A Randomized, Multicenter STudy to Evaluate the Effect of Secukinumab 300 mg s.c. Administered During 52 Weeks to Patients Suffering From New-onset Moderate to Severe Plaque Psoriasis as Early Intervention Compared to Standard Treatment With Narrow-band UVB (STEPIn Study)
Phase: PHASE4
Conditions: Plaque Psoriasis
Sponsor: Novartis Pharmaceuticals

Global Medical Affairs - General Medicine
Secukinumab (AIN457)
Clinical Trial Protocol CAIN457A2322 / NCT03020199 
A randomized, multicenter STudy to evaluate the Effect of 
secukinumab 300 mg s.c. administered during 52 weeks to 
patients suffering from new-onset moderate to severe 
plaque Psoriasis as early Intervention compared to 
standard treatment with narrow-band UVB (STEPIn study)
Document type:
Amended Protocol Version
EUDRACT number:
2015-002423-26
Version number:
02 (clean)
Clinical trial phase:
IV 
Release date:
26-Sep-2019
Property of Novartis
Confidential
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis
Clinical Trial Protocol Template Version 3.1 (February 2016)

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Table of contents
Table of contents .................................................................................................................2
List of tables ........................................................................................................................6
List of figures ......................................................................................................................6
List of abbreviations............................................................................................................7
Glossary of terms.................................................................................................................8
Protocol amendments ..........................................................................................................9
Protocol summary..............................................................................................................12
1
Introduction .......................................................................................................................15
1.1
Background............................................................................................................15
1.2
Purpose ..................................................................................................................16
2
Study objectives and endpoints .........................................................................................17
2.1
Primary objective...................................................................................................17
2.2
Secondary objectives .............................................................................................17
2.2.1
Key secondary objective .......................................................................17
2.2.2
Additional secondary objective.............................................................17
2.3
Exploratory objectives...........................................................................................17
3
Investigational plan ...........................................................................................................18
3.1
Study design...........................................................................................................18
3.2
Rationale for study design .....................................................................................22
3.3
Rationale for dose/regimen, route of administration and duration of treatment....22
3.4
Rationale for choice of comparator .......................................................................22
3.5
Purpose and timing of interim analyses/design adaptations..................................23
3.6
Risks and benefits..................................................................................................23
4
Population..........................................................................................................................25
4.1
Inclusion criteria ....................................................................................................25
4.2
Exclusion criteria...................................................................................................25
5
Treatment...........................................................................................................................27
5.1
Study treatment......................................................................................................27
5.1.1
Study and control drugs ........................................................................27
5.1.2
Additional treatment..............................................................................28
5.2
Treatment arms......................................................................................................28
5.3
Treatment assignment and randomization.............................................................29
5.4
Treatment blinding.................................................................................................29
5.5
Treating the patient................................................................................................29
5.5.1
Patient numbering .................................................................................30
5.5.2
Dispensing the study treatment.............................................................30

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5.5.3
Handling of study and additional treatment..........................................30
5.5.4
Instructions for prescribing and taking study treatment........................31
5.5.5
Permitted dose adjustments and interruptions of study treatment ........32
5.5.6
Rescue medication ................................................................................32
5.5.7
Concomitant medication .......................................................................33
5.5.8
Prohibited medication ...........................................................................33
5.5.9
Emergency breaking of assigned treatment code..................................35
5.6
Study completion and discontinuation...................................................................36
5.6.1
Study completion and post-study treatment..........................................36
5.6.2
Discontinuation of study treatment .......................................................36
5.6.3
Withdrawal of consent ..........................................................................36
5.6.4
Loss to follow up...................................................................................37
5.6.5
Early study termination by the sponsor.................................................37
5.6.6
Discontinuation during the Follow-up Epoch.......................................37
6
Visit schedule and assessments .........................................................................................38
6.1
Information to be collected on screening failures..................................................43
6.2
Patient demographics/other baseline characteristics .............................................43
6.2.1
Smoking history ....................................................................................44
6.2.2
Relevant medical history/current medical conditions...........................44
6.2.3
Prior and concomitant medications.......................................................44
6.2.4
Determination of tuberculosis status.....................................................44
6.2.5
Other baseline characteristics................................................................46
6.3
Treatment exposure and compliance .....................................................................46
6.4
Efficacy..................................................................................................................47
6.4.1
Assessment of body surface area and psoriasis area severity index .....47
49
49
6.4.4
Investigator’s global assessment mod 2011..........................................49
6.4.5
Appropriateness of efficacy assessments..............................................50
6.5
Safety.....................................................................................................................50
6.5.1
Physical examination ............................................................................50
6.5.2
Vital signs..............................................................................................51
6.5.3
Height and weight .................................................................................51
6.5.4
Laboratory evaluations..........................................................................51
6.5.5
Electrocardiogram.................................................................................52
6.5.6
Pregnancy..............................................................................................52
6.5.7
Appropriateness of safety measurements..............................................53

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6.6
Other assessments..................................................................................................53
6.6.1
Clinical outcome assessments...............................................................53
6.6.2
Resource utilization...............................................................................54
6.6.3
Pharmacokinetics ..................................................................................54
6.6.4
Immunological analysis of skin biopsies ..............................................54
55
7
Safety monitoring..............................................................................................................55
7.1
Adverse events.......................................................................................................55
7.2
Serious adverse events...........................................................................................57
7.2.1
Definition of serious adverse event.......................................................57
7.2.2
Serious adverse event reporting ............................................................58
7.3
Liver safety monitoring .........................................................................................58
7.4
Renal safety monitoring.........................................................................................58
7.5
Reporting of study treatment errors including misuse/abuse ................................59
7.6
Pregnancy reporting...............................................................................................59
7.7
Prospective suicidality assessment ........................................................................59
8
Data review and database management.............................................................................60
8.1
Site monitoring ......................................................................................................60
8.2
Data collection.......................................................................................................60
8.3
Database management and quality control............................................................60
8.4
Data Monitoring Committee..................................................................................61
8.5
Adjudication Committee........................................................................................61
9
Data analysis......................................................................................................................61
9.1
Analysis sets ..........................................................................................................61
9.2
Patient demographics and other baseline characteristics.......................................62
9.3
Treatments .............................................................................................................62
9.4
Analysis of the primary variable............................................................................63
9.4.1
Primary variable....................................................................................63
9.4.2
Statistical model, hypothesis, and method of analysis..........................63
9.4.3
Handling of missing values/censoring/discontinuations.......................63
9.4.4
Supportive analyses...............................................................................64
9.5
Analysis of secondary variables ............................................................................64
9.5.1
Key secondary variable.........................................................................64
9.5.2
Investigator’s global assessment mod 2011..........................................65
9.5.3
Safety variables .....................................................................................65
9.5.4
Resource utilization...............................................................................66
9.5.5
Pharmacokinetics ..................................................................................66

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9.5.6
DNA......................................................................................................66
66
9.5.8
PK/PD ...................................................................................................66
67
9.6
Analysis of exploratory variables ..........................................................................67
67
67
9.6.3
Investigator’s global assessment mod 2011 score and response over 
time........................................................................................................68
68
70
9.7
Interim analyses.....................................................................................................70
9.8
Sample size calculation..........................................................................................70
9.9
Power for analysis of secondary variables.............................................................71
10 Ethical considerations........................................................................................................72
10.1
Regulatory and ethical compliance........................................................................72
10.2
Informed consent procedures.................................................................................72
10.3
Responsibilities of the investigator and IRB/IEC..................................................72
10.4
Publication of study protocol and results...............................................................72
10.5
Quality control and quality assurance....................................................................73
11 Protocol adherence ............................................................................................................73
11.1
Protocol amendments.............................................................................................73
12 References .........................................................................................................................74
13 Appendix 1: Clinically notable laboratory values and vital signs.....................................76
14 Appendix 2: Patient-reported outcomes and skin type classification................................77
77
78
79
81
14.5
Skin type classification scale.................................................................................83

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List of tables
Table 3-1
Summary information for study arms ...................................................18
Table 5-1
Prohibited treatment (Arm A1, Arm A2 and Arm B1) .........................34
Table 5-2
Prohibited treatment (Arm C1 and Arm C2).........................................35
Table 6-1
Assessment schedule: Screening Epoch and Treatment Epoch (all 
arms)......................................................................................................39
Table 6-2
Assessment schedule: Continued Treatment Epoch, Weeks 52-104 
(Arms A2 and C2).................................................................................41
Table 6-3
Assessment schedule: Follow-up Epoch...............................................42
Table 6-4
Psoriasis area severity index scoring system ........................................48
Table 6-5
Investigator’s global assessment mod 2011 rating scale.......................50
Table 6-6
Schedule for the collection of skin biopsies..........................................55
List of figures
Figure 3-1
Study design – Main Study ...................................................................20
Figure 3-2
Study design – Mechanistic Sub-study .................................................21
Figure 6-1
Tuberculosis screening flowchart .........................................................46

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List of abbreviations
AE
Adverse event
 
BSA
Body surface area
CRO
Contract research organization
 
ECG
Electrocardiogram
eCRF
Electronic case report form 
EOS
End of study
FAS
Full analysis set
GCP
Good clinical practice
 
IEC
Independent ethics committee
IGA
Investigator’s global assessment 
IMID
Immune-mediated inflammatory disease
IL
Interleukin
IRB
Institutional review board
IRT
Interactive response technology
LLN
Lower limit of normal 
MCMC
Markov Chain Monte Carlo
MedDRA
Medical dictionary for regulatory activities 
nb-UVB
Narrow-band ultraviolet light B 
PASI
Psoriasis area and severity index
SAE
Serious adverse event
 
TB
Tuberculosis
 
ULN
Upper limit of normal 
 

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Glossary of terms
Dosage
Dose of the study treatment given to the patient in a time unit (e.g.,
100 mg once a day, 75 mg twice a day)
Enrollment
Point/time of patient entry into the study at which informed consent 
must be obtained (e.g., prior to starting any of the procedures 
described in the protocol)
Epoch
A part of the study which serves a specific purpose. Typical epochs 
are: screening, treatment, and follow-up
Medication number
A unique identifier on the label of each investigational drug package
Patient number
A unique number assigned to each patient upon signing the informed 
consent 
Personal data
Patient information collected by the investigator that is transferred to 
Novartis for the purpose of the clinical study. This data include
patient identifier information, study information, and biological 
samples
Randomization number
A unique identifier assigned to each randomized patient, 
corresponding to a specific treatment arm assignment
Study drug/treatment
Any single drug or combination of drugs administered to the patient 
as part of the required study procedures; includes investigational 
drug(s), placebo/comparator active drug run-ins or background 
therapy
Study treatment 
discontinuation 
Point/time when the patient permanently stops taking study treatment 
prior to the defined study treatment completion date 
Variable
A measured value or assessed response that is determined in 
specific assessments and used in data analysis to evaluate the drug 
being tested in the study
Withdrawal of consent 
Withdrawal of consent from the study occurs only when a patient 
does not want to participate in the study any longer, and does not 
allow any further collection of personal data

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Protocol amendments
Protocol Amendment 02 of 26-Sep-2019
Amendment rationale 
Amendment 02 was implemented to provide additional details for the statistical analysis and
increase the patient recruitment rate by loosening one inclusion criterion.
The study is currently ongoing. The changes were made mainly to improve the understanding 
and execution of the protocol and will not have an impact either on the patients’ safety or on
the objectives of the study. 
Changes to the protocol
Changes to specific sections are shown in the track changes version of the protocol using strike 
through red font for deletions and red underlined for insertions.
The following modifications were made to the protocol: 

The glossary of terms was updated with new definitions of personal data and withdrawal
of consent 

Clarification was added that subjects who discontinue the study during the Follow-up 
Epoch will have all assessments of end of study (EOS) performed 

Inclusion criterion 3 was modified by allowing earlier episodes of mild psoriasis 
resolved spontaneously within 6 months. The reason for this change was that some
subjects did not proceed into screening because they could have had symptoms of 
psoriasis previously, but without a proper diagnosis. In consensus with medical experts, 
subjects with such a history would not change the scientific value of the study, nor the 
study population, and hence this inclusion criterion was slightly loosened to improve 
study recruitment

Withdrawal of consent language was modified to align with the requirements of the 
General Data Protection Regulation 

 
 
 
Additionally, clarification was provided that physical 
examination at Week 104 has to be recorded in the source documents at the site

Table 6-3 was updated with the definition of EOS 

The hypothesis testing for the efficacy analyses was modified to 1-sided tests at 2.5% 
significance level instead of 2-sided at 5% significance level 

Age and body mass index were included as covariates for the analyses 

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
The Wald test was replaced by the Fisher’s exact test, which is mainly used when the 
sample size is small or the proportions are extreme. This study is of adequate size and 
the Wald test was proposed. However, responses for the key secondary endpoint are 
expected to be low; therefore, it was decided that the Fisher’s exact test is more 
appropriate

Clarification was added that missing data for the primary endpoint and the key 
secondary endpoint will be imputed with modified multiple imputation method

The power of the key secondary endpoint was re-assessed after considering dropout 
rates

The assumptions for the sample size calculations were modified. The power calculations 
for the primary endpoint are now based on the asymptotic Wald test instead of on the 
Fisher’s exact test, as the accuracy of the Wald test increase in larger sample sizes and 
adequate response rates (which are expected for the primary endpoint). The software for 
the calculation was modified from nQuery Advisor® 7.0 to PASS 11
IRBs/IECs
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol are substantial and require IRB/IEC approval 
prior to implementation.
The changes herein affect the study-specific model ICF and the sub-study ICF. 
Protocol Amendment 01 of 11-Apr-2017
Amendment rationale 
The purpose of the amendment was to address requests from health authorities and to include 
modifications for improvement of the clarity of the protocol.
In addition, the upper limit of the age range was changed to better reflect the patient population 
and improve study recruitment. 
Changes to the protocol
Changes to specific sections are shown in the track changes version of the protocol using strike 
through red font for deletions and red underlined for insertions.
The following modifications were made to the protocol:

The investigator’s global assessment mod 2011 was included as additional secondary and 
exploratory objectives
 

The upper limit of the age range for inclusion of patients in the study was changed from 
40 years to 50 years

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
The risks-benefit section was updated with information on risks for secukinumab, biopsies 
and others 

The exclusion criterion involving barrier methods of contraception was modified to
include applicable countries beyond the UK 

The optional use of calcipotriol 50 µg/g and betamethasone 0.5 mg/g with nb-UVB was 
further clarified 

The number of patients per group in the Mechanistic Sub-study was reduced from 15 to 12 

The number of biopsies to be taken from lesional or resolved skin and from never-lesional
skin was corrected

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Protocol summary
Protocol number
CAIN457A2322
Title
A randomized, multicenter STudy to evaluate the Effect of secukinumab 
300 mg s.c. administered during 52 weeks to patients suffering from 
new-onset moderate to severe plaque Psoriasis as early Intervention 
compared to standard treatment with narrow-band UVB (STEPIn study)
Brief title
Study of the efficacy of early intervention with secukinumab 300 mg s.c. 
compared to narrow-band UVB in patients with new-onset moderate to 
severe plaque psoriasis 
Sponsor and clinical 
phase
Novartis 
Phase IV
Investigation type
Drug
Study type
Interventional 
Purpose and rationale
The purpose of this study is to determine whether early intervention with 
subcutaneous (s.c.) secukinumab 300 mg in patients with new-onset 
moderate to severe plaque psoriasis may lead to prolonged symptom-
free periods by preventing reactivation of old lesions or ultimately totally 
hindering the occurrence of new lesions, i.e., changing the natural 
course of the disease (Main Study). 
Primary objective 
To demonstrate that early treatment with secukinumab 300 mg s.c. 
(Arm A1) is superior to standard of care treatment with nb-UVB (Arm B1) 
in patients with new-onset moderate to severe plaque psoriasis with 
respect to patients achieving ≥90% improvement (reduction) in 
psoriasis area and severity index (PASI 90) response at Week 52. 
Secondary objectives
Key secondary objective
To evaluate the superiority of early treatment with secukinumab 
(Arm A1) versus nb-UVB (Arm B1) based on the proportion of all 
randomized patients who achieve at least PASI 90 at Week 104. 
Additional secondary objective
To evaluate the effects of early treatment with secukinumab (Arm A1) 
compared with nb-UVB (Arm B1) based on the proportion of all 
randomized patients who achieve at least investigator’s global 
assessment (IGA mod 2011) 0/1 response at Week 52.
Study design
The design consists of the Main Study involving all patients in Arms A1 
(A1a and A1b) and B1 (B1a and B1b) and a Mechanistic Sub-study,
which comprises 5 treatment arms (A1b, A2, B1b, C1, and C2). 
The Main Study will be multicenter, randomized, 2-treatment-arm 
(secukinumab and nb-UVB), parallel-group and open-label. 

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Population
The overall study population (Main Study and Mechanistic Sub-study) 
will consist of a total of 196 male and female patients aged between 
18 and 50 years inclusive.
Main Study
The Main Study will be conducted in patients with new-onset moderate 
to severe plaque psoriasis not previously treated with any systemic 
treatment or phototherapy. 
A total of 160 patients will be randomized to Arm A1 or Arm B1 in 
approximately 75 sites worldwide. Since a maximum screening failure 
rate of 20% is expected, approximately 245 patients will be screened. 
Mechanistic Sub-study
Any patient who consents can participate in the Mechanistic Sub-study. 
Patients with new-onset plaque psoriasis will be randomized to 
Arm A1b, Arm A2, or Arm B1b, those with chronic plaque psoriasis will 
be randomized to Arm C1 and Arm C2 (12 patients each). For Arm A1b 
or Arm B1b, the first 12 patients will be included on a first come first 
serve basis. 
Key inclusion criteria
Patients eligible for inclusion in this study must fulfill all of the following 
criteria:
1.
Able to understand and communicate with the investigator, 
willing and capable to comply with all study procedures, and 
provide written signed and dated informed consent (personally 
or by a witness) before any assessment is performed
2.
Aged 18 to 50 years inclusive 
3.
New-onset plaque psoriasis with appearance of the first 
psoriasis plaques within the last 12 months before 
randomization and naïve to any systemic treatment and 
phototherapy (Arm A1, Arm A2, and Arm B1). Episodes of mild 
psoriasis, which occurred at least 3 years before screening and 
resolved spontaneously within 6 months will be accepted
4.
Chronic plaque psoriasis with appearance of the first psoriasis 
symptoms 5 years or longer and intolerance or inadequate 
response to phototherapy or any systemic treatment including 
biologicals, except for IL-17A inhibitors (Arm C1 and Arm C2)
5.
Moderate to severe plaque psoriasis defined at screening and 
baseline by PASI ≥10, and body surface area (BSA) ≥10%, 
and IGA mod 2011 ≥3
Key exclusion criteria
Patients fulfilling any of the following criteria will not be eligible for 
inclusion in this study: 
1.
Forms of psoriasis other than plaque-type (e.g., pustular, 
erythrodermic, guttate, light sensitive, and drug induced) 
2.
Ongoing use of prohibited treatments
3.
Previous treatment with phototherapy or any systemic 
treatment
4.
Pregnant or nursing (lactating) women 
5.
Women of childbearing potential, defined as all women 
physiologically capable of becoming pregnant, unless they are 
using effective methods of contraception during the Treatment 
Epoch or longer if required by locally-approved prescribing 
information (e.g., 20 weeks in the EU and countries where 
applicable for secukinumab)

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Study treatment
Secukinumab (AIN457) 300 mg 
Narrow-band UVB 
Efficacy assessments

Body surface area and psoriasis area severity index

Investigator’s global assessment mod 2011
Safety assessments

Physical examination

Vital signs

Height and body weight

Laboratory evaluations (hematology, clinical chemistry, 
high-sensitivity C-reactive protein)

Electrocardiogram (ECG)

Pregnancy 

Adverse events
Data analysis
The primary efficacy variable is the proportion of patients who achieve 
PASI 90 at Week 52. The analysis for the primary objective will be 
based on the full analysis set (FAS).
For the primary analysis, the following hypothesis testing will be 
performed:
H01: psec = pnbUVB versus HA1: psec > pnbUVB
The primary analysis method for PASI 90 response at Week 52 will use 
a logistic regression model with treatment as an explanatory variable 
and significant covariates among baseline PASI score, age, and body 
mass index. The best subset of the significant covariates will be selected 
using a forward selection method. Interaction terms will also be 
considered, if significant, among the best subset of selected covariates 
and the treatment term.
The key secondary variable is the proportion of all randomized patients 
who achieve PASI 90 at Week 104. In order to reduce selection bias, all 
patients who do not achieve PASI 90 at Week 52 will also be included in 
the analysis at Week 104 using the PASI improvement obtained at 
Week 104 only. 
For the key secondary analysis, the following hypothesis testing will be 
performed:
H02: p*sec = p*nbUVB versus HA2: p*sec > p*nbUVB
Keywords
Psoriasis, IL-17A, secukinumab, narrow-band UVB, PASI

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1
Introduction
1.1
Background 
Psoriasis is an immune-mediated inflammatory disease (IMID) which may have a major impact 
on a patient’s life, especially when its intensity is moderate or severe. There is evidence that 
treatment of psoriasis during the first years is conservative and frequently based on topical 
agents which rarely clear lesions completely. Treatment with biologic systemic agents is often 
initiated only when topical agents, phototherapy and conventional systemic treatment have 
proved to be inadequate, even in patients with moderate to severe disease (Maza et al 2012).
Psoriatic skin lesions are a “riot” of disorder, featuring dense inflammatory cell infiltrates, 
massive proliferation, impaired differentiation of the epidermis, formation of new blood vessels, 
and alterations in lymphatic structures. With effective therapy, psoriatic lesions resolve without 
scarring, which is remarkable, given the number of neutrophils in psoriatic skin lesions and the 
scarring observed in other neutrophil-mediated disorders, including pyoderma gangrenosum. 
Successful treatment of psoriasis leads to resolution of epidermal thickness, reduction in the 
number of inflammatory cells, and return of previously affected skin to a clinically normal state. 
Once therapy is discontinued, psoriatic skin lesions tend to recur, usually at the same sites that 
were previously affected. Understanding and repairing the residual lesion in treated psoriatic 
skin may mean the difference between treating psoriasis and curing it.
There is evidence in other IMIDs (e.g., rheumatoid arthritis and Crohn’s disease) that targeted 
systemic treatment, including biologics given early in the treatment pathway, may improve 
short- and long-term patient outcomes. 
Both short- and long-term outcomes of early and intensive intervention in rheumatoid arthritis 
have clearly demonstrated benefits (Quinn et al 2005, Quinn et al 2012, van der Kooij 
et al 2009). In the BeSt study, 48% of the patients with initial intensive treatment with tumor 
necrosis factor alpha (TNFα) inhibitors and methotrexate could even stop the biologic treatment 
and remain in remission at year 4 of the study. 
A patient-centered therapeutic approach, undertaken early in the psoriasis treatment pathway 
(early intervention) with the goal of complete clearance, may improve control of cutaneous 
symptoms and may also modify the course of the disease and the associated burden. 
There is also evidence that – despite clinical clearance of psoriatic lesions – a subclinical 
inflammation may continue in the skin that may become clinical once treatment is stopped e.g., 
during or after a “drug holiday”. A possible explanation for this phenomenon can be found in 
the identification of a T-cell subset called tissue resident memory T cells (Trm) that has been 
proven to contribute to a tissue-localized immunological memory to viral infections of the skin 
(e.g., infections with herpes simplex virus).
This subtype of T cell has also been suggested to be a key player for generating chronicity of 
immune-mediated inflammatory or auto-reactive disorders like psoriasis (Clark 2015).
A newly published study identifies accumulation of IL-17 producing Trm cells in the lesional or 
resolved skin of patients with psoriasis, which remain in the skin after resolution of lesions 
during treatment with biologic therapy, indicating the importance of this subset also in psoriasis

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(Cheuk et al 2014). The presence of these cells in the skin may explain the chronicity of the 
disease and the reoccurrence of relapses to the same anatomic locations. 
Cheuk et al (2014) also showed that Trm cells in the psoriatic plaques produce interleukin 
(IL)-17A and IL-22 upon activation, supporting the notion of Trm cells in psoriasis as Th17 cells 
with IL-17A as a key effector cytokine. In addition to the direct pathogenic effect of IL-17A 
from T cells on keratinocytes, IL-17A is also released by granulocytes and mast cells and plays 
an important role in early attracting more immune cells to the target organ.
Based on the increasing knowledge of the altered balance of Trm cell subsets in psoriasis, 
inhibition of IL-17A early after disease onset may be a novel and important therapeutic 
approach interfering with the immune system before the establishment of extensive and chronic 
inflammation. This effect would be achieved in part by early blocking the recruitment of 
inflammatory cells, including Th17, and partly by blocking the key effector functions of Trm
cells.
Secukinumab is the first IL-17A inhibitor approved for the treatment of moderate to severe 
plaque psoriasis. It is hypothesized that early treatment with secukinumab in new-onset
moderate to severe plaque psoriasis may both block recruitment of inflammatory cells and 
antagonize the effect of the key cytokine IL-17A produced by a subset of T cells.
1.2
Purpose 
The purpose of this study is to determine whether early intervention with subcutaneous (s.c.) 
secukinumab 300 mg in patients with new-onset moderate to severe plaque psoriasis may lead 
to prolonged symptom-free periods by preventing reactivation of old lesions or ultimately 
totally hindering the occurrence of new lesions, i.e., changing the natural course of the disease
(Main Study). New-onset psoriasis here is defined as psoriasis diagnosed within the last 
12 months and not yet treated with systemic drugs or narrow-band ultraviolet light B (nb-UVB).
For the purpose of this study, early intervention with secukinumab will be compared with early 
intervention with nb-UVB. 
In addition, a sub-study will be included, which aims to mechanistically understand the impact 
of early and late short- or long-term intervention with secukinumab on skin biomarkers
(Mechanistic Sub-study). 

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2
Study objectives and endpoints
2.1
Primary objective
To demonstrate that early treatment with secukinumab 300 mg s.c. (Arm A1) is superior to 
standard of care treatment with nb-UVB (Arm B1) in patients with new-onset moderate to 
severe plaque psoriasis with respect to patients achieving ≥90% improvement (reduction) in 
psoriasis area and severity index (PASI 90) response at Week 52. 
2.2
Secondary objectives
2.2.1
Key secondary objective
To evaluate the superiority of early treatment with secukinumab (Arm A1) versus nb-UVB 
(Arm B1) based on the proportion of all randomized patients who achieve at least PASI 90 at 
Week 104.
2.2.2
Additional secondary objective
To evaluate the effects of early treatment with secukinumab (Arm A1) compared with nb-UVB 
(Arm B1) based on the proportion of all randomized patients who achieve at least investigator’s 
global assessment (IGA mod 2011) 0/1 response at Week 52.
2.3
Exploratory objectives
4. To explore the effects of treatment with secukinumab compared with nb-UVB based on 
the proportion of patients who achieve at least investigator’s global assessment (IGA mod 
2011) 0/1 response at Week 104 

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8. To explore in biopsies from lesional (or resolved) and never-lesional skin of patients the 
following immunological modifications: 

Mean changes in the total number of Trm in dermis and epidermis

Mean changes in the number of different subsets of T cells in resolved skin compared 
to lesional psoriasis Changes from baseline in the number of dermal lymphoid 
dendritic cells-T cell aggregates in the skin

Changes from baseline in inflammatory gene expression response in never-lesional
and lesional or resolved skin

Changes from baseline in inflammatory gene expression profiles in biopsies where 
tissue resident T cells have been ex-vivo activated by CD3-ligation

Systemic effect of secukinumab on biomarkers associated with moderate to severe 
plaque psoriasis and response to secukinumab
9. To explore the effects of treatment with secukinumab (Arms A1 and A2) compared with 
late secukinumab intervention (Arm C1 and Arm C2) with regard to: 

Immuno-pathological changes in the involved skin locations 

Epigenetic profiling of the skin 

Disease activity (measured by PASI, SAPIS and SGA)

Safety 
3
Investigational plan
3.1
Study design
Patients will be allocated to 3 main treatment arms: 

Arm A (patients with new-onset plaque psoriasis to be treated with secukinumab): 
composed of Arm A1 (A1a and A1b) and Arm A2

Arm B1 (patients with new-onset plaque psoriasis to be treated with nb-UVB): composed 
of Arm B1a and Arm B1b

Arm C (patients with chronic plaque psoriasis to be treated with secukinumab): composed 
of Arm C1 and Arm C2
An overview of the treatment arms is summarized in Table 3-1. 
Table 3-1
Summary information for study arms
Arm
Psoriasis 
duration
Study part 
Treatment
Treatment duration
A1a
new-onset 
Main 
Secukinumab
  52 weeks
A1b
new-onset 
Main and mechanistic
Secukinumab
  52 weeks
A2
new-onset 
Mechanistic 
Secukinumab
104 weeks
B1a
new-onset 
Main 
nb-UVB
  52 weeks
B1b
new-onset 
Main and mechanistic 
nb-UVB
  52 weeks
C1
chronic 
Mechanistic 
Secukinumab
  52 weeks
C2
chronic 
Mechanistic 
Secukinumab
104 weeks

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The design consists of a Main Study and a Mechanistic Sub-study. 
The Main Study will be multicenter, randomized, 2-treatment-arm (secukinumab and nb-UVB), 
parallel-group and open-label. It will include 3 clinical epochs (Screening Epoch, Treatment 
Epoch, and Follow-up Epoch) involving all patients in Arms A1 (A1a and A1b) and B1 (B1a
and B1b). 
The Mechanistic Sub-study will be open-label and comprise 5 treatment arms (A1b, A2, B1b, 
C1, and C2). It will include 2 epochs (Screening Epoch and Treatment Epoch) for patients in 
Arms C1 and C2. Patients from Arms A1b, A2, and B1b will undergo the 3 clinical epochs of 
the Main Study. 
Details of the Main Study and the Mechanistic Sub-study with the number of patients and 
treatment regimen for each arm are provided in the following sub-sections. The randomization 
to the treatment arms is outlined in Section 5.3. 
Screening Epoch
Patient’s eligibility for the study will be assessed at the screening visit (Day -28 to Day -1 before 
baseline) and at the baseline visit (see Table 6-1). 
Main Study
Treatment Epoch
At the baseline visit, eligible patients will be randomized to one of the following treatment arms
(see Figure 3-1): 

Arm A1: patients with new-onset plaque psoriasis will receive 300-mg secukinumab by
s.c. injection at baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until Week 48 inclusive

Arm B1: patients with new-onset plaque psoriasis will receive 1 or 2 cycles of nb-UVB of
12 weeks each with a maximum break of 28 weeks between cycles (patients with PASI 90
at Week 40 will not receive a second treatment cycle). Only during the first 4 weeks of
each cycle, nb-UVB treatment may be given in combination with topical calcipotriol
50 µg/g and betamethasone 0.5 mg/g
Follow-up Epoch
At the end of the Treatment Epoch at Week 52, all patients with ≥PASI 50 response from 
Arm A1 and Arm B1 will enter the Follow-up Epoch. Patients who do not achieve a PASI 50 
response, will have all assessments of EOS and be discontinued from the study. 
During the Follow-up Epoch, patients will not receive study treatment; they will be observed 
maximally until Week 208, and compared regarding the proportion of them who achieve PASI 
90 scores at Week 104.
Patients who relapse (those who experience a loss of 50% of the maximum improvement in 
PASI score achieved during the Treatment Epoch) will have all assessments of EOS and be 
discontinued from the study. 
If no relapse occurs, patients who achieve < PASI 90 at Week 52 in Arms A1 (A1a and A1b) 
and B1 (B1a and B1b) will be followed (according to the visit schedule outlined in Table 6-3)

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until Week 104, while patients who achieve ≥PASI 90 at Week 52 will be followed until Week
208. 
The investigator should provide ongoing adequate care for patients who relapse. If the 
investigator decides to continue treating the patients with secukinumab, a new loading dose of 
commercially available secukinumab could be considered. The treatment with secukinumab 
after relapse will be out of scope of the study. 
Figure 3-1
Study design – Main Study
BL = baseline, EOS = end of study, KSE = key secondary endpoint, nb-UVB=narrow-band ultraviolet 
B, PASI = psoriasis area and severity index, PE = primary endpoint, R = randomization. 
Mechanistic Sub-study
A separate informed consent will be obtained from study patients who agree on having skin 
biopsies taken and therefore become eligible for this Mechanistic Sub-study. Besides the 
biopsies, patients will undergo the same assessments as in the Main Study. 
Treatment Epoch
At the baseline visit, eligible patients will be allocated to one of the treatment arms of the 
Mechanistic Sub-study (see Figure 3-1 and Section 5.3): 

Arm A1b: secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 
3 and 4; and thereafter every 4 weeks until Week 48 inclusive (last dose administered at 
Week 48)

Arm A2: secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 
and 4; and thereafter every 4 weeks until Week 100 inclusive (last dose administered at 
Week 100)

Arm B1b: 1 or 2 cycles of nb-UVB of 12 weeks each with a maximum break of 28 weeks 
between cycles

Arm C1: secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 
and 4; and thereafter every 4 weeks until Week 48 inclusive (last dose administered at 
Week 48)

Arm C2: secukinumab 300 mg s.c. administered at baseline, once weekly at Weeks 1, 2, 3 
and 4; and thereafter every 4 weeks until Week 100 inclusive (last dose administered at 
Week 100)
Arm C1 and Arm C2 with patients having chronic psoriasis, will serve as control groups in the 
Mechanistic Sub-study. 
Skin biopsies will be taken from all patients who participate as described in Section 6.6.4. 

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Follow-up Epoch 
At the end of the Treatment Epoch, all patients with ≥PASI 50 response from Arm A1b and 
Arm B1b will enter the Follow-up Epoch. Patients who do not achieve a PASI 50 response, will 
have all assessments of EOS and be discontinued from the study. 
During the Follow-up Epoch, patients will not receive study treatment; they will be observed 
maximally until Week 208, and compared regarding the proportion of them who achieve PASI 
90 scores at Week 104. 
Patients who relapse (those who experience a loss of 50% of the maximum improvement in 
PASI score achieved during the Treatment Epoch) will have all assessments of EOS and be 
discontinued from the study. 
If no relapse occurs, patients who achieve < PASI 90 at Week 52 in Arms A1b and B1b will be 
followed (according to the visit schedule outlined in Table 6-3) until Week 104, while patients 
who achieve ≥ PASI 90 at Week 52 will be followed until Week 208.
For Arm A2, patients who achieve < PASI 90 at Week 104 will have their EOS assessment and 
stop participating in the study, while those who achieve ≥ PASI 90 will be followed (according 
to the visit schedule outlined in Table 6-3) until Week 208. 
Arms C1 and C2 will not be followed up. 
Figure 3-2
Study design – Mechanistic Sub-study
BL = baseline, EOS = end of study, KSE = key secondary endpoint, nb-UVB=narrow-band ultraviolet 
B, PASI = psoriasis area and severity index, PE = primary endpoint, R = randomization. 

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3.2
Rationale for study design
The rationale for an early intensive intervention in psoriasis is based on several years of 
experience of successful early intensive interventions in other chronic IMIDs, especially 
rheumatoid arthritis (Quinn et al 2005, Quinn et al 2012, van der Kooij et al 2009). The current 
hypothesis is that early intensive intervention with biologicals in the autoimmune process 
dampens the immune mechanism that leads to a chronic inflammatory disease. In rheumatoid 
arthritis it has been shown that early intervention can modify disease activity (in particular bone 
erosion) and severity outcomes. The effect of early intervention on disease severity has also 
been seen in Crohn’s disease and early intervention is a developing hypothesis in other IMIDs
like multiple sclerosis and psoriatic arthritis. 
Based on the increasing knowledge about the role of Trm cells in psoriasis, inhibition of IL-17A 
early after the onset of the disease may be a novel and important therapeutic approach 
interfering with the immune system before the establishment of extensive and chronic 
inflammation occurs. This effect would in part be through an early blockade of recruitment of 
inflammatory cells, including Th17 cells, and partly by blocking the key effector functions of 
Trm cells. The expected clinical outcome would be to change the natural course of the disease 
to a milder state by hindering spreading of psoriasis (Trm cells) to new anatomical locations or 
ultimately totally hindering reoccurrence of new lesions, i.e., inducing minimal disease activity. 
Besides the Main Study, a Mechanistic Sub-study (on skin biopsies) will be performed to 
investigate the effects of secukinumab and nb-UVB 
 
 
 
Due to the nature of the treatments given, the study will be open label. 
In order to reduce selection bias, all randomized patients will be involved in the analysis at 
Week 104 using the PASI improvements obtained at Week 52. 
The patient population will be described in more detail in the Section 4. 
3.3
Rationale for dose/regimen, route of administration and duration 
of treatment
Secukinumab 300 mg s.c. and dose regimen with an initial weekly induction at baseline, 
Weeks 1, 2, 3 and 4, followed by s.c. administration every 4 weeks up to Week 48 inclusive for 
Arms A1 and C1, and until Week 100 inclusive for Arms A2 and C2 is based on the Phase III 
registration program. Secukinumab will be given to patients with new-onset moderate to severe 
plaque psoriasis. This is an earlier intervention with biologic therapy than current standard 
clinical practice. However, the aim of the study is to demonstrate the benefit of early, intensive 
treatment with secukinumab and with the ultimate goal of altering the natural course with a 
reduced disease burden and need for treatment. 
3.4
Rationale for choice of comparator
The comparator treatment is nb-UVB, which may be combined with topical treatment 
(calcipotriol 50 µg/g and betamethasone 0.5 mg/g) during the first 4 weeks of each cycle, which 
is considered in many hospitals/investigational sites as the first treatment for patients with 

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moderate to severe plaque psoriasis. However, the literature states that reappearance of 
symptoms may occur as early as one month after the last session, suggesting that the effect of 
nb-UVB on the underlying inflammation in the skin is minimal or not long-lasting, though some 
reports mention relapse-free periods of up to 35 months (Ryu et al 2014).
In contrast to broadband UVB lamps, which emit light in a broad range over the UVB spectrum, 
including both the therapeutic wavelengths specific to the treatment of skin diseases, plus the 
shorter wavelengths responsible for sunburning (erythema), conventional nb-UVB lamps, emit 
light over a very short range of wavelengths (311 ± 2 nm;) concentrated in the therapeutic range, 
and minimally in the sunburning range. Nb-UVB is therefore theoretically safer and more 
effective than broadband UVB and has become the phototherapy treatment of choice for 
psoriasis, vitiligo, atopic dermatitis (eczema) and other photo-responsive skin disorders (Ryu et 
al 2014). 
In most countries, nb-UVB is indicated in moderate to severe psoriasis after the failure of topical 
treatment. The intensity of radiation and the interval between sessions may vary per country or 
even per site. Typically, one cycle of nb-UVB may comprise a period of 12 weeks with 2 to 3 
treatment sessions per week totaling 24 to 36 sessions per cycle. It is common practice to apply 
a second cycle within 1 year depending on the effect of the first one. As deep remission has 
proven to be a key factor for the successful maintenance of low disease activity after 
discontinuation of treatment in other IMIDs, a more aggressive treatment strategy will be
implemented in this study.
3.5
Purpose and timing of interim analyses/design adaptations
See Section 9.7 for details of interim analyses of the study. 
3.6
Risks and benefits
Risks
The potential risks for patients participating in this study are listed below.
Risks associated with the administration of secukinumab
At least 9642 patients with psoriasis, psoriasis arthritis, ankylosing spondylitis or rheumatoid 
arthritis, and healthy volunteers have received secukinumab treatment in Novartis-sponsored 
investigational clinical studies. 
Four placebo-controlled Phase III studies in plaque psoriasis were pooled to evaluate the safety 
of secukinumab in comparison to placebo up to 12 weeks after the initiation of treatment. In 
total, 2076 patients were evaluated (692 on 150 mg, 690 on 300 mg and 694 on placebo). 
Fewer injection site reactions were reported with secukinumab 1-mL pre-filled syringe 
(containing 150 mg secukinumab) than with etanercept, while the active treatment groups 
showed higher frequencies than placebo.
The safety data from the completed and ongoing studies including AEs and serious adverse 
events (SAEs), laboratory parameters and immunogenicity demonstrate a favorable safety 
profile. Observed risks included infections, in particular of the upper respiratory tract, 
neutropenia and hypersensitivity reactions that can be seen with the administration of foreign 
proteins. Most of the infections were non-serious, mild to moderate in severity, clinically easy

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to manage and did not lead to treatment discontinuation. Cases of neutropenia were uncommon, 
generally mild to moderate and transient, and did not lead to treatment discontinuation, and only 
a few cases were temporally associated with non-serious infections. 
Subjects with pre-existing malignancies within the past 5 years are generally excluded from 
studies with secukinumab, although there is no scientific basis to suggest that secukinumab 
would increase the risk for malignancies. Indeed, the majority of the preclinical data available 
in the literature suggest that blocking IL-17A may actually prevent tumor growth. 
Risks associated with nb-UVB
The main risk derived from the treatment with nb-UVB is the occurrence of “sun burn” leading 
to itching, irritation, redness of the skin, and tanning. These symptoms can mostly be avoided 
or moderated by adapting the radiation dose and the intervals between sessions. Calcipotriol 
(component of the combination product calcipotriol 50 μg/g and betamethasone 0.5 mg/g),
which may be given for the first 4 weeks of each cycle of nb-UVB, may also cause redness and 
itching. The risk of skin cancer is considered minimal. 
The risk to study patients will be minimized by complying with the eligibility criteria and study 
procedures and close clinical monitoring. 
Risks associated with the skin biopsy procedure
A skin biopsy is a routine procedure as part of the diagnostic practice in all dermatology clinics, 
which may cause bleeding and infections. Patients may have bruising, swelling, or pain in the 
area, and also develop scarring later on and might experience fainting caused by a drop in blood 
pressure. They may also have an allergic response from the anesthetic agent used for the 
procedure. Patients who are smokers or take steroids are at higher risk of having problems 
healing after the procedure. 
Other risks
Problems or side effects that are not currently known could also occur. 
The procedures done at each visit are standard medical procedures. Blood samples will be taken. 
The risks of taking blood may include fainting, pain and/or bruising. Rarely, there may be a 
small blood clot or infection where the needle punctures the skin. The blood pressure cuff may 
also cause discomfort or bruising of the upper arm. 
Benefits 
The potential benefits of an intervention with secukinumab may result in quick clearance of 
psoriatic plaques and prolong relapse-free periods or even complete prevention of relapses as 
hypothesized in this study for patients with new-onset psoriasis. Patients may benefit from 1 or 
2 years of treatment that has been proven to be safe and effective. 
Patients randomized to treatment with nb-UVB may also benefit from a reduction in psoriasis 
severity. 
All quality, non-clinical pharmacology and toxicology data, as well as the available clinical 
efficacy and safety data, are considered sufficient to expect a positive benefit/risk ratio for the 
treatment of the study patients. 

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4
Population
The overall study population (Main Study and Mechanistic Sub-study) will consist of a total of 
196 male and female patients aged between 18 and 50 years inclusive.
Main Study
The Main Study will be conducted in patients with new-onset moderate to severe plaque 
psoriasis not previously treated with any systemic treatment or phototherapy.
A total of 160 patients will be randomized to Arm A1 or Arm B1 in approximately 75 sites 
worldwide. Since a maximum screening failure rate of 20% is expected, approximately 
245 patients will be screened. 
Mechanistic Sub-study
Patients who consent to the additional biopsies will be able to participate in the Mechanistic 
Sub-study. Patients with new-onset plaque psoriasis will be randomized in 1:1:1 ratio to 
Arm A1b, Arm A2, or Arm B1b, those with chronic plaque psoriasis will be randomized in a 
1:1 ratio to Arm C1 and Arm C2 (12 patients each).
4.1
Inclusion criteria
Patients eligible for inclusion in this study must fulfill all of the following criteria:
1. Able to understand and communicate with the investigator, willing and capable to comply 
with all study procedures, and provide written signed and dated informed consent 
(personally or by a witness) before any assessment is performed
2. Aged 18 to 50 years inclusive 
3. New-onset plaque psoriasis with appearance of the first psoriasis plaques within the last 
12 months before randomization and naïve to any systemic treatment and phototherapy 
(Arm A1, Arm A2, and Arm B1). Episodes of mild psoriasis, which occurred at least 
3 years before screening and resolved spontaneously within 6 months will be accepted
4. Chronic plaque psoriasis with appearance of the first psoriasis symptoms 5 years or longer 
and intolerance or inadequate response to phototherapy or any systemic treatment 
including biologicals, except for IL-17A inhibitors (Arm C1 and Arm C2) 
5. Moderate to severe plaque psoriasis defined at screening and baseline by PASI ≥10, and 
BSA ≥10%, and IGA mod 2011 ≥3 
4.2
Exclusion criteria
Patients fulfilling any of the following criteria will not be eligible for inclusion in this study. 
No additional exclusions may be applied by the investigator, in order to ensure that the study 
population is representative of all eligible patients.
1. Forms of psoriasis other than plaque-type (e.g., pustular, erythrodermic, guttate, light 
sensitive, and drug induced) 
2. Ongoing use of prohibited treatments (see Section 5.5.8)
3. Previous treatment with phototherapy or any systemic treatment (Arm A1, Arm A2 and 
Arm B1)

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4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive human 
chorionic gonadotropin (hCG) laboratory test (> 5 mIU/mL)
5. Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during the 
Treatment Epoch or longer if required by locally-approved prescribing information (e.g., 
20 weeks in the EU and countries where applicable for secukinumab). Effective 
contraception methods include: 

Total abstinence (when this is in line with the preferred and usual lifestyle of the 
patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception

Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy) total hysterectomy or tubal ligation at least 6 weeks before taking study 
treatment. In case of oophorectomy alone, only when the reproductive status of the 
woman has been confirmed by follow up hormone level assessment

Male sterilization (at least 6 months prior to screening). For female patients on the 
study, the vasectomized male partner should be the sole partner for that patient

Barrier methods of contraception: condom or occlusive cap (diaphragm or 
cervical/vault caps). For countries where applicable, the use of spermicidal 
foam/gel/film/cream/ vaginal suppository will be allowed 

Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of 
contraception or placement of an intrauterine device (IUD) or intrauterine system 
(IUS) or other forms of hormonal contraception that have comparable efficacy (failure 
rate < 1%), for example hormone vaginal ring or transdermal hormone contraception
In case of use of oral contraception, women should have been stable on the same pill for a 
minimum of 12 weeks before taking study treatment.
Women are considered post-menopausal and not of 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 have had surgical bilateral 
oophorectomy (with or without hysterectomy) or tubal ligation at least 6 weeks ago. In the 
case of oophorectomy alone, only when the reproductive status of the woman has been 
confirmed by follow up hormone level assessment is she considered not of child bearing 
potential. 
6. Active ongoing inflammatory diseases other than psoriasis or psoriatic arthritis that might 
confound the evaluation of the benefit of secukinumab therapy
7. Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, 
pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions) which 
in the opinion of the investigator significantly immunocompromises the patient and/or 
places the patient at unacceptable risk for receiving an immunomodulatory therapy 
8. Significant medical problems, including but not limited to the following: uncontrolled 
hypertension (systolic: ≥160 mm Hg and/or diastolic blood pressure ≥95mmHg), 
congestive heart failure [New York Heart Association status Class III or IV] 
9. Serum creatinine concentration exceeding 176.8 μmol/L (2.0 mg/dL) at screening

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10. Screening total white blood cell count < 2 500/μL, or platelets < 100 000/μL, or 
neutrophils < 1 500/μL, or hemoglobin < 8.5 g/dL 
11. Active systemic infections during the last 2 weeks (exception: common cold) prior to 
randomization
12. Past medical history record of infection with human immunodeficiency virus (HIV), 
Hepatitis B or Hepatitis C prior to screening
13. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system within the past 5 years (except for basal cell carcinoma or actinic 
keratosis or carcinoma in situ [Bowen’s disease] that have been treated with no evidence 
of recurrence in the past 3 months; carcinoma in situ of the cervix or non-invasive 
malignant colon polyps that have been removed) 
14. History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis 
(TB) infection as defined by a positive QuantiFERON® TB-Gold In-Tube assay at 
Screening. Patients with a positive or indeterminate QuantiFERON® TB-Gold In-Tube 
assay may participate in the study if full TB workup (according to local 
practice/guidelines) completed within 12 weeks prior to Day1 (baseline) establishes 
conclusively that the patient has no evidence of active TB. If the presence of latent TB is 
established, then treatment must have been initiated and maintained according to local 
country guidelines prior to Day1 (baseline).
15. Any medical or psychiatric condition which, in the investigator’s opinion, would preclude 
the participant from adhering to the protocol or completing the study per protocol. 
16. History or evidence of ongoing alcohol or drug abuse, within the last 6 months before 
randomization 
17. Plans for administration of live vaccines during the study period or within 6 weeks prior to 
randomization. Use of any other investigational treatment within 30 days prior to baseline 
or within a period of 5 half-lives of the study treatment, whichever is longer
18. History of hypersensitivity to the study treatment or its excipients or to drugs of similar 
chemical classes including latex hypersensitivity
19. Patients with photosensitive disorders
5
Treatment
5.1
Study treatment
5.1.1
Study and control drugs
Study treatment
Secukinumab (AIN457) 300 mg will be administered in an open-label fashion according to 
label as 2 s.c. injections of secukinumab 150 mg (1-mL liquid formulation in a pre-filled 
syringe). Each 300-mg dose will be provided as 2 pre-filled syringes of 150-mg secukinumab 
in a single box. Each syringe is labeled as AIN457 150 mg/1 mL.

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Reference treatment
Narrow-band UVB applied in 1 or 2 cycles, each comprising a period of 12 weeks with 2 to 
3 treatment sessions per week totaling 24 to 36 sessions per cycle. The application will be 
performed according to the investigational site’s protocol, taking into account the patient’s skin 
type (Section 14.5). A maximum dose of 3 J/cm2 on the body and 1 J/cm2 on the face is 
recommended (Mehta and Lim 2016). 
5.1.2
Additional treatment
The patients in Arm B will be allowed to use topical treatment with calcipotriol 50 µg/g and 
betamethasone 0.5 mg/g applied once daily (50 grams will be the maximum amount that can be 
applied per week) in addition to nb-UVB only during the first 4 weeks of each cycle.
The topical cream will be used as per the sites’ standard procedure and as per the expert opinion 
of the principal investigator. 
5.2
Treatment arms
Main Study
Patients will be randomly assigned to one of the following 2 treatment arms (see Figure 3-1 and
Section 5.3). 
Arm A1: 80 patients (68 in Arm A1a and 12 in Arm A1b) with new-onset psoriasis will receive 
300 mg secukinumab by s.c. injection at baseline, Weeks 1, 2, 3, 4 and then every 4 weeks until 
Week 48 inclusive. 
Arm B1: 80 patients (68 in Arm B1a and 12 in Arm B1b) with new-onset psoriasis will receive 
1 or 2 cycles of nb-UVB of 12 weeks each with a maximum break of 28 weeks between cycles 
(patients with PASI 90 at Week 40 will not receive a second treatment cycle). Only during the 
first 4 weeks of each cycle, nb-UVB treatment should be applied in combination with topical 
calcipotriol 50 µg/g and betamethasone 0.5 mg/g.
Mechanistic Sub-study
The Mechanistic Sub-study includes patients qualifying for the Main Study who provide
additional consent for the collection of biopsies (Arms A1b, B1b), as well as patients who will 
only participate in the sub-study (Arms A2, C1, and C2): 

Twelve patients randomized to Arm A1b treated for 52 weeks with secukinumab 300 mg 
s.c. 

Twelve patients with new-onset psoriasis in Arm A2 treated for 104 weeks with 
secukinumab 300 mg s.c.

Twelve patients randomized to Arm B1b  treated with 1 or 2 cycles of nb-UVB of 12 
weeks each with a maximum break of 28 weeks between cycles

Twelve patients with chronic psoriasis (> 5 years) randomized to Arm C1 treated for 
52 weeks with secukinumab 300 mg s.c. 

Twelve patients with chronic psoriasis (> 5 years) randomized to Arm C2 treated for 
104 weeks with secukinumab 300 mg s.c. 

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The randomization ratios for the treatment arms in the Main Study and the Mechanistic 
Sub-study are outlined in Section 5.3. 
5.3
Treatment assignment and randomization 
At the baseline visit, all eligible patients will be randomized via the interactive response 
technology (IRT) system to Arm A1, or Arm B1 for the Main Study or to Arm A1b, Arm A2, 
Arm B1b, Arm C1, and Arm C2 for the Mechanistic Sub-study. Qualified site personnel will 
contact the IRT provider after the investigator has confirmed that the patient fulfills all the 
inclusion/exclusion criteria. The IRT system will assign a randomization number to the patient, 
which will be used to link the patient to a treatment arm, and will specify a unique medication 
number for the first package of study treatment to be dispensed to the patients. 
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased. A study patient randomization list will be produced by the 
IRT provider using a validated system that automates the random assignment of patient numbers 
to randomization numbers. These randomization numbers are linked to the different treatment 
arms, which in turn are linked to medication numbers. A separate medication list will be 
produced by or under the responsibility of Novartis Drug Supply Management using a validated 
system that automates the random assignment of medication numbers to packs containing the 
study treatment. 
Randomization of patients to the study treatment arms will be stratified by treatment status, i.e., 
naïve to any systemic treatment including phototherapy or non-naïve.
Stratum 1: Naïve patients
A total of 172 naïve patients will be randomized. 
Thirty-six patients will be randomized in a 1:1:1 ratio to Arm A1b (12 patients), Arm A2 
(12 patients) and Arm B1b (12 patients).
One hundred thirty-six patients will be randomized in a 1:1 ratio to Arm A1a (68 patients) and 
Arm B1a (68 patients). 
Stratum 2: Non-naïve patients
Twenty-four non-naïve patients will be randomized in a 1:1 ratio to Arm C1 (12 patients) and 
Arm C2 (12 patients). 
5.4
Treatment blinding 
Given the nature of the treatments, blinding cannot be applied in this study. Patients receiving 
nb-UVB treatment will mostly experience redness, itching and tanning due to the radiation. 
This can be minimized by adjusting the radiation dose or intervals, but effective radiation will 
always result in at least some redness of the skin, hence blinding is deemed impossible.
5.5
Treating the patient 
Sponsor qualified medical personnel will be readily available to advise on study related medical 
questions or problems.

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5.5.1
Patient numbering 
Each patient is uniquely identified by a Patient Number which is composed by the 4-digit site 
number assigned by Novartis and a 3-digit sequential number assigned by the investigator (e.g., 
Patient  at Site 
 will be assigned Patient Number 
). Once assigned to a patient, 
the Patient Number will not be reused. 
Upon signing the informed consent form, the investigator will assign the patient the next 
sequential number. The investigator or his/her staff will contact the IRT and provide the 
requested identifying information to register the patient into the IRT. The site must select the 
electronic Case Report Form (eCRF) book with a matching Patient Number from the Electronic 
Data Capture system to enter data. 
If the patient fails to be treated for any reason, the IRT must be notified within 2 days that the 
patient was not treated. The reason for not being treated will be entered on the Screening Epoch 
Disposition eCRF page.
5.5.2
Dispensing the study treatment
Each study site will be supplied with study treatment. The secukinumab treatment packaging 
has a 2-part label. A unique medication number is printed on each part of this label. 
At all visits where secukinumab is dispensed, the IRT system will allocate a medication number. 
Immediately before administration of the study treatment, the investigator or other qualified site 
personnel will detach the outer part of the label from the packaging and affix it to the source 
document (Drug Label Form) for that unique patient number. These documents will be kept in 
a secured location to which only site personnel will have access. The first dose of study 
treatment will be administered by a suitably qualified individual (nurse, physician, or other 
qualified site personnel). 
Once the home administration of study treatment applies, the investigator will dispense, 
supported by the IRT system, an appropriate number of investigational treatment packages for 
home administrations and detach the outer part of the label from the packaging as indicated 
above. 
5.5.3
Handling of study and additional treatment 
5.5.3.1
Handling of study treatment 
Study treatment must be received by designated site personnel at the study site, handled and 
stored safely and properly, and kept in a secured location to which only qualified site personnel 
has access. Upon receipt, all study treatment must be stored according to the instructions 
specified on the labels. Clinical supplies are to be dispensed only in accordance with the 
protocol. Technical complaints are to be reported to the respective Novartis Country Pharma 
Organization Quality Assurance.
The study treatment, i.e., secukinumab pre-filled syringes must be stored in a locked refrigerator 
at 2-8°C (36-46°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. Medication labels will be written in the local language 
and comply with the legal requirements of each country. They will include storage conditions 
for the study treatment, but no information about the patient.
Qualified site personnel must maintain an accurate record of the shipment and dispensing of 
study treatment in a drug accountability log which will be kept in the Pharmacy File in a secure 
location to which only qualified site staff will have access to. Monitoring of drug accountability 
will be performed by a field monitor. At the conclusion of the study, and as appropriate during 
its course, the investigator will return all unused study treatment, packaging and drug labels to 
an approved local or central depot for destruction as per local laws. The investigator will keep 
documentation evidence of destruction only in case the destruction happens at the site and a
copy of the completed drug accountability log to the Novartis assigned monitor or to the 
Novartis address provided in the investigator folder at each site. 
5.5.3.2
Handling of additional treatment 
Calcipotriol 50 µg/g and betamethasone 0.5 mg/g (given during the first 4 weeks of each cycle 
of nb-UVB treatment) should be stored at temperatures below 25°C. 
5.5.4
Instructions for prescribing and taking study treatment 
Secukinumab 300 mg s.c.
Secukinumab will be administered subcutaneously throughout the study. The first dose(s) of 
secukinumab will be administered under supervision at the study site. Self-administration by 
study patients at home will be allowed from the second dose or when the patient, after being 
instructed and trained, is qualified to self-inject at the discretion of the investigator. After Week 
4 (the last weekly administration of secukinumab), the patients will be contacted by the 
investigator or staff and be reminded to start the self-administration of secukinumab every 
4 weeks instead of every week. 
Secukinumab must be injected s.c. in never-lesional areas of the skin to one of the following 
body regions: front of thighs, or lower abdomen (but not the area 2 centimeters around the
navel). Investigator/qualified site staff can also inject secukinumab s.c. in the outer upper arms. 
Study treatment should not be injected into areas where the skin is tender, bruised, red, scaly or 
hard, and areas with scars or stretch marks should be avoided. As far as possible, the injection 
site should be changed from administration to administration throughout the study. 
Detailed instructions on the self-administration of the study treatment will be described in the 
instructions for use and provided to each patient. 
Patients will be provided with a patient diary. The investigator should indicate in the patient 
diary the dates of the self-administration of secukinumab injections at home and instruct the 
patient on how to complete it and to annotate any AEs and concomitant medication in the 
comments section. Patients will also be asked to return all used and unused medication and 
packaging at each scheduled study visit. The diary will be checked by the investigator or study 
nurse at the following site visit, the information has to be transferred to the eCRF and AEs have 
to be reported. At the end of the study, the site personnel should collect the paper diaries from 
the patients. 

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Narrow-band ultraviolet light B
Nb-UVB will be applied by experienced personnel according to the investigational site’s 
protocol. In general, it is aimed that one cycle consists of 2 to 3 sessions per week during 
12 weeks. Patients need to wear goggles during the procedure and men are asked to wear genital 
protection.
The patients could use topical treatment with calcipotriol 50 µg/g and betamethasone 0.5 mg/g 
applied once daily (50 grams will be the maximum amount that can be applied per week) in 
addition to nb-UVB during the first 4 weeks of each cycle to reflect the site’s standard procedure. 
During visits at the clinical sites, study assessments should be conducted before treatment 
administration. The first study treatment administration will occur at baseline, after all study 
scheduled assessments have been performed and only after the scheduled blood samples have 
been drawn (see Section 5.2, Table 6-1 and Table 6-2 for the details on secukinumab injections). 
At study visits when pre-dose blood samples or biopsies have to be taken, the study treatment 
will be administered only after the collection. 
 
All dates and times of injections administered during the study must be recorded on the Dosage 
Administration Record eCRF page. The date and exposure of nb-UVB will be recorded on the 
Dosage Administration Record eCRF page, whereas the potential use of additional topical 
treatment will be documented on the Concomitant Medication eCRF page. All kits of study 
treatment assigned by the IRT will be recorded/data based in the IRT. 
The investigator should promote compliance by instructing the patient, so the study treatment 
is administered exactly as prescribed and by stating that compliance is necessary for the 
patient’s safety and the validity of the study. The patient should be instructed to contact the 
investigator if he/she is unable for any reason to attend a study visit as scheduled, or if the 
patient is unable to take the study treatment as instructed. 
5.5.5
Permitted dose adjustments and interruptions of study treatment 
Interruptions or treatment dose adjustments will not be permitted for secukinumab. Any 
adaptation of the nb-UVB regimen that the site would normally do will be permitted, for 
example in case of excessive skin irritation with nb-UVB, and then the dose of radiation may 
be adapted, depending on investigator’s clinical judgement.
A maximum of 1 dose of secukinumab may be missed during a period of 52 weeks but not 
during the first 4 weeks of the Treatment Epoch.
During an nb-UVB cycle, a period of maximally 2 weeks may be inserted between consecutive 
sessions e.g., if a patient is ill or if a patient is on vacation.
If a dose is not administered to a patient, this deviation event must be recorded on the Dosage 
Administration Record eCRF page.
5.5.6
Rescue medication 
Rescue treatment will not be allowed during the first 52 weeks. Mild to moderate potency
glucocorticosteroids will be permitted during the Follow-up Epoch.

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5.5.7
Concomitant medication 
All treatments administered during the 6 months prior to start of study treatment (including any 
treatments started during the Screening Epoch) for any reason NOT including psoriasis will be 
entered in the Concomitant Medications eCRF page or the Procedures and Significant Non-drug 
Therapies eCRF page. Start date, end date, dose, unit, frequency, route and reason for 
administration or change are to be recorded in the concomitant medications/significant non-
drug therapies eCRF. The investigator/qualified site staff must instruct the patient to notify the 
study site about any new medications that he/she takes after being enrolled into the study. All 
medications, procedures and significant non-drug therapies (including physical therapy and 
blood transfusions) administered after the patient starts study treatment must be recorded. 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt the investigator should contact the monitor before randomizing a patient 
or allowing a new medication to be started. 
5.5.8
Prohibited medication
Use of the treatments displayed in Table 5-1 and Table 5-2 is NOT allowed after baseline. 
No other treatments for psoriasis than the study treatments and the additional use of calcipotriol 
50 µg/g and betamethasone 0.5 mg/g during the first 4 weeks in Arm B1 will be allowed during 
the Treatment Epoch. Bland emollients and topical glucocorticosteroid treatments of mild to 
moderate potency on the face, scalp, and/or genitoanal area for Arm A1, Arm A2, Arm B1, 
Arm C1, and Arm C2 are an exception. Exposure to UV light (e.g., sunbathing and/or the use 
of tanning devices) other than nb-UVB within the study, from enrollment to Week 104 of the 
study should be limited. Mild to moderate potency topical glucocorticosteroids will be allowed 
during the Follow-up Epoch.

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Table 5-1
Prohibited treatment (Arm A1, Arm A2 and Arm B1)
Prohibited treatments a, b
Washout period
(before baseline)
Secukinumab
No prior use allowed
Any biologic drug directly targeting IL-17A or the IL-17 receptor 
(other than secukinumab, e.g., brodalumab, ixekizumab)
No prior use allowed
Alefacept, briakinumab, efalizumab
No prior use allowed
Biological immunomodulatory agents other than the above listed 
(e.g., adalimumab, etanercept, infliximab)
No prior use allowed
Other systemic immunomodulatory treatments c (e.g., methotrexate, 
cyclosporine A, glucocorticosteroids [oral, i.v., intramuscular, s.c., 
intra-articular, transdermal], cyclophosphamide) and any treatment 
for psoriatic arthritis, except for NSAIDs
No prior use allowed
Any biologic drug directly targeting IL-12/IL-23 other than 
ustekinumab or IL-23 (e.g., guselkumab, tildrakizumab)
No prior use allowed
Other systemic psoriasis treatments (e.g., retinoids, fumarates, 
apremilast)
No prior use allowed
Photo-chemotherapy (e.g., psoralen plus UVA [PUVA]) or
phototherapy d
No prior use allowed
Topical treatment that is likely to impact signs and symptoms of 
psoriasis (e.g., vitamin D analogues, pimecrolimus, retinoids, 
Salicyl-Vaseline, salicylic acid, lactic acid, tacrolimus, tar, urea, 
-hydroxy or fruit acids) e
2 weeks
Live virus vaccinations
6 weeks
Any investigational treatment or participation in any interventional 
study
4 weeks or 5 half-lives 
(whichever is longer)
NSAID = nonsteroidal anti-inflammatory drug, UVA = ultraviolet light A
a) If the prohibited treatment is used during the study for any indication, patients must discontinue its 
use if they wish to continue in the study 
b) In case of undue safety risk for the patients, they should discontinue study treatment at the 
discretion of the investigator/qualified site staff. If patients treated with secukinumab receive a live 
virus vaccination during the study, they must discontinue study treatment
c) Inhalational glucocorticosteroids with only a topical effect (e.g., to treat asthma) are not considered 
systemic immunomodulatory treatments and are therefore acceptable
d) Phototherapy or photo-chemotherapy will not be allowed, except for nb-UVB in Arm B1
e) Topical treatment should be tapered-off during the Screening Epoch and stopped 12 hours prior to 
randomization; only mild to moderate topical glucocorticosteroids on the face, scalp, and/or genitoanal
area will be allowed. During the Treatment Epoch, bland emollients or topical glucocorticosteroid 
treatments of mild or moderate potency on the face, scalp, and/or genitoanal area will be allowed. Mild 
to moderate-potency topical glucocorticosteroids and bland emollients will be allowed during the 
Follow-up Epoch 

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Table 5-2
Prohibited treatment (Arm C1 and Arm C2)
Prohibited treatments a 
Washout period
(before baseline) b
Any biologic drug directly targeting IL-17A or IL-17 receptor (e.g., 
secukinumab, brodalumab, ixekizumab)
No prior use allowed
Alefacept, briakinumab, efalizumab
6 months
Biological immunomodulatory agents other than the above listed 
(e.g., adalimumab, etanercept, infliximab)
3 months
Other systemic immunomodulatory treatments c (e.g., methotrexate, 
cyclosporine A, glucocorticosteroids, cyclophosphamide) and any 
treatment for psoriatic arthritis, except for NSAIDs
4 weeks
Any biologic drug directly targeting IL-12/IL-23 other than 
ustekinumab or IL-23 (e.g., guselkumab, tildrakizumab)
6 months
Other systemic psoriasis treatments (e.g. retinoids, fumarates, 
apremilast)
4 weeks
Photo-chemotherapy (e.g., psoralen plus UVA [PUVA])
4 weeks
Phototherapy (e.g., UVA, UVB)
2 weeks
Topical treatment that is likely to impact signs and symptoms of 
psoriasis (e.g., vitamin D analogues, pimecrolimus, retinoids, 
Salicyl-Vaseline, salicylic acid, lactic acid, tacrolimus, tar, urea, 
-hydroxy or fruit acids) d
2 weeks
Live virus vaccinations 
6 weeks
Any investigational treatment or participation in any interventional 
study
4 weeks or 5 half-lives
(whichever is longer) 
a) If the prohibited treatment is used during the study for any indication, patients must discontinue its 
use if they wish to continue in the study
b) In case of undue safety risk for the patients, they should discontinue study treatment at the 
discretion of the investigator/qualified site staff. If patients treated with secukinumab receive a live 
virus vaccination during the study, they must discontinue study treatment
c) Inhalational glucocorticosteroids with only a topical effect (e.g., to treat asthma) are not considered 
systemic immunomodulatory treatments and are therefore acceptable 
d) Topical treatment should be tapered-off during the Screening Epoch and stopped 12 hours prior to 
randomization; only mild to moderate topical glucocorticosteroids on the face, scalp, and/or genitoanal 
area will be allowed. During the Treatment Epoch, bland emollients or topical glucocorticosteroid 
treatments of mild or moderate potency on the face, scalp, and/or genitoanal area will be allowed.
NSAID = nonsteroidal anti-inflammatory drug, UVA = ultraviolet light A, UVB = ultraviolet light B
5.5.9
Emergency breaking of assigned treatment code 
Not applicable. 

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5.6
Study completion and discontinuation
5.6.1
Study completion and post-study treatment 
A patient will be considered to have completed the study when he or she has completed the last 
visit planned in the protocol.
Patients who have been screened and have a screening visit recorded in the IRT system at the 
time that the planned enrolment number is met will be allowed to enter the study and be 
randomized if they are eligible.
The investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care.
For all patients a safety follow-up visit should be conducted (e.g., by telephone) 30 days after 
the last study visit or 12 weeks after the last dose of study treatment, whichever is later. The 
information to be collected at this follow-up visit includes concomitant medications, AEs, and 
survival status. 
5.6.2
Discontinuation of study treatment 
Discontinuation of study treatment for a patient occurs when study treatment is stopped earlier 
than planned in the protocol, and can be initiated by either the patient or the investigator. 
Study treatment must be discontinued under the following circumstances: 

Patient wish 

Pregnancy (see Section 6.5.6 and Section 7.6)

Use of prohibited treatment (see Table 5-1) 

Any other protocol deviation that results in a significant risk to the patient’s safety

Any laboratory abnormalities that in the judgment of the investigator, taking into 
consideration the patient’s overall status, prevents the patient from continuing 
participation in the study 

The investigator believes that patient’s continuation in the study would negatively impact 
the risk/benefit balance of study participation 
Patients who discontinue study treatment should NOT be considered withdrawn from the study. 
They should return for the assessments indicated in Table 6-1, Table 6-2, and Table 6-3, 
undergo an EOS visit, and then be discontinued from the study. If they fail to return for these 
assessments for unknown reasons, every effort (e.g., telephone, e-mail or letter) should be made 
to contact them as specified in Section 5.6.3. 
The investigator must also contact the IRT to register the patient’s discontinuation from 
treatment.
5.6.3
Withdrawal of consent 
Patients may voluntarily withdraw consent to participate in the study for any reason at any time. 
Withdrawal of consent occurs only when a patient:

Does not want to participate in the study anymore and

Does not allow further collection of personal data 

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In this situation, the investigator should make a reasonable effort (e.g., telephone, e-mail, letter) 
to understand the primary reason for the patient’s decision to withdraw his/her consent and 
record this information. 
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow up.
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the patient’s study withdrawal should be made as detailed in Table 6-1,
Table 6-2, and Table 6-3.
Novartis will continue to keep and use collected study information (including any data resulting 
from the analysis of a patient’s samples until their time of withdrawal) according to applicable 
law.
All biological samples not yet analyzed at the time of withdrawal will no longer be used, unless 
permitted by applicable law. They will be stored according to applicable legal requirements.
Patients who withdraw their consent to participate in the Mechanistic Sub-study, will still be 
able to participate in the Main Study provided they keep their consent to this part of the study. 
5.6.4
Loss to follow up 
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to withdraw, the investigator should show “due diligence” by contacting the patient, 
family or family physician as agreed in the informed consent and by documenting in the source 
documents the steps taken to contact the patient, e.g., dates of telephone calls, registered letters, 
etc. A patient should not be considered lost to follow up until his/her scheduled EOS visit has 
occurred. 
5.6.5
Early study termination by the sponsor 
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit-risk assessment of participating in the study, practical reasons, or for 
regulatory or medical reasons (including slow enrolment). Should this be necessary, the patient 
must be seen as soon as possible and treated as a prematurely withdrawn patient. The 
investigator may be informed of additional procedures to be followed in order to ensure that 
adequate consideration is given to the protection of the patient’s interests. The investigator will 
be responsible for informing the IRBs/IECs of the early termination of the study.
5.6.6
Discontinuation during the Follow-up Epoch
During the Follow-up Epoch, patients must be discontinued from the study under the following 
circumstances: 

Patient wish 

Pregnancy (see Section 6.5.6)

Use of prohibited treatment 

Any other protocol deviation that results in a significant risk to the patient’s safety

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
Occurrence of relapse
6
Visit schedule and assessments
Table 6-1, Table 6-2, and Table 6-3 list all of the assessments and indicates with an “X” the 
visits when they will be performed. An “S” indicates that the data for that assessment are to be 
recorded in the source documents at the site.
Patients should be seen for all visits on the designated day or as closely as possible to the 
originally planned visit. Missed or rescheduled visits should not lead to automatic 
discontinuation and will be discussed on an individual basis. The investigator and the patient 
can also request an unscheduled visit whenever necessary, especially during the treatment-free 
Follow-up Epoch where a worsening of symptoms and quality of life could occur, the 
investigator should remind the patient of this option. 
Patients who prematurely discontinue the study for any reason should be scheduled for an EOS
visit as soon as possible, at which time all of the assessments listed for the final visit (EOS) will 
be performed before any new treatment is initiated. All dispensed investigational product should 
be reconciled and the AEs and concomitant medications reconciled on the CRF.
At a minimum, patients will be contacted for safety evaluations during the 30 days following 
the last study visit or following the last administration of study treatment (see Section 5.6.1). 
Attempts to contact the patient should be recorded in the source documentation.

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Table 6-1
Assessment schedule: Screening Epoch and Treatment Epoch (all arms)
SE
Treatment Epoch
Visit number
SCa
1
2
3
4
5b
Time (weeks)
B
1
2
3
4
8
12
16
20
24
28
32
36
40
44
48
52
U
Secukinumab administration at the site 
X
X
X
X
Secukinumab administration at home
X
X
X
X
X
X
X
X
X
X
X
X
nb-UVB (Arm B1)
One or 2 cycles (of 12-week duration each)
Informed consent
X
Provide patient diary
S
Inclusion/exclusion criteria
X
X
Randomization 
X
Demographics
X
Medical history
X
X
Vital signs
X
X
X
X
X
X
X
Weight
X
X
Physical examination
S
S
S
S
S
S
S
Laboratory c
X
X
X
X
X
X
BSA determination
X
X
PASI assessment 
X
X
X
X
X
X
X
IGA mod 2011
X
X
X
X
X
X
QuantiFERON
X
hs-CRP
X
X
X
X
X
Serum β-hCG
X
Urine β-hCG
X
X
X
X
X
X
ECG
X

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SE
Treatment Epoch
Visit number
SCa
1
2
3
4
5b
Time (weeks)
B
1
2
3
4
8
12
16
20
24
28
32
36
40
44
48
52
U
Skin biopsies (Arm A1b, B1b, A2, C1, 
C2)
Baseline, Week 16 and Week 52
Prior/concomitant medication
X
X
X
AEs/SAEs
X
X
a) The screening visit will take place from Day -28 to Day -1 before baseline 
b) For Arms A1, B1 and C1 
c) Laboratory evaluations will include hematology and clinical chemistry 
The first dose of secukinumab will be administered under supervision at the study site and self-administration by study patients at home will be allowed 
from the second dose on, or when the investigator considers the patient is qualified to self-inject after being instructed and trained

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Table 6-2
Assessment schedule: Continued Treatment Epoch, Weeks 52-104 (Arms A2 and C2) 
Treatment Epoch (continued for Arms A2 and C2)
Visit number
5
6 a
7
8 a
9
10 a
11
12
Time (weeks)
52
56
60
64
68
72
76
80
84
88
92
96
100
104
U
Secukinumab administration at the site 
X
X
X
X
Secukinumab administration at home
X
X
X
X
X
X
X
X
X
Vital signs
X
X
X
X
X
X
Weight
X
X
Physical examination
S
S
S
S
S
Laboratory b
X
X
X
X
PASI assessment 
X
X
X
X
X
X
IGA mod 2011
X
X
X
X
X
hs-CRP
X
X
X
Urine β-hCG
X
X
X
X
Skin biopsies
X
X
Prior/concomitant medication
X
AEs/SAEs
X
The assessments for Week 52 are those shown in Table 6-1 and should be performed only once.
a) For Arms A2 and C2, Visits 6, 8, and 10 are home visits and not scheduled investigational site visits 
b) Laboratory evaluations will include hematology and clinical chemistry. 

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Table 6-3
Assessment schedule: Follow-up Epoch
Follow-up Epoch (Arm A1, B1, A2 a)
Visit number
6
8
10
11
12
13
14
15
16
17
18
19
20
21
Time (weeks)
64
76
88
100
104
116
128
140
152
164
176
188
200
EOSc
208
U
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Weight
X
X
Physical examination
S
S
S
S
S
Laboratory b
X
X
X
X
X
PASI assessment
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
IGA mod 2011
X
X
X
X
X
X
X
X
X
X
X
X
X
X
hs-CRP
X
X
X
X
Urine β-hCG
X
X
X
X
Skin biopsies
X 
X 
Prior/concomitant medication
X
X
AEs/SAEs
X
X
a) Arm A2 from Week 105 on. 
b) Laboratory evaluations will include hematology and clinical chemistry. 
c) EOS is defined as the last visit for a patient independently of whether the discontinuation or completion is planned as per protocol (Week 52, 104, or 
208 or due to relapse) or an early discontinuation. 

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6.1
Information to be collected on screening failures 
All patients who sign the informed consent, but discontinue prior to the first administration of 
study treatment are considered screening failures. The screening visit date, the Demography 
eCRF page, the Informed Consent eCRF page, the Inclusion/Exclusion eCRF page, and the 
Rescreening eCRF page must be completed for those patients who fail to enter the Treatment 
Epoch. Reporting of SAEs during the Screening Epoch should be followed as described in
Section 7.2. The Adverse Events eCRF page should be completed for any SAEs that occurred 
during the Screening Epoch. Potential AEs and hospitalizations that are not SAEs which may 
have occurred from the time of signing the informed consent until the time of screening failure 
will be followed by the investigator and collected only in the source data.
If a patient discontinues prior to randomization, the IRT provider should be notified, and the 
reason for the patient not being randomized will be entered on the Screening Epoch Disposition 
eCRF page. The screening visit date, the Demography eCRF page, the Informed Consent eCRF
page, and the Inclusion/Exclusion eCRF page must be completed.
Patients who fail screening for any reason may be rescreened. There will be no restriction on 
the number of times a potential patient may be rescreened or on how much time must pass from 
the date of screen failure and the date of rescreening. If a patient rescreens for the study, then 
the patient must sign a new informed consent form and be issued a new patient number prior to 
performing any study–related assessment or collecting any data for the screening visit for the 
patient under the new screening patient number. For all patients, the investigator/qualified site 
staff will record if the patient was rescreened on the Rescreening eCRF page and any applicable 
screening numbers the patient was issued prior to the current screening number. The date of the 
new informed consent signature must be entered on the Informed Consent eCRF page to 
correspond to the new screening patient number. 
The Withdrawal of Consent eCRF page must be completed if consent was withdrawn during 
the Screening Epoch before the patient was randomized.
For all patients who sign the informed consent and enter into the next period of the study, all 
AEs occurring after the informed consent is signed will be recorded on the Adverse Events
eCRF page.
Investigators will have the discretion to record abnormal test findings on the Medical History
eCRF page whenever, in their judgment, the test abnormality occurred prior to the informed 
consent signature. 
6.2
Patient demographics/other baseline characteristics 
All baseline assessments should be performed prior to the first study treatment administration. 
Depending on the assessment, these may be completed at the screening visit (e.g., demographics) 
or at baseline
 
Patient demographics and baseline characteristics will be collected at the screening visit. Data 
to be collected on all patients include: date of birth, age, sex, race, ethnicity, height, weight, and 
skin type (Section 14.5). 
The history of plaque psoriasis will be collected at the screening visit. The information to be 
collected includes the following:

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
Date of first diagnosis of plaque psoriasis by a physician

Presence of psoriatic arthritis (including questions on signs and symptoms captured in the 
eCRF) and the date of the first diagnosis by a physician

Use of psoriasis treatments, e.g., patients who used prescription treatments of family 
members suffering from psoriasis without having consulted a physician
6.2.1
Smoking history
The current and/or previous use of tobacco products will be recorded, as well as the estimated 
number of pack-years based on the approximate consumption per year. Non-smokers will be 
advised to not start smoking during the study.
6.2.2
Relevant medical history/current medical conditions 
Relevant medical history and current medical conditions, not including psoriasis or psoriatic 
arthritis, prior to signing of the informed consent will be recorded in the Medical History eCRF 
page. Whenever possible, diagnoses and not symptoms will be recorded.
Patients with Crohn’s disease will be eligible for the study but should be closely followed when 
randomized to secukinumab. 
Significant findings that are observed after the patient has signed the informed consent form 
and that meet the definition of an AE must be recorded in the Adverse Event eCRF page.
6.2.2.1
Psoriasis medical history/previous psoriasis therapies
Disease history will be collected at the screening visit. The information to be collected and 
entered in the Psoriasis History eCRF and Prior Psoriasis Therapies eCRF will include the 
following: 

Date of first diagnosis (by a physician) of plaque psoriasis 

Previous treatments of psoriasis (including previous use of biologic therapies, as well as 
phototherapy and/or photo-chemotherapy) and the reason for discontinuation of each
therapy

Presence of psoriatic arthritis and the date of first diagnosis (by a physician)
6.2.3
Prior and concomitant medications 
Concomitant medications and prior medications taken within the 6 months preceding study 
enrollment will be captured at the screening visit, and updated at baseline. 
6.2.4
Determination of tuberculosis status 
Determination of TB status will be required before administration of study treatment and should 
be performed as defined by local guidelines. Tuberculosis status must be determined by medical 
history, signs, symptoms, and TB testing (QuantiFERON® TB-Gold In-Tube assay).
Any significant findings will be recorded in the Tuberculosis Assessment eCRF page and the 
Medical History eCRF page, as necessary.

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QuantiFERON TB-Gold In-Tube assay
This test (Figure 6-1) will only be used to screen the patient population for latent TB infection 
(Doherty et al 2008) and determine patient’s eligibility for the study.
This blood-based assay is specific for Mycobacterium tuberculosis and is not influenced by 
previous bacillus Calmette-Guerin vaccination or exposure to other Mycobacteria species. In 
contrast to the purified protein derivative skin test, it is also insensitive to a booster effect, since 
the patient is not exposed to the vaccine. The assay measures the production of interferon-
gamma and presents it relative to negative and positive control samples (Manuel and Kumar 
2008).
The QuantiFERON®-TB Gold In-Tube assay will be supplied by the central laboratory. Details 
on the collection, shipment of samples and reporting of results by the central laboratory will be 
provided to investigators in the laboratory manual. 

If the test result is negative, the patient may be randomized

If the test result is positive, the investigator should perform workup for the test result as 
per local procedures:
o
Patients who are positive for latent TB per workup may be randomized to the study if 
sufficient treatment has been initiated according to local routine clinical practice and 
will be maintained for the prescribed duration
o
Patients who are positive for active TB per workup are not eligible for the study
o
Patients who are negative for TB (no signs of latent or active TB) per workup may be 
randomized to the study

If the test result is indeterminate, it is recommended to repeat it once. The investigator 
may decide to skip the repetition of the test and proceed directly to the workup (this is 
however not recommended). If a TB workup was conducted within 12 weeks prior to 
randomization, the results can be used to assess eligibility
o
If the second test is negative, the patient may be randomized 
o
If the second test is positive or indeterminate, the investigator should perform 
workup as per local guidelines. The patient will not be eligible for randomization if 
“active or latent TB are present” and will be untreated as per local guidelines 

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Figure 6-1
Tuberculosis screening flowchart 
The patient will not be eligible for randomization if active or latent TB are present and is untreated as 
per local guidelines. 
* If the result of the first QuantiFERON®-TB Gold In-Tube assay is indeterminate, the investigator may 
choose to repeat the assay or refer the patient for TB workup as per local guidelines.
** If the result of any assay is positive, or the result of 2 sequential assays is indeterminate, the 
investigator must refer the patient for TB workup as per local guidelines (if no workup of the 12 weeks 
prior to randomization is available). 
6.2.5
Other baseline characteristics 
Baseline characteristic data to be collected on all patients include (see also Table 6-1): 12-lead 
ECG, vital signs, hematology, clinical chemistry (all laboratory assessments will be performed 
in a central laboratory except where indicated), physical examination, height, weight, medical 
history, 
, as well as assessments of PASI, BSA and IGA 
mod 2011. A serum pregnancy test will be performed to women of childbearing potential. 
6.3
Treatment exposure and compliance 
All doses of study treatment administered will be recorded on the appropriate Dosage 
Administration Record eCRF page. Patient compliance to the study treatment should be 
assessed by qualified site personnel at each study visit using the study kits and documentation 
regarding study treatment dispensation and administration. 

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Compliance will also be assessed continuously during the conduct of the study by Novartis 
study personnel using medication kits and the corresponding documentation. Study treatment 
doses and the corresponding dates of self-administration at home should be documented in a 
self-administration log. Patients will be required to return the self-administration log as well as 
all dispensed study treatment at every visit to the investigational site for a compliance check.
6.4
Efficacy
All efficacy assessments should be performed prior to the administration of study treatment.
6.4.1
Assessment of body surface area and psoriasis area severity index
The investigator or trained qualified designee will complete the PASI assessment as indicated 
in Table 6-1, Table 6-2, and Table 6-3. Whenever possible, the same evaluator should perform 
this assessment at all visits.
The total BSA affected by plaque psoriasis will be estimated from the percentages of the 
affected areas, including head, trunk, upper limbs and lower limbs. 
The following calculations will be done: each reported percentage will be multiplied by the
factor that corresponds to the respective body region (head = 0.1, trunk = 0.3, upper limbs = 0.2, 
lower limbs = 0.4). The resulting 4 percentages will be added up to estimate the total BSA 
affected by plaque psoriasis. 
A PASI score (Fredriksson and Pettersson 1978, Gottlieb et al 2005) will be derived as indicated 
in Table 6-4. The head, trunk, upper limbs and lower limbs will be assessed separately for 
erythema, thickening (plaque elevation, induration), and scaling (desquamation). The average 
degree of severity of each sign in each of the 4 body regions will be assigned a score of 0-4. 
The area covered by lesions on each body region will be estimated as a percentage of the total 
area of that particular body region. Further practical details to help with the assessment are 
provided below:
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 BSA, respectively, the PASI score is calculated using the 
formula:
PASI = 0.1(EH+IH+DH)AH + 0.2(EU+IU+DU)AU + 0.3(ET+IT+DT)AT + 0.4(EL+IL+DL)AL
The keys for the letters are provided in Table 6-4.
PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a 
theoretic maximum of 72.0.
The baseline value for the analysis of the PASI will be collected at baseline.
Patients require a total BSA of 10% or more affected by plaque psoriasis and a PASI score of 
10 or more at screening and baseline to be eligible for this study.

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Table 6-4
Psoriasis area severity index scoring system
Body 
region
Erythema (E)
Thickening 
(plaque elevation, 
induration, I)
Scaling 
(desquamation, D)
Area score
(based on true 
area %, A) a
Head (H) b
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = no involvement
1 ≥0 to < 10%
2 = 10 to < 30%
3 = 30 to < 50%
4 = 50 to < 70%
5 = 70 to < 90%
6 = 90-100%
Trunk (T) c
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = no involvement
1 ≥0 to < 10%
2 = 10 to < 30%
3 = 30 to < 50%
4 = 50 to < 70%
5 = 70 to < 90%
6 = 90 -100%
Upper limbs 
(U)
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = no involvement
1 ≥0 to < 10%
2 = 10 to < 30%
3 = 30 to < 50%
4 = 50 to < 70%
5 = 70 to < 90%
6 = 90 -100%
Lower limbs 
(L) d
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = none 
1 = slight 
2 = moderate 
3 = severe
4 = very severe
0 = no involvement
1 ≥0 to < 10%
2 = 10 to < 30%
3 = 30 to < 50%
4 = 50 to < 70%
5 = 70 to < 90%
6 = 90 - 100%
a) Percentage (not score) of body region (not whole body) affected will be entered in the eCRF. 
b) Neck is assessed as part of the Head (H) body region. 
c) Axillae and groin are assessed as part of the Trunk (T) body region. 
d) Buttocks are assessed as part of the Lower limbs (L) body region. 

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Definitions of efficacy variables based on the psoriasis area severity index
The following definitions will be used in this study based on the CHMP guidelines for psoriasis 
(CHMP/EWP/2454/02):

PASI 50-89 response: patients who achieve ≥PASI 50, but < PASI 90 improvement 
(reduction) compared with baseline

PASI 90 response: patients achieving ≥90% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 90 responders 

PASI 100 response/remission: PASI = 0, complete clearance 

Relapse: when the achieved maximal PASI improvement from baseline is reduced by 
≥50% (CHMP/EWP/2454/02)
 
6.4.4
Investigator’s global assessment mod 2011
The impact of study treatment on psoriatic disease will be assessed by the IGA mod 2011 
(Langley et al 2015) at the times indicated in Table 6-1, Table 6-2 and Table 6-3. 
Patients require an IGA mod 2011 score at screening of ≥3 in order to participate in the study 
and the score will be recorded in the eCRF. 
The rating scale for overall psoriatic disease is shown in Table 6-5. 
The IGA mod 2011 used in this study is static, i.e., it refers exclusively to the patient’s disease 
state at the time of the assessments, and does not attempt a comparison with any of the patient’s 
previous disease states, whether at baseline or at a previous visit.

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Table 6-5
Investigator’s global assessment 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
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling
3
Moderate
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling
4
Severe
Bright to deep dark red coloration; severe thickening with hard 
edges; severe/coarse scaling covering almost all or all lesions
Note: involvement of nails is not part of the assessment
Based on this scale, patients will be considered as responders if they achieve a score of 0/1 and 
improve by at least 2 points compared with baseline. 
6.4.5
Appropriateness of efficacy assessments 
Psoriasis area severity index scores outcome measures, the assessment of the severity of the 
psoriasis symptoms and the extent to which the patient’s body area is affected by the disease, 
is mandated by the European Medicines Agency (EMA) for the clinical investigation of 
medicinal products for the treatment of psoriasis (CHMP/EWP/2454/02).
As indicated in Section 6.4.4, 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 Phase II secukinumab studies. In the modified scale, the 
categories “very severe” and “severe” have been condensed into a single category “severe” and 
the explanations/descriptions of the points on the scale have been improved to ensure 
appropriate differentiation between them.
6.5
Safety 
From baseline, all blood draws and safety assessments must be performed prior to study 
treatment administration. Appropriate safety assessments (e.g., evaluation of AEs and SAEs) 
should be repeated after dosing with study treatment.
6.5.1
Physical examination 
A complete physical examination will include the examination of general appearance, skin, 
neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, 
and extremities, and the vascular and neurological systems. If indicated based on medical 
history and/or symptoms, rectal, external genitalia, breast, and pelvic exams will be examined.
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present prior to signing the informed consent must be 
included in the Medical History eCRF page. Significant findings made after the first 
administration of investigational drug which meet the definition of an AE must be recorded on 
the Adverse Event section of the eCRF.

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6.5.2
Vital signs 
Vital signs include blood pressure and pulse measurements. After the patient has been sitting 
for 5 minutes, with the back supported and both feet placed on the floor, systolic and diastolic 
blood pressures will be measured 3 times using an automated validated device, e.g., OMRON, 
with an appropriately sized cuff. The repeat sitting measurements will be made at 1-2 minute 
intervals and the mean of the 3 measurements will be used. If the available cuff sizes are not 
large enough for the patient’s arm circumference, a sphygmomanometer with an appropriately 
sized cuff may be used.
If possible, assessments should be performed by the same study site staff member throughout 
the study.
Normal blood pressure will be defined as a systolic pressure of 90 to < 120 mm Hg, and a 
diastolic blood pressure of 60 to < 80 mm Hg under the measurement conditions outlined above. 
Notable blood pressure findings will be hypertension (systolic blood pressure of ≥140 mm Hg
and/or diastolic blood pressure of ≥90 mm Hg) or hypotension (systolic blood pressure of 
< 90 mm Hg and/or a diastolic blood pressure of < 60 mm Hg). A blood pressure indicative of 
prehypertension (systolic blood pressure of 120 to < 140 mm Hg and/or diastolic blood pressure 
of 80 to < 90 mm Hg) 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 rate will be a rate below 60 bpm 
(bradycardia) or above 100 bpm (tachycardia).
Whether action needs to be taken to address notable vital signs will be decided by the 
investigator, taking into account the overall status of the patient. No specific action is foreseen 
as part of the study protocol.
6.5.3
Height and weight 
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram (kg) in indoor clothing, 
but without shoes) will be measured.
6.5.4
Laboratory evaluations 
A central laboratory will be used for the analysis of blood and urine collected (with the 
exception of pregnancy tests). Details on the collection, shipment of samples and reporting of 
results by the central laboratory are provided to investigators in the laboratory manual. For the 
identification of notable values, the laboratory manual should be consulted. Whether action 
needs to be taken to address notable laboratory values will be decided by the investigator taking 
into account the overall status of the patient. No specific action is foreseen as part of the study 
protocol.
For clinically notable thresholds please refer to Appendix 1 or to the laboratory manual.
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. 

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6.5.4.2
Clinical chemistry
Blood urea, creatinine, total bilirubin, alkaline phosphatase, international normalized ratio, 
sodium, potassium, chloride, calcium, phosphorous, total protein, albumin, uric acid, and lipid 
panel will be measured.
For a local analysis of urine, dipsticks will be provided by the central laboratory to the sites for 
the assessment. Sites should record the results in the source documentation and report these in 
the eCRF for each patient.
6.5.4.3
High-sensitivity C-reactive protein
This marker will be assessed at the visits when clinical chemistry is performed (see Table 6-1,
Table 6-2, and Table 6-3). 
6.5.5
Electrocardiogram 
For the baseline visit an ECG must be recorded after 10 minutes rest in the supine position to 
ensure a stable baseline. The preferred sequence of cardiovascular data collection at baseline is 
ECG collection first, followed by vital signs, and blood sampling. The Fridericia QT correction 
formula (QTcF) should be used for clinical decisions.
Only clinically significant abnormalities should be reported in the eCRF Adverse Event page.
If the ECG findings are clinically relevant and would prevent the patient from participating in 
the study (taking into account the patient’s overall status and the medication profile), the patient 
should be recorded as a screen failure, should not be enrolled and should not receive treatment. 
Single 12-lead ECGs will be collected. The original ECGs, appropriately signed, should be 
collected and archived at the study site.
Each ECG tracing must be labelled with study number, patient initials, patient number, date and 
time, and filed in the study site source documents. Clinically significant ECG findings at 
baseline must be discussed with the sponsor before administration of study treatment.
6.5.6
Pregnancy 
A serum or urine β-hCG test will be performed in all pre-menopausal women as shown in
Table 6-1, Table 6-2, and Table 6-3.
All pre-menopausal women who are not sterile at screening will also have a urine pregnancy 
test performed locally. Any woman with a confirmed positive pregnancy test (hCG > 5 mIU/mL) 
during screening will not be eligible for randomization.
Women of childbearing potential should use an effective method of contraception while on 
treatment, or longer if required by locally-approved prescribing information (e.g., 20 weeks 
after the last dose in the EU and countries where applicable for secukinumab). A positive urine 
pregnancy test during the Treatment Epoch of 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, study treatment must be definitively discontinued, as described in Section 5.6.2.
If a β-hCG test is positive during the Follow-up Epoch, the patient will be discontinued from 
the study. 

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6.5.7
Appropriateness of safety measurements 
The safety assessments selected in this study are reliable and standard measures for a biologic 
immunomodulatory agent in adult patients with psoriasis. 
6.6
Other assessments 
6.6.1
Clinical outcome assessments 
6.6.1.1
Clinician-reported outcomes
6.6.1.1.1 Evaluation of psoriasis arthritis symptoms
Questions about signs and symptoms of psoriatic arthritis including pain, swelling and stiffness 
of the joints, neck, back, fingers, toes, and enthesis will be addressed and captured in the eCRF. 

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6.6.2
Resource utilization 
Not applicable.
6.6.3
Pharmacokinetics 
Not applicable. 
6.6.4
Immunological analysis of skin biopsies 
This study includes an optional biopsy collection which requires a separate informed consent if 
the patient agrees to participate in the Mechanistic Sub-study.
Skin biopsies will be taken from patients in Arm A1b, Arm A2, Arm B1b, Arm C1, and 
Arm C2 to assess the total number of Trm cells and subsets of these cells, especially those 
capable of producing IL-17A and IL-22 inflammatory mediators considered to be vital to 
maintain subclinical inflammation.
 
Punch biopsies from lesional or resolved skin (2 biopsies, 4 millimeters in diameter) and never-
lesional skin (1 biopsy, 3 millimeters in diameter) will be taken according to the schedule shown 
in Table 6-6. After collection, biopsies need to be transported on ice or dry ice within 24 hours 
to the laboratory (Karolinska Institute, Stockholm, Sweden) for further processing using a 
Novartis delegated service provider. 

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Table 6-6
Schedule for the collection of skin biopsies
Collection time
Arm
Baseline
Week 16
Week 52
Week 104
Week 208
A1b
X
X
X
X a
X a
A2
X
X
X
         X
X a
B1b
X
X
X
X a
X a
C1
X
X
X
C2
X
X
X
         X 
a) Only patients eligible for the Follow-up Epoch will have biopsies taken at the marked time points
Laboratory manuals will be provided with detailed information on sample collection, handling, 
and shipment. The sample collection date and exact time must be entered on the Sample 
Collection eCRF page.
 
7
Safety monitoring 
7.1
Adverse events 
An AE is any untoward medical occurrence (e.g., any unfavorable and unintended sign 
[including abnormal laboratory findings], symptom or disease) in a patient or clinical 
investigation subject after providing written informed consent for participation in the study until 
the EOS visit. Therefore, an AE may or may not be temporally or causally associated with the 
use of a medicinal (investigational) product. 
In addition, all reports of intentional misuse and abuse of the product are also considered an AE
irrespective if a clinical event has occurred. The occurrence of AEs must be sought by non-
directive questioning of the patient at each visit during the study. Adverse events also may be 
detected when they are volunteered by the patient during or between visits or through physical 
examination findings, laboratory test findings, or other assessments.
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria:

they induce clinical signs or symptoms 

they are considered clinically significant 

they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 

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baseline (randomization) or the previous visit, or values which are considered to be non-typical 
in patient with underlying disease. Investigators have the responsibility for managing the safety 
of individual patient and identifying AEs. Alert ranges for laboratory and other test 
abnormalities are included in Appendix 1.
Adverse events must be recorded in the Adverse Event eCRF page under the signs, symptoms 
or diagnosis associated with them, accompanied by the following information:

the severity grade:
o
mild: usually transient in nature and generally not interfering with normal 
activities
o
moderate: sufficiently discomforting to interfere with normal activities
o
severe: prevents normal activities

its relationship to the study treatment
o
no relationship to study treatment or other investigational treatment or
o
relationship to study treatment or
o
relationship to other investigational treatment or 
o relationship to both study treatment and other investigational treatment or 
indistinguishable 

its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved must be reported

whether it constitutes a SAE (see Section 7.2 for definition of SAE) and which seriousness 
criteria have been met 

action taken regarding the investigational treatment 
All AEs must be treated appropriately. Treatment may include one or more of the following: 

no action taken (e.g., further observation only) 

investigational treatment dosage increased/reduced

investigational treatment interrupted/withdrawn

concomitant medication or non-drug therapy given 

patient hospitalized/patient’s hospitalization prolonged (see Section 7.2 for definition of 
SAE)

its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown)
Once an AE is detected, it should be followed until its resolution or until it is judged to be 
permanent, and assessment must be made at each visit (or more frequently, if necessary) of any 
changes in severity, the suspected relationship to the study treatment, the interventions required 
to treat it, and the outcome.
Worsening of psoriasis in this study is evaluated via the use of PASI, IGA mod 2011 
 
assessments and is not expected to be captured as an AE in the eCRF. Exceptions include cases 
when a) a new type of psoriasis is diagnosed (e.g. guttate psoriasis), and b) the worsening of 
psoriasis is so severe that a qualitatively different status is reached. 
Information about common side effects already known about the study treatment can be found 
in the Investigator Brochure. This information will be included in the patient informed consent 

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and should be discussed with the patient during the study as needed. Any new information 
regarding the safety profile of the medicinal product that is identified between Investigator 
Brochure’s updates will be communicated as appropriate, for example, via an Investigator 
Notification or an Aggregate Safety Finding. New information might require an update to the 
informed consent and has then to be discussed with the patient. 
The investigator should also instruct each patient to report any new AE (beyond the protocol 
observation period) that the patient, or the patient’s personal physician, believes might 
reasonably be related to study treatment. This information should be recorded in the 
investigator’s source documents; however, if the AE meets the criteria of an SAE, it must also 
be reported to Novartis.
7.2
Serious adverse events 
7.2.1
Definition of serious adverse event
An SAE is defined as any AE (appearance of [or worsening of any pre-existing] undesirable 
sign[s], symptom[s] or medical conditions[s]) which meets any one of the following criteria:

is fatal or life-threatening 

results in persistent or significant disability/incapacity

constitutes a congenital anomaly/birth defect

requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:
o routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
o 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
o 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 
o social reasons and respite care in the absence of any deterioration in the patient’s 
general condition

is medically significant, e.g., defined as an event that jeopardizes the patient or may 
require medical or surgical intervention. All malignant neoplasms will be assessed as 
serious under “medically significant” if other seriousness criteria are not met.
Life-threatening in the context of a SAE refers to a reaction in which the patient was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (see 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 patient or might 
require intervention to prevent one of the other outcomes listed above. Examples of such events 
are intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization or development of dependency or 
abuse (see ICH-E2D Guideline).

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Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
7.2.2
Serious adverse event reporting 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 12 weeks following the last administration of study 
treatment must be reported to Novartis within 24 hours of learning of its occurrence. Any SAEs 
experienced after the 12-week period following the last administration of study treatment 
should only be reported to Novartis if the investigator suspects a causal relationship to study 
treatment. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at a 
different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event. 
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form; all applicable sections of the form must be completed in order to provide a clinically 
thorough report. The investigator must assess the relationship of each SAE to each specific 
component of the study treatment (if the study treatment consists of several components)
complete the SAE Report Form in English, and submit the completed form within 24 hours to 
Novartis. Detailed instructions regarding the submission process and requirements for signature 
are to be found in the investigator folder provided to each site.
Follow-up information is submitted as instructed in the investigator folder. Each re-occurrence, 
complication, or progression of the original event must be reported as a follow up to that event 
regardless of when it occurs. The follow-up information should describe whether the event has 
resolved or continues, if and how it was treated, and whether the patient continued or withdrew 
from study participation. 
If the SAE is not previously documented in the Investigator Brochure or Package Insert (new 
occurrence) and is thought to be related to the study treatment a Drug Safety and Epidemiology 
Department associate may urgently require further information from the investigator for health 
authority reporting. Novartis may need to issue an Investigator Notification to inform all 
investigators involved in any study with the same study treatment that this SAE has been 
reported. Suspected Unexpected Serious Adverse Reactions 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
Liver safety monitoring 
Not applicable. 
7.4
Renal safety monitoring 
Not applicable. 

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7.5
Reporting of study treatment errors including misuse/abuse 
A medication error is an unintended failure in the drug treatment process that leads to, or has 
the potential to lead to, harm to the patient (EMA/762563/2014).
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol.
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal product, 
which is accompanied by harmful physical or psychological effects.
Study treatment errors and uses outside of what is foreseen in the protocol will be collected in 
the dose administration record eCRF irrespective of whether or not associated with an AE/SAE 
and reported to Safety only if associated with an SAE. Misuse or abuse will be collected and 
reported in the safety database irrespective of it being associated with an AE/SAE.
Treatment error 
type
Document in DAR 
eCRF (Yes/No)
Document in AE 
eCRF
Complete SAE form
Unintentional study 
treatment error
Yes
Only if associated with 
an AE
Only if associated with an 
SAE
Misuse/abuse
Yes
Yes
Yes, even if not 
associated with a SAE
DAR = dose administration record 
7.6
Pregnancy reporting 
To ensure patient safety, each pregnancy occurring after signing the informed consent must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications.
Pregnancy must be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the local Novartis Drug Safety and Epidemiology Department. Pregnancy follow
up should be recorded on the same form and should include an assessment of the possible 
relationship to the study treatment. 
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE Report Form.
Pregnancy outcomes should be collected for the female partner of any male who take study 
treatment in this study. Consent to report information regarding these pregnancy outcomes 
should be obtained from the female partner. 
7.7
Prospective suicidality assessment 
Not applicable. 

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8
Data review and database management 
8.1
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and eCRF with the investigators and their staff. During 
the study, the field monitor will visit the site regularly to check the completeness of patient 
records, the accuracy of entries on the eCRF, the adherence to the protocol and to Good Clinical 
Practice (GCP) and the progress of enrollment. Key study personnel must be available to assist 
the field monitors during these visits.
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, ECGs, and the results of any other tests or assessments. All 
information on eCRFs must be traceable to these source documents in the patient’s file. The 
investigator must also keep the original informed consent form signed by the patient (a signed 
copy is given to the patient).
The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the 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 eCRF are performed according to the study-specific 
monitoring plan. No information in source documents about the identity of the study patients 
will be disclosed.
8.2
Data collection
Designated investigator staff will enter the data required by the protocol into the OC/RDC 
system. Designated investigator site staff will not be given access to the system until they have 
been trained. 
Automatic validation procedures within the system check for data discrepancies during and 
after data entry and, by generating appropriate error messages, allow the data to be confirmed 
or corrected online by the designated investigator site staff. The investigator must certify that 
the data entered into the eCRFs are complete and accurate. After database lock, the investigator 
will receive copies of the patient data for archiving at the investigational site.
8.3
Database management and quality control 
Novartis staff (or designated Contract Research Organization [CRO] staff) review the data 
entered into the eCRFs by investigator/qualified site staff for completeness and accuracy and 
instruct the investigator/qualified site staff to make any required corrections or additions. 
Queries are sent to the investigational site using an electronic data query. Investigator/qualified 
site staff is required to respond to the query and confirm or correct the data. If the electronic 
query system is not used, a paper Data Query Form will be faxed to the site. 
Investigator/qualified site staff will complete and sign the faxed copy and fax it back to Novartis 
staff that will make the correction to the database. The signed copy of the Data Query Form is 
kept at the investigator/qualified site staff site.

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Concomitant medications entered into the database will be coded using the World Health 
Organization (WHO) Drug Reference List, which employs the Anatomical Therapeutic 
Chemical classification system. Concomitant procedures, non-drug therapies and AEs will be 
coded using the Medical dictionary for regulatory activities (MedDRA) terminology.
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated CRO).
Patient-reported outcomes data will be collected from all patients. These data will be processed 
centrally and the results will be sent electronically to Novartis (or a designated CRO) or 
transferred by investigator/qualified site staff into the eCRF, respectively.
Randomization codes, data about study treatments dispensed to the patient, all IRT recorded 
dosage changes, and some efficacy data will be tracked using IRT. The system will be supplied 
by a vendor that will also manage the database. The database will be sent electronically to 
Novartis (or a designated CRO).
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. The 
code break functionality will remain available until study shut down or upon request of Novartis.
8.4
Data Monitoring Committee 
The implementation of a Data Monitoring Committee to review the safety data of this study is 
not planned. However, a Scientific Steering Committee is formed. The task of the Committee 
is to safeguard proper execution of the study and monitor the progress.
8.5
Adjudication Committee 
Not required.
9
Data analysis 
9.1
Analysis sets 
The following analysis sets will be used:

Full analysis set: The FAS will be comprised of all patients who were randomized to the 
study. Following the intent-to-treat principle, patients will be analyzed according to the 
treatment assigned at baseline

Safety set (SAF): The safety set includes all patients who took at least one dose of study 
treatment during the Treatment Epoch, whether or not they were randomized. Patients will 
be analyzed according to the treatment received
The treatment arms (see Section 5.2) for the analyses of data will include: 
Main Study

Sixty-eight patients from Arm A1a and 12 from Arm A1b

Sixty-eight patients from Arm B1a and 12 from Arm B1b

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Mechanistic Sub-study

Twelve patients from Arm A1b

Twelve patients from Arm A2 

Twelve patients from Arm B1b

Twelve patients from Arm C1

Twelve patients from Arm C2 
9.2
Patient demographics and other baseline characteristics 
Demographics and baseline characteristics
Summary statistics will be presented for continuous demographic and baseline characteristic 
variables for each treatment arm and for all patients in the FAS. The number and percentage of 
patients in each category will be presented for categorical variables for each treatment arm and 
for all patients. 
Medical history
Any condition entered as medical history or current medical conditions at baseline will be coded 
using the MedDRA dictionary. Medical history will be summarized for all patients in the FAS 
by system organ class and preferred term in the MedDRA dictionary. Summaries for psoriasis-
specific medical history will be provided.
Cardiovascular medical history assessed prior to randomization will also be summarized. 
9.3
Treatments 
The analysis of study treatment data will be based on the SAF. The duration of exposure to 
study treatment will also be summarized by treatment arm. 
Prior and concomitant treatments
Prior and concomitant treatments will be summarized by treatment arm in separate tables for 
the SAF and for the treatment epochs separately.
Prior treatments are defined as treatments taken and stopped prior to the first dose of study 
treatment. Any treatment given at least once between the day of first dose of randomized study 
treatment (baseline) and the last study visit will be a concomitant treatment, including those 
which were started pre-baseline and continued into the Treatment Epoch.
Treatments will be presented in alphabetical order, by ATC codes and main groups. Tables will 
also show the overall number and percentage of patients receiving at least one treatment of a 
particular ATC code and at least one treatment in a particular anatomical main group.
In addition, medical procedures and significant non-drug therapies as coded in MedDRA will 
be summarized.

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9.4
Analysis of the primary variable
The primary objective of this study is to demonstrate the superior efficacy of secukinumab 300 
mg s.c. compared to nb-UVB in patients with new-onset moderate to severe plaque psoriasis
with respect to patients achieving PASI 90 response at Week 52. 
9.4.1
Primary variable
The primary efficacy variable is the proportion of patients who achieve PASI 90 at Week 52. 
The analysis for the primary objective will be based on the FAS.
9.4.2
Statistical model, hypothesis, and method of analysis
For the primary analysis, the following hypothesis testing will be performed:
: 	
 =   : 	
 > 
where 	
 and  are the proportion of PASI 90 responders in the secukinumab 300 mg 
s.c. (Arm A1) and nb-UVB (Arm B1) groups, respectively.
The primary analysis method for PASI 90 response at Week 52 will use a logistic regression 
model with treatment as an explanatory variable and significant covariates among baseline 
PASI score, age, and body mass index. The best subset of the significant covariates will be 
selected using a forward selection method based on the likelihood ratio test. Interaction terms 
will also be considered, if significant, among the best subset of selected covariates and the 
treatment term.
Statistical significance will be evaluated at a 1-sided alpha level of 0.025. The estimated 
adjusted odds ratio for Arm A1 versus Arm B1 will be displayed along with the associated 
2-sided 95% confidence interval (equivalent to the 1-sided 97.5% confidence interval) and 
p-value.
If there are issues related to the convergence of the logistic regression model, the above 
hypothesis will be tested using a Wald test. 
The primary analysis is not expected to be influenced by the use of topical treatment within the 
first 4 weeks since, any effect will be worn off by Week 52. 
9.4.3
Handling of missing values/censoring/discontinuations
Missing data will be handled with a modified multiple imputation method. Patients who 
discontinued the study before Week 52 because of lack of efficacy or AEs will be considered 
non-responders. Missing values for other reasons will be inserted by means of the multiple 
imputation method. 
The multiple imputation method is a simulation-based approach where missing values are 
replaced by multiple Bayesian draws from the conditional distribution of missing data given the 
observed data and covariates, creating multiple completed data sets, which can then be analyzed 
using standard methods. Rubin (1987) presented rules how to combine the multiple sets of 
estimates to produce overall estimates and confidence intervals that adequately incorporate 
missing data uncertainty.

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Missing values for the “change from baseline PASI score” will be imputed simultaneously 
based on an underlying normal distribution and using the data augmentation procedure of 
Markov Chain Monte Carlo (MCMC) method. The change from baseline in PASI score appears 
to follow closer to a normal distribution than the actual PASI score. The imputations will be 
done separately for each treatment group. Further details will be provided in the statistical 
analysis plan.
9.4.4
Supportive analyses 
A non-responder imputation will be used as supportive analysis, i.e., a missing value of PASI 
90 response at Week 52 will be imputed with non-response regardless of the reason for missing 
data (e.g., premature study discontinuation, missed visit, administrative issues).
9.5
Analysis of secondary variables
9.5.1
Key secondary variable
The key secondary variable is the proportion of all randomized patients who achieve PASI 90 
at Week 104. In order to reduce selection bias, all patients who do not achieve PASI 90 at Week 
52 will also be included in the analysis at Week 104 using the PASI improvement obtained at 
Week 104 only. 
A patient who fails to achieve PASI 90 response at Week 104, irrespective of the responses 
over the past visits will be considered non-responder. Similarly, patients who achieved PASI 90 
response at Week 104, but not at any of the past visits will be considered responder. 
This would mean that if a patient achieves PASI 85 (85% improvement in PASI score compared 
to baseline) at Week 52, and the improvement in PASI increases to 90% at Week 104, the 
patient will be considered responder in the analysis at Week 104.
For the key secondary analysis, the following hypothesis testing will be performed:
: ∗
	
 = ∗
  : ∗
	
 > ∗

where ∗
	
 and ∗
 are the proportion of patients who achieve PASI 90 response at Week 
104 in the secukinumab 300 mg s.c. (Arm A1) and nb-UVB (Arm B1) groups respectively. This 
testing will be performed using an exact logistic regression analysis similar to the primary 
analysis, with the strategy below under consideration. 
Missing data will be handled similarly as for the primary endpoint analysis. Patients who relapse 
will be considered non-responders in addition to those who discontinue the study before 
Week 104 because of lack of efficacy or AEs.
In addition, the proportion of all randomized patients who achieve PASI 90 at 52 weeks after 
cessation of treatment will be analyzed as an exploratory supportive analysis using an exact
logistic regression analysis similar to the key secondary analysis. 
Testing strategy
Since the primary and the key secondary hypotheses are not mutually independent, an 
adjustment for multiplicity is considered here to control the alpha level (Type I error) i.e., 
familywise error rate. 

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This adjustment will be made using a hierarchical testing procedure, which states that first H01
will be tested at 1-sided α = 2.5% level of significance. The obtained p-value from the fitted 
logistic regression model will be divided by 2 and this resultant p-value needs to be considered. 
If the resultant p-value is smaller than 0.025, H01 is rejected at 2.5% significance level, 
concluding that there is strong evidence to consider that secukinumab is performing better than 
nb-UVB at Week 52. However, if this resultant p-value is greater than 0.025, H01 is not rejected 
at 2.5% significance level,  concluding that the evidence obtained from the observed sample is 
not strong enough to say that any one of the treatment arms is performing better than the other.
The testing sequence will continue to test H02 at α=2.5% (1-sided), only if H01 is rejected.
9.5.2
Investigator’s global assessment mod 2011
The secondary efficacy variable is the proportion of all randomized patients who achieve at 
least IGA 0/1 response at Week 52. Patients will be considered responders if they achieve a 
score of 0/1 and improve by at least 2 points compared with baseline.
This analysis will be based on the FAS.
The method for IGA 0/1 response at Week 52 will use a logistic regression model similar to the 
primary analysis, with treatment as an explanatory variable and the significant variables among 
baseline IGA score, age, and body mass index, and their interactions with treatment. Forward 
selection procedure based on the likelihood ratio test would be used to select the best subset of 
covariates. The estimated adjusted odds ratio for Arm A1 versus Arm B1 will be displayed 
along with the associated 95% confidence interval.
If there were issues related to the convergence of the logistic regression model, the above 
hypothesis will be tested using a 1-sided Wald test. 
Missing IGA 0/1 response values will be imputed with non-response regardless of the reason 
for the missing data (e.g., premature study discontinuation, missed visit, or administrative issue).
9.5.3
Safety variables 
All safety evaluations will be performed on the SAF. 
For the Main Study, the safety of secukinumab compared with nb-UVB will be evaluated. For 
the Mechanistic Sub-study, similar safety evaluations will be performed by treatment and study 
epoch.
Adverse events
Treatment emergent AEs (events started after the first dose of study treatment or events present 
prior to the first dose of study treatment but increased in severity based on preferred term) will 
be summarized. Only primary paths within MedDRA will be considered for AE reporting.
Adverse events will be summarized by presenting, for each treatment arm, the number and 
percentage of patients having any AE, having an AE in each primary system organ class and 
having each individual AE (preferred term). Summaries will also be presented for AEs by 
severity and for study treatment related AEs. If a patient reported more than one AE with the 
same preferred term, the AE with the greatest severity will be presented. If a patient reported 

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more than one AE within the same primary system organ class, the patient will be counted only 
once with the greatest severity at the system organ class level, where applicable. 
Separate summaries will be provided for psoriatic arthritis, death, SAEs, other significant AEs 
leading to discontinuation from the study, and AEs leading to study treatment discontinuation. 
In addition, exposure adjusted summaries including 95% confidence intervals for the 
occurrence rate of AEs in 100 patient years will be provided by treatment.
Laboratory data
The summary of laboratory evaluations will be presented for 2 groups of laboratory tests 
(hematology and clinical chemistry). Descriptive summary statistics for the changes from 
baseline to each study visit will be presented by test group, laboratory test, and treatment arm. 
Changes from baseline will only be summarized for patients with both baseline and 
post-baseline data. 
For each parameter, the maximum change from baseline within each study epoch will be 
analyzed analogously. 
In addition, shift tables will be provided for all parameters based on Common Toxicity Grade 
Criteria (CTC). The normal 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. These summaries will be presented by laboratory test 
and treatment arm. Shifts will be presented for most extreme post-baseline values.
Vital signs
Vital sign measurements will be analyzed using summary statistics for the change from baseline 
for each post-baseline visit and presented by vital sign and treatment arm. Changes from 
baseline will only be summarized for patients with both baseline and post-baseline values.
9.5.4
Resource utilization 
Not applicable. 
9.5.5
Pharmacokinetics 
Not applicable. 
9.5.6
DNA
Not applicable. 
 
 
 
9.5.8
PK/PD 
Not applicable. 

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9.6
Analysis of exploratory variables
This section describes the analyses for exploratory endpoints. 

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9.6.3
Investigator’s global assessment mod 2011 score and response over 
time
Treatment Arm A1 will be compared with Arm B1 based on IGA mod 2011 0/1 responses at 
Week 104 using a similar logistic regression model as described in Section 9.5.2. 
Further, IGA mod 2011 0/1 responses at each visit will be analyzed by means of a logistic 
regression model similar to the secondary analysis with treatment as a predictor variable and
the significant variables among baseline IGA mod 2011 score, age, and body mass index, and 
their interactions with treatment. Forward selection procedure based on the likelihood ratio test 
would be used to select the best subset of covariates. The estimated adjusted odds ratio will be 
displayed along with the associated 95% confidence interval. 
Missing IGA 0/1 response values will be imputed with non-response regardless of the reason 
for the missing data (e.g., premature study discontinuation, missed visit, or administrative issue). 
IGA mod 2011 score will be summarized descriptively, using number and percentages by visits.
For the treatment arms in the Mechanistic Sub-study, the above-stated analyses will also be 
repeated over the 52 weeks of the Treatment Epoch (i.e., until Week 52 for Arms A1b, B1b, 
and C1, and until Week 104 for Arms A2 and C2).

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9.7
Interim analyses 
A primary endpoint analysis is planned after all patients complete the visit at which the primary 
endpoint is assessed (Week 52). A key secondary endpoint analysis is planned if all patients 
have reached Week 104.
An interim analysis for the Mechanistic Sub-Study will be performed at Week 16. As this 
analysis at Week 16 will not involve any formal hypothesis testing, no adjustment for 
multiplicity will be required. 
Additional interim analyses might be conducted as regarded appropriate (e.g., to provide 
additional data for regulatory or publication purposes).
9.8
Sample size calculation
The sample size calculation is performed for the primary endpoint (proportion of PASI 90 
responders at Week 52) and the key secondary endpoint (proportion of all randomized patients 

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who achieve PASI 90 response at Week 104, see Section 9.9). The selected total sample size is 
160 patients, such that 80 patients are randomized in each arm.
The sample size calculation based on the proportion of PASI 90 responders at Week 104 was
performed using PASS 11.
The power calculations for the primary endpoint are based on the asymptotic Wald test to 
compare secukinumab 300 mg s.c. versus nb-UVB using the hierarchical method to adjust for 
multiplicity. Based on data (unpublished) and experiences from recent studies, it is assumed 
that the proportion of PASI 90 responders at Week 52 will be around 70% after early treatment 
with secukinumab 300 mg s.c. (Arm A1) and around 35% after 1 or 2 cycles of nb-UVB 
treatment (Arm B1). With assumed approximate 0% dropout rate in Arm A1, and 20% in Arm 
B1 until Week 52 due to lack of efficacy or AEs (considered non-responders), the response rate 
would change to 70% and 28%, respectively. Assuming an absolute difference of 42% in the 
proportion of patients achieving PASI 90 at Week 52, the sample size of 80 patients in each 
arm would provide 99.9% power at the 1-sided significance level of 0.025 using asymptotic 
Wald test for equality of proportions (using PASS 11).
For the Mechanistic Sub-study, additional 12 randomized patients will be treated for 104 weeks 
with secukinumab 300 mg s.c. (Arm A2), along with 12 patients each from Arm A1b and 
Arm B1b, and will serve as active groups. Further, 12 patients identified with chronic plaque 
psoriasis will be allocated to secukinumab 300 mg s.c. for 52 weeks (Arm C1) and another 
12 patients with chronic plaque psoriasis will be treated during 104 weeks with secukinumab 
300 mg s.c. (Arm C2), both serving as control groups for the Mechanistic Sub-study. As the 
Mechanistic Sub-study will not involve any formal testing of hypothesis, the sample size for it 
is obtained in an illustrative manner.
9.9
Power for analysis of secondary variables
Sample size calculation is based on the assumptions for the key secondary efficacy endpoint 
with adequate power.
The absolute difference in the proportion of PASI 90 responders at Week 104 is considered to 
be 18% (23% of responders in Arm A1, and 5% in Arm B1). With assumed approximate 7% 
dropout rate in Arm A1 and 16% in Arm B1 (considered non-responders) before Week 104 due 
to lack of efficacy, AEs or relapse, the response rates would decrease to 21% and 4%, 
respectively. Using Fisher’s exact test at 1-sided significance level of 0.025 with a power of 
around 89%, the sample size required is 80 patients in each treatment arm. 
This sample size of 80 patients per treatment arm would provide a power of around 99.9% for 
the secondary efficacy endpoint, using the asymptotic Wald test at 1-sided significance level of 
0.025, and assuming an absolute difference of 35% in the proportion of IGA 0/1 responders at 
Week 52 (considering 80% responders in Arm A1 and 45% in Arm B1). With assumed 
approximate 0% dropout rate in Arm A1 and 20% in Arm B1 before Week 52 (considered non-
responders), the response rates would change to 80% and 36%, respectively. 

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10
Ethical considerations 
10.1
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations (including European Directive 2001/20/EC, US CFR 21, and Japanese 
Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in the 
Declaration of Helsinki.
10.2
Informed consent procedures 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if incapable of doing 
so, after such consent has been provided by a legally acceptable representative(s) of the patient. 
In cases where the patient’s representative gives consent, the patient must be informed about 
the study to the extent possible given his/her understanding. If the patient is capable of doing 
so, he/she must indicate assent by personally signing and dating the written informed consent 
document or a separate assent form. Informed consent must be obtained before conducting any 
study-specific procedures (i.e., all of the procedures described in the protocol). The process of 
obtaining informed consent must be documented in the patient 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.
10.3
Responsibilities of the investigator and IRB/IEC 
Before initiating a study, the investigator/institution must obtain approval/favorable opinion 
from the IRB/IEC for the study protocol, written informed consent form, consent form updates, 
patient recruitment procedures (e.g., advertisements) and any other written information to be 
provided to patients. Prior to study start, the investigator is required to sign a protocol signature 
page confirming his/her agreement to conduct the study in accordance with these documents 
and all of the instructions and procedures found in this protocol and to give access to all relevant 
data and records to Novartis monitors, auditors, Novartis Quality Assurance representatives, 
designated agents of Novartis, IRBs/IECs, and regulatory authorities as required. If an 
inspection of the clinical site is requested by a regulatory authority, the investigator must inform 
Novartis immediately that this request has been made.
10.4
Publication of study protocol and results 
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 study will be either submitted for publication 
and/or posted in a publicly accessible database of clinical study results.

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10.5
Quality control and quality assurance Novartis maintains a robust
Quality Management system that includes all activities involved in quality 
assurance and quality control, including the assignment of roles and 
responsibilities, the reporting of results, and the documentation of actions and 
escalation of issues identified during the review of quality metrics, incidents, audits 
and inspections.
Audits of investigator sites, vendors, and Novartis systems are performed by Novartis Pharma 
Auditing and Compliance Quality Assurance, a group independent from those involved in 
conducting, monitoring or performing quality control of the clinical trial. The clinical audit 
process uses a knowledge/risk based approach. 
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal standard operating procedures, and are performed according to written 
Novartis processes. 
11
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances is an 
investigator allowed to collect additional data or conduct any additional procedures for any 
research related purpose involving any investigational drugs under the protocol.
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be implemented. 
11.1
Protocol amendments 
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 CFR 21, and Japanese Ministry of 
Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of 
Helsinki. 
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, where 
required, prior to implementation. Only amendments that are intended to eliminate an apparent 
immediate hazard to patients may be implemented immediately provided the health authorities 
are subsequently notified by protocol amendment and the reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 7 must be followed.

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References 
References are available upon request. 
Regulatory guidelines
CHMP/EWP/2454/02 (2004) Guideline on clinical investigation of medicinal products 
indicated for the treatment of psoriasis. London, 18 November.
EMA/762563/2014 (2015) Good practice guide on recording, coding, reporting and 
assessment of medication errors. Pharmacovigilance Risk Assessment Committee (PRAC). 
Literature articles
Cheuk S, Wikén M, Blomqvist L, et al (2014) Epidermal Th22 and Tc17 cells form a 
localized disease memory in clinically healed psoriasis. J Immunol; 192(7):3111-20.
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(6):1206-52.
Clark RA (2015) Resident memory T cells in human health and disease. Sci Transl Med; 
7(269):269rv1. 
Doherty SD, Van Voohes A, Lebwohl MG et al (2008) National Psoriasis Foundation 
consensus statement on screening for latent tuberculosis infection in patients with psoriasis 
treated with systemic and biologic agents. J Am Acad Dermatol; 59(2): 209-17. 
 
Fredriksson T, Pettersson U (1978) Severe psoriasis--oral therapy with a new retinoid. 
Dermatologica; 157(4):238-44. 
Gottlieb AB, Griffiths CE, Ho VC (2005) Oral pimecrolimus in the treatment of moderate to 
severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, dose-finding 
trial. Br J Dermatol; 152(6):1219-27.
Langley RG, Feldman SR, Nyirady J, van de Kerkhof P et al (2015) The 5-point 
Investigator’s Global Assessment (IGA) Scale: A modified tool for evaluating plaque 
psoriasis severity in clinical trials. J Dermatolog Treat; 26 (1):23-31. 
Manuel O, Kumar D (2008) QuantiFERON-TB Gold assay for the diagnosis of latent 
tuberculosis infection. Expert Rev Mol Diagn; 8(3):247-56. 
Maza A, Richard MA, Aubin F et al (2012) Significant delay in the introduction of systemic 
treatment of moderate to severe psoriasis: a prospective multicentre observational study in 
outpatients from hospital dermatology departments in France. Br J Dermatol; 167(3):643-8.
Mehta D, Lim HW (2016) Ultraviolet B phototherapy for psoriasis: review of practical 
guidelines. Am J Clin Dermatol; 17:125–33. 
Newcombe RG (1998) Two-sided confidence intervals for the single proportion: comparison 
of seven methods. Statistics in Medicine; 17:857-872. 
Quinn MA, Cox S (2005) The evidence for early intervention. Rheum Dis Clin North Am; 
31(4):575-89.

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Quinn MA (2012) Rheumatoid arthritis classification criteria: moving with the times. J 
Rheumatol; 39(11):2062-3. 
Reilly MC, Zbrozek AS, Dukes EM (1993) The validity and reproducibility of a work 
productivity and activity impairment instrument. Pharmacoeconomics; 4(5):353-65. 
Rubin DB (1987) Multiple imputation for non-response in surveys. New York: John 
Wiley & Sons. 
Ryu HH, Choe YS, Jo S, et al (2014) Remission period in psoriasis after multiple cycles of 
narrowband ultraviolet B phototherapy. J Dermatol; 41(7): 622-7.
van der Kooij SM, le Cessie S, Goekoop-Ruiterman YP et al (2009) Clinical and radiological 
efficacy of initial vs delayed treatment with infliximab plus methotrexate in patients with 
early rheumatoid arthritis. Ann Rheum Dis; 68(7):1153-8. 

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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.
Liver function and related variables 
Total bilirubin:
> 2 x ULN
Alkaline phosphatase:
> 2.5 x ULN
Renal function and electrolyte variables
Creatinine (serum):
> 1.5 x ULN
Potassium: 
> 6 mmol/L or < 3 mmol/L
Sodium: 
> 160 mmol/L or < 115 mmol/L
Urinalysis variable 
Protein urine dipstick: 
2+ (100 mg/dL)
Hematology variables 
Hemoglobin:
≥ 20 g/L decrease from baseline
Platelet count:
< lower limit of normal (LLN)
White blood cell count:
< 0.8 x LLN
Neutrophils:
< 0.9 x LLN
Eosinophils:
> 1.1 x ULN
Lymphocytes:
> 1.1 x ULN

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14.5
Skin type classification scale