treatment .......................................................39
5.5.10
Withdrawal of consent ..........................................................................40
5.5.11
Loss to follow-up ..................................................................................41
5.5.12
Emergency breaking of assigned treatment code..................................41
5.5.13
Study completion and post-study treatment..........................................41
5.5.14
Early study termination.........................................................................42
6
Visit schedule and assessments .........................................................................................42
6.1
Information to be collected on screening failures..................................................49
6.2
Subject demographics/other baseline characteristics.............................................49
6.2.1
Demographics .......................................................................................49
6.2.2
Psoriasis history / Prior psoriasis therapies...........................................49
6.2.3
Smoking history ....................................................................................49
6.2.4
Alcohol use history ...............................................................................50
6.2.5
Comorbidities – cardiovascular history ................................................50
6.2.6
Relevant medical history / Current medical conditions........................50
6.2.7
Prior and concomitant medications.......................................................50
6.2.8
Determination of tuberculosis status.....................................................50
6.2.9
Other baseline characteristics................................................................52
6.3
Treatment exposure and compliance .....................................................................52
6.4
Efficacy..................................................................................................................52


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6.4.1
Target (arterial vascular uptake) to background (venous blood pool) 
ratio from the aorta................................................................................53
6.4.2
Cardiometabolic biomarkers.................................................................54
6.4.3
Assessment of total body surface area (BSA) and Psoriasis Area and 
Severity Index (PASI)...........................................................................55
6.4.4
Investigator’s Global Assessment (IGA mod 2011) .............................57
6.4.5
Health-related quality of life (HRQoL).................................................58
6.4.6
Appropriateness of efficacy assessments..............................................58
6.5
Safety.....................................................................................................................59
6.5.1
Physical examination ............................................................................59
6.5.2
Vital signs..............................................................................................60
6.5.3
Height and weight .................................................................................60
6.5.4
Laboratory evaluations..........................................................................61
6.5.5
Pregnancy and assessments of fertility .................................................61
6.5.6
Appropriateness of safety measurements..............................................62
6.6
Other assessments..................................................................................................62
7
Safety monitoring..............................................................................................................62
7.1
Adverse events.......................................................................................................62
7.2
Serious adverse events...........................................................................................63
7.2.1
Definition of SAE .................................................................................63
7.2.2
SAE reporting........................................................................................64
7.3
Pregnancy reporting...............................................................................................65
8
Data review and database management.............................................................................66
8.1
Site monitoring ......................................................................................................66
8.2
Data collection.......................................................................................................66
8.3
Database management and quality control............................................................67
8.4
Data Monitoring Committee..................................................................................67
8.5
Adjudication Committee........................................................................................67
9
Data analysis......................................................................................................................67
9.1
Analysis sets ..........................................................................................................68
9.2
Subject demographics and other baseline characteristics......................................68
9.3
Treatments .............................................................................................................68
9.4
Analysis of the primary variable............................................................................69
9.4.1
Variable.................................................................................................69


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9.4.2
Statistical model, hypothesis, and method of analysis..........................69
9.4.3
Handling of missing values/censoring/discontinuations.......................69
9.4.4
Supportive analyses...............................................................................69
9.5
Analysis of secondary variables ............................................................................70
9.5.1
Efficacy variables..................................................................................70
9.5.2
Safety variables .....................................................................................70
9.5.3
Resource utilization...............................................................................71
9.5.4
Pharmacokinetics ..................................................................................71
9.5.5
Pharmacogenetics/pharmacogenomics .................................................71
9.5.6
Other biomarkers...................................................................................71
9.5.7
PK/PD ...................................................................................................71
9.6
Interim analyses.....................................................................................................71
9.7
Sample size calculation..........................................................................................71
10 Ethical considerations........................................................................................................71
10.1
Regulatory and ethical compliance........................................................................71
10.2
Informed consent procedures.................................................................................72
10.3
Responsibilities of the investigator and IRB/IEC..................................................72
10.4
Publication of study protocol and results...............................................................73
11 Protocol adherence ............................................................................................................73
11.1
Protocol Amendments ...........................................................................................73
12 References .........................................................................................................................73
13 Appendices ........................................................................................................................76
13.1
Appendix 1: Clinically notable laboratory values and vital signs .........................76
13.2
Appendix 2: Tuberculosis screening flowchart.....................................................77
13.3
Appendix 3: Psoriasis Area and Severity Index (PASI) and Body Surface Area 
(BSA).....................................................................................................................78
13.4
Appendix 4: Investigator’s Global Assessment (IGA mod 2011).........................79
13.5
Appendix 5: Dermatology Life Quality Index (DLQI) .........................................80
List of tables
Table 3-1
Clinical outcomes at Week 12 in adults with plaque psoriasis in Trials 
1 and 2...................................................................................................25
Table 3-2
Clinical outcomes at Week 12 in adults with plaque psoriasis in Trials 
3 and 4...................................................................................................25


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Table 5-1
Overview of study treatment.................................................................32
Table 5-2
Prohibited treatment..............................................................................38
Table 6-1
Assessment schedule.............................................................................44
Table 6-2
PASI scoring system .............................................................................56
Table 6-3
IGA mod 2011 rating scale ...................................................................57
List of figures
Figure 3-1
Study design..........................................................................................22


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List of abbreviations
AE
adverse event
ALT (SGPT)
alanine aminotransferase
ANCOVA
Analysis of covariance
AST (SGOT)
aspartate aminotransferase
BSA
Body Surface Area
CFR
US Code of Federal Regulations 
eCRF
electronic Case Report Form
CRO
Contract Research Organization
CV
cardiovascular
DICOM
Digital Imaging and Communication in Medicine
DLQI
Dermatology Life Quality Index
DS&E
Drug Safety & Epidemiology
DSM
Drug Supply Management
EDC
Electronic Data Capture
FDG-PET/CT
[18F]-fluorodeoxyglucose positron emission tomography with computer 
assisted tomography
GCP
Good Clinical Practice
hCG
human chorionic gonadotropin
HDL
high-density lipoprotein
HIV
human immunodeficiency virus
HRQoL
Health-related Quality of Life
IB
Investigator’s Brochure
ICF
informed consent form
ICH
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IFU
Instructions for Use (secukinumab)
IGA mod 2011
Novartis Investigator’s Global Assessment modified 2011


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IL
Interleukin
IMT
intima-media thickness
i.v.
intravenous
IRB
Institutional Review Board
IRT
Interactive Response Technology
IUD
intrauterine device
IUS
intrauterine system
LFT
Liver function test (raised serum transaminases and/or bilirubin levels)
LOCF
Last-observation-carried-forward
MedDRA
Medical dictionary for regulatory activities 
MRI
magnetic resonance imaging
MTX
methotrexate
OC/RDC
Oracle Clinical/Remote Data Capture
OTC
over-the-counter
PASI
Psoriasis Area and Severity Index
PFS
prefilled syringe
PUVA
psoralen ultraviolet A
SAE
serious adverse event
s.c.
subcutaneous
SUSAR
Suspected Unexpected Serious Adverse Reactions
SUV
standardized uptake value
TB
tuberculosis
TBR
target to background ratio
TCS
topical corticosteroids
ULN
upper limit of normal
UV
ultraviolet
UVA
ultraviolet A
UVB
ultraviolet B
WBC
white blood cells
WHO
World Health Organization 


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Glossary of terms
Assessment
A procedure used to generate data required by the study
Cohort 
A group of newly enrolled patients treated at a specific dose and 
regimen (i.e. treatment group) at the same time
Control drug
Any drug (an active drug or an inactive drug, such as a placebo) 
which is used as a comparator to the drug being tested in the trial
Dose level
The dose of drug given to the patient (total daily or weekly etc.)
Enrollment
Point/time of patient entry into the study at which informed consent 
must be obtained (i.e. prior to starting any of the procedures described 
in the protocol)
Medication number
A unique identifier on the label of each investigational/study drug 
package in studies that dispense medication using an IRT system
Protocol
A written account of all the procedures to be followed in a trial, which 
describes all the administrative, documentation, analytical and clinical 
processes used in the trial.
Period
A portion of the study which serves a specific purpose. Typical periods
are: screening/recruitment, wash-out, treatment, and follow-up
Premature subject/patient 
withdrawal
Point/time when the patient exits from the study prior to the planned 
completion of all study treatment administration and/or assessments; 
at this time all study treatment administration is discontinued and no 
further assessments are planned, unless the patient will be followed 
for progression and/or survival
Randomization number
A unique identifier assigned to each randomized patient, 
corresponding to a specific treatment arm assignment
Study 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.”
Study treatment
All investigational drug(s) whose properties are being tested in the 
study as well as their associated treatment controls. 
This includes any placebos, any active controls, as well as approved 
drugs used outside of their indication/approved dosage or tested in a 
fixed combination. 
Investigational treatment generally does not include protocol-specified 
concomitant background therapies  when these are standard 
treatments in that indication
Study treatment 
discontinuation
Point/time when patient permanently stops taking study treatment  for 
any reason; may or may not also be the point/time of premature 
patient withdrawal
Subject Number 
A number assigned to each patient who enrolls into the study 
Variable
A measured value or assessed response that is determined in specific 
assessments and used in data analysis to evaluate the drug being 
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Amendment 3
Rationale for amendment
The purpose of Amendment 3 is to revise the list of cardiometabolic biomarkers under 
investigation in this study.  The following sections have been updated to reflect the correct 
cardiometabolic biomarkers:

Protocol Summary

Section 2.2

Section 6.4

Section 6.4.2
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined font for insertions.
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committees (IECs) and Health Authorities as required.
.


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Protocol summary
Protocol number
CAIN457AUS02
Title
A 
randomized, 
double-blind, 
placebo-controlled, 
parallel-group, 
multicenter study to evaluate  the effect of secukinumab on aortic 
vascular inflammation and cardiometabolic biomarkers after 12 weeks of 
treatment, compared to placebo, and up to 52 weeks of treatment with 
secukinumab in adult subjects with moderate to severe chronic plaque-
type psoriasis
Brief title
Study to evaluate the effect of secukinumab compared to placebo on 
aortic vascular inflammation in subjects with moderate to severe plaque 
psoriasis
Sponsor and Clinical 
Phase
Novartis / Phase IV
Investigation type
Drug
Study type
Interventional
Purpose and rationale
Secukinumab targets Interleukin 17a (IL-17a), which is increasingly 
understood to be a critical component of the pathophysiology of psoriasis,
and evolving research
also suggests that IL-17 may promote 
cardiovascular disease. This study will provide a comparison of 
secukinumab to placebo with respect to aortic vascular inflammation at 
12 weeks of treatment, and up to 52 weeks of treatment in subjects with 
moderate to severe plaque psoriasis.
Primary Objective(s) 
To evaluate the effect of secukinumab compared to placebo on aortic 
vascular inflammation with respect to the change from baseline in the 
target (arterial vascular uptake) to background (venous blood pool) ratio 
from the aorta
Secondary Objectives

To evaluate the effect of secukinumab compared to placebo with 
respect to change from baseline in cardiometabolic biomarkers 
(cardiometabolic 
function 
[lipid 
particle 
size, 
HDL 
function 
(cholesterol efflux)], measures of inflammation [TNF-Alpha, IL-6, C-
reactive protein, GlycA], adiposity [leptin and adiponectin], insulin 
resistance [insulin levels/glucose to yield HOMA-IR], and markers 
predictive of diabetes [apolipoprotein B, ferritin, IL-2 receptor A, IL-
18, and fetuin-A]) at Week 12

To evaluate the effect of secukinumab compared to placebo in 
subjects with moderate to severe chronic plaque-type psoriasis with 
respect to change from baseline in the PASI 75, 90 and 100 
response rates at Week 12

To evaluate the effect of secukinumab compared to placebo in 
subjects with moderate to severe chronic plaque-type psoriasis with 
respect to the Investigator’s Global Assessment mod 2011 (IGA mod 
2011) 0 or 1 response at Week 12


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
To evaluate the effects of secukinumab compared to placebo with 
respect to change from baseline in the Dermatology Life Quality 
Index (DLQI) total score at Week 12

To evaluate the clinical safety and tolerability of secukinumab as 
assessed by vital signs, clinical laboratory variables, and adverse 
event monitoring
Study design
This is a randomized, double-blind, placebo-controlled, parallel-group, 
multicenter study in approximately 84 subjects with moderate to severe 
plaque psoriasis. The study consists of four periods:  Screening (from 1 
to 4 weeks); Double-blind Treatment Period (12 weeks); Double-blind 
Induction Period (4 weeks); and Open-label Treatment Period (36 
weeks).
At Visit 2, eligible subjects will be randomized in a 1:1 ratio to one of two 
treatment groups – secukinumab or placebo. At the end of the Double-
blind Treatment Period, all subjects receiving placebo will be switched to 
secukinumab treatment for the remainder of the study. 
Population
The study population will consist of male and female subjects at least 18 
years of age with moderate to severe plaque-type psoriasis who are
candidates for systemic therapy or phototherapy.
Inclusion criteria

Provide written, signed and dated informed consent before any study-
related activity is performed; where relevant, a legal representative will
also sign the informed study consent according to local laws and 
regulations

Males and females ≥18 years of age at time of screening

Clinical diagnosis of chronic plaque-type psoriasis at least 6 months 
prior to randomization as determined by subject interview of his/her 
medical history and confirmation of diagnosis through physical 
examination by the Investigator

Moderate to severe plaque psoriasis as defined at Baseline by:
o
≥10% Body Surface Area (BSA) involvement and
o
PASI score of ≥12 and
o
IGA mod 2011 score of ≥3 (based on a scale of 0 – 4)

Candidate for systemic therapy, defined as having plaque psoriasis 
inadequately controlled by:
o
topical treatment and/or
o
phototherapy and/or
o
previous systemic therapy

Physical examination and FDG-PET/CT scan without clinically 
significant findings that would meaningfully alter the risk-benefit 
profile of secukinumab in the Investigator’s opinion, and clinical 
laboratory results within laboratory reference ranges, or abnormal 
results that are deemed to be not clinically significant by the 
Investigator


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Exclusion criteria

Forms of diagnosed psoriasis other than chronic plaque psoriasis
(e.g., erythrodermic, generalized or localized pustular psoriasis, or new 
onset guttate psoriasis)

Previous exposure to secukinumab or any other biologic drug directly 
targeting IL-17A or IL-17RA receptors (e.g., ixekizumab, or 
brodalumab)

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

Ongoing use of prohibited psoriasis treatments (e.g., topical or 
systemic corticosteroids,
other topical medications, systemic 
psoriasis treatments oral or biological, UV therapy)

Women of child-bearing potential not using effective methods of 
contraception, pregnant or nursing women

Positive serology for human immunodeficiency virus (HIV), hepatitis
B or C infection, or known history of other severe, recurrent or 
persistent infections

Any underlying condition which significantly immunocompromises 
the subject and/or places the subject at unacceptable risk for
receiving an immunomodulatory therapy

History of an ongoing, chronic or recurrent infectious disease, or
evidence of tuberculosis infection

Plans for administration of live vaccines during the study period or 6 
weeks before randomization
Study drug and control 
drug
Study drug:

Secukinumab, liquid formulation in a prefilled syringe (PFS) for 
subcutaneous injection
Control drug:

Placebo to secukinumab, liquid formulation in a prefilled syringe 
(PFS) for subcutaneous injection
Efficacy assessments

Target (arterial vascular uptake) to background (venous blood pool) 
ratio from the aorta as measured by FDG-PET/CT

Cardiometabolic biomarkers: (cardiometabolic function [lipid particle 
size, HDL function (cholesterol efflux)], measures of inflammation 
[TNF-Alpha, IL-6, C-reactive protein, GlycA], adiposity [leptin and 
adiponectin], insulin resistance [insulin levels/glucose to yield HOMA-
IR], and markers predictive of diabetes [apolipoprotein B, ferritin, IL-2 
receptor A, IL-18, and fetuin-A])

PASI: Psoriasis Area and Severity Index

IGA mod 2011: Investigator’s Global Assessment modified 2011


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
DLQI: Dermatology Life Quality Index
Safety assessments

Adverse events and serious adverse events

Laboratory assessments (e.g., hematology, clinical chemistry, viral 
serology, serum and urine pregnancy)

Vital signs, 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 subjects will be 
available for analysis.
Unless otherwise specified, all statistical tests will be conducted against a 
two-sided alternative hypothesis, employing a significance level of 0.05.
The following analysis sets will be used for the statistical reporting and 
analyses:
Randomized Set: The randomized set includes all subjects who were 
randomized.
Safety Set: The Safety Set includes all subjects who received at least one 
dose of study medication. Subjects will be analyzed according to 
treatment received.
Full Analysis Set:  The Full Analysis Set includes all subjects to whom 
study 
medication 
has 
been 
assigned. 
Subjects 
inappropriately 
randomized (e.g., IRT was called in error for randomization of a screen 
failed subject) will be excluded from this analysis set.  
Data will be summarized with respect to demographic and baseline 
characteristics 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.
The primary efficacy variable is the change from baseline in the target 
(arterial vascular uptake) to background (venous blood pool) ratio from 
the aorta. Target to background ratio is considered the standard reporting 
variable based on FDG-PET/CT scans in vascular studies (see Section 
6.4.1). The primary analysis time point will be at Week 12.
The primary efficacy variable will be analyzed by an analysis of 
covariance (ANCOVA) model with treatment, baseline, and body weight 
(<90 kg, ≥90 kg) as explanatory variables. The least squares means of 
the two treatment groups, least squares mean difference of the treatment 
groups, 95% confidence interval for the difference in the two treatment 
groups, and p-value based on the fitted linear model will be reported.  
Missing data will be imputed using the last-observation-carried-forward 
(LOCF) method. If a subject has no post-baseline value, the missing 
value will not be imputed and the subject will be removed from the 


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analysis.
A supportive nonparametric analysis will be performed to examine the 
consistency of results if the assumption of normality for the distribution of 
the primary efficacy variable is not tenable. For this supportive analysis, 
the primary efficacy variable will be analyzed using the stratified Wilcoxon 
rank-sum test with modified ridit scores (van Elteren’s test), adjusting for 
body weight (<90 kg, ≥90 kg) (Stokes, Davis, and Koch, 2012).
The primary analysis and supporting analysis of the primary efficacy 
variable will be based on the Full Analysis Set.
The secondary efficacy variables are the following:
•
Change from baseline in each biomarker (see Section 6.4)
•
PASI 75 response (yes, no)
•
PASI 90 response (yes, no)
•
PASI 100 response (yes, no)
•
IGA mod 2011 score of 0 or 1 (yes, no)
•
Change from baseline in DLQI total score
Change from baseline in each biomarker and change from baseline in 
DLQI total score will be analyzed at each time point using the same 
ANCOVA model as for the primary efficacy variable, and missing data will 
be imputed using the LOCF method.
IGA mod 2011 score of 0 or 1 and PASI 75 / 90 / 100 responses will be 
analyzed at each time point using the Cochran-Mantel-Haenszel test to 
compare secukinumab and placebo, adjusting for body weight (<90 kg, 
≥90 kg) (Stokes, Davis, and Koch, 2012). A 95% confidence interval for 
the difference between the two treatment groups in the proportion of 
subjects who are responders will be calculated using the normal 
approximation to the binomial distribution. For response (yes, no) at 
Week 12 (and other time points), a subject with a missing assessment 
will be considered as a responder (yes) if the subject meets the response 
criterion at the time of premature discontinuation from the study. 
Otherwise, the subject will be considered as a non-responder (no).
Analyses of the secondary efficacy variables will be based on the Full 
Analysis Set.
The assessment of safety will be based mainly on the frequency of 
adverse events and laboratory data. Other safety data (e.g., vital signs 
and special tests) will be considered, as appropriate.
Analysis of safety data will be based on the Safety Set.
The sample size was based on change from baseline in the target 
(arterial vascular uptake) to background (venous blood pool) ratio (TBR) 
from the aorta. Using a t-test, a clinically important mean treatment 
difference of 0.15, a (common) standard deviation (SD) of 0.196, an 
allocation ratio of 1:1, a two-sided significance level of 0.05, and a power 
of 0.90, it was determined that approximately 74 subjects (37 in each 


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treatment group) are necessary (nQuery Advisor 7.0) (Bissonnette et al 
2013; Tawakol et al 2013). Without adjusting for multiplicity, the sample 
size of 74 subjects will also provide at least 0.90 power for other 
biomarkers (see Section 6.4.2) if the treatment difference is 0.76 SD or 
smaller. The general threshold for clinical importance is 1 SD. Allowing 
for a loss to follow-up rate of 0.10, approximately 84 subjects (42 in each 
treatment group) will be randomized.
Key words
Plaque psoriasis, vascular inflammation, secukinumab, biologic, 
monoclonal antibody


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1
Introduction
1.1
Background
Psoriasis is a chronic, immune-mediated, inflammatory skin condition characterized by 
exacerbations and remissions. It is estimated to affect approximately 2% of the US population 
(National Psoriasis Foundation 2014).
Psoriasis is associated with defects in high-density lipoprotein (HDL) function, insulin resistance, 
and increased aortic vascular inflammation as measured by [18F]-fluorodeoxyglucose positron 
emission tomography with computer assisted tomography (FDG-PET/CT). These changes found 
in FDG-PET/CT would be the equivalent to a decade of aging in an individual without psoriasis
(Mehta et al 2011). Patients with moderate to severe psoriasis have an increased risk of 
myocardial infarction, stroke, and cardiovascular (CV) death independent of traditional risk 
factors (Gelfand et al 2006; Gelfand et al 2009; Mehta et al 2010; Ogdie et al 2015). 
Observational data suggest that immune modulation with methotrexate or TNF inhibitors can 
lower the risk of major cardiovascular events in this at-risk population (Roubille et al 2015). 
Interleukin 17a (IL-17a; also known as IL-17) is increasingly understood to be a critical 
component of the pathophysiology of psoriasis and evolving literature suggests that IL-17 may 
also promote cardiovascular disease (Abbas et al 2015; Erbel et al 2014; Karbach et al 2014). 
Secukinumab is a recombinant high-affinity fully human monoclonal anti-human IL-17A 
antibody of the immunoglobulin (Ig) G1/κ-class. Secukinumab binds to human IL-17A and
neutralizes the bioactivity of this cytokine. Secukinumab has demonstrated efficacy in reducing 
psoriasis skin severity. Psoriasis skin severity directly relates to vascular inflammation and 
cardiovascular comorbidity (Naik et al 2015; Yeung et al 2013). Moreover, IL-17 has been shown 
to activate endothelial cells, promote platelet aggregation and associate with activated neutrophils, 
therefore, blockade of this pathway would benefit these key aspects of atherogenesis (Erbel et al 
2011).
As it has been demonstrated that psoriasis is an independent risk factor for myocardial infarction, 
cutting edge approaches have since been developed to measure the impact of psoriasis on 
pathways known to be causally related to vascular events (e.g., HDL function, aortic vascular 
inflammation). For example, the primary outcome for this study is aortic vascular inflammation 
as measured by FDG-PET/CT which allows for the anatomical localization and measurement of 
CD68+ macrophage metabolic activity. 
Vascular inflammation is quantified using target to background ratio (TBR) which measures the 
PET signal in the aorta relative to background (i.e., venous blood pool) and is a widely used 
metric. Aortic inflammation measured by FDG-PET/CT is reliable (operator independent) (Mehta 
et al 2012), strongly predictive of future cardiovascular events (Figueroa et al 2013), and is 
highly sensitive to changes from risk factor modification (statins) (Tawakol et al 2013) to 
therapeutic lifestyle changes (Lee et al 2008) known to lower the risk of cardiovascular events. 


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Therefore, FDG-PET/CT represents an important method of measuring cardiovascular disease 
and risk.
1.2
Purpose 
The purpose of this study is to evaluate the effect of secukinumab compared to placebo on aortic 
vascular inflammation in subjects with moderate to severe plaque psoriasis. In addition, this study
will evaluate the effect of longer-term treatment with secukinumab (up to 52 weeks) on aortic vascular 
inflammation.
2
Study objectives
2.1
Primary objective(s)
The primary objective is to evaluate the effect of secukinumab 300 mg s.c. compared to placebo 
on aortic vascular inflammation with respect to the change from baseline in the target (arterial 
vascular uptake) to background (venous blood pool) ratio from the aorta. The primary analysis 
time point will be at Week 12.
2.2
Secondary objectives

To evaluate the effect of secukinumab compared to placebo with respect to change from 
baseline in cardiometabolic biomarkers (cardiometabolic function [lipid particle size, HDL 
function (cholesterol efflux)], measures of inflammation [TNF-Alpha, IL-6, C-reactive 
protein, GlycA], adiposity [leptin and adiponectin], insulin resistance [insulin levels/glucose 
to yield HOMA-IR], and markers predictive of diabetes [apolipoprotein B, ferritin, IL-2 
receptor A, IL-18, and fetuin-A]) at Week 12

To evaluate the effect of secukinumab compared to placebo in subjects with moderate to 
severe chronic plaque-type psoriasis with respect to change from baseline in the PASI 75, 90 
and 100 response rates at Week 12

To evaluate the effect of secukinumab compared to placebo in subjects with moderate to 
severe chronic plaque-type psoriasis with respect to the Investigator’s Global Assessment 
mod 2011 (IGA mod 2011) 0 or 1 response at Week 12

To evaluate the effects of secukinumab compared to placebo with respect to change from 
baseline in the Dermatology Life Quality Index (DLQI) total score at Week 12

To evaluate the clinical safety and tolerability of secukinumab as assessed by vital signs, 
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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 84 subjects with moderate to severe chronic plaque-type psoriasis will be 
randomized from approximately 10 investigative sites in the United States.
The study consists of four periods:  Screening (from 1 to 4 weeks); Double-blind Treatment 
Period (12 weeks); Double-blind Induction Period (4 weeks); and Open-label Treatment Period 
(36 weeks). A schematic of the study design and visits is presented in Figure 3-1, while a detailed 
visit and assessment schedule can be found in Table 6-1.
Safety, efficacy and patient-reported outcome (PRO) assessments will be performed according to 
the visit schedule (Table 6-1).
All doses of study treatment will be self-administered. Self-administration of the study 
treatment refers to subject self-injection or injection by a trained caregiver regardless of 
whether self-administration occurs at the study site or at home. Instruction and training will 
be provided by site staff to subjects prior to self-injection.
3.1.1
Screening period (Screening to randomization)
The duration of the screening period will be up to four weeks (28 days). Screening will be used to 
assess subject eligibility and to taper subjects off prohibited medications and treatments.
3.1.1.1
Visit 2 (Baseline)
Visit 2/Baseline should take place once all screening activities have been performed, and all 
results have been received and are confirmed to be within acceptable ranges for the subject to 
continue in the study. The Baseline visit should occur no later than 28 days after the initiation of 
screening.
At Visit 2, all Visit 2/Baseline assessments indicated in Table 6-1 should be performed with the 
exception of subject randomization via IRT and subject self-administration of study treatment.
Subjects must not be randomized until the clinical reading scan report from the FDG-
PET/CT has been received and reviewed to ensure there are no clinically important 
findings that would preclude a subject from continuing in the study. Because the receipt of 


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the report may take up to 24 hours, the Baseline visit is allowed to occur over a two-day period
(+1 additional day if needed).
Once the scan report is reviewed and no clinically important findings are identified, the site 
should then proceed immediately with subject randomization via IRT and administration of the 
initial dose of study treatment.
If the FDG-PET/CT scan report does contain clinically important findings, consultation with the 
Medical Monitor/appropriate medical experts and additional testing/work-up may be required to 
determine if the subject is eligible to continue in the study or must be discontinued. In these cases,
a +7-day window after the completion of the FDG-PET/CT scan is allowed to randomize and 
administer the first dose of study treatment.
3.1.2
Double-blind treatment period (Randomization through Week 12 pre-
dose)
The Double-blind Treatment Period is defined as Randomization through Week 12 (prior to the 
Week 12 dose). 
At the start of the Double-blind Treatment Period, eligible subjects will be randomized via 
Interactive Response Technology (IRT) in a 1:1 ratio to one of two treatment groups 
(secukinumab 300 mg or placebo).  Subjects must be randomized and receive their first dose 
of study treatment no later than 7 days after the FDG-PET/CT scan.

Secukinumab: secukinumab 300 mg (two s.c. injections of the secukinumab 150 mg dose) 
once weekly for five weeks (at Randomization, Weeks 1, 2, 3, and 4) followed by a dose after 
four weeks at Week 8 (last dose during Double-blind Treatment Period).

Placebo: placebo (two s.c. injections of 150 mg secukinumab placebo per dose) once per 
week for five weeks (at Randomization, Weeks 1, 2, 3 and 4) followed by a dose after four 
weeks at Week 8 (last dose during Double-blind Treatment Period).
During the Double-blind Treatment Period, all subjects will attend study visits at Randomization, 
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 for both treatment 
groups prior to subjects receiving their Week 12 dose.
All subjects who discontinue study treatment prematurely for any reason before the end of 
Double-blind Treatment Period should return to the study site for the performance of the Visit 
8/Week 12 End of Treatment 1 (EOT1) assessments. The EOT1 visit should be scheduled 28 
days (± 7 days) after the last dose of study treatment.
3.1.2.1
Visit 8 (Week 12)
At Visit 8, all Visit 8/Week 12 assessments indicated in Table 6-1 should be performed with the 
exception of subject self-administration of the Week 12 dose and dispensation of the study 
treatment for the at-home dosing at Weeks 13, 14, and 15. Subjects must not self-administer 


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the Week 12 dose of study treatment until the clinical reading scan report from the FDG-
PET/CT has been received and reviewed to ensure there are no clinically important 
findings that would preclude a subject from continuing in the study. Because the receipt of 
the report may take up to 24 hours, Visit 8/Week 12 is allowed to occur over a two-day period
(+1 additional day if needed).
Once the scan report is reviewed and no clinically important findings are identified, the site 
should then proceed immediately with subject administration of the Week 12 dose and 
dispensation of the study treatment for the Weeks 13, 14, and 15 at-home dosing.
If the FDG-PET/CT scan report does contain clinically important findings, consultation with the 
Medical Monitor/other appropriate medical experts, and additional testing/work-up may be 
required to determine if the subject is eligible to continue in the study or must be discontinued. In 
these cases, a +7-day window after the completion of the FDG-PET/CT scan is allowed for the 
subject to administer the Week 12 dose.
3.1.3
Double-blind induction period (Week 12 dose through Week 15 dose)
All subjects who complete the Double-blind Treatment Period will enter the Double-blind 
Induction Period. 
During the Double-blind Induction Period, subjects randomized to placebo during the Double-
blind Treatment Period will be switched over to treatment with secukinumab 300 mg. The 
Double-blind Induction Period is defined as the Week 12 dose through the Week 15 dose. 
Subjects must administer the Week 12 dose no later than 7 days after the Week 12 FDG-
PET/CT scan.

Secukinumab: Subjects who were randomized to the secukinumab treatment group at Visit 
2/Baseline will continue to self-administer secukinumab 300 mg (two s.c. injections of the 
150 mg dose) at Week 12. In order to maintain the blind, these subjects will undergo a sham 
induction with weekly placebo injections at Weeks 13, 14, and 15. 

Placebo: Subjects who were randomized to the placebo treatment group at Visit 2/Baseline
will begin to self-administer secukinumab 300 mg (two s.c. injections of the secukinumab 150 
mg dose) weekly for four weeks at Weeks 12, 13, 14, and 15.
Self-administration of the Week 12 dose will take place at the study site, while the doses at 
Weeks 13, 14, and 15 will be self-administered at home.
All subjects who discontinue study treatment prematurely for any reason before the end of 
Double-blind Induction Period should return to the study site for the performance of the Visit 
14/Week 52 End of Treatment 2 (EOT2) assessments. The EOT2 visit should be scheduled 28 
days (± 7 days) after the last dose of study treatment.
3.1.4
Open-label treatment period (Week 16 through Week 52)
All subjects 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 subjects in 


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the Open-label Treatment 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 subjects who discontinue study treatment 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 
14/Week 52 End of Treatment 2 (EOT2) assessments. The EOT2 visit should be scheduled 28 
days (± 7 days) after the last dose of study treatment.
Figure 3-1
Study design
3.2
Rationale of 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 subjects 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 


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efficacy at a point in time for which efficacy data from currently approved biologic therapies are 
available. However, as the study design provides for treatment duration of up to 52 weeks, it also 
allows for the assessment of longer-term safety and tolerability of secukinumab in this population. 
For subjects randomized to receive placebo at Visit 2/Baseline, the 52-week treatment duration 
allows these subjects the opportunity to receive up to 40 weeks of treatment with secukinumab.
Patients with moderate to severe psoriasis have a clinically significant increased risk of major 
cardiovascular events and mortality independent of traditional risk factors. Treatments that 
improve not only the skin manifestations of psoriasis but also its cardiovascular co-morbidities 
are of intense clinical and scientific interest. Measurement of aortic inflammation by FDG-
PET/CT is a reproducible, operator independent, prognostic marker of future vascular events
(Figueroa et al 2013; Mehta et al 2012). Furthermore, it responds to statins and modulates in a 
short time frame (i.e., within 12 weeks) unlike alternative approaches such as carotid intima-
media thickness (IMT) and MRI-based measures of wall thickness (Tawakol et al 2013).
3.3
Rationale of 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 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 
subjects 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.
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.  
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, 


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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 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 


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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 and 2 are presented in Table 3-1.
Table 3-1
Clinical outcomes at Week 12 in adults with plaque psoriasis in Trials 1 
and 2
Trial 1
Trial 2
Secukinumab
300 mg
(N=245)
n (%)
Secukinumab
150 mg
(N=245)
n (%)
Placebo
(N=248)
n (%)
Secukinumab
300 mg
(N=327)
n (%)
Secukinumab
150 mg
(N=327)
n (%)
Placebo
(N=326)
n (%)
PASI 75 
response
200 (82)
174 (71)
11 (4)
249 (76)
219 (67)
16 (5)
IGA of 
clear or 
almost clear
160 (65)
125 (51)
6 (2)
202 (62)
167 (51)
9 (3)
The results of Trials 3 and 4 are presented in Table 3-2.
Table 3-2
Clinical outcomes at Week 12 in adults with plaque psoriasis in Trials 3 
and 4
Trial 3
Trial 4
Secukinumab
300 mg
(N=59)
n (%)
Secukinumab
150 mg
(N=59)
n (%)
Placebo
(N=59)
n (%)
Secukinumab
300 mg
(N=60)
n (%)
Secukinumab
150 mg
(N=61)
n (%)
Placebo
(N=61)
n (%)
PASI 75 
response
44 (75)
41 (69)
0 (0)
52 (87)
43 (70)
2 (3)
IGA of 
clear or 
almost clear
40 (68)
31 (53)
0 (0)
44 (73)
32 (52)
0 (0)
Examination of age, gender, and race subgroups did not identify differences in response to 
secukinumab among these subgroups. Based on post-hoc sub-group analyses in subjects with 
moderate to severe psoriasis, subjects with lower body weight and lower disease severity may 
achieve an acceptable response with secukinumab 150 mg.
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 and in 72% (126/174) of subjects treated with secukinumab 150 mg. Trial 1 subjects who 
were clear or almost clear on the IGA at Week 12 also maintained their responses in 74% 


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(119/160) of subjects treated with secukinumab 300 mg and in 59% (74/125) of subjects treated 
with secukinumab 150 mg. Similarly in Trial 2, PASI 75 responders maintained their responses in 
84% (210/249) of subjects treated with secukinumab 300 mg and in 82% (180/219) of subjects 
treated with secukinumab 150 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 
and in 68% (113/167) of subjects treated with secukinumab 150 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©.
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, 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. 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.
Pre-treatment evaluation of 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 subjects with a past history of latent or active TB in whom an adequate course of 
treatment cannot be confirmed. Subjects receiving secukinumab should be monitored closely for 
signs and symptoms of active TB during and after treatment.
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.
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.


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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.
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.
In summary, the expected overall safety profile of secukinumab from a mechanism of action 
perspective is anticipated to be comparable to, or better than, that of other approved cytokine 
targeting therapies.
The risk to subjects in this trial will be minimized by compliance with the eligibility criteria and 
close clinical monitoring.
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. It is 
therefore considered appropriate to initiate this study. It is unclear if there is an additional benefit 
for vascular inflammation in psoriasis subjects, and therefore, this study is being conducted to 
evaluate this question.
The Investigator’s Brochure (IB) provides a more detailed review of the pre-clinical and clinical 
information on secukinumab.
4
Population
The study population will consist of male and female subjects at least 18 years of age with 
moderate to severe chronic plaque psoriasis that requires systemic therapy as defined by 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 approximately 84 subjects in approximately 10 centers in the 
United States. Assuming a 20% screen failure rate, 105 subjects will need to be screened to 
provide the targeted number of randomized subjects.
Subjects who drop out after they have been randomized will not be replaced.
4.1
Inclusion criteria
Subjects eligible for inclusion in this study have to fulfill all of the following criteria:


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1. Provide written, signed and dated informed consent before any study-related activity is 
performed; where relevant, a legal representative will also sign the informed study consent
according to local laws and regulations
2. Males and females ≥18 years of age at time of screening
3. Clinical diagnosis of chronic plaque-type psoriasis at least 6 months prior to randomization as 
determined by subject interview of his/her medical history and 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 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 plaque psoriasis inadequately controlled 
by:

topical treatment and/or

phototherapy and/or

previous systemic therapy
6. Physical examination and FDG-PET/CT scan without clinically significant findings that 
would meaningfully alter the risk-benefit profile of secukinumab in the Investigator’s opinion, 
and clinical laboratory results within laboratory reference ranges, or abnormal results that are 
deemed to be not clinically significant by the Investigator, in consultation with the Medical 
Monitor, and noted in the source documents
4.2
Exclusion criteria
Subjects 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 subjects.
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. Subjects not willing to limit UV light exposure (e.g., sunbathing and/or use of tanning 
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6. Ongoing use of prohibited psoriasis treatments (e.g., topical or systemic corticosteroids, other 
topical medications, systemic psoriasis treatments oral or biological, UV therapy); washout 
periods detailed in the protocol must be followed (Table 5-2)
7. Use of any investigational drug within 4 weeks prior to Randomization, or within a period of 
5 half-lives of the investigational treatment prior to Randomization, whichever is longer
8. Subjects using cholesterol-lowering medication (e.g., statins) and not on a stable dose for at 
least 90 days prior to randomization and unable to remain on a stable dose for the duration of 
the study
9. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive human
chorionic gonadotropin (hCG) laboratory test
10. 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 treatment. Effective contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the subject. 
Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation methods) 
and withdrawal are not acceptable methods of contraception

Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy) 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 m prior to screening); for female subjects on the study, the 
vasectomized male partner should be the sole partner for that subject

Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault 
caps) with spermicidal foam/gel/film/cream/ vaginal suppository

Use of oral, 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

Placement of an intrauterine device (IUD) or intrauterine system (IUS)
In case of use of oral contraception, women should have been stable on the same pill for a 
minimum of 12 weeks before taking study treatment.
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) or tubal ligation at least 6
weeks ago. In case of oophorectomyalone, only when the reproductive status of the
woman has been confirmed by follow up hormone level assessment is she considered not 
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11. Current severe progressive or uncontrolled disease which in the judgment of the Investigator
renders the patient unsuitable for the trial or puts the subject at increased risk (e.g., 
uncontrolled diabetes as evidenced by hemoglobin A1c ≥7%, myocardial infarction within 6 
months prior to screening, unstable ischemic heart disease, cerebrovascular accident)
12. Significant medical problems, including but not limited to the following: uncontrolled 
hypertension with measured systolic >180 mmHg and/or diastolic >95 mmHg, congestive 
heart failure (New York Heart Association [NYHA] status of class III or IV
13. Serum creatinine level >2.0 mg/dL (>176.8 µmol/L) or fasting blood glucose ≥150 mg/dL or 
hemoglobin A1c ≥7% at screening
14. 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
15. History of lymphoproliferative disease or any known malignancyor 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)
16. 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. Subjects with a positive QFT test 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 subject 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
17. Positive serology for human immunodeficiency virus (HIV), hepatitis B or C infection, or 
known history of other severe, recurrent or persistent infections
18. 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 subject and/or places the subject at
unacceptable risk for receiving an immunomodulatory therapy
19. Active systemic infections during the 2 weeks prior to randomization (exception: common 
cold) or any infection that reoccurs on a regular basis
20. Plans for administration of live vaccines during the study period or 6 weeks before 
randomization
21. Any medical or psychiatric condition which, in the Investigator’s opinion, would preclude the 
subject from adhering to the protocol or completing the study per protocol
22. History or evidence of ongoing substance abuse within 12 months prior to screening, or not 
willing to limit alcohol use to ≤14 drinks per week within 4 weeks prior to Baseline and 
throughout the duration of the study
23. History of hypersensitivity to constituents of the study treatment and/or subjects who are 
allergic to rubber or latex (the needle cap of the single-use prefilled syringe for secukinumab 


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and placebo may contain natural rubber latex which may cause allergic reactions in latex 
sensitive individuals)
24. Subjects 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
Protocol requested treatment
5.1.1
Study treatment
The following study treatments will be used:

Study drug
o
Secukinumab 150 mg; 1 ml liquid formulation in a single-use prefilled syringe (PFS)

Control drug
o
Placebo to secukinumab 150 mg; 1 ml liquid formulation in a single-use prefilled 
syringe (PFS)
Study drug: secukinumab 300 mg
Secukinumab for subcutaneous (s.c.) injection is provided in a prefilled syringe (PFS) containing 
150 mg secukinumab. Each secukinumab 300 mg dose is given as two s.c. injections of 150 mg.
Control drug: placebo
Placebo to secukinumab 150 mg for s.c. injection is provided in a matching prefilled syringe (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.
Secukinumab 150 mg prefilled syringes and placebo prefilled syringes will be supplied by
Novartis.
All study treatments will be labeled appropriately.
5.1.2
Additional study treatment
No additional treatment beyond study treatment is requested for this trial.
5.2
Treatment groups
At Visit 2/Baseline, eligible subjects will be randomized to one of the following two treatment 
groups in a ratio of 1:1, with approximately 42 subjects per group:
1. Secukinumab group:  Subjects (or trained caregivers) will self-administer (or administer to 
the subject) a dose of secukinumab 300 mg s.c. (two injections of the 150 mg prefilled 


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syringes) once weekly for five weeks (at Randomization, 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 during the Double-blind Induction Period, placebo s.c. doses (two injections of the 
placebo to 150 mg prefilled syringe) will be self-administered by the subjects (or trained 
caregivers) at Weeks 13, 14 and 15.
2. Placebo group:  Subjects (or trained caregivers) will self-administer (or administer to the 
subject) a dose of placebo s.c. (two injections of the placebo prefilled syringes) once weekly 
for five weeks (at Randomization, Weeks 1, 2, 3, and 4), followed by a dose after four weeks 
at Week 8. 
Beginning at Week 12, all subjects in the placebo group will be switched to treatment with 
secukinumab 300 mg s.c. Subjects will receive a dose of secukinumab 300 mg s.c. 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.
All subjects who enter the Double-blind Induction Period will self-administer the Week 12 dose 
following the completion of all assessments scheduled to be performed at Visit 8/Week 12 (Table 
6-1).
The treatment groups and dosing frequency are also described in Table 5-1 below.
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 Rand, Wks 
1, 2, 3, 4 and 8
2x s.c. secukinumab 150 
mg injection at  Wk 12
2x s.c. secukinumab 150 
mg PBO injection at Wks 
13, 14 and 15
2x s.c. secukinumab 
150 mg injection at  
Wks 16 - 48
Placebo (PBO)
2x s.c. secukinumab 150 
mg PBO injection at Rand, 
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  
Wks 16 – 48
DB = Double-blind; OL = Open-label; Rand = Randomization; Wk = Week
5.3
Treatment Assignment, randomization
At Visit 2/Baseline, all eligible subjects will be randomized via Interactive Response Technology 
(IRT) to one of two treatment groups. The Investigator or his/her delegate will contact the IRT 
after confirming that the subject fulfills all the inclusion/exclusion criteria. The IRT will assign a 
randomization number to the subject, which will be used to link the subject to a treatment group
and will specify a unique medication number for the first box of study treatment to be dispensed 
to the subject. The randomization number will not be communicated to the caller.


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The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from subjects and Investigators/site staff. A 
subject randomization list will be produced by the IRT provider using a validated system that 
automates the random assignment of subject numbers to randomization numbers. These 
randomization numbers are linked to the two 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 (DSM) using a validated system that automates the 
random assignment of medication numbers to boxes containing the study treatments(s).
The randomization scheme for subjects will be reviewed and approved by a member of the 
Novartis Biostatistics Group.
5.4
Treatment blinding
Subjects, 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 52, 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 subjects 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 subject-level data will remain blinded 
until the end of the trial.
Unblinding will only occur in the case of subject emergencies (see Section 5.5.12), 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 52 will be performed when all subjects have 
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5.5
Treating the subject
5.5.1
Subject numbering
Each subject is uniquely identified by a Subject Number which is composed by the site number 
assigned by Novartis and a sequential number assigned by the Investigator. Once assigned to a 
subject, the Subject Number will not be reused. 
Upon signing the informed consent form, the subject 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 subject to register them into the IRT. The site should select the 
eCRF book with a matching Subject Number from the EDC system to enter data. 
If a subject fails to be randomized for any reason, the IRT must be notified that the subject was 
not randomized. The reason for not being randomized will be entered on the Screening Phase
Disposition eCRF.
5.5.2
Dispensing the study treatment
Each study site will be supplied by Novartis with secukinumab and placebo treatment in 
packaging of identical appearance. The secukinumab and placebo treatment packaging has a 2-
part label. A unique medication number is printed on each part of this label.
Investigator/qualified site staff will identify the study treatment box(es) to dispense to the 
subject by contacting the IRT and obtaining the unique medication number(s). Immediately 
before dispensing the study treatment to the subject, site staff will detach the outer part of the
label from the box and affix it to the Drug Label Form source document for that subject.
IRT will assign secukinumab or placebo at each visit from Randomization to Week 48. All 
boxes of investigational treatment assigned by the IRT will be recorded/databased in the IRT 
system.
5.5.3
Handling of study treatment
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly, and kept in a secured location to which only the Investigator and designated 
site staff have access. Upon receipt, all study treatment should 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 via the Clinical Trial Drug Supply Complaint 
Review Form, 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. 


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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 subject except for 
the medication number.
The Investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
monitors during site visits or remotely, and at the completion of the trial. Subjects 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.
5.5.3.1
Handling of other study treatment
Not applicable.
5.5.4
Instructions for prescribing and taking study treatment
Throughout the duration of the study, all doses of study treatment (secukinumab 300 mg and
placebo) will be self-administered subcutaneously (s.c.) by the subject (or trained caregiver)
after all study assessments for each visit have been completed. The prefilled syringes will be
provided by the site staff to the subject, 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 subject.
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. Instructions on the self-administration of the study 
treatment and disposal of used prefilled syringes are detailed in the secukinumab Instructions
For Use (IFU) document and will be provided to each subject.
At the beginning of the study, the Investigator/qualified site staff will determine if self-
administration is appropriate for the subject, e.g., manual dexterity, ability to follow the IFU. If
a subject requires a caregiver to administer study treatment, the caregiver will be trained by the 
Investigator/qualified site staff. If a caregiver is not available at a particular visit or the subject is
having problems with self-administration, the Investigator/qualified site staff may administer the
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A different body site should be chosen each time a dose is administered. 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 far as
possible, the injection site should be changed from administration to administration throughout
the study. Subjects should self-administer the study treatment to one of the following body
regions, changing the injection site routinely: the front of the thighs, the lower stomach area 
(abdomen) but not the area two inches around the navel. In cases where a caregiver will 
administer the study treatment, the upper outer arms may also be used as an injection site.
The first
study treatment self-administration
will occur
at
Visit 2/Baseline
after 
inclusion/exclusion criteria have been confirmed, all scheduled study assessments have been
performed, and the clinical report from the Visit 2/Baseline FDG-PET/CT scan has been received 
and reviewed with no clinically important findings that would preclude the subject from 
continuing in the study. The first dose of study treatment will take place under the supervision of
the Investigator/qualified site staff. The subject will be instructed on the use of the 
secukinumab/placebo prefilled syringe via review of the secukinumab IFU. At subsequent
visits,
the
Investigator/qualified
site
staff 
will
observe
the
self-administration
of
secukinumab/placebo at the site.
Administration
Each dose of study treatment (two prefilled syringes of secukinumab 150 mg or placebo) will be
packed in an individual box. For further details about study treatment storage and handling,
please refer to the secukinumab IFU distributed as training material for the study.
During the Double-blind Treatment Period (from Randomization through Week 8), subjects
will self-inject a total of 12 secukinumab or placebo injections (two injections per visit). 
During the Double-blind Induction Period (from Week 12 through Week 15), subjects will
self-inject a total of 8 injections (two injections at Week 12, and two injections at home at Weeks 
13, 14 and 15).
During the Open-label Treatment Period (from Week 16 through Week 52), subjects will self-
inject a total of 18 injections (two injections per visit at Weeks 16, 24, 32, 40, and 48 and two 
injections at home at Weeks 20, 28, 36, and 44).
Date and time of secukinumab or placebo self-administrations during the study must be recorded
on the Dosage Administration Record eCRF.
5.5.5
Permitted dose adjustments and interruptions of study treatment
Study treatment dose adjustments and/or interruptions are not permitted.
5.5.6
Rescue medication
Rescue medication is not permitted in this study.


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5.5.7
Concomitant treatment
All treatments administered during the six months prior to the Randomization visit (including any 
treatments started during the screening period) for any reason NOT including psoriasis will be 
entered on the Prior and Concomitant Medications eCRF or the Surgical and Medical Procedures 
eCRF with the reason for administration.
Psoriasis treatments used from the time the subject started to treat his/her psoriasis will be 
reported on the Prior Psoriasis Therapy eCRF. All topical treatments, systemic treatments, and 
phototherapies for psoriasis administered prior to randomization will be recorded (Section 
6.2.2).
The Investigator should instruct the subject to notify site staff about any new treatments he/she
takes after the start of the study treatment. All medications and significant non-drug therapies
(including physical therapy and blood transfusions) administered after the subject starts study
treatment must be recorded on the Prior and Concomitant Medications eCRF or the Surgical and 
Medical Procedures eCRF as appropriate. Information recorded will include indication for use, 
dosage, and dates of administration.
5.5.8
Prohibited Treatment
Use of any treatments displayed in Table 5-2 that could confound the efficacy of the study drug
are not allowed during the study for any indication; wash-out periods for these treatments are 
provided in Table 5-2. If the use of these treatments is required, then the subject must not be 
randomized into the study.
The Investigator/qualified site staff must instruct the subject to notify them about any new 
treatments he/she takes after the start of the study treatment. All prohibited medications and 
significant non-drug therapies administered after the subject starts study treatment must be 
listed on the Prior and Concomitant Medications eCRF and the Surgical and Medical Procedures
eCRF as appropriate, or the Concomitant Medications-Topical Corticosteroids eCRF for any TCS
used after randomization.
If a prohibited treatment listed in Table 5-2 was used during the study, the subject must 
discontinue use of the prohibited treatment if he/she wishes to continue in the study. If, in the 
Investigator’s clinical judgment, the subject’s use of a prohibited treatment presents an 
undue safety risk for the subject, the subject must be discontinued from study treatment as per
Section 5.5.9. 
If a subject receives a live virus vaccination during the study, the subject must discontinue study
treatment and complete an end-of-treatment visit (either Visit 8/Week 12 EOT1 or Visit 
14/Week 52 EOT2).
Any other protocol deviation that results in a significant risk to the subject’s safety will be 
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Exposure to light
Subjects will be advised to limit exposure to ultraviolet (UV) light (including sunbathing and/or
use of UV tanning devices) during the study to avoid possible effects on psoriasis.
Table 5-2
Prohibited treatment
Prior Therapy (Before Visit 2/Baseline)
Prohibited Treatments†, ‡
Washout Period
(before Randomization)
Secukinumab
No prior use allowed
Any biologic drug directly targeting IL-17 or the IL-17 receptor
(other than secukinumab)
No prior use allowed
Alefacept, briakinumab, efalizumab, ustekinumab
6 months
Biological immunomodulating agents other than above
(e.g., adalimumab, infliximab, etanercept)
3 months
Cholesterol-lowering medication (e.g., statins)
Dose must be stable for ≥90 days 
prior to randomization and remain 
stable for the duration of the study
Other systemic immunomodulating treatments§ [e.g., MTX,
cyclosporine A, corticosteroids (oral, i.v., intramuscular, s.c.,
intra-articular, transdermal)§, 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
Any 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
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, and 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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†If the prohibited treatment was used during the study for any indication, the subject must discontinue use of the 
prohibited treatment if he/she wishes to continue in the study.
‡
In case of undue safety risk for the subject as determined by the Investigator, the subject should discontinue 
study treatment. If the subject receives a live virus vaccination during the study, the subject must discontinue 
study treatment.
§
Inhaled CS with only a topical effect (e.g., to treat asthma) are not considered “systemic immunomodulating
treatments” and are therefore acceptable as co-medication.
5.5.9
Discontinuation of study treatment
Subjects may voluntarily discontinue study treatment for any reason at any time. They may be 
considered withdrawn if they state an intention to withdraw, fail to return for visits, or become 
lost to follow-up for any other reason. Subjects who prematurely withdraw from the study will not 
be replaced.
If discontinuation occurs for any reason during the study, the Investigator/qualified site staff
must make every effort to determine the primary reason for a subject’s discontinuation from the
study. This information will then be recorded on the End of Treatment eCRF for either the 
Double-blind Treatment Period (Visit 8/Week 12 EOT1), or the Double-blind Induction and 
Open-label Treatment Periods (Visit 14/Week 52 EOT2) as appropriate.
Study treatment must be discontinued and the subject withdrawn from the study if the 
Investigator on balance believes that continuation would be detrimental to the subject’s well-
being. Study treatment must be discontinued under the following circumstances:

Emergence of the following AEs: AEs that in the judgment of the Investigator/qualified 
site staff, taking into account the subject’s overall status, prevent the subject from 
continuing study treatment (for example, sepsis or serious infection);

Any laboratory abnormalities that in the judgment of the Investigator/qualified site staff, 
taking into consideration the subject’s overall status, prevents the subject from continuing 
study treatment;

Pregnancy (see Section 6.5.6 and Section 7.3);

Ongoing use of any prohibited treatment, use of a prohibited treatment that results in an 
undue safety risk for the subject as per the Investigator’s clinical judgment, or receipt of a 
live virus vaccine during the study (as detailed in Section 5.5.8);

Emergency unblinding;

Any other protocol deviation that results in a significant risk to the subject’s safety or 
significantly affects the validity of the study assessments.
Subjects who discontinue study treatment should undergo an end of study visit and then be 
discontinued from the trial.

Double-blind Treatment Period: For subjects who discontinue study treatment prematurely 
before the end of the Double-blind Treatment Period, the Visit 8/Week 12 EOT1 assessments 
should be performed. NOTE: Consultation with the Medical Monitor is required to 


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determine if the FDG-PET/CT scan assessment should be performed during the 
discontinuation visit.

Double-blind Induction and Open-label Treatment Periods:
For subjects who 
discontinue study treatment prematurely before the end of the Double-blind Induction or 
Open-label Treatment Periods, Visit 14/Week 52 EOT2 visit should be performed. NOTE: 
Consultation with the Medical Monitor is required to determine if the FDG-PET/CT 
scan assessment should be performed during the discontinuation visit.
Study treatment must be discontinued after emergency unblinding.
The appropriate personnel from the site and Novartis will assess whether study treatment should 
be discontinued for any subject whose treatment code has been broken inadvertently for any 
reason.
Scheduling of the end of treatment discontinuation visit
At the time of the end of study discontinuation visit, IF it has been approximately 4 weeks post
last dose of study treatment, THEN the assessments for Visit 8/Week 12 EOT1 (for early
discontinuation during the Double-blind Treatment Period) or for Visit 14/Week 52 EOT2
(for early discontinuation during Double-blind Induction or Open-label Treatment Periods)
should be completed.
IF it has not been approximately 4 weeks post last dose of study treatment at the time of the end 
of study discontinuation visit, THEN the subject should be scheduled to return 4 weeks post last
dose for their Visit 8/Week 12 (for early discontinuation during the Double-blind Treatment 
Period) or Visit 14/Week 52 (for early discontinuation during the Double-blind Induction or
Open-label Treatment Periods) assessments.
The Investigator/site staff must also contact the IRT to register the subject’s discontinuation from 
the study.
5.5.10
Withdrawal of consent
Subjects may voluntarily withdrawal consent to participate in the study for any reason at any time.
Withdrawal of consent occurs only when a subject does not want to participate in the study 
anymore, and does not 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.
If a subject withdraws consent, the Investigator must make every effort (e.g., telephone, email, 
letter) to determine the primary reason for this decision and record this information. Study 
treatment must be discontinued and no further assessments conducted. All biological material that 
has not been analyzed at the time of withdrawal must not be used. Further attempts to contact the 
subject are not allowed unless safety findings require communication or follow-up.


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5.5.11
Loss to follow-up
For subjects whose status is unclear because they fail to appear for study visits without stating an 
intention to withdraw, the Investigator should show "due diligence" by contacting the subject, 
family or family physician as agreed in the informed consent and by documenting in the source 
documents steps taken to contact the subject, e.g., dates of telephone calls, registered letters, etc. 
5.5.12
Emergency breaking of assigned treatment code
Emergency breaking of the assigned treatment code should only be undertaken when it is 
essential to treat the subject safely and efficaciously. Most often, study treatment discontinuation 
and knowledge of the possible treatment assignments are sufficient to treat a study subject 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 subject, he/she must provide the requested
subject identifying information and confirm the necessity to break the treatment code for the
subject. The Investigator will then receive details of the study treatment for the specified subject
and a fax or email confirming this information. The system will automatically inform Novartis
and CRO study personnel that the code has been broken.
It is the Investigator’s responsibility to ensure that there is a procedure in place to allow access to 
the IRT in case of emergency.
Study treatment must be discontinued in the event of an emergency unblinding.
5.5.13
Study completion and post-study treatment
A subject’s individual study participation is completed once Visit 14/Week 52 of Open-label 
Treatment has been completed. After this date, any SAEs that occur in the following 30 days 
must be reported. The Investigator will also follow any AEs for which there is no outcome that 
can be reported at the final study visit. 
The study as a whole will be completed once all randomized subjects have completed the study
as per the protocol and the clinical database has been locked. Recruitment into the study will be 
terminated by the sponsor once the targeted number of randomized subjects has been met or is 
foreseen to be met with the subjects already in screening. Subjects who have been screened and
have a screening visit recorded in the IRT system at the time that the planned enrollment number
is met will be allowed to enter the trial and to be randomized if they are eligible.
Upon completion of their study participation, subjects will return to individual treatment, as 
determined by their treating physician.
The Investigator must provide follow-up medical care for all subjects who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care.


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5.5.14
Early study termination
The study can be terminated at any time for any reason by Novartis. Should this be necessary, the 
subject should be seen as soon as possible and treated as a prematurely withdrawn subject (as 
described in Section 5.5.9). The Investigator may be informed of additional procedures to be 
followed in order to ensure that adequate consideration is given to the protection of the subject’s 
interests. The Investigator will be responsible for informing the Institutional Review 
Board/Independent Ethics Committee (IRBs/IECs) of the early termination of the trial.
6
Visit schedule and assessments
Table 6-1 lists all of the assessments and indicates with an “X” when the assessments are to be 
performed.
Subjects should be seen for all visits on the designated day or as close as possible to the 
original planned visit schedule (recommended visit windows are in Table 6-1. Every effort 
should be made to respect the time frame for the Visit 8/Week 12 visit.
At a minimum, subjects will be contacted for safety evaluations during the 30 days following the 
last study visit, including a final contact at the 30-day point. Documentation of attempts to 
contact the subject should be recorded in the source documentation.
Visit windows
A “visit window” will be allowed during the study as follows:

Screening Period
o
+2 days (for a total of up to 30 days)

Double-blind Treatment Period
o
± 2 days for Visits 3-8

Open-label Treatment Period
o
± 7 days for Visits 9-14
Rescreening
Rescreening may be allowed under certain conditions. Requests from the Investigator/site staff 
to rescreen subjects 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 subject was 
previously randomized into the study.
If a subject rescreens for the study, the subject must sign a new ICF and be issued a new
subject number. The date of the new informed consent signature should correspond to the new
subject number. Informed consent for a rescreened subject must be obtained prior to performing
study-related assessments or collecting any data for the Screening Visit. For rescreening, all


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screening assessments must be performed as per protocol, except for the tuberculosis (TB) work
up, if applicable, if performed not more than 12 weeks before randomization.
If the date of a 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 subject must repeat the 
QuantiFERON test performed by the central laboratory.
Unscheduled visits
Subjects may be seen at any time for an unscheduled visit, e.g., if they experience deterioration
of psoriasis or AEs that in the opinion of the Investigator/qualified site staff need intervention
or repeat laboratory testing. The assessment(s) performed at an unscheduled visit must include 
at minimum: an assessment of concomitant medication and procedures/significant non-
drug therapies, vital signs, and an AE/SAE assessment. Any additional assessments 
performed are at the Investigator/qualified site staff’s discretion. 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
Unscheduled Visit D
Visit
1
2
3
4
5
6
7
8 / 
EOT1
A,B
9
10
11
12
13
14 / 
EOT2
C
Week
-4 to 
BLE
BL
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
Visit window (Days)
±2
±2
±2
±2
±2
±2
±7
±7
±7
±7
±7
±7
Assessment
Obtain informed consent
X
Demographics
X
Inclusion/exclusion criteriaF
X
X
Smoking and alcohol history
X
Psoriasis history / Prior
psoriasis therapy / Psoriatic 
arthritis history
X
Cardiovascular medical 
history
X
Cardiovascular disease 
family history
X
Medical history / Current 
medical conditions
X
Prior and concomitant 
medications / Surgical and 
medical procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physical examinationF
X
X
X
X
X
Xd
Height
X


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Period
SCR
Double-blind Treatment Period
Double-blind 
Induction 
Period
Open-label Treatment Period
Unscheduled Visit D
Visit
1
2
3
4
5
6
7
8 / 
EOT1
A,B
9
10
11
12
13
14 / 
EOT2
C
Week
-4 to 
BLE
BL
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
Visit window (Days)
±2
±2
±2
±2
±2
±2
±7
±7
±7
±7
±7
±7
Assessment
Weight
X
X
X
X
X
X
X
X
X
X
X
Xd
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
Lab analysis: Safety panel 
(chemistry, hematology)G
X
X
X
X
Xd
Fasting labs: plasma 
glucose
X
Viral serology lab analysis: 
HIV, Hepatitis B and C G
X
Xd
QuantiFERON® TB-Gold 
In-Tube test G,H
X
Xd
Serum pregnancy test G,I
X
Xd
Urine pregnancy test 
(local)J
X
X
X
Xd
FDG-PET CTK
XL
XM
X
Blood sample for cardio-
metabolic biomarkersG
X*
X
X
X*
X
X
X*
PASI
X
X
X
X
X
X
X
X
X
X
X
Xd
IGA mod 2011
X
X
X
X
X
X
X
X
X
X
X
Xd
Alcohol use assessment
X
X
X
X
X
X
X
X
X
X
X
X
Xd
DLQI
X
X
X
X
X
X
X


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Period
SCR
Double-blind Treatment Period
Double-blind 
Induction 
Period
Open-label Treatment Period
Unscheduled Visit D
Visit
1
2
3
4
5
6
7
8 / 
EOT1
A,B
9
10
11
12
13
14 / 
EOT2
C
Week
-4 to 
BLE
BL
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
Visit window (Days)
±2
±2
±2
±2
±2
±2
±7
±7
±7
±7
±7
±7
Assessment
AE/SAE assessment N
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization via IRT
X
Subject self-administration 
of study treatment at site
X
X
X
X
X
X
X
X
X
X
X
X
Dispense study treatment to 
subject for at-home dosing
X
X
X
X
X
Subject self-administration 
of study treatment at home 
and completion of Self-
Administration LogO
X
X
X
X
X
X
X
At-home Dosing Phone 
ReminderF,P
X
X
X
X
X
Check Self-Administration 
Log and returned 
used/unused study 
treatment and packagingF,Q
X
X
X
X
X
Xd
AE=adverse event; BL = Baseline; DLQI=Dermatology Life Quality Index; EOT1=End of Treatment 1; EOT2=End of Treatment 2; FDG-PET CT=18-
fluorodeoxyglucose positron emission tomography with computer assisted tomography; HIV=human immunodeficiency virus; IGA=Investigator’s Global 
Assessment; IRT=Interactive Response Technology; PASI=Psoriasis Area and Severity Index; SAE=Serious Adverse Event; SCR=Screening; 
TB=tuberculosis
* At Visits 2, 8, and 14, subjects are required to be fasting for a minimum of 8 hours prior to the blood sample collection for cardiometabolic biomarkers 


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Period
SCR
Double-blind Treatment Period
Double-blind 
Induction 
Period
Open-label Treatment Period
Unscheduled Visit D
Visit
1
2
3
4
5
6
7
8 / 
EOT1
A,B
9
10
11
12
13
14 / 
EOT2
C
Week
-4 to 
BLE
BL
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
Visit window (Days)
±2
±2
±2
±2
±2
±2
±7
±7
±7
±7
±7
±7
Assessment
A Subjects will complete all Visit 8/Week 12 assessments prior to administration of study treatment 
B Visit 8/Week 12 assessments must be performed for subjects who discontinue treatment during the Double-blind Treatment Period. Consultation with 
the Medical Monitor is required to determine if the FDG-PET/CT scan assessment should be performed during the discontinuation visit.
C Visit 14/Week 52 assessments must be performed for subjects who discontinue treatment prematurely during the Double-blind Induction or the Open-
label Treatment Periods. Consultation with the Medical Monitor is required to determine if the FDG-PET/CT scan assessment should be performed during the 
discontinuation visit.
D Unscheduled visit – concomitant medications, vital signs, and AE/SAE assessment are required for an unscheduled visit; all other assessments are 
performed at the discretion of the Investigator
E Visits 1 and 2 must not be performed on the same day
F These assessments are supported by and stored within the source documentation. Data relating to inclusion/exclusion criteria are captured in the 
corresponding eCRF.
G Samples will be shipped to a central laboratory for analysis
H A repeat QuantiFERON® TB-Gold In-Tube test is recommended if the result of the first QuantiFERON® TB-Gold In-Tube test is “indeterminate”. The 
subject must be referred for a follow-up tuberculosis workup (as per local guidelines) if either the first or the repeat test is “positive” or if the results of 
both tests are “indeterminate”. If the first test is indeterminate, the Investigator may decide not to repeat the test and to proceed directly to the workup, 
though this is not recommended. The subject will not be eligible for randomization if “active tuberculosis is present “or if “latent tuberculosis is present 
and is untreated as per local guidelines.
I A serum pregnancy test is not required for a woman who is sterile or who is post-menopausal.
J A urine pregnancy test is not required for a woman who is sterile or who is post-menopausal. In the event of a positive urine pregnancy test, study 
treatment must be withheld and a serum pregnancy test performed at the same visit.
K The FDG-PET/CT scan will be performed at each site’s local imaging center. A clinical reading scan report will be provided to the site within 24 hours of 
the scan by the local imaging center.


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Period
SCR
Double-blind Treatment Period
Double-blind 
Induction 
Period
Open-label Treatment Period
Unscheduled Visit D
Visit
1
2
3
4
5
6
7
8 / 
EOT1
A,B
9
10
11
12
13
14 / 
EOT2
C
Week
-4 to 
BLE
BL
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
Visit window (Days)
±2
±2
±2
±2
±2
±2
±7
±7
±7
±7
±7
±7
Assessment
L The Visit 2/Baseline FDG-PET/CT scan report must have been reviewed with no clinically significant findings prior to randomization and administration 
of the initial dose of study treatment (see Section 3.1.1.1 for additional information). Randomization must occur 7 days or less from date of FDG-PET/CT 
scan.
M The Visit 8/Week 12 FDG-PET/CT must have been reviewed with no clinically significant findings prior to the administration of the Visit 8/Week 12 
dose (see Section 3.1.2.1 for additional information). Subjects must administer their Week 12 dose 7 days or less from the date of their Week 12 FDG-
PET/CT scan. 
N AE/SAE assessment includes injection site reactions 
O Subjects will self-administer study treatment at home at these time points and will record each dose administered at home in their Self-Administration 
Dosing Log
P Site staff to contact subject via telephone to assess subject compliance with at-home dosing and completion of Self-Administration Log
Q The at-home administrations of study treatment will be recorded by the subject on the Self-Administration Log which must be returned to the site at the 
next visit along with the used/unused study treatment and the outer boxes for a compliance check.


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6.1
Information to be collected on screening failures
All subjects who sign informed consent but discontinue prior to randomization at Visit 2 are 
considered screening failures.
If a subject discontinues prior to randomization at Visit 2, the IRT must be notified about the 
discontinuation, and the primary reason for the screen failure should be entered in the 
Screening Phase Disposition eCRF.
The Screening Visit Date, Demography, Informed Consent, Inclusion/Exclusion Criteria, 
Subject Rescreening, and the Screening Phase Disposition eCRFs must be completed. The
Adverse Event eCRF and a paper SAE form must be completed for any serious adverse event
(SAE) that occurs during the screening period. Adverse events that are not SAEs will be
followed by the Investigator and collected only in the source data. The W ithdrawal of
In formed C onsent eCRF must be completed if consent was withdrawn during the Screening
period before the subject was randomized.
6.2
Subject demographics/other baseline characteristics
All baseline assessments should be performed prior to the first study treatment administration.
6.2.1
Demographics
Subject demographic data to be collected on all subjects include: date of birth, subject initials, 
sex, race, ethnicity and child-bearing potential (for females only).
6.2.2
Psoriasis history / Prior psoriasis therapies
Disease history will be collected at the screening visit. The information to be collected and 
entered in the eCRF includes the following:

date of first diagnosis of plaque psoriasis (by a physician);

previous psoriasis treatments (including previous use of systemic therapies, as well as
phototherapy and/or photochemotherapy), duration of exposure, and the reason for
discontinuation of each therapy;

presence of psoriatic arthritis and the date of first diagnosis (by a physician).
6.2.3
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.


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6.2.4
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.
Current alcohol use will be assessed throughout the duration of the study at the 
scheduled visits as indicated in Table 6-1.
6.2.5
Comorbidities – cardiovascular history
Any information pertaining to cardiovascular medical history assessed prior to randomization 
should be reported on the Cardiovascular History eCRF.
Additionally, family history of certain cardiovascular diseases will also be collected.
6.2.6
Relevant medical history / Current medical conditions
Relevant medical history/current medical conditions, not including psoriasis or psoriatic arthritis,
will be recorded on the Medical History eCRF. 
Relevant medical history/current medical conditions will include data up to six months prior to
signing of the informed consent. Whenever possible, diagnoses (and not symptoms) will be 
recorded.
Significant findings that are observed after the subject has provided informed consent, and that
meet the definition of an AE, must be recorded on the Adverse Event 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.
6.2.7
Prior and concomitant medications
Concomitant medications and prior medications taken over the six months preceding study 
enrollment will be captured at the Screening visit, and updated at Visit 2/Baseline.
6.2.8
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 subject’s TB status.


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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 subjects. This test will only be used to determine subject’s eligibility for the trial. The test
will be used to screen the subject population for latent tuberculosis infection (Doherty, Van 
Vorhees and Lebwohl l 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 subject 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).
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 subject with a positive or indeterminate test must be recorded
in the eCRF.

If the test result is negative, the subject may be randomized

If the test result is positive, the Investigator should perform a TB workup for the test result as 
per local procedures.

Subjects positive for latent TB per workup may be randomized to the trial if sufficient
treatment has been initiated according to local routine clinical practice and will be
maintained for the prescribed duration.

Subjects positive for active TB per workup are not eligible for the study.

Subjects negative for TB (no signs of latent or active TB) per workup may be randomized
to the trial.

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 subject may be randomized.

If the second test is positive or indeterminate, the Investigator should perform a TB 
workup as per local guidelines. The subject 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 13 (Appendix 2) to see a schematic of the tuberculosis screening 
process and subject eligibility with respect to TB testing.


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6.2.9
Other baseline characteristics
Baseline characteristic data to be collected on all subjects include (all labs are central except 
where indicated) (see also Table 6-1):

vital signs, hematology, clinical chemistry, viral serology (HIV, Hepatitis B and Hepatitis 
C), serum pregnancy, physical examination, height, weight; PASI, IGA mod 2011; 
DLQI.
6.3
Treatment exposure and compliance
All administered doses of secukinumab or placebo will be recorded on the Dosage
Administration Record eCRF. Compliance will be assessed by Novartis and CRO study
personnel using the Dosage Administration Record eCRF, medication numbers, Drug Label Form
information, and information collected by IRT.
Subjects 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. Subjects will be instructed to return to the study site at 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. Subjects 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. At the final study visit (Visit 14/Week 52), the subject’s Self-
Administration Log will be retained in the subject’s source documents. 
The Investigator/qualified site staff should promote compliance by instructing subjects to attend
the study visits as scheduled, to take the study treatments exactly as prescribed, and by 
reiterating that compliance is necessary for subject safety and the validity of the study.
Additionally, sites will be instructed to contact subjects via telephone at the time of 
scheduled at-home dosing to check compliance and to ensure completion of the Self-
Administration 
Log. 
Likewise, 
subjects
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.
6.4
Efficacy
The primary efficacy variable is the change from baseline in the target (arterial vascular uptake) 
to background (venous blood pool) ratio from the aorta. The primary analysis time point will be 
at Week 12.
The secondary efficacy variables are the following:

Change from baseline in cardiometabolic biomarkers (cardiometabolic function [lipid particle 
size, HDL function (cholesterol efflux)], measures of inflammation [TNF-Alpha, IL-6, C-
reactive protein, GlycA], adiposity [leptin and adiponectin], insulin resistance [insulin 


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levels/glucose to yield HOMA-IR], and markers predictive of diabetes [apolipoprotein B, 
ferritin, IL-2 receptor A, IL-18, and fetuin-A])

PASI 75 response (yes, no)

PASI 90 response (yes, no)

PASI 100 response (yes, no)

IGA mod 2011 score of 0 or 1 (yes, no)

Change from baseline in DLQI total score
All efficacy assessments should be performed prior to the administration of study treatment and 
at all scheduled study visits as indicated in Table 6-1. 
Patient Reported Outcomes (PRO)
PROs should be collected prior to the Investigator performing any efficacy assessments:

DLQI
Efficacy assessments (Investigator)
The following efficacy assessments performed by the Investigator will be completed for all 
subjects:

PASI

IGA mod 2011
6.4.1
Target (arterial vascular uptake) to background (venous blood pool) ratio 
from the aorta
Subjects will undergo vascular inflammation imaging assessments with full-body FDG-PET/CT 
scans at three scheduled visits – Visit 2/Baseline, Visit 8/Week 12 and Visit 14/Week 52 (see 
Table 6-1). The FDG-PET/CT scans will be conducted at each investigative site’s local imaging 
center and the whole process should take approximately 3 hours to complete.
Subjects will be required to fast for a minimum of 8 hours prior to the imaging assessment. At the 
imaging center, the subject’s glucose level will be checked by finger stick test and results should 
not exceed 150 mg/dL. If the glucose level exceeds 150 mg/dL, consultation with the Medical 
Monitor prior to the imaging will be required to determine if the subject is eligible to continue in 
the study. The whole-body PET/CT scan will be initiated approximately 120 minutes (± 10 
minutes) after intravenous administration of [18F]-fluorodeoxyglucose (FDG).
Within approximately 24 hours after the completion of the FDG-PET/CT scan, the local nuclear 
medicine personnel will issue a clinical report determining if the subject has any clinically 
significant findings which would preclude the subject’s continued participation in the study.
The arterial uptake of FDG will be measured by the standardized uptake value (SUV) max 
divided by the venous SUV mean (Mehta et al 2012). This will yield a target to background ratio 


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(TBR) which is considered the standard reporting variable in FDG-PET/CT vascular studies. The 
PET/CT images obtained from each site’s local imaging center will be de-identified and should 
be sent to the 
 Imaging Lab within 1-3 days where trained nuclear 
medicine personnel will undertake a qualitative review of the PET/CT images. During this review, 
two-dimensional (2D) circular regions of interests (ROIs) will be manually placed on the PET 
images around the external aortic contour, around the hepatic margin, and around articular spaces 
on all transverse slices passing through these structures using low-dose CT images for anatomic 
guidance. The images will then be sent to the central core 
Imaging Lab for measuring the SUVs. The 
 central PET/CT readers will be blinded to time 
and treatment via Digital Imaging and Communication in Medicine (DICOM) file editing applied 
by the 
.
The mean aortic SUV will be calculated for five segments of the aorta: ascending aorta, aortic 
arch, descending thoracic aorta, suprarenal abdominal aorta, and infrarenal abdominal aorta. 
These segments are defined to consider separately various regions of aortic disease that are 
associated with different clinical phenotypes (e.g., aortic arch disease with stroke, abdominal 
aortic disease with abdominal aortic aneurysm).
6.4.2
Cardiometabolic biomarkers
The following cardiometabolic biomarkers will be analyzed centrally at an analytical laboratory:

Cardiometabolic function: lipid particle size, HDL function (cholesterol efflux);

Inflammation: TNF-Alpha, IL-6, C-reactive protein, GlycA;

Adiposity: leptin and adiponectin;

Insulin resistance: insulin levels/glucose to yield HOMA-IR;

Markers predictive of diabetes: apolipoprotein B, ferritin, IL-2 receptor A, IL-18, and 
fetuin-A.
Blood samples for cardiometabolic biomarkers will be collected at the scheduled time points as 
indicated in Table 6-1. 
Subjects will be required to fast for a minimum of 8 hours prior to the blood draw for the 
cardiometabolic biomarkers at the following visits only:

Visit 2/Baseline

Visit 8/Week 12

Visit 14/Week 52.
A laboratory manual will be provided by the central laboratory with detailed information on 
biomarker sample collection, handling and shipment.


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6.4.3
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 subject. The Investigator is only responsible for 
collecting the components or scoring signs and total regional area. PASI calculations, including 
changes over time, will be done electronically, not by the Investigator.
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 6-3. 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 6-2.
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 is 
provided in Section 13 (Appendix 3).


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Table 6-2
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%
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):


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
PASI 75 response: subjects achieving ≥75% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 75 responders

PASI 90 response: subjects achieving ≥90% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 90 responders

PASI 100 response/remission: complete clearing of psoriasis (PASI=0)
6.4.4
Investigator’s Global Assessment (IGA mod 2011)
The IGA mod 2011 will be conducted for overall psoriatic disease as indicated in Table 6-1. It is
recommended that the same evaluator conducts the assessment throughout the study wherever
possible.
Subjects require an IGA mod 2011 score at Randomization of 3 or 4 in order to participate in 
the study. Based on this scale, a subject will be considered as an IGA 0 or 1 responder if they 
achieve a score of 0 or 1, and improve by at least 2 points on the IGA scale at a given time 
point compared to their score at Randomization (Baseline).
The IGA mod 2011 rating scale for overall psoriatic disease is shown in Table 6-3.
The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the subject’s 
disease state at the time of the assessments, and does not attempt a comparison with any of the 
subject’s previous disease states, whether at baseline or at a previous visit.
The IGA mod 2011 score will be recorded in the eCRF.
Table 6-3
IGA mod 2011 rating scale
Score
Short description
Detailed description
0
Clear
No signs of psoriasis. Post-inflammatory hyperpigmentation may be 
present
1
Almost clear
Normal to pink coloration of lesions; no thickening; no to minimal 
focal scaling
2
Mild disease
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling
3
Moderate disease
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling
4
Severe disease
Bright to deep dark red coloration; severe thickening with hard 
edges; severe / coarse scaling covering almost all or all lesions
NOTE: Involvement of the nails is not part of the assessment.


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6.4.5
Health-related quality of life (HRQoL)
The impact of psoriasis on various aspects of the subject’s health-related quality of life (HRQoL) 
will be assessed by the following validated instrument which will be performed at the scheduled 
study visits as indicated in Table 6-1:

Dermatology Life Quality Index (DLQI)
The quality of life assessment should be completed by the subject prior to being seen by the 
study physician (Investigator or qualified site staff) who will perform the Investigator
assessments.
The subject should be given sufficient space and time to complete the paper questionnaire. The
study coordinator should check the questionnaire for completeness and encourage the subject to
complete any missing responses.
Before the subject’s clinical examination, the Investigator should review the completed
questionnaire for responses that may indicate potential AEs or SAEs. If AEs or SAEs are
confirmed, the Investigator must record the events as per instructions given in Section 7 of the
protocol.
Investigators should not encourage subjects to change the responses reported in the completed 
questionnaire.
A copy of the DLQI is provided in Section 13 (Appendix 5).
6.4.5.1
Dermatology Life Quality Index (DLQI)
The Dermatology Life Quality Index (DLQI) is a 10-item general dermatology disability 
index designed to assess health-related quality of life in adult subjects with skin diseases such as
eczema, psoriasis, acne, and viral warts (Finlay and Khan, 1994). The measure is self-
administered and includes domains of daily activities, leisure, personal relationships, symptoms 
and feelings, treatment, and work/school. The measure is widely used; it has been tested across 
32 different skin conditions and is available in 55 languages. The recall period is the last week,
and the instrument requires 1 to 2 minutes for completion.
Each item has four response categories, ranging from 0 (not at all) to 3 (very much). "Not 
relevant" is also a valid response and is scored as 0. The DLQI total score is a sum of the 10
questions. Scores range from 0 to 30 and higher scores indicate greater health-related 
quality-of-life impairment. Additionally, each subscale of the DLQI may be analyzed separately.
The DLQI questionnaire (date of publication 1994) will be completed by the subject as indicated
in Table 6-1.
6.4.6
Appropriateness of efficacy assessments 
The primary efficacy assessment is aortic vascular inflammation measured by FDG-PET/CT, an 
important imaging biomarker and surrogate marker for future vascular risk. FDG-PET/CT is 


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reliable and predictive of future vascular events independent of other cardiovascular biomarkers, 
and improves rapidly (i.e., within four weeks) with interventions known to reduce vascular risk 
(i.e., statins). It is increasingly used as a surrogate marker for novel agents being studied in FDA 
regulated trials assessing novel strategies for CV risk reduction. Alternative assessments such as 
carotid IMT and MRI-based measures of wall thickness change only slowly and thus would 
require longer term trials in which use of placebo would not be feasible. Secondary efficacy 
assessments include biomarkers that are well established markers of inflammation and 
cardiovascular risk.
The PASI score is a standard and validated measurement for chronic plaque psoriasis.
The IGA mod 2011 scale has been developed by Novartis in collaboration with health
authorities, in particular the FDA. It is based on the previous version of the scale which was used
in the Phase II secukinumab studies. In the modified scale, the two “very severe” and “severe”
categories 
have
been
condensed 
into
a
single
category 
of
“severe”,
and
the 
explanations/descriptions of the points on the scale have been improved to ensure appropriate 
differentiation between the points.
6.5
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.
Safety assessments will be performed as indicated in Table 6-1:

Evaluation of all AEs and SAEs (including injection site reactions and occurrence of 
infections)

Physical examination

Vital signs

Height and weight

Laboratory evaluations

Hematology

Clinical chemistry

Viral serology

Pregnancy and assessments of fertility.
6.5.1
Physical examination 
A complete physical examination will be performed by a professionally trained physician or 
health professional licensed to perform physical examinations, and listed on FDA Form 1572. 
The physical examination, including general appearance, will be performed at the scheduled 
study visits as indicated in Table 6-1. 


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If indicated, based on medical history and/or symptoms, additional exams may be performed at
the discretion of the Investigator/qualified site staff.
If possible, assessments for an individual subject should be performed by the same 
Investigator/qualified 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 subject 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 must be recorded in the subject’s 
Adverse Event eCRF (Section 7).
6.5.2
Vital signs
Vital signs (including blood pressure and pulse measurements) will be assessed at scheduled
study visits as indicated in Table 6-1.
After the subject has been sitting for at least five minutes, with back supported and both feet
placed on the floor, systolic and diastolic blood pressure (BP) will be measured using a
validated device with an appropriately sized cuff. In case the cuff sizes available are not large
enough for the subject’s arm circumference, a sphygmomanometer with an appropriately sized
cuff may be used. The BP measurement will be recorded in the Vital Signs eCRF.
If possible, assessments should be performed by the same site staff throughout the study.
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 subject. No specific action is foreseen
as part of the study protocol.
6.5.3
Height and weight 
Height and body weight (in indoor clothing but without shoes) will be measured at scheduled 
study visits as indicated in Table 6-1. If possible, body weight assessments should be performed 
using the same scale throughout the study.


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6.5.4
Laboratory evaluations 
A central laboratory will be used for analysis of all specimens collected. Details on the collection, 
shipment of samples, and reporting of results by the central laboratory will be provided to 
Investigators in the Laboratory Manual.
Refer to the Laboratory Manual for identification of laboratory reference range values, notable 
values, and the schema for notification of site staff and Novartis for out of range values.
Section 13 (Appendix 1) shows the expanded laboratory ranges and the clinically notable 
abnormalities of key laboratory tests.
6.5.4.1
Hematology
Hemoglobin, hematocrit, red blood cell count, white blood cell count with differential 
(neutrophils including bands, lymphocytes, monocytes, eosinophils, basophils) and platelet
count will be measured at scheduled study visits as indicated in Table 6-1.
6.5.4.2
Clinical chemistry
Blood urea, creatinine, total bilirubin, ALT (SGPT), AST (SGOT), GGT, alkaline phosphatase, 
and hemoglobin A1c (HbA1c) will be measured at scheduled study visits as indicated in Table 6-
1; HbA1c will be measured at screening only.
6.5.4.3
Fasting laboratory evaluations
Fasting (8 hour duration with water ad libitum) laboratory tests will be performed at screening 
and will include:

Plasma glucose
6.5.4.4
Viral serology
Viral serology will be performed at screening and will include:

Hepatitis screening: Hepatitis B surface antigen (HBsAg); Hepatitis C virus antibody 
(HCVAb)

HIV screening: HIV 1/2
To be eligible for randomization, subjects must have “non-reactive” serology results at screening. 
6.5.5
Pregnancy and assessments of fertility 
At the Screening visit, a serum β-hCG pregnancy test will be performed in all women except 
those who are sterile or post-menopausal. Any woman with a confirmed positive pregnancy
test during screening is not eligible for randomization.


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Starting at Visit 2/Baseline, all women except those who are sterile or post-menopausal will 
have a local urine pregnancy test at scheduled study visits as indicated in Table 6-1.
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 subject must be discontinued from the study as described in Section 5.5.9.
6.5.6
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.
6.6
Other assessments
No additional tests will be performed on subjects entered into this study.
7
Safety monitoring
7.1
Adverse events
An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and unintended 
sign [including abnormal laboratory findings], symptom or disease) in a patient or clinical 
investigation subject after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. Study treatment includes the study drug under evaluation and 
the comparator treatment or placebo that is given during any phase of the study. Medical
conditions/diseases present at the time of screening are only considered AEs if they worsen
after the subject has signed informed consent.
For all subjects who sign informed consent and who are randomized into the Double-blind 
Treatment Period of the study will have all adverse events that occur after informed consent
is signed recorded on the Adverse Event CRF.
The occurrence of adverse events should be sought by non-directive questioning of the subject at 
each visit during the study. Adverse events also may be detected when they are volunteered by 
the subject during or between visits or through physical examination, laboratory test, 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; and/or

they require therapy. 


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Clinically significant abnormal laboratory values or test results should 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 subject with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
subject and identifying adverse events. Alert ranges for labs and other test abnormalities are 
included in Appendix 1.
Adverse events should be recorded in the Adverse Events eCRF under the signs, symptoms or 
diagnosis associated with them, accompanied by the following information:

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

Relationship to the study treatment

Duration (start and end dates or if continuing at final exam)

Whether it constitutes a serious adverse event (SAE - See Section 7.2 for the definition of 
SAE)

Action taken regarding study treatment

Concomitant medication(s) taken or non-drug therapies given

Outcome.
Once an adverse event is detected, it should be followed until its resolution or until it is judged to 
be permanent. An assessment should be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the study treatment, the interventions 
required to treat it, and the outcome.
Information about common side effects already known about the study drug can be found in the 
Investigator Brochure (IB) or will be communicated between IB updates in the form of 
Investigator Notifications (INs). This information will be included in the subject informed 
consent and should be discussed with the subject during the study as needed.
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


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
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 subject’s general 
condition

is medically significant, i.e. defined as an event that jeopardizes the subject 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 subject 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 more severe (see 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 subject 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 (see Annex IV, ICH-E2D Guideline).
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
All AEs (serious and non-serious) are captured on the eCRF, SAEs also require individual 
reporting to DS&E as per Section 7.2.2.
7.2.2
SAE reporting
To ensure subject safety, every SAE, regardless of causality, occurring after the subject has 
provided informed consent and until 30 days after the last study visit must be reported to Novartis 
within 24 hours of learning of its occurrence. Any SAEs experienced after the 30 days period 
should only be reported to Novartis if the Investigator suspects a causal relationship to study 
treatment. 
Recurrent episodes, complications, or progression of the initial SAE must be reported as follow-
up to the original episode, regardless of when the event occurs. This report must be submitted 


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within 24 hours of the Investigator receiving the follow-up information. An SAE that is 
considered completely unrelated to a previously reported one should be reported separately as a 
new event.
Information about all SAEs (either initial or follow up information) is collected and recorded on 
the paper Serious Adverse Event Report Form. The Investigator must assess the relationship to 
each specific component of study treatment (if study treatment consists of several drugs)
complete the SAE Report Form in English, and send the completed, signed form by fax within 24 
hours after awareness of the SAE to the local Novartis Drug Safety and Epidemiology 
Department. The telephone and fax number of the contact persons in the local department of 
Drug Safety and Epidemiology, specific to the site, are listed in the investigator folder provided 
to each site. The original copy of the SAE Report Form and the fax confirmation sheet must be 
kept with the case report form documentation at the study site. Follow-up information should be 
provided using a new paper SAE Report Form stating that this is a follow-up to a previously 
reported SAE
Follow- up information provided should describe whether the event has resolved or continues, if 
and how it was treated, whether the treatment code was broken or not and whether the subject
continued or withdrew from study participation. Each re-occurrence, complication, or progression 
of the original event should be reported as a follow-up to that event regardless of when it occurs.
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 investigational 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 investigational 
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
Pregnancy reporting
To ensure subject safety, each pregnancy occurring while the subject is on study treatment must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of the 
birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications.
Pregnancy should be recorded on the Clinical Trial Pregnancy Form and be reported by the 
Investigator/qualified site staff 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 must be reported on the SAE Report Form.


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8
Data review and database management
8.1
Site monitoring
At a site initiation visit or at an investigator’s meeting, a Novartis representative will review the 
protocol and eCRFs with the Investigators and their staff. During the study, Novartis employs 
several methods of ensuring protocol and GCP compliance and the quality/integrity of the sites’ 
data. The field monitor will visit the site to check the completeness of subject records, the 
accuracy of entries on the eCRFs, 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 specifications. Key investigator staff must be available to assist the 
field monitor during these visits.  Continuous remote monitoring of each site’s data may be 
performed by a CRO. Additionally, a CRO may analyze data and identify risks and trends for site 
operational parameters, and provide reports to the Novartis Clinical Team to assist with trial 
oversight.
The Investigator must maintain source documents for each subject in the study, consisting of case 
and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or assessments. 
All information on eCRFs must be traceable to these source documents in the subject's file. The 
Investigator must also keep the original informed consent form signed by the subject (a signed 
copy is given to the subject).
The Investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the eCRF entries. 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 CRFs are performed according to the study-specific monitoring plan. 
No information in source documents about the identity of the subjects will be disclosed.
8.2
Data collection
Designated investigator staff will enter the data required by the protocol into the Electronic Case 
Report Forms (eCRFs) using fully validated software that conforms to US 21 CFR Part 11 
requirements. Designated investigator site staff will not be given access to the EDC system until 
they have been trained.
Automatic validation programs check for data discrepancies 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 via electronic approval that the data entered into the eCRFs 
are complete and accurate. After database lock, the Investigator will receive copies of the subject
data for archiving at the investigational site.


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8.3
Database management and quality control
A CRO working on behalf of Novartis will review the data entered into the eCRFs 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 electronic 
data query. Designated investigator site staff is required to respond to the query and confirm or 
correct the data. 
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 (including cardiometabolic biomarkers) will be processed centrally and the 
results will be sent electronically to a designated CRO.
FDG-PET/CT scans will be read and analyzed centrally and the results will be sent electronically 
to a designated CRO.
A PRO questionnaire will be completed by the subject on paper, and the data transcribed into the 
eCRF by investigator site staff.
Randomization codes and data about all study drug(s) dispensed to the subject will be tracked 
using an Interactive Response Technology (IRT). The system will be supplied by a vendor, who 
will also manage the database. The database will be sent electronically to 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 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.
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It is planned that the data from all centers that participate in this protocol will be combined, so 
that an adequate number of subjects will be available for analysis.
Unless otherwise specified, all statistical tests will be conducted against a two-sided alternative 
hypothesis, employing a significance level of 0.05.
Efficacy, safety, and other data will be summarized.  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 from baseline to each time point will be reported by 
treatment group.
9.1
Analysis sets 
The following analysis sets will be used for the statistical reporting and analyses:
Randomized Set: The randomized set includes all subjects who were randomized.
Safety Set: The Safety Set includes all subjects who received at least one dose of study 
medication.  Subjects will be analyzed according to treatment received.
Full Analysis Set:  The Full Analysis Set includes all subjects to whom study medication has 
been assigned.  Subjects inappropriately randomized (e.g., IRT was called in error for 
randomization of a screen failed subject) will be excluded from this analysis set.  Following the 
intent-to-treat principle, subjects will be analyzed according to the treatment they were assigned 
to at randomization.
9.2
Subject demographics and other baseline characteristics 
Data will be summarized with respect to demographic and baseline characteristics for the 
Randomized Set and the Full Analysis Set.
9.3
Treatments 
The number of subjects and the length of time (in days) exposed to each treatment will be 
summarized for the Safety Set. Note that during the Double-blind Treatment Period, all subjects 
will receive their last dose of study treatment at Visit 7/Week 8.
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.  Summaries for cardiovascular and psoriasis-
specific medical history will be provided as well.


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9.4
Analysis of the primary variable
9.4.1
Variable
The primary efficacy variable is the change from baseline in the target (arterial vascular uptake) 
to background (venous blood pool) ratio from the aorta.  Target to background ratio is considered 
the standard reporting variable based on FDG-PET/CT scans in vascular studies (see Section 
6.4.1). The primary analysis time point will be at Week 12.
9.4.2
Statistical model, hypothesis, and method of analysis
Let µj denote the population mean of change from baseline in the target to background ratio from 
the aorta at Week 12 for treatment group j, j = 0, 1, where 0 corresponds to placebo and 1 
corresponds to secukinumab.  
The following null hypothesis (H0) will be tested against the alternative hypothesis (HA):
H0: µ1 – µ0 = 0 
HA: µ1 – µ0 ≠0
The primary efficacy variable will be analyzed by an analysis of covariance (ANCOVA) model 
with treatment, baseline, and body weight (<90 kg, ≥90 kg) as explanatory variables.  The least 
squares means of the two treatment groups, least squares mean difference of the treatment groups, 
95% confidence interval for the difference in the two treatment groups, and p-value based on the 
fitted linear model will be reported.  
The primary analysis of the primary efficacy variable will be based on the Full Analysis Set.
9.4.3
Handling of missing values/censoring/discontinuations
Missing data will be imputed using the last-observation-carried-forward (LOCF) method. If a 
subject has no post-baseline value, the missing value will not be imputed and the subject will be 
removed from the analysis.
9.4.4
Supportive analyses 
A supportive nonparametric analysis will be performed to examine the consistency of results if 
the assumption of normality for the distribution of the primary efficacy variable is not 
tenable. For this supportive analysis, the primary efficacy variable will be analyzed using the 
stratified Wilcoxon rank-sum test with modified ridit scores (van Elteren’s test), adjusting for 
body weight (<90 kg, ≥90 kg) (Stokes, Davis, and Koch, 2012).


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9.5
Analysis of secondary variables
9.5.1
Efficacy variables 
The secondary efficacy variables are the following:

Change from baseline in each biomarker (see Section 6.4)

PASI 75 response (yes, no)

PASI 90 response (yes, no)

PASI 100 response (yes, no)

IGA mod 2011 score of 0 or 1 (yes, no)

Change from baseline in DLQI total score
Change from baseline in each biomarker and change from baseline in DLQI total score will be 
analyzed at each time point using the same ANCOVA model as for the primary efficacy variable, 
and missing data will be imputed using the LOCF method.
IGA mod 2011 score of 0 or 1 and PASI 75 / 90 / 100 responses will be analyzed at each time 
point using the Cochran-Mantel-Haenszel test to compare secukinumab and placebo, adjusting 
for body weight (<90 kg, ≥90 kg) (Stokes, Davis, and Koch, 2012). A 95% confidence interval 
for the difference between the two treatment groups in the proportion of subjects who are 
responders will be calculated using the normal approximation to the binomial distribution. For 
response (yes, no) at Week 12 (and other time points), a subject with a missing assessment will 
be considered as a responder (yes) if the subject meets the response criterion at the time of 
premature discontinuation from the study. Otherwise, the subject will be considered as a non-
responder (no).
Analyses of the secondary efficacy variables will be based on the Full Analysis Set.
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 (e.g., vital signs and special tests) will be considered, as appropriate.
Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of subjects 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 the Week 12 visit will be included 
in the database for the analysis at the primary analysis time point (Week 12).
Laboratory variables will be summarized. 
Analysis of safety data will be based on the Safety Set.


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9.5.3
Resource utilization
Not applicable
9.5.4
Pharmacokinetics
Not applicable.
9.5.5
Pharmacogenetics/pharmacogenomics
Not applicable.
9.5.6
Other biomarkers
Not applicable.
9.5.7
PK/PD
Not applicable.
9.6
Interim analyses
The primary analysis at Week 12 is considered an interim analysis. As Week 12 is the primary 
analysis time point, no adjustment to the significance level of 0.05 will be made.
9.7
Sample size calculation
The sample size was based on change from baseline in the target (arterial vascular uptake) to 
background (venous blood pool) ratio (TBR) from the aorta.  Using a t-test, a clinically important 
mean treatment difference of 0.15, a (common) standard deviation (SD) of 0.196, an allocation 
ratio of 1:1, a two-sided significance level of 0.05, and a power of 0.90, it was determined that 
approximately 74 subjects (37 in each treatment group) are necessary (nQuery Advisor 7.0) 
(Bissonnette et al 2013; Tawakol et al 2013). Without adjusting for multiplicity, the sample size 
of 74 subjects will also provide at least 0.90 power for other biomarkers (see Section 6.4.2) if the 
treatment difference is 0.76 SD or smaller. The general threshold for clinical importance is 1 SD.
Allowing for a loss to follow-up rate of 0.10, approximately 84 subjects (42 in each treatment 
group) will be randomized.
10
Ethical considerations
10.1
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented 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 21 CFR, and Japanese Ministry of 
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Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of 
Helsinki.
10.2
Informed consent procedures 
Eligible subjects may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if incapable of doing so, 
after such consent has been provided by a legally acceptable representative(s) of the subject. In 
cases where the subject’s representative gives consent, the subject should be informed about the 
study to the extent possible given his/her understanding. If the subject is capable of doing so, 
he/she should 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 (i.e., all of the procedures described in the protocol). The process of 
obtaining informed consent should be documented in the subject source documents. 
Novartis will provide to Investigators in a separate document a proposed informed consent form 
that complies with the ICH 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 monitor after IRB/IEC approval.
Women of child bearing potential should be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order to 
participate in the study they must adhere to the contraception requirement for the duration of the 
study. If there is any question that the subject will not reliably comply, they should not be entered 
in the study.
10.3
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the Investigator/institution should 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, subject recruitment procedures (e.g., 
advertisements) and any other written information to be provided to subjects. Prior to study start, 
the Investigator is required to sign a protocol signature page confirming his/her agreement to 
conduct the study in accordance with these documents and all of the instructions and procedures 
found in this protocol and to give access to all relevant data and records to Novartis monitors, 
auditors, Novartis Quality Assurance representatives, designated agents of Novartis, IRBs/IECs, 
and regulatory authorities as required. If an inspection of the clinical site is requested by a 
regulatory authority, the Investigator must inform Novartis immediately that this request has been 
made.
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10.4
Publication of study protocol and results 
Novartis assures that 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.
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 subjects should be 
administered as deemed necessary on a case by case basis. Under no circumstances should an 
Investigator collect additional data or conduct any additional procedures for any research related 
purpose involving any investigational drugs.
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. All 
significant protocol deviations will be recorded and reported in the CSR.
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 subjects may be implemented immediately provided the Health Authorities are subsequently 
notified by protocol amendment and the reviewing IRB/IEC is notified. Notwithstanding the need 
for approval of formal protocol amendments, the Investigator is expected to take any immediate 
action required for the safety of any subject included in this study, even if this action represents a 
deviation from the protocol. In such cases, the reporting requirements identified in Section 7
Safety Monitoring should be followed.
12
References
References are available upon request.
Abbas A et al. (2015) Interleukin 23 levels are increased in carotid atherosclerosis: possible role 
for the interleukin 23/interleukin 17 axis. Stroke; 46(3):793-9.
Bissonnette R et al. (2013) Effects of the tumor necrosis factor-α antagonist adalimumab on 
arterial inflammation assessed by positron emission tomography in patients with psoriasis: results 
of a randomized controlled trial. Circ Cardiovasc Imaging; 83-90.


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Chobanian AV, Bakris GL, Black HR (2003) Seventh report of the joint national committee on
prevention, detection, evaluation, and treatment of high blood pressure. Hypertension; 42:1206–52.
Committee for medicinal products for human use (CHMP), European Medicines Agency for the
Evaluation of Medicines for Human Use. (2004) Guideline on clinical investigation of medicinal
products indicated for the treatment of psoriasis. CHMP/EWP/2454/02 corr. document. London,
UK
Doherty SD, Van Voorhees A, Lebwohl MG (2008) National psoriasis foundation consensus 
statement on screening for latent tuberculosis infection in patients with psoriasis treated with 
systemic and biologic agents. J. Am. Acad. Dermatol; 59 (2): 209–217.
Erbel C et al. (2014) IL-17A influences essential functions of the monocyte/macrophage lineage 
and is involved in advanced murine and human atherosclerosis. J Immunol; 193(9): 4344-55.
Erbel C et al. (2011) Expression of IL-17A in human atherosclerotic lesions is associated with 
increased inflammation and plaque vulnerability. Basic Res Cardiol; 106:125-34.
Figueroa AL, et al. (2013) Measurement of arterial activity on routine FDG PET/CT images 
improves prediction of risk of future CV events. JACC Cardiovasc Imaging; 1250-9.
Finlay AY, Khan GK (1994) Dermatology Life Quality Index (DLQI): A simple practical 
measure for routine clinical use. Clin Exp Dermatol; 19:210–16.
Fredriksson T, Pettersson U (1978) Severe psoriasis—oral therapy with a new retinoid. 
Dermatologica; 157:238–44.
Gelfand J, et al (2006) Risk of myocardial infarction in patients with psoriasis. JAMA; 
296(14):1735-41.
Gelfand J, et al (2009) The risk of stroke in patients with psoriasis. J Invest Dermatol; 
129(10):2411-8.
Gottlieb A, Griffiths CEM, Ho VC, et al (2005) Efficacy and tolerability of oral pimecrolimus in
the treatment of moderate to severe chronic plaque type psoriasis: a double-blind, multicentre,
randomized dose-finding trial. Br J Dermatol; 152:1219-27.
Karbach S et al. (2014) Interleukin 17 drives vascular inflammation, endothelial dysfunction, and 
arterial hypertension in psoriasis-like skin disease. Arterioscler Thromb Vasc Bio; 34(12):2658-
68.
Lee SJ, et al. (2008) Reversal of vascular 18F-FDG uptake with plasma high-density lipoprotein 
elevation by atherogenic risk reduction. J Nucl Med; 1277-82.
Manuel O, Kumar D (2008) QuantiFERON-TB Gold assay for the diagnosis of latent tuberculosis
infection. Expert Rev Diagn; 8(3): 247-56.
Mehta N et al. (2012) Quantification of atherosclerotic plaque activity and vascular inflammation 
using [18-F] fluorodeoxyglucose positron emission tomography/computed tomography (FDG-
PET/CT). J Vis Exp; 22(63):e3777.


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Mehta N, et al. (2012) Abnormal lipoprotein particles and cholesterol efflux capacity in patients 
with psoriasis. Atherosclerosis; 218-21.
Mehta N, et al. (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; 1031-39.
Mehta N, et al. (2010) Patients with severe psoriasis are at increased risk of cardiovascular 
mortality: cohort study using the General Practice Research Database. European Heart Journal; 
1000-6.
Naik H, et al. (2015) Psoriasis area severity index score positively associates with vascular 
inflammation by FDG PET/CT. J Invest Dermatol; (135): S35-S35.
National Psoriasis Foundation (2014) Statistics. Available from:
https://www.psoriasis.org/learn_statistics. [18 March 2014].
Ogdie A, et al (2015) Risk of major cardiovascular events in patients with psoriatic arthritis, 
psoriasis and rheumatoid arthritis: a population-based cohort study. Ann Rheum Dis; 74(2):326-
32.
Roubille C et al. (2015) The effects of tumour necrosis factor inhibitors, methotrexate, non-
steroidal anti-inflammatory drugs and corticosteroids on cardiovascular events in rheumatoid 
arthritis, psoriasis and psoriatic arthritis: a systematic review and meta-analysis. Ann Rheum Dis; 
74:480-9.
Stokes ME, Davis CS, Koch GG (2012) Categorical data analysis using the SAS system. 3rd ed; 
Cary, NC: SAS Institute, Inc.
Tawakol A, et al. (2013) Intensification of statin therapy results in a rapid reduction in 
atherosclerotic inflammation: results of a multi-center FDG-PET/CT feasibility study. JACC;
909-17.
Weisman S, Pollack CR, Gottschalk RW (2003) Psoriasis disease severity measures: comparing
efficacy of treatments for severe psoriasis. J Dermatolog Treat; 14:158-65.
Yeung H, et al. (2013) Psoriasis severity and the prevalence of major medical comorbidity: a 
population-based study. JAMA Dermatol; 149(10):1173-9.


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13
Appendices
13.1
Appendix 1: Clinically notable laboratory values and vital signs
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. Notable values for blood pressure and pulse are presented in Section 6.5.2.
Whether or not any action needs to be taken to address notable laboratory or vital signs 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.
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 and electrolyte variables
Creatinine (serum)
> 1.5 x ULN
Hematology values
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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13.2
Appendix 2: Tuberculosis screening flowchart


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13.3
Appendix 3: Psoriasis Area and Severity Index (PASI) and Body 
Surface Area (BSA)


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13.4
Appendix 4: Investigator’s Global Assessment (IGA mod 2011)


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13.5
Appendix 5: Dermatology Life Quality Index (DLQI)


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SAP_001.pdf: 
Clinical Development
AIN457A/Secukinumab®
CAIN457AUS02 / NCT02690701
A randomized, double-blind, placebo-controlled, parallel-
group, multicenter study to evaluate the effect of 
secukinumab on aortic vascular inflammation and 
cardiometabolic biomarkers after 12 weeks of treatment, 
compared to placebo, and up to 52 weeks of treatment with 
secukinumab in adult subjects with moderate to severe 
chronic plaque-type psoriasis
Statistical Analysis Plan (SAP)
Author:
Trial Statisticians:
Document type:
SAP Documentation
Document status:
Amendment v 3.0
Release date:
2-Aug-2018
Number of pages:
35
Property of Novartis
For business use only
May not be used, divulged, published or otherwise disclosed
without the consent of Novartis


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Document History – Changes compared to previous final version of SAP
Date
Time
point
Reason for update
Outcome for update
Section and title
impacted
(Current)
09.02.2016
Prior
to
DBL
SAP first version 1.0 is created
Final version 1.0
20.06.2016
Prior
to
DBL
To keep
consistency with
latest protocol
Family history of cardiovascular
disease is added in page 12
In addition:
Section 2.3.3
16.5.2017
Prior
to
DBL
29.5.2017
Prior
to
DBL
version
To keep
consistency with
standard analysis/
Master Analysis
Plan
As discussed in
Dry-run meeting
with CTT
2) PASI and IGA response
are changed to PASI
and IGA score in page
12
ii) SAS code is updated in page
24
iii) Correction of typos
iv) Protocol deviation list is
updated
Addition of day of last dose of
randomized study treatment
Elaboration of duration of
exposure and addition of visit
window
Re-modified the definition of Prior
and concomitant medication
Elaboration of handling of missing
data and remodified the definition,
as per protocol, of non-responder
imputation
Overall safety analysis
specification
Cardiometabolic biomarker data
will additionally be analyzed using
stratified Wilcoxon rank sum test if
the data does not satisfy normality
condition
One correction is made in notable
criteria for pulse rate
Spelling and format correction
Section 2.3.3
Section 5.4.1
Section 5.5
Section 2.1.1
Section 2.4.1
Section 2.4.2
Section 2.7.3
Section 2.8
Section 2.7.2 and
Section 4
Section 2.8.4.2
10.08.2017
Prior
to
DBL
As discussed with
CTT
Visit window for target to
background ratio and
cardiometabolic biomarker data
Section 2.4.1.1
11.08.2017
Prior
to
As discussed with
CTT
Visit windows are updated
Section 2.4.1.1


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Date
Time
point
DBL
Reason for update
Outcome for update
Section and title
impacted
(Current)


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Table of contents
Table of contents..................................................................................................................4
List of abbreviations ............................................................................................................6
1
Introduction..........................................................................................................................7
1.1
Study design.............................................................................................................7
1.2
Study objectives.......................................................................................................8
2
Statistical methods...............................................................................................................9
2.1
Data analysis general information ...........................................................................9
2.1.1
General definitions................................................................................10
2.2
Analysis sets ..........................................................................................................11
2.3
Patient disposition, demographics and other baseline characteristics ...................11
2.3.1
Patient disposition.................................................................................11
2.3.2
Demographics........................................................................................12
2.3.3
Baseline characteristics .........................................................................12
2.4
Treatments (study treatment, rescue medication, concomitant therapies,
compliance)............................................................................................................14
2.4.1
Study treatment exposure and compliance............................................14
2.4.2
Prior, concomitant and post therapies ...................................................18
2.5
Analysis of the primary objective..........................................................................18
2.5.1
Primary efficacy variable ......................................................................18
2.5.2
Statistical hypothesis, model, and method of analysis ..........................19
2.5.3
Handling of missing values/censoring/discontinuations.......................19
2.5.4
Supportive analyses...............................................................................19
2.6
Analysis of the key secondary objective................................................................19
2.7
Analysis of secondary efficacy objectives.............................................................19
2.7.1
Secondary efficacy variables.................................................................19
2.7.2
Statistical hypothesis, model, and method of analysis ..........................20
2.7.3
Handling of missing values/censoring/discontinuations.......................21
2.8
Safety analyses.......................................................................................................21
2.8.1
Adverse events (AEs)............................................................................21
2.8.2
Deaths....................................................................................................22
2.8.3
Laboratory data .....................................................................................23
2.8.4
Other safety data....................................................................................24
2.9
Pharmacokinetic variables.....................................................................................24
2.10
PD and PK/PD analyses.........................................................................................24


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2.11
Patient-reported outcomes......................................................................................24
2.12
Biomarkers.............................................................................................................24
25
2.14
Interim analysis......................................................................................................25
3
Sample size calculation .....................................................................................................25
4
Change to protocol specified analyses ...............................................................................26
5
Appendix............................................................................................................................26
5.1
Imputation rules .....................................................................................................26
5.1.1
AE date imputation................................................................................26
5.1.2
Concomitant medication date imputation .............................................28
5.2
AEs coding/grading ...............................................................................................29
5.3
Laboratory variables derivations ...........................................................................29
5.4
Statistical models...................................................................................................29
5.4.1
Primary analysis ....................................................................................29
5.4.2
Key secondary analysis .........................................................................30
5.5
Rule of exclusion criteria of analysis sets ..............................................................30
6
References..........................................................................................................................35


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List of abbreviations
AE
Adverse event
ANCOVA
Analysis of covariance
BSA
Body Surface Area
CMB
Cardio metabolic biomarker
CSR
Clinical Study Report
DLQI
Dermatology Life Quality Index
eCRF
Electronic Case Report Form
FAS
Full Analysis Set
FDG-PET/CT
[18F]-fluorodeoxyglucose positron emission tomography with computer assisted
tomography
GCP
Good Clinical Practice
HDL
high-density lipoprotein
HIV
human immunodeficiency virus
ICH
International Conference on Harmonization of Technical Requirements for
Registration of Pharmaceuticals for Human Use
IGA mod 2011
Novartis Investigator’s Global Assessment modified 2011
IL
Interleukin
IRT
Interactive Response Technology
LLN
Lower Limit of Normal
LOCF
Last-observation-carried-forward
MedDRA
Medical Dictionary for Drug Regulatory Affairs
PASI
Psoriasis Area and Severity Index
PFS
prefilled syringe
PK
Pharmacokinetics
PRO
Patient-reported Outcomes
RAN
Randomized Set
SAF
Safety set
SAP
Statistical Analysis Plan
SAS
Statistical Analysis Software
SOC
System Organ Class
s.c
Subcutaneous
TB
Tuberculosis
TBR
Target to background ratio
ULN
Upper Limit of Normal


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1
Introduction
This statistical analysis plan (SAP) describes the statistical methodologies, which will be
used in the phase IV clinical trial (CAIN457AUS02). This is a randomized, double blind,
placebo- controlled, parallel group, multicenter study in adult subjects with moderate to
severee chronic plaque-type psoriasis in the United States.
The purpose of this study is to evaluate the effect of secukinumab compared to placebo on
aortic vascular inflammation and cardiometabolic biomarkers after 12 weeks of treatment, in
subjects with moderate to severe plaque-type psoriasis. In addition, this study will evaluate
the effect of longer-term treatment with secukinumab (up to 52 weeks) on aortic vascular
inflammation.
1.1
Study design
In this study, there are four periods:
Screening: The screening period is between Week -4 to Baseline (B) visit, the duration of
screening period will be up to four weeks (28 days).
Double-blind
Treatment
Period: The double-blind treatment period is defined ad
Randomization through Week 12 (prior to Week 12 dose), which is a total of 12 weeks time.
Double-blind Induction Period: The double-blind induction period is defined as the Week
12 dose through Week 15 dose, which is a total of 4 weeks time.
Open-label Treatment Period: The open-label treatment period is defined as the Week 16
though Week 52, which is a total of 36 weeks time.
Note: Baseline visit is Week 0 (Visit 2).
A   schematic   of   the   study    design   and   visits   is   presented   in   figure   below:
For more details, see study protocol, Section 3.1


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All doses of study treatment will be self-administered. Self-administration of the study
treatment refers to subject self-injection or injection by a trained caregiver regardless of
whether self-administration occurs at the study site or at home.
Approximately 84 subjects with moderate to severe chronic plaque -type psoriasis will be
randomized from approximately 10 investigative sites in the United States. Assuming a 20%
screen failure rate, 105 subjects will need to be screened to provide the targeted number of
randomized subjects. Subjects who drop out after they have been randomized will not be
replaced.
At the start of the Double-blind Treatment Period, eligible subjects will be randomized via
Interactive Response Technology (IRT) in a 1:1 ratio to one of two treatment groups
(secukinumab 300 mg or placebo).
Assessments for the primary efficacy variable will be performed at Week 12 for both
treatment groups prior to subjects receiving their Week 12 dose.
Primary analysis at Week 12 will be considered as the interim analysis. As Week 12 is the
primary analysis time point, no adjustment to the significance level of 0.05 will be made.
1.2
Study objectives
Primary objective
The primary objective is to evaluate the effect of secukinumab 300 mg s.c. compared to
placebo on aortic vascular inflammation with respect to the change from baseline in the target
(arterial vascular uptake) to background (venous blood pool) ratio from the aorta. The primary 
analysis time point will be at Week 12.
Secondary objectives
To evaluate the effect of secukinumab compared to placebo with respect to change from
baseline in cardio metabolic biomarkers (cardio metabolic function [lipid particle size, HDL
function (cholesterol efflux)], measures of inflammation [TNF-Alpha, IL-6, C reactive protein, 
GlycA], adiposity [leptin and adiponectin], insulin resistance [insulin levels/glucose to yield
HOMA-IR], and markers predictive of diabetes [apolipoprotein B, ferritin, IL-2 receptor
A, IL-18, and fetuin-A]) at Week 12
To evaluate the effect of secukinumab compared to placebo in subjects with moderate to
severe chronic plaque-type psoriasis with respect to change from baseline in the PASI 75, 90
and 100 response rates at Week 12
To evaluate the effect of secukinumab compared to placebo in subjects with moderate to
severe chronic plaque-type psoriasis with respect to the Investigator’s Global Assessment
mod 2011 (IGA mod 2011) 0 or 1 response at Week 12
To evaluate the effects of secukinumab compared to placebo with respect to change from
baseline in the Dermatology Life Quality Index (DLQI) total score at Week 12


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To evaluate the clinical safety and tolerability of secukinumab as assessed by vital signs,
clinical laboratory variables, and adverse event monitoring.
2
Statistical methods
2.1
Data analysis general information
Novartis Business Services will perform the statistical analysis.
Data will be analyzed by the statistical software SAS, Version 9.4 according to Section 9
(Data Analysis) of the study protocol which will also be available in Appendix 16.1.1 of the
Clinical Study Report (CSR). Important information is given in the following sections and
details are provided, as applicable, which will also be in Appendix 16.1.9 of the CSR.
At the Week 12 primary analysis time point, only the independent statistician and
programmer(s) from Novartis will be unblinded in order to perform the interim analysis. The
same SAP will be used for interim analysis.
It is planned that the data from all centers that participate in this protocol will be combined, so 
that an adequate number of subjects will be available for analysis.
Unless otherwise specified, all statistical tests will be conducted against a two-sided
alternative hypothesis, employing a significance level of 0.05.
Efficacy, safety, and other data will be summarized as follows:

for continuous variables, descriptive summary statistics (number of subjects, mean,
standard deviation, median, 25th and 75th percentiles, interquartile range, minimum, and
maximum) at each time point and for change from baseline to each visit will be reported
by treatment group.


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
for categorical variables, frequency and percentage will be presented at each time point by
treatment group. Percentages will be calculated with respect to the number of subjects by
treatment in the analysis set of interest.
2.1.1
General definitions
2.1.1.1
Study treatment
Secukinumab 300 mg (two s.c. injections of the secukinumab 150 mg dose) will be
considered as study treatment throughout the study, which will be compared with placebo
(two s.c. injections of 150 mg secukinumab matching placebo per dose).
The treatment groups and dosing frequency are described in Table 2-1 below:
Table 2-1
Overview of study treatment
Treatment group
DB
Treatment
Period
(Rand – Wk 12 pre-dose)
Secukinumab 300 mg
2x s.c. secukinumab 150
mg injection at Rand, Wks
1, 2, 3, 4 and 8
Placebo (PBO)
DB Induction Period
(Wk 12 – Wk 15 )
2x s.c. secukinumab 150
mg injection at Wk 12
2x s.c. secukinumab 150
mg PBO injection at Wks
13, 14 and 15
OL Treatment Period
(Wk 16 – Wk 52)
2x s.c. secukinumab
150 m g i n j e c t i o n
a t Wks 16 – 48
2x s.c. secukinumab 150
mg PBO injection at Rand,
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 m g i n j e c t i o n
a t Wks 16 – 48
DB = Double-blind; OL = Open-label; Rand = Randomization; Wk = Week
2.1.1.2
Study day
The day of first administration of the double blind randomized treatment will be considered as 
study day 1. All other study day will be labeled relative to study day 1. The descriptor “study
day 0” will not be used.
The day for a particular event on or after the study day 1 will be calculated as: 
(date of event) – (date of first dose) + 1.
For example study day 2, study day 3… will be one day, two days… after study day 1, and
respectively.
The day before study day 1 will be calculated as:
(date of event) – (date of first dose).
For example study day -1, study day -2,…, will be one day, two days,…, before study day 1
respectively.


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2.1.1.3
Baseline and post-baseline assessments
Baseline assessments are defined as the last assessment before the first dose of double-blind
randomized study treatment, which is typically the last assessment taken before study drug
administration at Visit 2. If the baseline assessments are missing, then the last available
measurement before the first dose of study treatment will be considered as baseline.
All the assessments after first dose of study treatment will be considered as post -baseline
assessments. Therefore, Visit 3 and later visits will be considered as post-baseline visit.
Any procedure performed between Visit 1 and Visit 2 will be considered as screening
assessment.
2.1.1.4
Day of last dose of randomized study treatment
The date of last dose will be collected via the CRF. 
Duration of exposure is defined in Section 2.4.1.
If a subject discontinued early, then the last visit during the treatment period is considered
(e.g., last visit in the induction period, if patient discontinued from the induction period) to
calculate the duration of exposure.
On-treatment is defined as assessments within last dose plus 84 days.
2.2
Analysis sets
The following analysis sets will be used for the statistical reporting and analyses:
Randomized Set: The randomized set includes all subjects who were randomized.
Safety Set: The Safety Set includes all subjects who received at least one dose of study
medication. Subjects will be analyzed according to treatment received.
Full Analysis Set: The Full Analysis Set includes all subjects to whom study medication has
been assigned. Subjects inappropriately randomized (e.g., IRT was called in error for
randomization of a screen failed subject) will be excluded from this analysis set. Following
the intent-to-treat principle, subjects will be analyzed according to the treatment they were
assigned to at randomization.
Rule for exclusion criteria from analysis sets: See Appendix 5-5.
2.3
Patient disposition, demographics and other baseline
characteristics
2.3.1
Patient disposition
The number of subjects screened will be presented along with the reasons for screen failures
for all subjects as specified in the screening phase disposition eCRF.
The number and percentage of subjects screened, randomized, completed study periods
(treatment period 1 and treatment period 2), and discontinued the study prematurely including


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the reason for discontinuation will be presented by overall and study periods for each
treatment group for all screened subjects.
Patients withdrawing consent will be listed with reason for withdrawal.
The number and percentage of subjects with protocol deviations (see Appendix 5-5) will be
tabulated by treatment and listed separately by treatment groups.
2.3.2
Demographics
The following demographic data collected at Visit 2 will be summarized by treatment for the
Full analysis set and the Randomized set:

age (in years)

sex (male/female)

race (Caucasian/black/Asian/native American/pacific islander/unknown/other)

ethnicity (non-Hispanic or Latino/Hispanic or Latino)

Child-bearing potential (able to bear child/post-menopausal/sterile - of child bearing age).
2.3.3
Baseline characteristics
The following baseline characteristics data will be summarized by treatment groups for the
Full analysis set and the Randomized set:
Psoriasis history / Prior psoriasis therapies
Psoriasis history and prior psoriasis therapies collected at Visit 1 will be summarized by
treatment group.
Duration of plaque psoriasis will be calculated as follows:
Date of Visit 1 – Date of first diagnosis of plaque psoriasis + 1.
This duration will be summarized descriptively.
The type of prior psoriasis therapy (biologic systemic therapy, non -biologic systemic therapy,
topical, phototherapy, photochemotherapy) and the respective duration of exposures will be
reported along with the reason of discontinuation of the therapy. This data will also be listed.
Smoking history
Smoking history collected at Visit 1 will be summarized by treatment in terms of estimated
number of pack-years based on the approximate consumption per-year.
The subject’s tobacco usage status (never, current, former) will be collected and frequency
and percentage of different status will be presented by treatment.
Time since last date of tobacco use (for former category) will be calculated as follows:
Date of Visit 1 – Date of last use of tobacco + 1. This duration will be summarized
descriptively by treatment.


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Alcohol use history
Alcohol use history will be summarized by treatment in terms of estimated number of
alcoholic drinks consumed per day captured at Visit 1.
Time since last date of alcohol consumption will be calculated as follows:
Date of Visit 1 – Date of last alcohol consumption + 1.
This duration will be summarized descriptively by treatment.
Comorbidities – cardiovascular history
Cardiovascular history will be summarized using frequencies and percentages by categories
specified in the eCRF, ongoing status and treatment. Duration of cardiovascular diseases
ongoing at Visit 1 will be summarized descriptively. Frequency and the percentage of the
occurrence of each category will be presented. Also, frequency and percentage of ongoing
cardiovascular disease will be presented. This data will also be listed.
In addition, family history of cardiovascular disease will be summarized descriptively. This
data will also be listed.
Relevant medical history / Current medical conditions
Relevant medical history / current medical conditions will include data up to six months prior
to signing of the informed consent and not including psoriasis or psoriatic arthritis and
cardiovascular histories. Any condition entered on the relevant medical history / current
medical conditions CRF will be coded using the MedDRA dictionary and summarized by
System Organ Class (SOC) and Preferred Term (PT). This data will also be listed with
ongoing treatments flagged.
Tuberculosis status
Presence of tuberculosis is assessed at Visit 1 which includes tuberculosis workup conducted
(yes/no), result of workup (active, latent, no – tuberculosis diagnosed/present) and
tuberculosis therapy started (yes/no). This data will be summarized by treatment.
Other baseline characteristics
In addition, the following variables collected at baseline will be summarized by treatment:

height (in cm)

weight (in kg)

pulse (beats/min)

blood pressure (mmHg)

hematology

clinical chemistry

viral serology


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
HIV 1/2

Hepatitis B

Hepatitis C

serum pregnancy

PASI score

IGA mod 2011 score

DLQI total score
2.4
Treatments (study treatment, rescue medication, concomitant
therapies, compliance)
2.4.1
Study treatment exposure and compliance
The duration of exposure to study treatments will be presented based on safety set.
Duration of exposure is defined as the time from first dose of study treatment to the time of
treatment switch (for subjects who switch treatment) or end of treatment period. For subjects
who discontinue duration of exposure will be the last visit in the corresponding treatment
period. For example if a subject discontinues during induction period, this will be the
discontinuation date from induction period recorded on the induction period completion CRF
page.
Duration of exposure (days) = min (last study visit (including follow-up if applicable) date,
last dose date +84) – first dose date +1
Duration of exposure (years) = duration of exposure (days) / 365.25
The duration in days will be summarized by treatment, descriptively and using frequencies
and percentages for categories: “≥4 weeks”, “≥12 weeks”, “≥16 weeks”, and “≥52 weeks”.`
More precisely, duration of exposure will be summarized for following categories:
“any exposure”, “≥1 week”, “≥2 weeks”, “≥3 weeks”, “≥4 weeks”, “≥8 weeks”, “≥12 weeks”,
“≥16 weeks”, “≥28 weeks”, “≥40 weeks” and “≥52 weeks”.
Compliance as percentage of injections administered will be calculated as the number of
injections applied (based on documented study drug administrations and syringe counts as
given in the dosage administration record eCRF page) divided by the number of injections
scheduled per protocol.
Compliance (%) = 100*(total no of injections administered)/ (no. of injections prescribed).
Compliance to study treatment will be summarized descriptively and by categories:
<80% and 80% to 100%, by treatment.
2.4.1.1
Visit window
Visit-windows will be used for the data that is summarized by visit; they are based on the


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study evaluation schedule and comprise a set of days around the nominal visit day. For any
assessment, there are the protocol defined scheduled visits around which visit windows were
created to cover the complete range of days within the study. In the following tables, the days
are counted since the first dose of study treatment (study days) for safety assessments, and the
days are counted since the date of randomization for efficacy assessments. These visit
windows apply to measurements taken at every visit. For assessments collected less often
different visit windows will be applied as detailed below. When visit windows are used, all
visits will be re-aligned, i.e., they will be mapped into one of the visit windows. E.g., if the
Week 4 visit of a subject is delayed and occurs on Day 46 instead of on Day 29, say, it will be
re-aligned to visit window Week 8. In the case of major deviations from the visit schedule, or
due to unscheduled visits, several assessments of a subject may fall in a particular visit
window (either scheduled or unscheduled). Statistical  approaches to handle multiple
assessments in a given visit window are specified below.
Table 1-1
Assessment windows for PASI and IGA assessment:
Analysis Visit
Week
Scheduled Day
Visit Window
Baseline
BSL
1
-28 day to Day 1
Week 4
4
29
Day 2-43
Week 8
8
57
Day 44-71
Week 12
12
85
Day 72-99
Week 16
16
113
Day 100-141
Week 24
24
169
Day 142-197
Week 32
32
225
Day 198-253
Week 40
40
281
Day 254-309
Week 48
48
337
Day 310-351
Week 52
52
365
Day >=352
Table 1-2
Assessment windows for DLQI
Analysis Visit
Week
Scheduled Day
Visit Window
Baseline
BSL
1
-28 day to Day 1
Week 12
12
85
Day 72-99
Week 24
24
169
Day 100-197
Week 32
32
225
Day 198-253
Week 40
40
281
Day 254-309
Week 48
48
337
Day 310-351
Week 52
52
365
Day >=352
Note: Range of visit windows are discussed and agreed with CTT.


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The analysis visit will be used for listing of visit and period for safety data.
Multiple assessments within visit windows
When there are multiple assessments in a particular visit window, the following rules
are applied to select one value “representing” the subject in summary statistics in a visit
window.

For baseline assessment:
For efficacy analyses, baseline is the last assessment (including unscheduled visits) obtained
before the randomization. All assessments obtained after randomization are considered as
post-baseline unless otherwise specified.
For safety analyses, baseline is the last assessment (including unscheduled visits) obtained
before the first dose of study treatment. All assessments obtained after the first dose of study
drug are considered as post-baseline unless otherwise specified.

For post-baseline visit  windows the following applies (unless otherwise specified):
•
for quantitative variables, the closest to the actual visit is chosen (if two assessments
have the same distance, then the earlier one will be chosen);
•
for qualitative variables, the worst record is selected. It is noted that in the
analyses performed, worst case is always well defined (e.g., for urine protein values “+”
and “++”, the worst case is defined as “++”),
•
in case qualitative variables are based on quantitative variables, e.g. PASI 75 response, the
visit will be assigned to the quantitative variable, and this visit will be used for the derived
qualitative variable.
Note: Target to background ratio (TBR) and cardiometabolic biomarker (CMB) data will be
analyzed as per CRF visit. In CMB data analysis, if the patient is discontinued then the
discontinued study visit will be mapped for analysis to the next visit of the last available
assessment before discontinuation with in the same treatment period.


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Table 2-4
Rules for selecting values for analysis
Timing of
measurement
Type of data
Rule
Baseline
All data
The last measurement prior to first dose – note
this may include measurements taken on the
day of randomization (e.g. lab).
Post-baseline safety
Summary visit information
(e.g. lab, ECG, vital etc.)
The (non-missing) measurement closest to the
target day will be used.
In the event two measurements are taken
equally apart (e.g. 1 day before target date and
1 day after) the first one will be used.
If two measurements are taken on the same day
then select the first one (using the time).
If two measurements are taken on the same
date/time then use the first visit number
(assuming this is the planned visit).
If two measurements are taken on the same
date/time/CRF visit then use the average of two
assessments
Post-baseline
efficacy
All data except DLQI, EQ-
5D
and health assessment,
PGIC
The measurement closest to the
target day will be used. In the
event two measurements are
taken equally apart (e.g., 1 day
before target date and 1 day
after), the earlier one will be
used.
If two measurement are taken on the same day
then select the first one using eCRF visit
number.
Post-baseline safety
Summary visit information
(e.g. laboratory values,
vital signs, etc.)
The (non-missing) measurement closest to the
target day will be used. In the event two
measurements are taken equally apart (e.g., 1
day before target date and 1 day after), the
earlier one will be used.
If two measurements are taken on the same day
then select the first one (using the time).
If two measurements are taken on the same
date/time then use the first eCRF visit number
(assuming this is the planned visit).If two
measurements are taken on the same
date/time/eCRF visit number then take the
average value of these two results.
Post-baseline safety
Notable abnormalities (e.g.
The most extreme measurement in the window


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Timing of
measurement
Type of data
Rule
and efficacy
vital signs, PGIC) and
CTCAE grading for
laboratory values
will be used. Note this means a subject can
have a notably high and notably low
measurement within a window
Post-baseline efficacy
FDG –PET scan
Data will be analyzed as per CRF captured visit
Cardiometabolic biomarker
Data will be analyzed as per CRF captured visit
but for discontinued patients only discontinued
visit will be mapped to the next visit of the last
available assessment before discontinuation
within the same treatment period
2.4.2
Prior, concomitant and post therapies
Prior or concomitant medication will be identified based on recorded or imputed start and end 
dates of medication taken, as follows:
Prior medication: Treatments taken and stopped prior to first dose of study treatment.
Concomitant medication: Any medication administered at least once between the day of first
dose of randomized study treatment and the last day of study visit (including those which
were started pre-baseline and continued into the treatment period), other than study
medication, will be considered as concomitant medication.
Concomitant medications excluding tropical corticosteroid will be summarized.
Medications will be identified and presented in alphabetical order, using Novartis drug and
therapy dictionary (NovDTD) and by Anatomical Therapeutic Chemical (ATC) codes and
grouped by anatomical main group (the first level of the ATC codes).
Prior, concomitant medications will be summarized by treatment using frequency counts and
percentages for Safety Set, in separate tables.
Tables will also show the overall number and percentage of subjects receiving at least one
drug of a particular ATC code and at least one drug in a particular anatomical main group. In
addition, concomitant use of tropical corticosteroid will be summarized separately by
treatment.
Treatment use for indication, dose and date of administration will be listed. Duration of
exposure will be presented by treatment if treatment is stopped during study period. Ongoing
treatments will be flagged.
2.5
Analysis of the primary objective
2.5.1
Primary efficacy variable
The primary efficacy variable is the change from baseline in the target (arterial vascular
uptake) to background (venous blood pool) ratio from the aorta obtained via FDG-PET/CT


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scans at Week 12. Baseline is defined as the target to background ratio at Visit 2. Patients will
be included in the analysis if they have both baseline and post-baseline assessments.
TBRmax (in the dataset) at each visit will be used for analysis. The primary analysis will be 
based on Full Analysis Set.
2.5.2
Statistical hypothesis, model, and method of analysis
The primary efficacy variable will be analyzed by an analysis of covariance (ANCOVA)
model with treatment, baseline, and body weight (<90 kg, ≥90 kg) as explanatory variables.
Following null hypothesis (H0) will be tested against the alternative hypothesis (HA):
H0: μ1 – μ0 = 0
HA: μ1 – μ0 ≠ 0
where μ1 and μ0 denote the population mean of change from baseline in the target to
background ratio from the aorta at Week 12 for secukinumab group and placebo group,
respectively.
The least squares means of the two treatment groups, least squares mean difference , and 95%
confidence interval for the difference in the two treatment groups will be presented along with
the p-value based on the fitted linear model.
2.5.3
Handling of missing values/censoring/discontinuations
If a subject has no post-baseline value, the missing value will not be imputed and the subject
will be removed from the analysis.
2.5.4
Supportive analyses
A supportive nonparametric analysis will be performed to examine the consistency of results
if the assumption of normality for the distribution of the primary efficacy variable is not
tenable. For this supportive analysis, the primary efficacy variable will be analyzed using the
stratified Wilcoxon rank-sum test with modified ridit scores (van Elteren’s test), adjusting for
body weight (<90 kg, ≥90 kg) (Stokes, Davis, and Koch, 2012). Supportive analysis will be
based on Full Analysis Set.
In addition, changes from baseline in each of the five segments of aorta (ascending aorta, 
aortic arch, descending thoracic aorta, suprarenal abdominal aorta, infrarenal abdominal aorta) 
will be analyzed similar to the analyses of the primary efficacy variable.  
2.6
Analysis of the key secondary objective
There is no key secondary objective.
2.7
Analysis of secondary efficacy objectives
Analyses of the secondary efficacy analysis will be based on Full Analysis Set.
2.7.1
Secondary efficacy variables
The secondary efficacy variables are the following:
Change from baseline in each biomarker (specified in Section 2.7.2.1)
PASI 75 response (yes, no)


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PASI 90 response (yes, no)
PASI 100 response (yes, no)
IGA mod 2011 score of 0 or 1 (yes, no)
Change from baseline in DLQI total score
2.7.2
Statistical hypothesis, model, and method of analysis
2.7.2.1
Cardiometabolic Biomarkers
Change from baseline in each cardometabolic biomarker, described in Section 2.12, will be
analyzed at each time point using the same ANCOVA model as for the primary efficacy
variable.
In addition, change from the baseline in each biomarker will be analyzed using the stratified
Wilcoxon rank -sum test with modified ridit scores (van Elteren’s test), adjusting for body
weight (<90 kg, ≥90 kg) (Stokes, Davis, and Koch, 2012) if the normality assumption for
the variable is not tenable. The analysis will be based on Full Analysis Set.
2.7.2.2
Psoriasis Area and Severity Index (PASI)
PASI 75 / 90 / 100 responses will be analyzed at each time point using the Cochran-Mantel-
Haenszel test to compare secukinumab and placebo, adjusting for body weight (<90 kg, ≥90
kg) (Stokes, Davis, and Koch, 2012). A 95% confidence interval for the difference between
the two treatment groups in the proportion of subjects who are responders will be calculated
using the normal approximation to the binomial distribution.
In addition, the PASI responses by visit will be summarized by treatment.
2.7.2.3
Investigator’s Global Assessment (IGA mod 2011)
IGA mod 2011 (0 or 1) response will be analyzed at each time point using the Cochran-
Mantel-Haenszel test to compare secukinumab and placebo, adjusting for body weight (<90
kg, ≥90 kg). A 95% confidence interval for the difference between the two treatment groups
in the proportion of subjects who are responders will be calculated using the normal
approximation to the binomial distribution. In addition, the IGA mod 2011 responses by visit
will be summarized by treatment.
2.7.2.4
Dermatology Life Quality Index (DLQI)
Change from baseline in DLQI total score will be analyzed at each time point using the same
ANCOVA model as for the primary efficacy variable. In addition, DLQI total score will be
summarized by visit and treatment.


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2.7.3
Handling of missing values/censoring/discontinuations
For continuous secondary efficacy variables with more than one post-baseline assessment (i.e.
cardiometabolic biomarkers and DLQI score), missing data will be imputed using the last-
observation-carried-forward (LOCF) method. Baseline value will not be carried forward. If a
subject has no post-baseline value, the missing value will not be imputed and the subject will
be removed from the analysis.
For the subject who switch treatment after end of treatment period 1 (EOT 1), values of EOT1 
are not carried forward to treatment period 2 (EOT 2).
For binary secondary efficacy variables (i.e. PASI 75,90,100 response and IGA mod 2011 0
or 1 response) at Week 12 (and other time points), a subject with a missing assessment will be 
considered as a responder (yes) if the subject meets the response criterion at the time of
premature discontinuation from the study. Otherwise, the subject will be considered as a
non-responder (no).
2.8
Safety analyses
Analysis of safety data will be based on the Safety Set.
Any adverse event will be coded using the MedDRA dictionary for the Safety Set.
Treatment groups for evaluation
The summaries of evaluation will be reported for treatment period 1 and entire treatment
period, respectively.
The following groups will be used for treatment period 1:

Secukinumab 300mg

Placebo
The following groups will be used for entire treatment period:

Secukinumab 300mg

Placebo / Secukinumab 300 mg
2.8.1
Adverse events (AEs)
All treatment emergent adverse events starting on or after the first dose of study treatment and 
until the last dose of study treatment plus 7 days (30 days for serious adverse events [SAEs])
will be included in all summaries and listings. Adverse events occurring after signing of
informed consent but before first dose of study treatment and those occurring after 7 days of
last study treatment (30 days for SAEs) will be listed only.


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All adverse events will be coded using the MedDRA dictionary and summarized by system
organ class and preferred term using frequency and percentage.
Primary system organ classes will be sorted alphabetically and, within each primary system
organ class, the preferred terms will be sorted in descending order of frequency.
If a patient reported more than one adverse event with the same preferred term, the adverse
event will be counted only once. If a patient reported more than one adverse event within the
same primary system organ class, the patient will be counted only once at the system organ
class level.
In addition following information will be listed by treatment group:

Severity grade

Relationship to the study treatment

Duration

Whether it constitutes a serious adverse event

Action taken regarding study treatment

Concomitant medication(s) taken or non-drug therapies given

Outcome
Serious Adverse Event (SAE)
Number and percentage of patients with serious adverse events, regardless of study drug
relationship, will be presented by primary system organ class and preferred term. Primary
system organ classes will be sorted alphabetically and, within each primary system organ
class, the preferred terms will be sorted in descending order of frequency.
If a patient reported more than one adverse event with the same preferred term, the adverse
event will be counted only once. If a patient reported more than one adverse event within the
same primary system organ class, the patient will be counted only once at the syste m organ
class level.
All SAEs will be listed.
Adverse events and serious adverse events up to and including the Week 12 visit will be
included in the database for the analysis at the primary analysis time point (Week 12).
2.8.1.1
Adverse events of special interest / grouping of AEs
Not applicable.
2.8.2
Deaths
Any death occurring between study day 1 and last day of treatment exposure + 30 days will be
summarized by system organ class and preferred term for each treatment group and listed
along with primary reason for death. Death occurring in the screening period and after 30 days
of last dose of study treatment will be flagged.


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2.8.3
Laboratory data
Descriptive summary statistics for the change from baseline to study visit will be presented by 
laboratory variable and treatment group. Change from baseline will only be summarized for
subjects with both baseline and post-baseline values and will be calculated as:
change from baseline = post-baseline value – baseline value
For each variable, the maximum change (maximum decrease and maximum increase) from
baseline, if appropriate for each study phase, will be analyzed analogously.
In addition, shift tables will be provided for all variables to compare a subject’s baseline
laboratory evaluation relative to the visit’s observed value. For the shift tables, the reference
laboratory ranges will be used to evaluate whether a particular laboratory test value was
normal, low, or high for each visit value relative to whether or not the baseline value was
normal, low, or high. If appropriate, the shifts to the most extreme laboratory test value within
a treatment phase (either initial or entire) will be presented as well (including category “high
and low”). These summaries will be presented by laboratory variable and treatment group.
The expanded laboratory ranges and the clinically notable abnormalities of key laboratory
variables are given below:
Table 2-2
Criteria for notable abnormalities
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
Alkalinephosphatase
> 1.5 x ULN
Renal function and electrolyte variables
Creatinine (serum)
> 1.5 x ULN
Hematology values
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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2.8.4
Other safety data
2.8.4.1
ECG and cardiac imaging data
Not applicable.
2.8.4.2
Vital signs
Descriptive summary statistics for change from baseline for each post-baseline visit will be
presented by vital signs, weight stratum, and treatment groups. Change from baseline will be
calculated only for the subjects with both baseline and post-baseline values and will be
calculated as:
Change from baseline = post-baseline value – baseline value
The number and the percentage of subjects with notable vital signs will be presented. The
criteria for notable vital sign abnormalities are provided in Table 2-3 below:
Table 2-3
Criteria for notable vital sign abnormalities
Vital signs (unit)
Normal measure
Notable abnormality
Systolic blood pressure (mmHg)   90 to <120 mmHg
>= 140 mmHg (hypertension) or
< 90 mmHg (hypotension)
Diastolic
blood
pressure
(mmHg)
60 to <80 mmHg
>= 90 mmHg (hypertension) or
< 60 mmHg (hypotension)
Pulse (bpm)
60 to 100(bpm)
> 100 bpm (tachycardia) or
< 60 bpm (bradycardia)
Note: 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, Bakris, and Black 2003).
A listing of the newly-occurring notably abnormal vital sign will be provided.
2.9
Pharmacokinetic variables
Not applicable.
2.10
PD and PK/PD analyses
Not applicable.
2.11
Patient-reportedoutcomes
Not applicable for this section.
2.12
Biomarkers
The following cardiometabolic biomarkers will be analyzed individually:

cardiometabolic function [lipid particle size, HDL function (cholesterol efflux)]

measures of inflammation [TNF-Alpha, IL-6, C reactive protein, GlycA]


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
adiposity [leptin and adiponectin]

insulin resistance [insulin levels/glucose to yield HOMA-IR]
markers predictive of diabetes [apolipoprotein B, ferritin, IL-2 receptor A, IL-18, and fetuin-
A]
The analysis method is given in section 2.7.2.1.
2.14
Interim analysis
The primary analysis at Week 12 will be considered as interim analysis. As Week 12 is the
primary analysis time point, no adjustment to the significance level of 0.05 will be made.
3
Sample size calculation
The sample size was based on change from baseline in the target (arterial vascular uptake) to
background (venous blood pool) ratio (TBR) from the aorta. Using a t-test, a clinically
important mean treatment difference of 0.15, a (common) standard deviation (SD) of 0.196,
an allocation ratio of 1:1, a two-sided significance level of 0.05, and a power of 0.90, it was
determined that approximately 74 subjects (37 in each treatment group) are necessary (nQuery 
Advisor 7.0) (Bissonnette et al, 2013; Tawakol et al, 2013). Without adjusting for multiplicity,
the sample size of 74 subjects will also provide at least 0.90 power for other biomarkers if the
treatment difference is 0.76 SD or smaller. The general threshold for clinical importance is 1
SD. Allowing for a loss to follow-up rate of 0.10, approximately 84 subjects (42 in each
treatment group) will be randomized.


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4
Change to protocol specified analyses
Missing data will not be imputed using last-observation-carried-forward (LOCF) method for
primary efficacy variable, since there is only one post-baseline visit.
For continuous secondary efficacy variables with more than one post-baseline assessment,
missing data will be imputed using multiple imputation (in addition to LOCF).
For cardiometabolic biomarker, if the normality assumption is not tenable, additionally data
will be analyzed using stratified Wilcoxon rank sum test.
5
Appendix
This section will be used later for drafting CSR Appendix 16.1.9.
5.1
Imputation rules
5.1.1
AE date imputation
The following table explains the notation used in  the logic matrix. Please note that
missing start dates will not be imputed.
Day
Month
Year
Partial Adverse Event Start Date
Not used
MON
YYYY
Treatment Start Date (TRTSTD)
Not used
TRTM
TRTY
The following matrix explains the logic behind the imputation.
MON
MISSING
MON < TRTM
MON = TRTM
MON > TRTM
YYYY
MISSING
NC
Uncertain
NC
Uncertain
NC
Uncertain
NC
Uncertain
YYYY < TRTY
( D )
BeforeTreatment Start
( C )
BeforeTreatment Start
( C )
BeforeTreatment Start
( C )
BeforeTreatment Start
YYYY = TRTY
(B)
Uncertain
( C )
BeforeTreatment Start
(A)
Uncertain
(A)
After Treatment Start
YYYY > TRTY
(E)
After Treatment Start
(A)
After Treatment Start
(A)
After Treatment Start
(A)
After Treatment Start
The following table is the legend to the logic matrix.
If AE end date is complete and AE end date < Treatment start date or AE end date is partial
and AE imputed end date < Treatment start date, then AE start reference = min (informed
consent date, earliest visit date from SV) Else if AE end date is partial, AE end date > =
Treatment start date or AE is ongoing, then AE start reference = treatment start date.


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Relationship
Time imputation
Before AE start reference
Partial date indicates AE start
date prior to AE start reference
After AE start reference
Partial date indicates AE start
date after AE start reference
Uncertain
Partial date insufficient to
determine relationship of AE
start date to AE start reference
Imputation Calculation
NC/Blank
No convention
(A)
MAX( 01MONYYYY, AE start
reference+1day)
(B)
AE start reference+1
(C)
15MONYYYY
(D)
01JULYYYY
(E)
01JANYYYY
Complete date
No date imputation
If time is captured for the study
Case1: if AE start date is not
equal to AE start reference then
do the following:
If minutes missing then
AESTMF = M and time is
imputed to hh:00
If minutes missing then
AESTMF = H and time is
imputed to 00:00
Case2: if AE start date = AE
start reference then AESTMF =
H and time is imputed to
treatment start time + 1 hour
Adverse Event End Date Imputation
Imputed date = date part of original date, if complete date
Imputed date = min (completion/discontinuation visit date, DEC 31, date of death), if month 
is missing
Imputed date = min (completion/discontinuation visit date, last day of the month, date of 
death), if day is missing
Adverse Event End Time Imputation
If the AE end date is complete and time is captured in the study then:
Case 1. if AE end date is not equal to Treatment end date, then do the following:
if minutes missing then time is imputed to hh:00 if time missing then time is imputed to 00:00
Case 2: if AE end date = Treatment end date then time is imputed to treatment end time
If the AE end date is partial then end time is imputed to 00:00.


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Imputed Date Flag
If year of the imputed date is not equal to YYYY then date flag = Y
else if month of the imputed date is not equal to MON then date flag = M
else if day of the imputed date is not equal to day of original date then date_flag = D
else date flag = null
Imputed Time Flag
If hours of the imputed time is not equal to hours of original time then time flag = H
else if minutes of the imputed time is not equal to minutes of original time then time flag = M
else time flag = null.
5.1.2
Concomitant medication date imputation
This algorithm is used when event is the partial start date of the concomitant medication.
The following table explains the notation used in the logic matrix. Please note that
missing start dates will not be imputed.
Day
Month
Year
Partial CM Start Date
Not used
MON
YYYY
Treatment Start Date ( TRTSDT)
Not used
TRTM
TRTY
The following matrix explains the logic behind the imputation.
MON
MISSING
MON < TRTM
MON = TRTM
MON > TRTM
YYYY
MISSING
(C2)
Uncertain
(C1)
Uncertain
(C1)
Uncertain
(C1)
Uncertain
YYYY < TRTY
(D)
BeforeTreatment Start
(A)
BeforeTreatment Start
(A)
BeforeTreatment Start
(A)
BeforeTreatment Start
YYYY = TRTY
(C2)
Uncertain
(A)
BeforeTreatment Start
(C1)
Uncertain
(B)
After Treatment Start
YYYY > TRTY
(E)
After Treatment Start
(B)
After Treatment Start
(B)
After Treatment Start
(B)
After Treatment Start
The following table is the legend to the logic matrix.
Relationship
Before Treatment Start
Partial date indicates CMD start date prior to Treatment Start Date
After Treatment Start
Partial date indicates CMD start date after Treatment Start Date
Uncertain
Partial date insufficient to determine relationship of CMD start date relative to Treatment
Start Date
Imputation Calculation
(A)
15MONYYYY
(B)
01MONYYYY
(C1 or C2)
IF
relative reference start = before treatment start THEN TRTSDT-1
ELSE IF relative reference start = ‘ ’ THEN TRTSDT+1
(D)
01JULYYYY


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Concomitant Medication End Date Imputation
If not ongoing then -
Imputed date = date part of CMENDTC,  if complete date
Imputed date = min(completion/discontinuation visit date,  DEC 31) , if month is missing,
(C2, D, E)
Imputed date = min(completion/discontinuation visit date, last day of the Month) , if day is
missing. (A, B, C1)
Concomitant Medication Date Flag
If not a complete date then
Y - If year of the imputed date is not equal to YYYY else M – If month of the imputed date is
not equal to MON else D.
5.1.2.1
Prior therapies date imputation
Same as above
5.1.2.2
Post therapies date imputation
Same as above
5.1.2.3
Other imputations
Same as above
5.2
AEs coding/grading
NA
5.3
Laboratory variables derivations
NA
5.4
Statistical models
5.4.1
Primary analysis
ANCOVA model for change from baseline in the target (arterial vascular uptake) to
background (venous blood pool) ratio from the aorta at Week 12
Change = intercept+ treatment + body weight stratum (<90kg, ≥90 kg) + baseline value + error.
The SAS procedure MIXED will be used with the following code:
proc mixed
data=<….>;
class trtmnt bws;
model change = trtmnt bws blv;
lsmeans
trtmnt / cl diff;
(E)
01JANYYYY


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run;
where
chnage = change from the baseline at Week 12
trtmnt   = Treatment
bws
= body weight stratum (< 90 kg,>= 90kg)
blv= baseline value .
Results will be presented with raw mean and standard error of the baseline value, with least
squares mean and standard error for treatment effects and least squares mean, standard error,
associated two-sided 95% confidence interval, and two-sided p-value for the treatment
contrast.
A Q-Q plot will be performed to check the normality of primary variable.
5.4.1.1
Supportive analysis
Stratified Wilcoxon rank-sum test will be performed and implemented in SAS using PROC
FREQ with CHM2 SCORES = MODRIDIT option.
5.4.2
Key secondary analysis
Not applicable.
5.5
Rule of exclusion criteria of analysis sets
Table 5.1
Protocol deviations that cause subjects to be excluded from analysis
Deviation
Description of Deviation
Exclusion in Analyses
ID
Severity code
INCL0
1
Patients have not signed
Informed Consent Form prior to
initiation of any study-related
procedure.
Age criteria not met
Excluded from FAS and
SAF
3
Excluded from none of
the analysis set
0
INCL0
Date of diagnosis of plaque
psoriasis is greater than or
equal to 6 months prior to
randomization
No Moderate to severe plaque
psoriasis at Baseline Visit
Excluded from none of
the analysis set
0
INCL0
Excluded from none of
the analysis set
0
INCL0
Subject with systemic therapy
are not inadequately controlled
by topical treatment and/or
phototherapy and/or previous
systemic therapy for Plaque
psoriasis.
Excluded from none of
the analysis set
0


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Deviation
ID
Description of Deviation
Exclusion in Analyses
Severity code
INCL06
Physical examination, FDG-
PET/CT scan without clinically
significant findings, clinical
laboratory results within
laboratory ref ranges or
abnormal results are deemed to
be not clinically significant.
Excluded from none of
0
the analysis set
EXCL01
Forms of psoriasis other than
chronic plaque-type psoriasis
Excluded from none of
0
the analysis set
EXCL02
Medication induced psoriasis or
medication exacerbation
psoriasis
EXCL03
Previous exposure to
secukinumab or any other
biologic drug targeting IL-17A or
the IL-17RA
EXCL04
Diagnosis of other ongoing
active skin diseases or skin
infections or inflammatory
diseases other than psoriasis.
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
EXCL05
Unwillingness to limit UV light
exposure (sunbathing and/or
use of tanning devices)
EXCL06
Prohibited medications
used/washout period not
observed/Other treatments
known to worsen psoriasis not
stable for 4 weeks before
randomization
EXCL07
Use of Other investigational
drugs within 5 half-lives or 4
weeks prior to randomization,
whichever is longer
EXCL08
Use of unstable dose of
cholesterol-lowering
medications for at least 90 days
prior to randomization
EXCL09
Pregnant or Nursing (lactating)
women at randomization and/or
any post-randomization visit.
EXCL10
Women of childbearing
potential who do not agree to
be compliant with protocol-
specified contraception during
the study
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set


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Deviation
ID
Description of Deviation
Exclusion in Analyses
Severity code
EXCL11
Current and/or uncontrolled
underlying condition(s) which in
the judgement of investigator
renders the patient unsuitable
for the study.
EXCL12
Current and/or uncontrolled
significant medical problems
EXCL12A
Subject randomized with signs
of uncontrolled hypertension
(≥180 systolic/ 95 diastolic
mmHg)
EXCL12B
Subject randomized with signs
of uncontrolled hypertension
(≥180 systolic/ 95 diastolic
mmHg)
EXCL13
Serum creatinine levels are
greater than 2.0mg/dL or fasting
blood glucose level is greater
than or equal to 150mg/dL or
hemoglobin A1c greater than or
equal to 7% at screening.
EXCL14
Total white blood cells count
less than 2500 /ul or
thrombocytes less than
1,00,000 /ul or neutrphils less
than 1500 /ul or hemoglobin
less than 8.5 g/dL at screening
EXCL15
History of lymphoproliferative
disease/ any known
malignancy/ history of
malignancy of any organ
system in past 5 years
EXCL16
History of active
tuberculosis/latenttuberculosis
after the protocol specified time
EXCL17
Past or ongoing medical history
record of HIV, hepatitis B or
hepatitis C prior to screening
EXCL18
Current and/or uncontrolled
underlying condition(s) which
significantly
immunocompromises and/or
places a patient at risk, in the
Investigator's opinion
EXCL19
Active systemic infections
(other than common cold)
during the two weeks before
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set


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Deviation
ID
Description of Deviation
Exclusion in Analyses
Severity code
randomization
EXCL20
Subjects with live vaccination
within 6 weeks prior to
randomization or any time
during the study
EXCL21
Presence of a medical or
psychiatric condition that
renders subject unable to
adhere to protocol/complete the
study
EXCL22
History or evidence of drug or
alcohol abuse within the 12
months prior to screening.
EXCL22A
History or evidence of not
willing to limit alcohol use to
less than or equal to 14 drinks
per week within 4 weeks prior to
screening or anytime during the
study.
EXCL23
History of hypersensitivity to
constituents of study treatment
and/or allergic to rubber or latex
EXCL24
Subjects who are not able
and/or not willing to self-
administer secukinumab
injections or who have no
trained caregiver available to
administer the injections
TRT01
Incorrect, missed or partial
doses of study medication
administered by subject
TRT02
Incorrect study drug
administered at any time during
the study
COMD01
Use of prohibited treatment at
any time during the study after
randomization
COMD02
Receipt of a live virus
vaccination during the study
OTH01
Missing psoriasis efficacy
assessment at any endpoints
(IGA, PASI)
OTH02
ICH-GCP non-compliance of
study site in the study
OTH03
Informed consent process or
documentation deficiencies
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set
Excluded from none of
0
the analysis set


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Deviation
ID
Description of Deviation
Exclusion in Analyses
Severity code
OTH04
First drug administration and/or
Excluded from none of
0
Date of Visit 2 is not within 7
the analysis set
days of Baseline (Visit 2) FDG-
PET/CT scan
OTH05
Failure to perform key study
Excluded from none of
0
procedures (example FDG-
the analysis set
PET/CT scan, cardiometabolic
biomarker blood draw)
WITH1
ICF withdrawn but patient
Excluded from none of
0
continuing in the study
the analysis set
Protocol deviations will lead to subject classification into the analysis sets as follows:
Analysis set exclusions based on population codes
Analysis set
Population codes that cause a subject to be
excluded
RAN
NA
SAF
2, 3
FAS
1, 3
Population code text
Population Code
Population code text
0
INCLUDE IN EVERYTHING
1
EXCLUDE FROM FULL ANALYSIS SET (FAS)
2
EXCLUDE FROM SAFETY SET (SAF)
3
EXCLUDE FROM FAS AND SAF
Unless otherwise stated, summary tables, figures and listings will be on all 
subjects included in the analysis set under consideration.
Table 5.2
Subject Classification
Analysis Set
PD ID that
cause subjects to be excluded
Non-PD criteria that cause
subjects to be excluded
RAN
NA
Not randomized
FAS
As mentioned in table 5.1
Not in RAN;
Inappropriatelyrandomized
SAF
As mentioned in table 5.1
No double-blind study drug taken


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6
References
Bissonnette R et al. (2013) Effects of the tumor necrosis factor-α antagonist adalimumab on
arterial inflammation assessed by positron emission tomography in patients with psoriasis:
results of a randomized controlled trial. Circ Cardiovasc Imaging; 83-90.
Chobanian AV, Bakris GL, Black HR (2003) Seventh report of the joint national committee on
prevention, detection, evaluation, and treatment of high blood pressure. Hypertension;
42:1206–52.
Stokes ME, Davis CS, Koch GG (2012) Categorical data analysis using the SAS system. 3rd
ed; Cary, NC: SAS Institute, Inc.
Tawakol A, et al. (2013) Intensification of statin therapy results in a rapid reduction in
atherosclerotic inflammation: results of a multi-center FDG-PET/CT feasibility study. JACC;
909-17.
[AIN457A efficacy MAP M3 Amendment 5], available in Cabinets//CREDI Projects
/A/AIN457A/Administrative files/CIS (Clinical Information Sciences)/Biostatistics
[AIN457 safety MAP M3 Amendment 4], available in Cabinets//CREDI Projects/A/AIN457A
/Administrative files/CIS (Clinical Information Sciences)/Biostatistics