A Randomized, Multicenter 28 Week Study to Compare the Efficacy and Safety of Combining Cosentyx (Secukinumab) (4-weekly, 300 mg s.c.) With a Lifestyle Intervention to Cosentyx Therapy Alone in Adult Patients With Moderate to Severe Plaque-type Psoriasis and Concomitant Metabolic Syndrome, Followed by a 28 Week Extension Period
Phase: PHASE4
Conditions: Psoriasis, Metabolic Syndrome
Sponsor: Novartis Pharmaceuticals



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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 5 
List of abbreviations ............................................................................................................ 6 
Glossary of terms ................................................................................................................. 8 
Protocol summary .............................................................................................................. 10 
Amendment 1 ........................................................................................................................... 14 
Amendment 2 ........................................................................................................................... 15 
1 
Introduction ....................................................................................................................... 17 
1.1 
Background ............................................................................................................ 17 
1.2 
Purpose .................................................................................................................. 19 
2 
Study objectives and endpoints ......................................................................................... 20 
3 
Investigational plan ........................................................................................................... 22 
3.1 
Study design........................................................................................................... 22 
3.2 
Rationale for study design ..................................................................................... 23 
3.3 
Rationale for dose/regimen, route of administration and duration of treatment .... 24 
3.4 
Rationale for choice of comparator ....................................................................... 25 
3.5 
Purpose and timing of analyses ............................................................................. 25 
3.6 
Risks and benefits .................................................................................................. 25 
4 
Population .......................................................................................................................... 27 
4.1 
Inclusion criteria .................................................................................................... 27 
4.2 
Exclusion criteria ................................................................................................... 29 
5 
Treatment ........................................................................................................................... 31 
5.1 
Study treatment ...................................................................................................... 31 
5.1.1 
Investigational and control drugs .......................................................... 31 
5.1.2 
Additional treatment .............................................................................. 31 
5.2 
Treatment arms ...................................................................................................... 32 
5.3 
Treatment assignment and randomization ............................................................. 33 
5.4 
Treatment blinding ................................................................................................. 33 
5.5 
Treating the patient ................................................................................................ 33 
5.5.1 
Patient numbering ................................................................................. 33 
5.5.2 
Dispensing the study drug ..................................................................... 33 
5.5.3 
Handling of study and additional treatment .......................................... 34 
5.5.4 
Instructions for prescribing and taking study treatment/ for 
participating in the lifestyle intervention program ................................ 34 

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5.5.5 
Permitted dose adjustments and interruptions of study treatment/ 
interruptions of lifestyle intervention .................................................... 35 
5.5.6 
Rescue medication ................................................................................ 35 
5.5.7 
Concomitant medication ....................................................................... 35 
5.5.8 
Prohibited medication ........................................................................... 36 
5.5.9 
Emergency breaking of assigned treatment code .................................. 38 
5.6 
Study completion and discontinuation ................................................................... 38 
5.6.1 
Study completion and post-study treatment .......................................... 38 
5.6.2 
Discontinuation of study treatment ....................................................... 38 
5.6.3 
Withdrawal of informed consent ........................................................... 39 
5.6.4 
Loss to follow-up .................................................................................. 40 
5.6.5 
Early study termination by the sponsor ................................................. 40 
6 
Visit schedule and assessments ......................................................................................... 40 
6.1 
Information to be collected on screening failures .................................................. 43 
6.2 
Patient demographics/other baseline characteristics ............................................. 43 
6.2.1 
Demographics ....................................................................................... 43 
6.2.2 
Psoriasis medical history/previous psoriasis therapies ......................... 43 
6.2.3 
Smoking history .................................................................................... 43 
6.2.4 
Relevant medical history/current medical conditions ........................... 43 
6.2.5 
Prior and concomitant medications ....................................................... 44 
6.2.6 
Cardiovascular and metabolic medical history ..................................... 44 
6.2.7 
Determination of the tuberculosis status ............................................... 44 
6.3 
Treatment exposure and compliance ..................................................................... 47 
6.4 
Efficacy .................................................................................................................. 47 
6.4.1 
PASI/ BSA ............................................................................................ 47 
6.4.2 
Biomarkers of glucose and lipid metabolism ........................................ 50 
6.4.3 
Biomarkers of systemic inflammation .................................................. 50 
6.4.4 
Weight and height ................................................................................. 50 
6.4.5 
Waist and hip circumference ................................................................. 50 
 
 50 
6.4.7 
Appropriateness of efficacy assessments .............................................. 51 
6.5 
Safety ..................................................................................................................... 51 
6.5.1 
Physical examination ............................................................................ 51 
 
 52 
6.5.3 
Height and weight ................................................................................. 52 
 
 52 

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6.5.5 
Electrocardiogram (ECG) ..................................................................... 53 
6.5.6 
Pregnancy and assessments of fertility ................................................. 53 
6.5.7 
Appropriateness of safety measurements .............................................. 53 
6.6 
Other assessments .................................................................................................. 53 
6.6.1 
Clinical Outcome Assessments (COAs) ............................................... 53 
6.6.2 
Resource utilization ............................................................................... 55 
6.6.3 
Pharmacokinetics .................................................................................. 55 
6.6.4 
DNA sampling ...................................................................................... 55 
6.6.5 
Biomarker substudy .............................................................................. 55 
7 
Safety monitoring .............................................................................................................. 55 
7.1 
Adverse events ....................................................................................................... 55 
7.2 
Serious adverse events ........................................................................................... 57 
7.2.1 
Definition of SAE ................................................................................. 57 
7.2.2 
SAE reporting........................................................................................ 58 
7.3 
Liver safety monitoring ......................................................................................... 59 
7.4 
Reporting of study treatment errors including misuse/abuse ................................ 60 
7.5 
Pregnancy reporting ............................................................................................... 61 
8 
Data review and database management ............................................................................. 61 
8.1 
Site monitoring ...................................................................................................... 61 
8.2 
Data collection ....................................................................................................... 62 
8.3 
Database management and quality control ............................................................ 62 
8.4 
Data Monitoring Committee .................................................................................. 63 
8.5 
Adjudication Committee ........................................................................................ 63 
9 
Data analysis ...................................................................................................................... 63 
9.1 
Analysis sets .......................................................................................................... 63 
9.2 
Patient demographics and other baseline characteristics ....................................... 63 
9.3 
Treatments ............................................................................................................. 63 
9.3.1 
Study treatment ..................................................................................... 63 
9.3.2 
Prior and concomitant treatment ........................................................... 64 
9.4 
Analysis of the primary variable(s) ....................................................................... 64 
9.4.1 
Primary Variable(s) ............................................................................... 64 
9.4.2 
Statistical model, hypothesis, and method of analysis .......................... 64 
9.4.3 
Handling of missing values/censoring/discontinuations ....................... 65 
9.4.4 
Sensitivity analyses ............................................................................... 65 
9.5 
Analysis of secondary variables ............................................................................ 65 
9.5.1 
Efficacy variables .................................................................................. 65 

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9.5.2 
Safety variables ..................................................................................... 65 
9.5.3 
Resource utilization ............................................................................... 66 
9.5.4 
Pharmacokinetics .................................................................................. 66 
9.5.5 
DNA ...................................................................................................... 66 
9.5.6 
Biomarkers ............................................................................................ 66 
9.5.7 
PK/PD ................................................................................................... 66 
 
 66 
9.7 
Time points of analysis .......................................................................................... 67 
9.8 
Sample size calculation .......................................................................................... 67 
10 Ethical considerations ........................................................................................................ 68 
10.1 
Regulatory and ethical compliance ........................................................................ 68 
10.2 
Informed consent procedures ................................................................................. 68 
10.3 
Responsibilities of the investigator and IRB/IEC .................................................. 68 
10.4 
Publication of study protocol and results............................................................... 69 
10.5 
Quality Control and Quality Assurance ................................................................. 69 
11 Protocol adherence ............................................................................................................ 69 
11.1 
Protocol amendments ............................................................................................. 69 
12 References ......................................................................................................................... 70 
13 Appendix 1: Clinically notable laboratory values and vital signs ..................................... 73 
14 Appendix 2: Liver event definitions and follow-up requirements .................................... 74 
 
List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 20 
Table 5-1 
Prohibited treatments by period (for any indication) ............................ 36 
Table 6-1 
Assessment schedule ............................................................................. 42 
Table 7-1  
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 61 
Table 14-1  
Liver Event Definitions ......................................................................... 70 
Table 14-2  
Liver Event Follow Up Requirements .................................................. 71 
 
List of figures 
Figure 3-1 
Study design .......................................................................................... 22 
Figure 6-1 
Tuberculosis screening flowchart ......................................................... 46 
 

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List of abbreviations 
 
AE 
Adverse Event 
AHA 
American Heart Association 
ALT 
Alanine Aminotransferase 
AST 
Aspartate Aminotransferase 
b.i.d. 
twice a day 
BMI 
Body Mass Index 
CFR 
US Code of Federal Regulations  
CD 
Cluster of differentiation 
CDS 
Core Data Sheet (for marketed drugs)  
CRF 
Case Report/Record Form (paper or electronic) 
CPO 
Country Pharma Organization 
CRO 
Contract Research Organization 
C-SSRS  
Columbia Suicide Severity Rating Scale 
CTC 
Common Terminology Criteria 
CTRD  
Clinical Trial Results Database  
CTX 
Carboxy-terminal collagen crosslinks 
DS&E 
Drug Safety & Epidemiology 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
eSource 
Electronic Source 
GCP 
Good Clinical Practice 
HbA1c 
Hemoglobin A1c 
HDL 
high-density lipoprotein 
HOMA-IR 
Homeostatic model assessment for insulin resistance 
hsCRP 
high-sensitivity C-reactive Protein 
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IDF 
International Diabetes Federation 
IEC 
Independent Ethics Committee 
IL 
Interleukin 
IL-1Ra 
IL-1 receptor antagonist 
IL-18bp 
IL-18 binding protein 
i.v. 
intravenous 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
LDL 
low-density lipoprotein 
LFT 
Liver function test  
M30 assay 
Keratin 18 fragments that contain the M30 epitope 
MedDRA 
NAFLD 
Medical dictionary for regulatory activities 
Non-alcoholic fatty liver disease  
NHLBI 
National Heart, Lung and Blood Institute 

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NT-proBNP 
N-terminal Brain Natriuretic Peptide 
PC 
Personal Computer 
P1NP 
Procollagen type 1 amino-terminal propeptide 
OC/RDC 
Oracle Clinical/Remote Data Capture  
o.d. 
once a day 
OPG 
Osteoprotegerin 
p.o. 
oral(ly) 
RANKL 
Receptor activator of nuclear factor kappa B ligand 
sThy-1 
soluble Thy-1 
SAE 
Serious Adverse Event 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TD 
Study Treatment Discontinuation 
TNF 
Tumor necrosis factor 
WHO 
World Health Organization  
WoC 
Withdrawal of Consent 

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Glossary of terms 
 
Cohort  
A specific group of patients/subjects fulfilling certain criteria 
Control drug 
Drugs(s) used as a comparator to reduce assessment bias, preserve 
blinding of investigational drug, assess internal study validity, and/or 
evaluate comparative effects of the investigational drug 
Dosage 
Dose of the study treatment given to the patient in a time unit (e.g. 100 
mg once a day, 75 mg twice a day) 
Electronic Data Capture 
(EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical 
study data using data collection systems, such as Web-based 
applications, interactive voice response systems and clinical laboratory 
interfaces. 
EDC includes the use of Electronic Case Report Forms (eCRFs) which 
are used to capture data transcribed from paper source forms used at 
the point of care. 
eSource 
eSource Direct Data Entry (DDE) refers to the capture of clinical study 
data electronically, at the point of care. eSource Platform/Applications 
reduce the use of paper capture source data during clinical visits.  
eSource combines source documents and case report forms (eCRFs) 
into one application, allowing for the real time collection of clinical trial 
information to sponsors and other oversight authorities, as 
appropriate. 
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 portion of the study which serves a specific purpose. Typical epochs 
are: screening/recruitment, wash-out, treatment, and follow-up 
Investigational drug 
The drug whose properties are being tested in the study; this definition 
is consistent with US CFR 21 Section 312.3 and is synonymous with 
“investigational new drug” or “investigational medicinal product.” 
Medication pack number 
A unique identifier on the label of each investigational drug package 
Part  
A single component of a study which contains different objectives or 
populations within that single study. Common parts within a study are: 
a single dose part and a multiple dose part, or a part in 
patients/subjects with established disease and in those with newly-
diagnosed disease. 
Patient/subject ID  
A unique number assigned to each patient upon signing the informed 
consent  
Randomization number 
A unique identifier assigned to each randomized patient, 
corresponding to a specific treatment arm assignment 
Source Data/Document 
Source data refers to the initial record, document, or primary location 
from where data comes. The data source can be a database, a 
dataset, a spreadsheet or even hard-coded data, such as paper or 
eSource. 
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 (TD) 
When the patient permanently stops taking study treatment prior to the 
defined study treatment completion date  

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Variable 
A measured value or assessed response that is determined in specific 
assessments and used in data analysis to evaluate the drug being 
tested in the study 
Withdrawal of consent 
(WoC) 
Withdrawal of consent from the study is defined as when a patient 
does not want to participate in the study any longer, and does not want 
any further visits or assessments, and does not want any further study 
related contact, and does not allow analysis of already obtained 
biologic material 
 

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Protocol summary 
 
Protocol number 
CAIN457ADE08 
Full Title 
A randomized, multicenter 28 week study to compare the efficacy 
and safety of combining Cosentyx (Secukinumab) (4-weekly, 300 mg 
s.c.) with a lifestyle intervention to Cosentyx therapy alone in adult 
patients with moderate to severe plaque-type psoriasis and 
concomitant metabolic syndrome, followed by a 28 week extension 
period 
Brief title 
 
Comparison of Secukinumab 300 mg combined with a lifestyle 
intervention to Secukinumab alone for the treatment of moderate to 
severe psoriasis patients with concomitant metabolic syndrome  
Sponsor and Clinical 
Phase 
Novartis, Phase IV  
Investigation type 
Drug in combination with behavioral change  
Study type 
Interventional  
Purpose and rationale Around 40% of moderate to severe psoriasis patients are affected by 
concomitant metabolic syndrome, making it one of the clinically 
most relevant comorbidities (Love et al., 2011). Psoriasis as well as 
the metabolic syndrome are both characterized by a state of low-
grade systemic inflammation (e.g. in the skin, joints, adipose tissue, 
liver or vascular endothelium). This shared pathophysiology makes 
systemic inflammation an attractive target for the treatment of both 
diseases. Secukinumab as well as lifestyle intervention are able to 
reduce systemic inflammation.  
This trial is designed to answer the question whether the 
combination of Secukinumab with lifestyle intervention can 
primarily improve skin symptoms and secondly cardiometabolic 
status more than Secukinumab alone in psoriasis patients with 
concomitant metabolic syndrome by targeting the shared 
pathophysiology behind both diseases, which is systemic 
inflammation. 
Primary Objective(s)  
The primary objective of the study is to demonstrate that the 
combination of Secukinumab with lifestyle intervention results in 
higher psoriasis treatment efficacy compared to Secukinumab alone 
in psoriasis patients with concomitant metabolic syndrome. 
Secondary Objectives 
Objective 1: To explore treatment efficacy of Secukinumab 
combined with lifestyle intervention in comparison to Secukinumab 
alone. 

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Objective 2: To evaluate the effect of Secukinumab combined with 
lifestyle intervention in comparison to Secukinumab alone on 
systemic inflammation. 
Objective 3: To evaluate the effect of Secukinumab combined with 
lifestyle intervention in comparison to Secukinumab alone on 
glucose metabolism. 
Objective 4: To evaluate the effect of Secukinumab combined with 
lifestyle intervention in comparison to Secukinumab alone on lipid 
metabolism. 
Objective 5: To evaluate the effect of Secukinumab combined with 
lifestyle intervention in comparison to Secukinumab alone on body 
weight. 
Objective 6: To evaluate the effect of Secukinumab combined with 
lifestyle intervention in comparison to Secukinumab alone on 
systolic and diastolic blood pressure. 
Objective 7: To evaluate the effect of Secukinumab combined with 
lifestyle intervention in comparison to Secukinumab alone on 
health-related quality of life and mental well-being. 
Study design 
This study is a randomized, multi-center, open label, parallel group, 
active comparator-controlled study with a duration of 28 weeks and 
a 28 week extension phase.  
Population 
This study is planned to enroll approximately 760 patients in 
Germany with moderate to severe plaque-type psoriasis and 
concomitant metabolic syndrome, aged ≥18 years. 
Key Inclusion criteria 
Key inclusion criteria are: 
1. Written informed consent must be obtained before any 
assessment is performed.  
2. Men or women of at least 18 years of age at the time of 
screening. 
3. Patients with moderate to severe plaque-type psoriasis who 
are candidates for systemic therapy. 
4. Fulfillment of metabolic syndrome diagnosis criteria (see 
section 4.1 for details) at screening visit. 
5. Willingness and motivation to actively participate in the 
lifestyle intervention, which means patients need to be 
willing to increase physical activity and to change dietary 
habits in order to achieve weight loss. 
Key Exclusion criteria 
Key exclusion criteria are: 
1. Forms of psoriasis other than chronic plaque-type (e.g., 
pustular, erythrodermic and guttate psoriasis) at screening. 

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2. Previous exposure to Secukinumab or any other biologic 
drug directly targeting IL17A or the IL17A receptor (e.g. 
Brodalumab, Ixekizumab). 
3. History of hypersensitivity to Secukinumab, trehalose-
dihydrate, 
L-histidine, 
L-histidinhydrochloride-
monohydrate, L-methionine, polysorbate 80, water for 
injection, or to substances of similar chemical classes. 
4. Diagnosis of type 1 diabetes. 
5. Significant, progressive or uncontrolled medical problems at 
baseline which according to the opinion of the Investigator 
render the subject unsuitable for the trial - also in regard to 
participation in the lifestyle intervention - or put the subject 
at increased risk when participating in the trial. 
Study treatment 
• Secukinumab 300 mg s.c. 
• Secukinumab 300 mg s.c. in combination with a lifestyle 
intervention 
Efficacy assessments 
Key efficacy assessments are: 
• PASI score 
• Body weight 
• Waist and hip circumference 
• Systolic and diastolic blood pressure 
• Biomarkers of glucose and lipid metabolism as well as 
systemic inflammation: HbA1c, fructosamine, fasting plasma 
glucose, total cholesterol, LDL, HDL, triglycerides, hsCRP 
Key safety 
assessments 
Key safety assessments are: 
• Adverse event monitoring 
•  Physical examination 
•  Monitoring of laboratory markers in blood and urine  
Other assessments 
Other assessments include:  
• Patient reported outcomes: DLQI, WHO-5, self-assessed 
itch, pain and scaling 
Data analysis 
The null hypothesis to be rejected is that the odds of response at 
Week 28 are equal in both treatment groups. The corresponding 
alternative hypothesis is that the odds of response at Week 28 are 
higher under Secukinumab combined with lifestyle intervention 
compared to Secukinumab alone. The primary analysis will be 

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performed comparing treatments with respect to the primary 
efficacy variable in a logistic regression model with the factors 
treatment, center and covariate baseline PASI. The odds ratio and 
its 95% confidence interval (CI) and p-value will be given. The null 
hypothesis of equal odds will be rejected if the 2-sided p-value from 
the logistic regression model for the factor “treatment” is < 0.05; 
however, superiority of Secukinumab combined with lifestyle 
intervention will be claimed only if the direction is correct, i.e. if the 
odds of response are larger under Secukinumab combined with 
lifestyle intervention. 
Key words 
plaque-type psoriasis, metabolic syndrome, Secukinumab, lifestyle 
intervention, systemic inflammation, metabolism 

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Amendment 1 
The original protocol is amended in order to align details of the protocol with the patient 
documents of the lifestyle intervention program (“Lesebuch”) and in order to complement the 
protocol with a few details that make the study procedure more clear: 
 
• Section 5.5.3.2: Additional explanation about the time point (visit 2) when patients in 
arm B receive the materials which are part of the lifestyle intervention   
• Section 6.5.4.1: Two laboratory markers are additionally captured at visit 1. 
• Section 6: Additional explanatory footnote for table 6-1. 
• Section 6.4.5: Waist circumference measurement method is adapted in order to align it 
with the patient documents of the lifestyle intervention program (“Lesebuch”). 
 
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red font for insertions. 
 
All protocol changes which are part of this amendment are non-substantial. 

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Amendment 2 
The protocol is being amended in order to incorporate a biomarker sub-study. Moreover, 
regulations of study treatment discontinuations are being improved, minor inconsistencies are 
being corrected and clarifications are being added. 
 
• The interaction of psoriasis and its major comorbidity, metabolic syndrome, is well 
established on an epidemiologic level, showing that more than 40% of psoriasis 
patients are affected by concomitant metabolic syndrome (Love et al., 2011). On the 
other hand, the understanding of the detailed molecular mechanisms underlying this 
interaction is still poor. Low-grade systemic inflammatory processes are thought to be 
a “common root” and driving force in the pathophysiology of both diseases. 
Furthermore, other diseases may also be associated with psoriasis and concomitant 
metabolic syndrome, including osteoporosis and non-alcoholic fatty liver disease. The 
purpose of this biomarker sub-study is to investigate markers that are implicated in the 
molecular mechanism of these diseases in subjects with psoriasis and metabolic 
syndrome in order to better understand their individual contributions as well as their 
interplay before and during treatment with Secukinumab (300 mg, 4-weekly s.c.) 
combined with lifestyle intervention in comparison to Secukinumab alone. The 
analyzed biomarkers will include but will not be limited to those linked to lipid, 
glucose, muscle and bone metabolism, liver fibrosis and steatosis, heart failure, as 
well as to inflammatory processes. Due to logistic challenges, not all study sites will 
be able to participate in the sub-study. It is planned to conduct the sub-study in a 
subgroup of 100 patients to be recruited in participating sites; 50 treated with 
Secukinumab and lifestyle intervention and 50 treated with Secukinumab alone. At 
baseline (week 0), week 16 and week 28 the following markers will be assessed: Free 
fatty acid serum profile, soluble Thy-1 (sThy-1), adiponectin, leptin, insulin, 
homeostatic model assessment for insulin resistance (HOMA-IR), proinsulin, 
interleukin (IL-) 6, tumor necrosis factor (TNF-) alpha, keratin 18 fragments that 
contain the M30 epitope (M30 assay),  IL-1 beta, IL-1 receptor antagonist (IL-1Ra), 
IL-18, IL-18 binding protein (IL-18bp), procollagen type 1 amino-terminal propeptide 
(P1NP), carboxy-terminal collagen crosslinks (CTX), receptor activator of nuclear 
factor kappa B ligand (RANKL), osteoprotegerin (OPG), sclerostin, N-terminal brain 
natriuretic peptide (NT-proBNP), cluster of differentiation (CD) 154, and a 30-panel 
multiplex inflammatory cytokine and chemokines panel. The additional risks of 
participating in the biomarker sub-study are those of blood sampling. Blood sampling 
will occur at time points where standard blood sampling is scheduled as well, and will 
not require additional venipuncture. Participation in the sub-study does not 
negatively affect the overall risk-benefit ratio for participation in the study. 
Patients eligible for inclusion in the biomarker sub-study will be recruited at study 
sites participating in the biomarker sub-study. Written informed consent for the 
biomarker sub-study must be obtained before any assessment for the biomarker sub-
study is performed. The markers will be assessed centrally. Clinically significant 
abnormal laboratory values will also be assessed by the investigator for adverse event 
reporting for the following parameters of the biomarker sub-study: Adiponectin, 

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leptin, insulin, HOMA-IR, proinsulin, IL-6, TNF-alpha, M30 assay, NT-proBNP. 
Endpoints of the biomarker sub-study will be analyzed using an MMRM-model as 
described in section 9.5.1. Descriptions of the biomarker sub-study have been added to 
the sections 2, 3.1, 3.6, 4.1, 6, 6.6.5, 7.1, 9.5.6, and 9.6. 
• Section 5.6.2 and table 5-1: After study treatment discontinuation (i.e. discontinuation 
of secukinumab, lifestyle intervention or both) the patient will now continue to attend 
regular study visits as per visit schedule and all assessments will be performed as 
planned. If one study treatment is discontinued (i.e. secukinumab or lifestyle 
intervention) this should not lead to discontinuation of the other, unless there is a reason 
for discontinuation of the other. If a study treatment is discontinued, adequate 
replacement for this treatment may be sought outside of the study despite continued 
study participation. 
• Table 6-1: Clarification that physical examination and drug accounting will only be 
performed at unscheduled visits, if necessary as determined by the treating physician. 
• Section 6.2.2: Clarification that topical therapies are only collected for the last 24 month 
prior to signing the informed consent. 
• Section 6.5.4.3.: Clarification that urine microscopy assessment, if needed, will be 
performed locally and correction of parameters assessed with the dipstick measurement. 
• Section 9.5.1: Clarification that PASI assessments will also be performed at weeks 1, 2 
and 3 and addition of missing secondary endpoints. 
• Section 9.5.2.2: Change of wording from serum chemistry to clinical chemistry to align 
with the rest of the protocol. 
• The list of abbreviations has been updated. 
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red font for insertions. 
 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities (HA). The changes 
described in this amended protocol require IRB/IEC and HA approval prior to implementation. 

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1 
Introduction 
1.1 
Background  
 
Psoriasis is a chronic relapsing disease of the skin characterized by variable clinical features. 
The lesions are classified as erythemato-squamous, which indicates that both the vasculature 
(erythema) and the epidermis (increased scale formation) are involved (Christophers et al 
2003, Griffiths et al 2007). Plaque-type psoriasis (also called plaque or chronic plaque 
psoriasis) is the most frequent clinical presentation and therefore, also called psoriasis vulgaris. 
The erythematous plaques are well defined with sharp borders. In approximately one-third of 
patients, more than 10% of the body is covered, and this is termed moderate to severe psoriasis. 
Treatment of moderate to severe psoriasis is based on phototherapy, systemic treatment (e.g. 
Methotrexate, cyclosporine, acitretin) and biologics like tumor necrosis factor alpha (TNFα) - 
inhibitors, anti-IL 12/23-antibodies or anti-IL17-antibodies.  
Secukinumab (AIN457) is a recombinant high-affinity fully human monoclonal anti-human 
IL17A antibody of the immunoglobulin (Ig) G1/κ-class. Secukinumab binds to human IL17A 
and neutralizes the bioactivity of this cytokine. IL-17A is the central cytokine of a newly 
defined subset of inflammatory T cells, the Th17 cells which, in several animal models, are 
pivotal in multiple autoimmune and inflammatory processes. IL17A is mainly produced by 
memory effector CD4+ and CD8+ T lymphocytes and is being recognized as one of the 
principal pro-inflammatory cytokines in immune mediated inflammatory diseases like 
Psoriasis. Its neutralization targets the underlying pathophysiology of Psoriasis, and as a 
consequence is able to provide relief of psoriatic symptoms. Secukinumab has been shown to 
be superior to other biologics such as the TNF-α antagonist Etanercept (Langley et al 2014) 
and the IL-12/-23 antagonist Ustekinumab (Thaci et al., 2015) in clearing skin of subjects with 
moderate to severe psoriasis with a comparable safety profile. Secukinumab (Cosentyx®) was 
approved in 2014 in Japan, and 2015 in USA, EU, Switzerland, and other countries for the 
treatment of moderate to severe plaque psoriasis in adults with a recommended dose of 300 
mg administered as two subcutaneous injections of 150 mg. 
Psoriasis is today understood as a systemic disease causing a state of systemic low-grade 
inflammation affecting more tissues than just the skin (Reich, 2012; Ryan et al., 2015). 
Psoriasis is associated with a range of comorbidities, among which the metabolic syndrome 
plays a central role, affecting more than 40% of the psoriasis patient population (Love et al., 
2011). The metabolic syndrome is defined by a cluster of interconnected components which are 
insulin resistance, obesity, dyslipidemia and elevated blood pressure, resulting in elevated risk 
for development of type 2 diabetes, coronary heart disease or non-alcoholic fatty liver disease 
(NAFLD) (Alberti et al., 2009; Kassi et al., 2011). Insulin resistance can be regarded as a key 
factor, promoting the other components (Kassi et al., 2011). All individual components of the 
metabolic syndrome show elevated prevalence in psoriasis patients, with odds ratios around 2 
compared to a healthy control population (Augustin et al., 2010).  
Besides the above mentioned strong epidemiologic association between psoriasis and the 
metabolic syndrome, these two diseases show a clear pathophysiologic overlap in form of 
systemic low-grade inflammation, which appears to serve as a “common root” of both diseases 

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and potentially is the reason for their close association (Takahashi et al., 2012; Toussirot et al., 
2014): Metabolic syndrome and foremost its two key components insulin resistance and obesity, 
are today understood as a state of systemic low-grade inflammation, similar to the 
understanding of psoriasis as a systemic inflammatory disease. During the last two decades a 
still growing body of evidence has shown clear association between inflammation and 
cardiometabolic disorders. The central role of TNFα or IL-1ß in the development of insulin 
resistance, ß-cell failure, vascular inflammation and atherosclerosis are just a few examples, the 
emerging role of hsCRP as a predictive marker for cardiovascular events another one. Adipose 
tissue, liver tissue or the vascular endothelium are typical examples for sites of inflammation in 
obesity/ metabolic syndrome and low-grade systemic inflammation is considered to be the key 
link between obesity and its related comorbidities (Shoelson et al., 2009; Esser et al., 2014). 
Adipose tissue secreted hormones - so called adipokines - have systemic immunologic impact, 
including influence on psoriatic skin, some of pro-inflammatory (e.g. visfatin, resistin) others 
of anti-inflammatory character (adiponectin) (Gerdes et al., 2011).  Adipokine secretion is 
heavily dysregulated in psoriasis patients and their pathophysiologic role receives growing 
attention including their role as mediators of cardiometabolic comorbidities in psoriasis and 
obesity (Coimbra et al., 2016). 
Insulin resistance, a key criterion of the metabolic syndrome diagnosis, is also a key component 
of psoriasis pathophysiology, reflected in the so called “psoriatic march” concept, which 
describes the inflammation-driven expansion of insulin resistance throughout the vascular 
endothelium and psoriatic skin lesions in psoriasis patients (Boehncke et al., 2007; Boehncke 
et al., 2011).  
Considering the interconnected pathophysiology of both diseases it seems highly promissing to 
try shared approaches for the treatment of psoriasis and its major comorbidity, the metabolic 
syndrome, based on a deeper understanding of the common mechanism behind these diseases, 
which is systemic inflammation.  
Lifestyle intervention is the long-established gold standard for the treatment of obesity and 
metabolic syndrome. Several clinical studies have proven the ability of lifestyle interventions 
to induce weight loss and achieve cardiometabolic benefits, which are mainly improvement of 
glucose and lipid metabolism, as well as reductions in systolic and diastolic blood pressure 
(Yamaoka et al., 2012). Weight loss and the above mentioned cardiometabolic improvements 
are associated with preventive effects, such as cardiovascular risk reduction and lowering of the 
risk of progression from prediabetes to type 2 diabetes. These improvements would be of high 
benefit to the psoriasis patient population, considering their elevated cardiovascular risk profile 
(Reich, 2012). 
Even more important for the present study, lifestyle interventions (weight loss and increased 
physical activity) have shown positive effects in the treatment of psoriasis: Weight reductions 
are associated with improvements in Psoriasis Area and Severity Index (PASI) scores 
(Debbaneh et al., 2014) and pilot studies have shown improvements of response to conventional 
systemics or biologics when combined with lifestyle interventions (Gisondi et al., 2008; Al-
Mutairi et al., 2014). Weight reduction and increased physical activity are associated with 
suppression of systemic inflammation (Petelin et al., 2014). Furthermore a recent study by 
Coimbra et al. has shown that concomitant metabolic syndrome in psoriasis patients inhibits the 
suppressive effects of psoriasis therapy on systemic inflammation and IL17-signalling, thereby 

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reducing the length of remission (Coimbra et al., 2016). This indicates that tissue inflammation 
present in metabolic syndrome, especially adipose or liver tissue inflammation, can serve as a 
secondary source of systemic inflammation after successful control of skin inflammation by 
psoriasis therapy. This gives us another reason to target systemic inflammation caused by 
metabolic syndrome in addition to skin inflammation. Clinical studies have shown the 
reversibility of adipose and liver tissue inflammation present in obesity: Weight loss has been 
shown to reduce immune cell infiltration in adipose and liver tissue (Cancello et al., 2005; 
Schmitz et al., 2016). 
Blockade of IL-17A with Secukinumab is also known to control systemic inflammation, shown 
for example by hsCRP suppression under Secukinumab therapy (Novartis data on file).  
From a clinical perspective the appropriate treatment of cardiometabolic comorbidities in 
psoriasis patients by the use of a professional concomitant lifestyle modification is potentially 
of high relevance to treating dermatologists, as these comorbidities affect around 40% of the 
patient population, are often difficult to treat and are key determinants of patients´ 
cardiovascular risk profile. 
It is of further interest in this context that several current systemic treatment options for psoriasis 
have well-described negative side effects on psoriasis´ cardiometabolic status (Gisondi et al., 
2015).  Methotrexate for example should be prescribed with caution in the presence of obesity, 
diabetes, NAFLD and reduced kidney function because of increased risk of liver fibrosis and 
drug toxicity. Cyclosporine can induce or worsen arterial hypertension, increase insulin 
resistance and worsen dyslipidemia and hyperuricemia. Acitretin favors hypertriglyceridemia 
and hypercholesterinemia. In contrast to that, no negative metabolic side effects are known for 
Secukinumab.  
Taken together, further improvement of efficacy and positive cardiometabolic effects of 
Secukinumab in combination with lifestyle intervention would be an innovative approach 
enabling physicians and patients to achieve both treatment goals with one integrated treatment 
concept, well-controlled psoriasis and cardiovascular risk factor control. 
1.2 
Purpose  
This trial is designed to answer the question whether the combination of Secukinumab with 
lifestyle intervention can primarily improve skin symptoms and secondly cardiometabolic 
status more than Secukinumab alone in psoriasis patients with concomitant metabolic syndrome 
by dual targeting of the shared pathophysiology behind both diseases, which is systemic 
inflammation.   
 
 

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2 
Study objectives and endpoints 
Table 2-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary Objective(s) 
• To demonstrate that the combination of 
Secukinumab (300 mg, 4-weekly s.c.) 
with lifestyle intervention results in 
higher psoriasis treatment efficacy than 
Secukinumab alone in psoriasis patients 
with concomitant metabolic syndrome 
Endpoint(s) for primary objective(s)  
• Percentage of patients achieving 
PASI90 at week 28 in both 
randomized treatment arms, 
Secukinumab alone and Secukinumab 
combined with lifestyle intervention 
Secondary Objective(s) 
• To explore treatment efficacy of 
Secukinumab (300 mg, 4-weekly s.c.) 
combined with lifestyle intervention in 
comparison to Secukinumab alone 
• To evaluate the effect of Secukinumab 
(300 mg, 4-weekly s.c.) combined with 
lifestyle intervention in comparison to 
Secukinumab alone on systemic 
inflammation 
• To evaluate the effect of Secukinumab 
(300 mg, 4-weekly s.c.) combined with 
lifestyle intervention in comparison to 
Secukinumab alone on glucose 
metabolism 
• To evaluate the effect of Secukinumab 
(300 mg, 4-weekly s.c.) combined with 
lifestyle intervention in comparison to 
Secukinumab alone on lipid metabolism 
• To evaluate the effect of Secukinumab 
(300 mg, 4-weekly s.c.) combined with 
lifestyle intervention in comparison to 
Secukinumab alone on body weight and 
waist circumference 
• To evaluate the effect of Secukinumab 
(300 mg, 4-weekly s.c.) combined with 
lifestyle intervention in comparison to 
Secukinumab alone on systolic and 
diastolic blood pressure 
• To evaluate the effect of Secukinumab 
(300 mg, 4-weekly s.c.) combined with 
Endpoint(s) for secondary objective(s) 
• 
PASI75, 90 and 100 as well as absolute 
PASI scores in both treatment arms at 
week 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 
 
• 
hsCRP 
in 
both 
treatment 
arms 
throughout the duration of the core 
study 
 
 
• 
HbA1c, 
fructosamine 
and 
fasting 
plasma glucose in both treatment arms 
throughout the duration of the core 
study 
 
• 
Total cholesterol, LDL, HDL and 
triglycerides in both treatment arms 
throughout the duration of the core 
study 
 
• Waist circumference, body weight and 
BMI in both treatment arms throughout 
the duration of the core study 
 
• Systolic and diastolic blood pressure in 
both treatment arms throughout the 
duration of the core study 
 
 
• 
Absolute DLQI, relative change of 
DLQI, proportion of patients with 

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Objective(s) 
Endpoint(s) 
lifestyle intervention in comparison  to 
Secukinumab alone on health-related 
quality of life, itch, pain and scaling as 
well as mental well-being 
 
 
DLQI 0/1, absolute WHO-5, relative 
change in WHO-5, absolute self-
assessed itch, pain, scaling, relative 
change in self-assessed itch, pain, 
scaling 
in 
both 
treatment 
arms 
throughout the duration of the core 
study 
 
 
 
 

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This study is designed as a randomized, open-label, parallel-group, active comparator-
controlled trial with two treatment arms. The design is shown in Figure 3-1. 
Core study: After providing informed consent patients will be screened for eligibility for a 
period of 1-4 weeks prior to inclusion into the study. If eligible, patients will then be randomized 
to one of the two treatment arms, which are the following: 
• Arm A: Patients in arm A receive a regular induction followed by 4-weekly 
maintenance treatment with Secukinumab 300 mg s.c. until week 28, where they 
complete the core study. The last Secukinumab injection is performed at week 24. 
• Arm B: Patients in arm B receive a regular induction followed by 4-weekly maintenance 
treatment with Secukinumab 300 mg s.c. until week 28. The last Secukinumab injection 
is performed at week 24. In addition to Secukinumab treatment patients in arm B 
participate in a lifestyle intervention program. 
A biomarker sub-study will be conducted during the core study in a subgroup of 100 patients 
(50 from each treatment arm).  
The core study ends at week 28.  
Extension period: After 28 weeks the study continues with an extension period, during which 
lifestyle intervention is offered to all patients, irrespective of their prior treatment arm. This 
means that patients of arm B, who are willing to, can continue their previously started lifestyle 
intervention program and patients of arm A, who are willing to, can start the lifestyle 
intervention program at the beginning of the extension period. All patients, irrespective of 
their decision whether to start/ continue lifestyle intervention or not, have to participate 
in the extension period and visit their dermatologic study center for scheduled visits. The 
extension period ends at week 56, where all patients complete the study. There will be no study 
drug supply during the extension period. The treating physician can chose psoriasis therapy 
freely according to his discretion.  
3.2 
Rationale for study design  
This study design was chosen in order to be able to demonstrate that the combination of 
Secukinumab (300 mg, 4-weekly s.c.) with lifestyle intervention results in higher psoriasis 
treatment efficacy compared to Secukinumab alone in psoriasis patients with concomitant 
metabolic syndrome. Therefore a randomized study set up with two treatment arms was chosen, 
arm B, where patients receive Secukinumab treatment combined with lifestyle intervention and 
arm A as active comparator control group, where patients receive Secukinumab alone.  
The design enables assessment of the additional effects of concomitant lifestyle 
intervention on psoriasis treatment efficacy of Secukinumab as well as on metabolic status 
of the patients. 
The open-label design is a consequence of the lifestyle intervention, which would be very 
difficult to blind. This might theoretically lead to a certain bias concerning psoriasis severity 
assessments (PASI), as investigators could expect patients receiving additional lifestyle 
intervention to show stronger improvements. On the other hand lifestyle intervention is no drug 
therapy and is not established as therapeutic intervention in psoriasis therapy, which limits the 
bias. Furthermore the study includes an extension period, which offers lifestyle intervention to 

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all patients and which includes a final PASI assessment at the end of the extension period, 
thereby further limiting the bias. Other, secondary objectives, like improvement of glucose and 
lipid metabolism, reduction of blood pressure, weight loss or changes in biomarker levels are 
based on laboratory parameters (HbA1c, lipid panel, biomarkers) or technical measurements 
(blood pressure, body weight), where the influence of a potential bias is highly limited.  
The extension period was designed for five reasons: First it enables the assessment of long-term 
sustainability of weight loss and lifestyle changes induced by the lifestyle intervention and 
second it helps to answer the question whether continued lifestyle intervention is necessary to 
maintain weight loss and other beneficial effects. Third it offers motivated patients of arm B 
the chance to receive continued support. Fourth it compensates for the disadvantage patients of 
arm A had, who were not allowed to participate in lifestyle intervention during the core study. 
And the fifth reason is that it helps to answer the question whether patients still benefit from a 
lifestyle intervention even if a systemic therapy has been initiated 28 weeks ago. 
3.3 
Rationale for dose/regimen, route of administration and duration 
of treatment  
The efficacy and safety of Secukinumab 300 mg s.c. for the treatment of moderate-to-severe 
plaque psoriasis has been demonstrated in the Phase 3 clinical trial program. The 300 mg s.c. 
dose of Secukinumab delivered the most clinically meaningful benefit to patients compared to 
the 150 mg s.c. dose across all pivotal studies for all time points (Week 12 to Week 52). 
Furthermore 300 mg is the approved dosing and was therefore selected for this study. The dose 
interval for the initial treatment period (i.e. once every week for the first 4 weeks, followed by 
once every 4 weeks until Week 24) has been selected because the phase 3 clinical trial program 
demonstrated a strong efficacy response to treatment at this dose interval and because this is the 
approved dose interval for Secukinumab.  
Pre-filled syringes (PFS) have been selected for Secukinumab s.c. administration in this study 
as these have been successfully used by patients in the Phase 3 clinical studies, which showed 
the use of PFS was safe and well tolerated. Self-injection with the PFS, following the approved 
and utilized instructions for use, showed no significant safety hazards and was found to be 
acceptable to study participants and to the competent authorities for other Secukinumab studies 
(CAIN457A2312 and CAIN457A3301).  
Secukinumab 300 mg s.c. treatment is combined with a lifestyle intervention. Lifestyle 
intervention, consisting of diet modification and increased physical activity, is a long-
established therapy and gold standard for the treatment of metabolic syndrome. Furthermore 
weight loss and increased physical activity were shown to reduce systemic inflammation, which 
is, as described in section 1, a shared pathophysiological process of psoriasis and metabolic 
syndrome. Therefore synergies of lifestyle intervention and Secukinumab therapy can be 
expected, as IL17A blockade with Secukinumab is also known to control systemic 
inflammation, shown for example by hsCRP suppression under Secukinumab therapy. 
Dual targeting of systemic inflammation by Secukinumab and lifestyle intervention is expected 
to improve skin symptoms more than Secukinumab alone and rearrange deteriorated metabolic 
status at the same time. 

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all indications evaluated. Secukinumab-specific treatment-emergent Anti-Drug Antibodies 
(ADA) were detected across the Phase 2 and 3 program in a minimal number of patients (0.7%), 
who were ADA-negative prior to Secukinumab exposure. Treatment-emergent ADAs were not 
associated with a loss of efficacy or alteration of pharmacokinetics in patients with assessable 
data. No severe or serious hypersensitivity reactions or administration reactions were reported 
in any patients with treatment-emergent ADAs. Long term safety data for up to 3 years did not 
reveal any new and unexpected adverse events. 
Secukinumab has the potential to increase the risk of infections. In clinical studies, most of the 
infections were of mild or moderate intensity. No increased susceptibility to tuberculosis was 
reported from clinical studies. Exacerbations of Crohn’s disease, in some cases serious, were 
observed in clinical studies in both patients receiving Secukinumab and placebo. In clinical 
studies, urticaria and rare cases of anaphylactic reactions have been observed in patients 
receiving Secukinumab. There are no adequate data from the use of Secukinumab in pregnant 
women. Animal studies do not indicate direct or indirect harmful effects with respect to 
pregnancy, embryonic/fetal development, parturition or postnatal development. It is not known 
whether Secukinumab is excreted in human milk. The effect of Secukinumab on human fertility 
has not been evaluated. Animal studies do not indicate direct or indirect harmful effects with 
respect to fertility. The Investigator’s Brochure (IB) provides a more detailed review of the pre-
clinical and clinical information on Secukinumab. 
In summary, the overall benefits of treatment with Secukinumab outweigh the risks. 
Half of the patients in the present study are randomized to receive concomitant lifestyle 
intervention in addition to Secukinumab therapy. Lifestyle intervention is the gold standard for 
the treatment of obesity and other components of the metabolic syndrome. Lifestyle 
interventions have been proven safe and effective in several studies (Knowler et al. 2002, 
Tuomilehto et al. 2001, Kulzer et al. 2014). A systematic review of 11 randomized controlled 
studies of lifestyle interventions shows their ability to induce weight loss and cardiometabolic 
benefits, which are mainly improvement of glucose and lipid metabolism, as well as reductions 
in systolic and diastolic blood pressure (Yamaoka et al., 2012). Weight loss and above 
mentioned cardiometabolic improvements are associated with preventive effects, meaning 
lower cardiovascular risk and lower risk of progression from prediabetes to type 2 diabetes. The 
targeted weight loss is >5% of baseline weight, as this extent of weight loss was previously 
shown to be sufficient to achieve cardiometabolic benefits and associated preventive effects 
(Lindstrom J, 2006). Furthermore the benefit of weight loss in the treatment of psoriasis was 
shown in first pilot studies, as mentioned in section 1 (Naldi et al., 2014, Al-Mutairi et al., 
2014). The lifestyle intervention applied in this study is based on education about nutrition, 
metabolism, effects of nutrition and physical activity on metabolic syndrome as well as on 
active support in weight loss and increased physical activity. Furthermore it includes the use of 
digital tracking devices. Potential risks of lifestyle intervention can be regarded as minimal. 
Patients who do not qualify for dietary changes and increased physical activity because of any 
medical condition, such as cardiac comorbidities (e.g. congestive heart failure), type 1 diabetes, 
or because any other medical conditions that would put them at risk when participating in the 
lifestyle intervention, will be excluded from the study, in order to minimize the risk. 
Furthermore patients with type 2 diabetes who receive insulin-based therapy or sulfonylurea 
agents/analogues are excluded from the study due to their increased risk for hypoglycemia when 
combining these medications with changes in diet and physical activity and due to the limited 

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ability to lose weight under these medications (weight gain is a well-known side effect of insulin 
and sulfonylurea agents/analogues). Patients with type 2 diabetes receiving other medications, 
such as DPP4 inhibitors, are allowed to participate in the study, as lifestyle intervention is the 
guideline-recommended basic therapy for any patient with type 2 diabetes (NVL Therapie des 
Type-2-Diabetes), and offers benefit for them, which outweighs the potential small risk of 
hypoglycemia or ketoacidosis in the case of metformin. The treating family physicians of the 
patients participating in the lifestyle intervention will be notified about the participation in the 
lifestyle intervention, so they can adequately monitor them and adjust their antidiabetic or 
antihypertensive medication. 
Based on the current knowledge no interactions with negative consequences between 
Secukinumab therapy and lifestyle intervention can be expected. On the contrary, it is the goal 
of this study to assess potential positive effects of the combined application. The risk will be 
further minimized by close clinical and laboratory monitoring of participating patients at all 
study visit. 
The additional risks of participating in the biomarker sub-study are those of blood sampling. 
Blood sampling will occur at time points where standard blood sampling is scheduled as well, 
and will not require additional venipuncture. Participation in the sub-study does not negatively 
affect the overall risk-benefit ratio for participation in the study. 
4 
Population 
The study is conducted in Germany and the study population consists of a representative group 
of male and female patients (≥18 years old) with moderate to severe plaque-type psoriasis and 
concomitant metabolic syndrome according to International Diabetes Federation (IDF), 
American Heart Association (AHA), and National Heart, Lung and Blood Institute (NHLBI) 
consensus definition from 2009 (Alberti et al., 2009). The goal is to randomize a total of 
approximately 760 patients in approximately 100 sites in Germany. Considering analyses of 
prior studies and the inclusion criterion metabolic syndrome, a screening failure of 30 % is 
expected, making screening of approximately 1100 patients necessary in order to provide the 
required number of patients. 
4.1 
Inclusion criteria 
Patients/subjects eligible for inclusion in this study must fulfill all of the following criteria: 
1. Written informed consent must be obtained before any assessment is performed.  
2. Men or women of at least 18 years of age at the time of screening. 
3. Patients must be able to understand and communicate with the investigator and must be 
willing and able to comply with all study procedures. 
4. Patients with moderate to severe plaque-type psoriasis who are candidates for systemic 
therapy, diagnosed at least 6 month before randomization and baseline value of  
• PASI > 10 and 

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• DLQI > 10 and 
• Body Surface Area (BSA) affected by plaque-type psoriasis ≥ 10% 
5. Fulfillment of Metabolic Syndrome definition (Alberti et al., 2009), which means 
fulfillment of ≥3 of the following criteria at screening visit: 
• Fasting (8 hours) plasma glucose ≥ 100 mg/dl or ongoing antidiabetic drug 
treatment (defined as: metformin, DPP4 inhibitors, GLP1 analogues, SGLT2 
inhibitors) 
• Abdominal obesity defined by elevated waist circumference (measured as 
defined in section 6.4.5): Male: ≥94 cm, female: ≥80 cm (except for patients of 
Asian, South or Central American ethnicity, for whom the cut off values are: 
Male: ≥90 cm, female: ≥80 cm) 
• Fasting (8 hours) triglycerides ≥ 150 mg/dl or ongoing drug treatment for 
elevated triglycerides (defined as: fibrates or nicotinic acid). 
• Fasting (8 hours) HDL-C < 40 mg/dl in men or < 50 mg/dl in women or ongoing 
drug treatment for reduced HDL-C (defined as: fibrates, nicotinic acid or 
statins). 
• Resting blood pressure: Systolic blood pressure  ≥ 130 and/ or diastolic blood 
pressure ≥ 85 mmHg (measured as defined in section 6.4.6) or ongoing 
antihypertensive drug treatment [defined as: ACE inhibitors, beta blockers, 
angiotensin receptor antagonists (e.g. Valsartan), aldosterone receptor 
antagonists, diuretics, nitrates, calcium channel blockers (e.g. Verapamil, 
Nifedipin), Aliskiren, Clonidin, alpha1 receptor antagonists (e.g. Doxazosin), 
Dihydralazin, Minoxidil, Moxonidin or Methyldopa]. 
6. Willingness and motivation to actively participate in a lifestyle intervention, which 
means patients need to be willing to increase physical activity and to change dietary 
habits. 
Patients eligible for inclusion in the biomarker sub-study will be recruited at study sites 
participating in the biomarker sub-study. Written informed consent for the biomarker sub-study 
must be obtained before any assessment for the biomarker sub-study is performed. 
 

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4.2 
Exclusion criteria 
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients. 
1. Forms of psoriasis other than chronic plaque-type (e.g. pustular, erythrodermic and 
guttate psoriasis) at screening. 
2. Previous exposure to Secukinumab or any other biologic drug directly targeting IL17A 
or the IL17A receptor (e.g. Brodalumab, Ixekizumab). 
3. Exposure to anti-TNF treatment during 1 year prior to baseline. 
4. Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, 
calcium channel inhibitors or lithium) at screening. 
5. History of hypersensitivity to Secukinumab, trehalose-dihydrate, L-histidine, L-
histidinhydrochloride-monohydrate, L-methionine, polysorbate 80, water for injection, 
or to substances of similar chemical classes. 
6. History of latex hypersensitivity. 
7. Ongoing participation (including safety follow-up period) in other interventional or non-
interventional studies in any dermatological indication 
8. Ongoing use of prohibited treatments. Washout periods detailed in the protocol have to 
be adhered to (Table 5-1). Note: Administration of live vaccines 6 weeks prior to 
baseline (visit 2) or during the study period is also prohibited. 
9. Diagnosis of type 1 diabetes. 
10. Patients with diagnosed type 2 diabetes, if they fulfill one or more of the following 
conditions: 
• uncontrolled type 2 diabetes, meaning HbA1c > 8.0%,  
• pharmacological therapy with one or more of the following agents: Insulin, 
sulfonylurea agents/analogues, thiazolidinediones/glitazones 
11. Insufficiently controlled, severe arterial hypertension (systolic blood pressure ≥ 160 
mmHg and/or diastolic blood pressure ≥ 95 mmHg) with urgent need for therapy 
initiation or foreseeable need for medication change during the duration of the core 
study. 
12. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of 
enrollment, or within 30 days until the expected pharmacodynamic effect has returned 
to baseline, whichever is longer; or longer if required by local regulations. 
13. 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 
hCG laboratory test. 
14. Active ongoing inflammatory diseases other than psoriasis and psoriatic arthritis (PsA) 
that might confound the evaluation of the benefit of Secukinumab therapy.  

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15. Underlying conditions (including, but not limited to metabolic, hematologic, renal, 
hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) 
which in the opinion of the investigator significantly immunocompromises the subject 
and/or places the subject at unacceptable risk for receiving an immunomodulatory 
therapy.  
16. Significant, progressive or uncontrolled medical problems at baseline which according 
to the opinion of the Investigator render the subject unsuitable for the trial - also in 
regard to participation in the lifestyle intervention - or put the subject at increased risk 
when participating in the trial (e.g. broken leg, congestive heart failure NYHA III/IV, 
uncontrolled hypertension with systolic ≥ 160 mmHg and/or diastolic ≥ 95 mmHg, 
severe uncontrolled asthma) 
17. Medical history of myocardial infarction or angina pectoris   
18. 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. 
19. Serum creatinine level exceeding 2.0 mg/dl (176.8 μmol/L) at screening 
20. Total white blood cell (WBC) count < 2,500/μl, or platelets < 100,000/μl or 
neutrophils < 1,500/μl or hemoglobin < 8.5 g/dl at screening. 
21. Active systemic infections during the last two weeks (exception: common cold) prior 
to baseline (visit 2) or any infection that reoccurs on a regular basis. 
22. History of an ongoing, chronic or recurrent infectious disease, or evidence of 
tuberculosis infection as defined by a positive QuantiFERON TB-Gold test (QFT) at 
screening. Subjects with a positive or indeterminate QFT test may participate in the 
study if full tuberculosis work up (according to local practice/guidelines) was 
completed within 12 weeks prior to visit 2 and establishes conclusively that the subject 
has no evidence of active tuberculosis. If presence of latent tuberculosis is established, 
then appropriate treatment must have been initiated at least 4 weeks prior to baseline 
(visit 2) and maintained according to local guidelines. 
23. Past medical history record or current infection with HIV, hepatitis B or hepatitis C 
prior to baseline (visit 2). 
24. History of lymphoproliferative disease or any known malignancy or history of 
malignancy of any organ system treated or untreated within the past 5 years, regardless 
of whether there is evidence of local recurrence or metastases (except for Bowen’s 
disease, or basal cell carcinoma or actinic keratoses that have been treated with no 
evidence of recurrence in the past 12 weeks prior to baseline (visit 2); carcinoma in 
situ of the cervix or non-invasive malignant colon polyps that have been removed). 
25. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor 
tolerability or lack of access to veins). 
26. History or evidence of ongoing alcohol or drug abuse, within the last six months 
before baseline (visit 2). 
27. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using basic methods of contraception during 
dosing of investigational drug for at least 20 weeks after the end of Secukinumab 
treatment. Basic contraception methods include: 

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• Total abstinence (when this is in line with the preferred and usual lifestyle of the 
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception 
• Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking 
investigational drug. In case of oophorectomy alone, only when the reproductive 
status of the woman has been confirmed by follow up hormone level assessment 
• Male sterilization (at least 6 m prior to screening). For female subjects on the 
study, the vasectomized male partner should be the sole partner for that subject 
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps).  
• Use of oral, (estrogen and progesterone), injected or implanted hormonal methods 
of contraception or other forms of hormonal contraception that have comparable 
efficacy (failure rate <1%), for example hormone vaginal ring or transdermal 
hormone contraception or placement of an intrauterine device (IUD) or intrauterine 
system (IUS) 
• In case of use of oral contraception women should have been stable on the same 
pill for a minimum of 3 months before taking investigational drug. 
• 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), total 
hysterectomy or tubal ligation at least six weeks ago. In the case of oophorectomy 
alone, only when the reproductive status of the woman has been confirmed by 
follow up hormone level assessment is she considered not of child bearing 
potential.  
5 
Treatment 
5.1 
 Study treatment 
5.1.1 
Investigational and control drugs 
During the core study patients in both treatment arms, A and B, receive the same study drug 
supplied by Novartis and appropriately labeled:  
Secukinumab 300 mg, provided as two s.c. injections of 1 ml prefilled syringe (PFS). Each 1 
ml syringe contains 150 mg Secukinumab. 
5.1.2 
Additional treatment 
Patients in arm B receive additional treatment in form of a lifestyle intervention. 
The lifestyle intervention is based on a structured and standardized program, closely guiding 
patients with metabolic syndrome with the primary goal to improve their metabolic status and 
to lose weight. The program and its content is designed by the 
 under the 

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leadership of Prof. Dr. med.
 
 especially for this trial. It is tailored to the needs of the trial´s patient population and 
optimized for combination with Secukinumab therapy. Patients are individually and regularly 
supervised by qualified trainers. They receive standardized education in nutrition, physical 
activity and metabolism, they learn about effects of nutrition and physical activity and they are 
consulted how to change their habits, their diet and how to increase their physical activity level. 
The lifestyle intervention actively enforces patient´s own motivation for lifestyle changes, with 
the goal to induce long-lasting changes in nutritional and physical activity habits leading to 
sustained weight reduction and improvement of metabolic status. Patients receive tracking 
devices, which support patient´s own motivation. The program is conducted in a standardized 
way, meaning that educational material and teaching is standardized and trainers, who perform 
the lifestyle intervention, have received standardized instructions (workshop and written 
information) before they can instruct patients. All trainers have to participate in a workshop 
conducted by 
 to qualify for counseling of the patients. The trainers are also 
instructed to report (serious) adverse events that are mentioned by the patient during the lifestyle 
intervention program or that occur during the training within 24 hours to the respective 
investigator. The investigator will assess whether the event constitutes a non-serious or serious 
adverse event and report it, if applicable. The main principle of the lifestyle intervention 
program is based on the programs applied in two milestone trials in the field of lifestyle 
intervention in patients with metabolic syndrome (Knowler et al., 2002; Tuomilehto et al., 
2001). Details of the lifestyle intervention program are given in a separate manual.    
 
 
5.2 
Treatment arms  
Core study: The study has two different treatment arms: 
• Arm A: Patients in arm A receive therapy with Secukinumab 300 mg s.c., which 
consists of two injections with 150 mg prefilled syringes at weeks 0, 1, 2, 3, 4, 8, 12, 
16, 20 and 24 (last injection is performed at week 24) 
• Arm B: Patients in arm B receive therapy with Secukinumab 300 mg s.c., which consists 
of two injections with 150 mg prefilled syringes at weeks 0, 1, 2, 3, 4, 8, 12, 16, 20 and 
24 (last injection is performed at week 24). In addition they participate in a lifestyle 
intervention program. 
Extension period: After 28 weeks the study continues with an extension period, during which 
lifestyle intervention is offered to all patients, irrespective of their prior treatment arm. This 
means that patients of arm B, who are willing to, can continue their previously started lifestyle 
intervention program and patients of arm A, who are willing to, can start the lifestyle 
intervention program at the beginning of the extension period. The extension period ends at 
week 56. There will be no study drug supply during the extension period. The treating physician 
is free to choose suitable psoriasis therapy for each patient. 

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5.3 
Treatment assignment and randomization  
Patients will be randomized in a 1:1 ratio to one of the two treatment arms at randomization 
visit. Randomization will be performed by the use of sealed envelopes. The investigator or 
his/her delegate will open the sealed envelope after confirming that the patient fulfills all ex- 
and inclusion criteria. The envelope will assign a randomization number to the patient, which 
can be used to link the patient to a treatment arm.  
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from patients and investigator staff. A patient 
randomization list will be produced by the 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. 
The randomization scheme for patients will be reviewed and approved by a member of the 
Randomization Group. 
At randomization visit an eligible patient will be given the lowest available randomization 
number. This number assigns the patient to one of the treatment arms. The investigator will 
enter the randomization number on the case report form (CRF). 
5.4 
Treatment blinding  
Not applicable, as this study has an open label design.  
5.5 
Treating the patient 
Sponsor qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
5.5.1 
Patient numbering 
Each patient is uniquely identified in the study by a combination of his/her center number and 
patient number. The center number is assigned by Novartis to the investigative site. Upon 
signing the informed consent form, the patient is assigned a patient number by the investigator. 
At each site, the first patient is assigned patient number 1, and subsequent patients/subjects are 
assigned consecutive numbers (e.g. the second patient is assigned patient number 2, the third 
patient is assigned patient number 3). Once assigned to a patient, a patient number will not be 
reused. If the patient fails to be randomized for any reason, the reason for not being randomized 
will be entered on the Screening Log. Additional information to be collected on Screening 
Failures is described in Section 6.1. 
5.5.2 
Dispensing the study drug  
Each study site will be supplied with study drug in packaging of identical appearance. Due to 
the open-label design of the study the study drug is not specifically labelled with medication 
numbers. 

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5.5.3 
Handling of study and additional treatment  
5.5.3.1 
Handling of study treatment  
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly, and kept in a secured location to which only the investigator and designees 
have access. Upon receipt, all study treatment must be stored according to the instructions 
specified on the labels. Clinical supplies are to be dispensed only in accordance with the 
protocol. Technical complaints are to be reported to the respective Novartis Germany Quality 
Assurance. 
5.5.3.2 
Handling of additional treatment  
Dermatologic study site personnel will instruct patients how to contact their lifestyle 
intervention trainer in order to participate in the lifestyle intervention program. For patients 
randomized to receive concomitant lifestyle intervention it is mandatory to participate in the 
lifestyle intervention and to show up to the counseling appointments scheduled. All patient 
materials which are part of the lifestyle intervention (Lese-/Arbeitsbuch, information flyer, 
activity tracker, Theraband, scale, tape measure) are given to patients in arm B at randomization 
visit (study visit 2). 
5.5.4 
Instructions for prescribing and taking study treatment/ for 
participating in the lifestyle intervention program  
The first study treatment administration will occur at baseline (visit 2) after the 
inclusion/exclusion criteria have been confirmed and all study scheduled assessments have been 
performed.  
All doses of study treatment are administered at the study site by study site personnel or by the 
patient himself under the supervision of study site personnel. All study assessments, including 
blood withdrawal and completion of Patient Reported Outcomes (PROs), i.e. DLQI, should be 
completed prior to the injection of study treatment. The flow of work and the consecutive steps 
of assessments including Clinical Outcome Assessments (COA) are given in Section 6. 
In single, exceptional cases where a visit needs to be skipped e.g. due to business/ working 
travels of the patient, home administration of study treatment by the patient himself without 
supervision is allowed at the discretion of the investigator for up to one time per patient between 
week 8 and week 24. In these cases the investigator is allowed to provide the patient at most 
one dose of study treatment (2 pre-filled syringes) in advance. Study treatment must be 
transported in a suitable cooled bag, which will be provided at the study sites. During home 
administrations subjects are expected to contact the investigator/site staff in case they are 
experiencing any AE/SAE or have any concerns or are unable for any reason to take the study 
treatment as prescribed. A visit should be scheduled as close as possible to the time of the per 
protocol planned visit which had to be skipped. At this visit all assessments of the skipped visit 
should be performed but no study drug will be administered. 
Irrespective of self-administration or administration by study site personnel, the first 
Secukinumab administration at baseline (visit 2) will take place at the study site. In case the 
patient considers self-administration he must be instructed through the site staff by explaining 

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the Instructions For Use (IFU) on how to self-inject via the pre-filled syringe. After providing 
detailed explanations/instructions, subjects will then be asked to raise any questions. Thereafter, 
they will proceed with self-injection. In case of self-administration the investigator is obliged 
to make sure that injections are performed correctly and exactly as prescribed. In case of doubt 
about patient´s ability or willingness to perform injections reliably and correctly the investigator 
can decide to prohibit self-administration.  
The study treatment solution must be injected in non-affected areas of the skin. 
Pre-filled syringes should be kept at 2 to 8°C (36°F and 46°F), never be frozen, and should 
be protected from light. Prior to administration, the boxes containing the pre-filled syringes 
should be allowed to adapt to room temperature unopened for about 20 minutes before 
administration. Patients should return used syringes to the study site for drug accounting and 
disposal. 
All dosages prescribed and dispensed to the patient and all dose changes during the study must 
be recorded on the Dosage Administration Record CRF 
The investigator must promote compliance by instructing the patient to take the study treatment 
exactly as prescribed and by stating that compliance is necessary for the patient’s safety and the 
validity of the study.  
The lifestyle intervention program has scheduled counseling visits where the patients meet their 
trainer. These visits are defined in a separate manual. For patients randomized to concomitant 
lifestyle intervention it is mandatory to participate in the program and to show up for the 
counseling visits. Participation in the lifestyle intervention counseling visits must be recorded 
in the eCRF. The investigator should explain to the patient that participation in the program and 
showing up to all counseling visits is mandatory, necessary for the validity of the study and 
yields benefit for the patient. 
5.5.5 
Permitted dose adjustments and interruptions of study treatment/ 
interruptions of lifestyle intervention  
Treatment interruptions and dose adjustments of study treatment are not permitted. If a dose 
was not or incorrectly administered, this deviation must be recorded on the Dosage 
Administration Record CRF.  
The same applies for the lifestyle intervention: Stopping participation (e.g. not showing up to 
counseling visits) or skipping counseling visits of the program is not permitted. Participation in 
the lifestyle intervention program must be recorded in the eCRF. 
5.5.6 
Rescue medication 
Use of rescue medication is not permitted in this study. 
5.5.7 
Concomitant medication  
The investigator must instruct the patient to notify the study site about any new medications 
he/she takes after the patient was enrolled into the study. All medications, procedures and 
significant non-drug therapies (including physical therapy and blood transfusions) administered 

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after the patient was enrolled into the study must be recorded in the concomitant medications / 
significant non-drug therapies eCRF. 
Each concomitant drug must be individually assessed against all exclusion 
criteria/prohibited medication. If in doubt the investigator should contact the Novartis 
medical monitor before randomizing a patient or allowing a new medication to be started. 
Please see table 5-1 for details on prohibited and concomitant medication.  
5.5.8 
Prohibited medication 
Use of the treatments displayed in the below table is NOT allowed during the respective period.  
Table 5-1 
Prohibited treatments by period (for any indication) 
Prohibited treatments during the core 
studya, b, g, h 
Washout period  
(before baseline, i.e. visit 2) 
Secukinumab and other IL-17  and IL-17 receptor antagonists 
(e.g. Ixekizumab, Brodalumab) 
No prior use allowed   
Biologicals targeting TNF (e.g. Etanercept, Adalimumab, 
Infliximab) 
No use 1 year prior to 
baseline visit (visit 2) allowed 
Alefacept, Briakinumab, Efalizumab, Ustekinumab 
6 month  
Biological immunomodulating agents other than above   
12 weeks  
Other systemic immunomodulating treatments 
(e.g. Methotrexate, cyclosporine A, corticosteroidsc, 
cyclophosphamide)  
4 weeks  
Other systemic psoriasis treatmentsd (e.g. retinoids, fumarates, 
apremilast) 
4 weeks 
Photochemotherapy (e.g. systemic PUVA, Balneo-PUVA, 
topical PUVA)  
4 weeks  
Phototherapy (e.g., UVA, UVB, Balneo-Phototherapy without 
psoralen derivatives)  
2 weeks  
Topical treatment that is likely to impact signs and symptoms of 
psoriasis (vitamin D analogues, Tacrolimus, Pimecrolimus 
potent corticosteroids, salicylvaseline, salicylic acid, lactic acid, 
tar, alpha-hydroxy or fruit acids)e. 
2 weeks 
Live virus vaccinations*** 
6 weeks 
Any investigational treatment (including anti IL23p19) or 
participation in any interventional trial 
4 weeks or 5 half-lives 
(whichever is longer) 
The following glucose-lowering agents: Insulin, sulfonylurea 
agents/analogues, thiazolidinediones/glitazones 
12 weeks 
 
 
 
It is forbidden to start therapy with one of the 
following medications during the core studyf:  
 
 

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Prohibited treatments during the core 
studya, b, g, h 
Washout period  
(before baseline, i.e. visit 2) 
Cholesterol- or lipid lowering agents(e.g. HMG-CoA-
inhibitors/statins, fibrates, nicotinic acid, ezetimibe, 
colestyramin, colestipol) 
Antihypertensive drugs (e.g. ACE-inhibitors, angiotensin-
receptor antagonists, ß-blockers, aldosterone receptor 
antagonists, diuretics, nitrates, calcium channel blockers (e.g. 
Verapamil, Nifedipin), Aliskiren, Clonidin, alpha1 receptor 
antagonists (e.g. Doxazosin), Dihydralazin, Minoxidil, Clonidin, 
Moxonidin or Methyldopa)  
Glucose-lowering agents (e.g. Metformin, DPP4 inhibitors, 
SGLT2 inhibitors, GLP1 analogues etc.) 
If a patient has already been taking one of these medications on 
a stable dose for at least 12 weeks before baseline (visit 2), 
he can be enrolled in the study and continue to take them during 
the study, except for the glucose-lowering agents insulin, 
sulfonylurea agents/analogues and thiazolidinediones/ 
glitazones, which are not allowed during the core study.  
 
Dose adjustments or withdrawal of the following 
medications should be avoided during the core 
study: 
Cholesterol- or lipid lowering agents (e.g. HMG-CoA-
inhibitors/statins, fibrates, nicotinic acid, ezetimibe, 
colestyramin, colestipol) 
 
 
 
 
Prohibited treatments during extension 
period 
 
There are no treatment restrictions during the extension 
period, any treatments can be used. 
 
 
 
 
a If a prohibited treatment of psoriasis was used during the study, the subject should discontinue use of the prohibited treatment if 
he/she wishes to continue in the study.  
b In case of undue safety risk for the subject, the subject should discontinue study treatment at the discretion of the investigator. 
If the subject received a live virus vaccination during the study, the subject must discontinue study treatment. 
c Oral, i.v., i.m., s.c.,. Exceptions: Inhalative corticosteroids (CS) with only a topical effect (e.g., to treat asthma) are not considered 
“systemic immunomodulating treatments” and are therefore acceptable as co-medication. The use of intra-articular and peri-
articular corticosteroids is permitted throughout the study for treatment of symptoms of psoriatic arthritis that cannot be sufficiently 
controlled by study treatment and/or concomitant non-steroidal anti-inflammatory drugs (NSAIDS). 
d There is no restriction on the use of anti-histamines and on the use of corticosteroids in the eye, nose or the ear 
e Mild to moderate topical corticosteroids are allowed only during the screening period if used only on the face, scalp 
and/or anogenital area. The use must be stopped 12 hours prior to first study medication administration. Urea (up to 
5%) is allowed throughout the complete study, but must also be stopped 12 hours prior to each study visit. 

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f Urgent medical cases are excluded from this regulation. These cases have to be documented in the eCRF.  
*** Inactivated virus vaccinations are allowed 
g If study treatment for psoriasis (i.e. secukinumab) is discontinued during the core study, then all restrictions for prohibited 
psoriasis treatments are lifted and the patient may be treated with concomitant topical, conventional systemic and/or biologic 
psoriasis treatments and/or phototherapy. 
h If the lifestyle intervention is discontinued during the core study, then all restrictions for prohibited treatments for metabolic 
syndrome are lifted and the patient may be start other concomitant treatments for metabolic syndrome and/or change the dosage 
of treatments for metabolic syndrome that are already being administered. 
5.5.9 
Emergency breaking of assigned treatment code  
Not applicable as the study has an open-label design. 
5.6 
Study completion and discontinuation  
5.6.1 
Study completion and post-study treatment  
A patient will be considered to have completed the core study when the patient has completed 
the last visit planned of the core study. During the following extension period lifestyle 
intervention is offered to all patients. Patients from arm B can continue their already ongoing 
lifestyle intervention, patients from arm A can start a lifestyle intervention. In case a patient 
from arm B does not want to continue his lifestyle intervention during the extension period or 
a patient from arm A does not want to start a lifestyle intervention, he still has to participate in 
the extension period, which means he has to show up for dermatological study visits during the 
extension period.  
During the extension phase no study drug will be supplied by Novartis. Investigators or treating 
physicians are free to choose suitable therapies for continued psoriasis treatment. 
The investigator must provide follow-up medical care for all subjects who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care. 
5.6.2 
Discontinuation of study treatment  
Discontinuation of study treatment for a patient occurs when study treatment (Secukinumab or 
lifestyle intervention or both) is stopped earlier than the protocol planned duration and can be 
initiated by either the patient or the investigator.  
The investigator must discontinue study treatment (Secukinumab or lifestyle intervention or 
both) for a given patient if, on balance, he/she believes that continuation would negatively 
impact the risk/benefit of trial participation. 
Study treatment must be discontinued under the following circumstances:  
• Patient wish  
• Pregnancy (see Section 6.5.6 and Section 7.6) 
• Use of prohibited treatment as per recommendations in Table 5-1 
• Any situation in which study participation might result in a safety risk to the patient 
• Emergence of the following adverse events: AEs that in the judgment of the 
investigator/qualified site staff, taking into account the subject’s overall status prevent the 
subject from continuing study treatment 

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• Any laboratory abnormalities that in the judgment of the investigator, taking into 
consideration the subject’s overall status, prevents the subject from continuing 
participation in the study 
• Severe infections  
If discontinuation of study treatment occurs during the core study, the patient should NOT be 
considered withdrawn from the study.  
After study treatment discontinuation (i.e. discontinuation of secukinumab, lifestyle 
intervention or both) the patient will continue to attend regular study visits as per visit schedule 
and all assessments will be performed as planned. If one study treatment is discontinued (i.e. 
secukinumab or lifestyle intervention) this should not lead to discontinuation of the other, unless 
there is a reason for discontinuation of the other (see above for a list of reasons for 
discontinuation). 
If a study treatment is discontinued, adequate replacement for this treatment may be sought 
outside of the study despite continued study participation: 
• If secukinumab is discontinued, adequate concomitant drug treatment for psoriasis may 
be administered outside of the study. This does not require withdrawal of the patient 
from the study. In this case, there are no restrictions for concomitant psoriasis treatments 
(including topical, conventional systemic and biological drug treatments and 
phototherapy), even if the patient is still participating in the core or extension study 
period. 
• If lifestyle intervention is discontinued, adequate concomitant treatment for metabolic 
syndrome may be administered outside of the study. This does not require withdrawal 
of the patient from the study. In this case, there are no restrictions for concomitant 
treatments of metabolic syndrome (including but not limited to drug treatments or other 
lifestyle interventions, dose adjustments and/or new treatments are permitted), even if 
the patient is still participating in the core or extension study period. 
The reason for study treatment discontinuation should be recorded in the eCRF. 
5.6.3 
Withdrawal of informed consent  
Patients/subjects may voluntarily withdraw consent to participate in the study for any reason at 
any time. Withdrawal of consent from the study is defined as when a patient: 
• Does not want to participate in the study anymore/ Does not want to participate in the 
lifestyle intervention any more 
and 
• Does not want any further visits or assessments 
and 
• Does not want any further study related contacts 
and 
• Does not allow analysis of already obtained biologic material 

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In this situation, the investigator must make every effort (e.g. telephone, e-mail, letter) to 
determine the primary reason for the patient’s decision to withdraw his/her consent and record 
this information.  
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing.  
Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the patient’s study withdrawal should be made as detailed in the 
assessment table below. 
5.6.4 
Loss to follow-up  
For subjects whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the investigator must show "due diligence" by 
documenting in the source documents steps taken to contact the subject, e.g. dates of telephone 
calls, registered letters, etc. A patient cannot be considered as lost to follow-up until the time 
point of his/her scheduled end of study visit has passed. 
5.6.5 
Early study termination by the sponsor  
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit risk assessment of participating in the study, practical reasons, or for 
regulatory or medical reasons (including slow 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 Institutional Review Board/Independent Ethics Committee 
(IRBs/IECs) of the early termination of the trial. 
6 
Visit schedule and assessments 
Table 6-1 lists all of the assessments and indicates with an “x” when the visits are performed. 
Patients should be seen for all study visits on the designated day, or as close to it as 
possible. Recommended study visit windows are +/- 2 days for visits 2 – 6, +/- 5 days for 
visits 7 – 12 and +/- 7 days for visits E1 – E3. The same visit windows are recommended 
for the lifestyle intervention visits associated to the study visits. 
Missed or rescheduled visits should not lead to automatic discontinuation. Patients who 
prematurely discontinue the study for any reason should be scheduled for a visit as soon as 
possible, at which time all of the assessments listed for the final visit will be performed. In case 
of premature discontinuation during the core study the final visit is the week 28 visit, in the case 
of premature discontinuation during the extension period the final visit is the week 56 visit. At 
this final visit, all dispensed investigational product should be reconciled and the adverse event 
and concomitant medications reconciled on the CRF. 

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Table 6-1 lists assessments that are recorded in the clinical database (marked “X” if entered via 
the eCRF or “C” if entered centrally, e.g. via a central laboratory) and assessments that are 
source documentation only (marked “S”). Assessments that are source documentation only will 
not be entered into the eCRF.  
If for any reason the subject is a screen failure, the subject may be re-screened. There is no 
restriction on the number of times a potential subject may be re-screened or on how much time 
must pass from the date of screen failure and the date of re-screening. 
If a subject re-screens for the study, then the subject must sign a new ICF and be issued a new 
subject number prior to any screening assessment being conducted for the subject under the 
new screening subject number. For all subjects, the investigator/qualified site staff will record 
if the subject was re-screened on the re-screening eCRF and any applicable screening numbers 
the subject was issued prior to the current screening number. The date of the new informed 
consent signature must be entered on the Informed Consent eCRF to correspond to the new 
screening subject number. For re-screening, all screening assessments must be performed per 
protocol, except for the tuberculosis (TB) work up if applicable, if performed not more than 12 
weeks before randomization. 
 
 
 

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5 Only if necessary according to the treating physician  
6 Patients must show up in fasting (8 hours) state     
 
   
8 For patients in arm B 
9 Only for participating patients 
 
 
6.1 
Information to be collected on screening failures  
All patients/subjects who have signed informed consent but not entered into the next period will 
have the study completion page for the screening period, demographics, inclusion/exclusion, 
and serious adverse event (SAE) data collected. Adverse events that are not SAEs will be 
followed by the investigator and collected only in the source data. 
6.2 
Patient demographics/other baseline characteristics  
6.2.1 
Demographics 
Subject demographic data will include: year of birth, gender, race, and child-bearing potential 
as well as postmenopausal status (for females only). 
6.2.2 
Psoriasis medical history/previous psoriasis therapies 
The following information should be collected and entered in the Psoriasis History eCRF in 
addition to pre-psoriasis therapies:  
• The date of first symptoms of plaque-type psoriasis  
• The date of first diagnosis of plaque-type psoriasis  
• The previous treatments of psoriasis (including phototherapy and/or photochemotherapy) 
and the reason for discontinuation. If a Novartis drug (e.g. Sandimmun/ cyclosporine A) 
was discontinued due to an adverse event, abuse/ misuse or pregnancy a spontaneous report 
needs to be sent to the local Novartis Patient Safety department. Topical therapies are only 
collected for the last 24 month prior to signing the informed consent. 
• The presence of psoriatic arthritis and date of first diagnosis  
6.2.3 
Smoking history 
The current and/or previous use of tobacco products will be recorded prior to randomization, 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. 
6.2.4 
Relevant medical history/current medical conditions 
Relevant medical history and current medical conditions present before signing the informed 
consent should be recorded in the Medical History eCRF. 
Relevant medical history/current medical condition data includes data prior to signing of the 
informed consent and until the start of study treatment. Whenever possible, diagnoses and not 
symptoms should be recorded. 
Any information pertaining to psoriasis medical history assessed prior to randomization should 
be reported on the corresponding eCRF. 

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6.2.5 
Prior and concomitant medications 
Prior medications taken over the 6 months preceding study enrollment will be captured at the 
screening visit. Medication taken parallel to the study treatment will be captured as concomitant 
medication on all following visits.  
6.2.6 
Cardiovascular and metabolic medical history 
Relevant cardiovascular and metabolic medical history (e.g. diabetes, hypertension, 
hypercholesterinemia) will be assessed in the cardiovascular and metabolic medical history 
eCRF. 
6.2.7 
Determination of the tuberculosis status 
Determination of the tuberculosis (TB) status should be done during the screening phase. The 
TB status must be determined by medical history, signs, symptoms, TB testing (QuantiFERON-
TB Gold assay). Any significant findings should be recorded in the TB assessment eCRF and 
the Medical History eCRF, as deemed necessary.  
QuantiFERON TB-Gold In-Tube assay 
A QuantiFERON® TB-Gold In-Tube assay (QFT) to screen a population for latent tuberculosis 
infection (Doherty et al., 2008) will be used at Screening to evaluate the subjects’ eligibility for 
the study. This blood-based assay is specific for Mycobacterium tuberculosis and is not 
influenced by previous Bacillus Calmette-Guérin vaccination or by exposure to other 
Mycobacteria species. Furthermore, this test, in contrast to the purified protein derivative (PPD) 
skin test, is also insensitive to a booster effect since the subject is not exposed to the vaccine.  
The assay measures the production of interferon-gamma and presents it relative to a negative 
and a positive control sample (Manuel and Kumar, 2008). The QuantiFERON®-TB Gold assay 
test will be supplied by the central laboratory. Details on the collection, shipment of samples 
and reporting of results by the central laboratory are provided to investigators in the study-
specific laboratory manual. 
Positive or indeterminate tests must be recorded on the Tuberculosis assessment eCRF; the 
workflow of sample handling in case of positive or indeterminate test results is provided in 
Figure 6-1.  
• If the test result is negative, the subject may be randomized. 
• If the test result is positive, the investigator should perform a work-up for the test result as 
per local procedures. If a TB work-up was conducted prior to the screening of the subject, 
results of the work-up can be used to assess eligibility if the work-up was conducted within 
12 weeks prior to randomization. 
• Subjects positive for latent TB per work-up may be randomized to the trial if sufficient 
treatment has been initiated according to local routine clinical practice and will be 
maintained for the prescribed duration. Subjects positive for active TB per work-up are 
not eligible for the study. Subjects negative for TB (no signs of latent or active TB) per 
work-up may be randomized to the trial. 

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• If the test result is indeterminate, the investigator may repeat the test once or may 
proceed directly to perform the work-up for the test result as per local procedures. This 
action is at the discretion of the investigator. If a TB work-up was conducted prior to the 
screening of the subject, results of the work-up can be used to assess eligibility if the work-
up was conducted within 12 weeks prior to randomization. 
• If the second test is negative, the subject may be randomized. 
• If the second test is positive, the investigator should perform work-up as per local 
guidelines. Subjects positive for latent TB per work-up may be randomized to the trial 
if sufficient treatment has been initiated according to local routine clinical practice and 
will be maintained for the prescribed duration. Subjects positive for active TB per 
work-up are not eligible for the study. Subjects negative for TB (no signs of latent or 
active TB) per work-up may be randomized to the trial. 
• If the second test is again indeterminate, the investigator should perform follow-up for 
the test result as per local procedures. Subjects tested positive for latent TB per work-
up may be randomized to the trial if sufficient treatment has been initiated according to 
local routine clinical practice.  Subjects positive for active TB per work-up are not 
eligible for the study. Subjects negative for TB per work-up (no signs of latent or active 
TB) may be randomized to the trial if the work-up was conducted 12 within weeks prior 
to randomization. 
• If eligibility is being assessed with only 1 test result and a TB work-up (i.e., no second 
TB test will be performed), the TB test to assess eligibility must have been done via the 
central laboratory for the study within the screening phase (within 4 weeks prior to 
initial study drug administration) and TB work-up will only be considered if it will be 
completed within 12 weeks prior to initial study drug administration. Subjects positive 
for latent TB per work-up may be randomized to the trial if sufficient tuberculosis 
treatment has been initiated according to local routine clinical practice and will be 
maintained for the prescribed duration. Subjects positive for active TB per work-up are 
not eligible for the study. Subjects negative for TB per work-up (no signs of latent or 
active TB) may be randomized to the trial. 
 

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Figure 6-1 
Tuberculosis screening flowchart 
 
 

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6.3 
Treatment exposure and compliance  
All doses of study treatment administration will be recorded on the appropriate Dosage 
Administration Record eCRF page (visit specific and summary pages). Compliance to the 
planned site administration schedule is expected to be high since the study treatment will be 
administered by the investigator or in the presence of the investigator or study personnel at pre-
defined visits (except 1 allowed home administration in selected cases at the discretion of the 
investigator). Compliance will also be assessed and confirmed by a field monitor by drug 
accountability logs, by documentation and by the qualified site personnel that is responsible for 
treatment dispensation, preparation, administration and accountability. 
The same applies for the lifestyle intervention, participation in all lifestyle intervention 
counseling visits will be recorded in the eCRF. 
6.4 
Efficacy  
All efficacy assessments should be performed prior to the administration of study treatment. 
All other remaining study visit procedures (e.g. laboratory sample collection, vital signs, waist/ 
hip circumference measurement, questionnaires etc.) must also be completed prior to 
administration of study treatment.  
6.4.1 
PASI/ BSA 
Assessment of total body surface area (BSA) and Psoriasis Area and Severity 
Index (PASI) 
The investigator or trained qualified designee will complete the PASI assessment as indicated 
in Table 6-1. Whenever possible, the same evaluator should perform this assessment at all visits. 
The total BSA affected by plaque-type psoriasis will be estimated from the percentages of areas 
affected, including head, trunk, upper limbs and lower limbs (see below for full details of the 
PASI assessment). The following calculations will be done: Each reported percentage will be 
multiplied by its respective body region corresponding factor (head = 0.1, trunk = 0.3, upper 
limbs = 0.2, lower limbs = 0.4). The resulting four percentages will be added up to estimate the 
total BSA affected by plaque-type psoriasis.  
The PASI scoring system is further described in Table 6-3. 
A PASI score (Fredriksson and Pettersson, 1978; Weisman et al., 2003; Gottlieb et al., 2005) 
will be derived as indicated in Table 6-3. The head, trunk, upper limbs and lower limbs are 
assessed separately for erythema, thickening (plaque elevation, induration), and scaling 
(desquamation). The average degree of severity of each sign in each of the four body regions is 
assigned a score of 0-4. The area covered by lesions on each body region is estimated as a 
percentage of the total area of that particular body region. 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 

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4. When scoring the severity of erythema, scales should not be removed. 
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the body surface area, respectively, the PASI score is calculated 
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 6-2. 
PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a 
theoretic maximum of 72.0. 
The baseline value for analysis of the PASI is collected at the Randomization Visit. 
If results of BSA and PASI assessment fulfill criteria for an (serious) adverse event, the 
investigator has to document it accordingly. 

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Table 6-2 
The PASI scoring system 
Body 
region 
Erythema (E) 
Thickening 
(plaque elevation, 
induration, I) 
Scaling 
(desquamation, D) 
Area score 
(based on true 
area %, A)* 
Head (H)† 
0=none  
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-<10% 
2=10-<30% 
3=30-<50% 
4=50-<70% 
5=70-<90% 
6=90-100% 
Trunk (T)‡ 
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-<10% 
2=10-<30% 
3=30-<50% 
4=50-<70% 
5=70-<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-<10% 
2=10-<30% 
3=30-<50% 
4=50-<70% 
5=70-<90% 
6=90-100% 
Lower 
limbs (L)§ 
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-<10% 
2=10-<30% 
3=30-<50% 
4=50-<70% 
5=70-<90% 
6=90-100% 
*Percentage (not score) of body region (not whole body) affected will be entered in the eCRF 
†Neck is assessed as part of the Head (H) body region 
‡Axillae and groin are assessed as part of the Trunk (T) body region 
§Buttocks are assessed as part of the Lower limbs (L) body region 
Definitions of efficacy variables based on PASI 
The following definitions will be used in this study based on the CHMP guidelines for psoriasis 
(CHMP/EWP/2454/02 2004): 
• PASI 50 response: subjects achieving ≥50% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 50 responders 
• PASI 75 response: subjects achieving ≥75% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 75 responders 
• PASI 90 response: subjects achieving ≥90% improvement (reduction) in PASI score 
compared to baseline are defined as PASI 90 responders 
• PASI 100 response / remission: complete clearing of psoriasis (PASI=0) 

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6.4.2 
Biomarkers of glucose and lipid metabolism  
Biomarkers of glucose metabolism: HbA1c, fructosamine and fasting plasma glucose. 
Biomarkers of lipid metabolism: Total cholesterol, triglycerides, LDL, HDL. 
These markers will be assessed as part of the routine or fasting laboratory, time points are shown 
in table 6-1. 
6.4.3 
Biomarkers of systemic inflammation 
Biomarker of systemic inflammation: hsCRP 
This marker will be assessed as part of the routine laboratory, time points are shown in table 6-
1. 
6.4.4 
Weight and height 
Height and body weight will be measured as listed in table 6-1, height in centimeters (cm) and 
body weight in kilogram (kg) (to the nearest 0,1 kg). 
Height and body weight will be measured in indoor clothing, but without shoes. Whenever 
possible, body weight assessment should be performed by the same study site staff member; the 
same scale should be used throughout the study. 
6.4.5 
Waist and hip circumference 
Waist and hip circumference will be measured as listed in table 6-1, both in centimeters (cm). 
Waist circumference measurement is taken with a tape measure at the approximate 
midpoint between the inferior margin of the last palpable rib and the top of the iliac crest 
(as suggested by WHO and IDF). The accuracy of waist and hip circumference measurements 
depends on corrects tightness and positioning of the measuring tape: Measurements should be 
made with a stretch-resistant tape, which should be snug around the body parallel to the 
floor/ in a horizontal plane. The tape should not be pulled so that tight that it is constricting. 
A standardized tape supplied by Novartis has to be used. 
6.4.6 
Blood pressure and pulse 
Resting blood pressure will be assessed at every scheduled visit as indicated in Table 6-1 
according to the 2013 European Society for Cardiology guidelines for the management of 
arterial hypertension (Mancia et al., 2013). Whenever possible, assessments should be 
performed by the same study site staff member throughout the study. It is crucial that blood 
pressure is measured in the resting state and therefor appropriate resting conditions are ensured: 
Coffee, black tea, caffeine and smoking must be avoided before the measurement is performed. 
After the subject has been sitting and resting in a quiet environment for five minutes, 
with back supported and both feet placed on the floor, systolic and diastolic blood pressure 
will be measured twice (measurements separated by 2 minutes) using an automated, 
validated device, with an appropriately sized cuff. A standard bladder (12-13 cm wide and 35 
cm long) should be used, but a larger and a smaller bladder have should be available for large 
(arm circumference >32 cm) and thin arms. The cuff should be at the heart level of the patient. 
Measurements will be recorded in the source documentation and the average of the two 

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measurements will be entered on the Vital Signs eCRF. The same applies for the pulse 
measurement. 
6.4.7 
Appropriateness of efficacy assessments  
PASI/ BSA: PASI scores outcome measures, the assessment of the severity of the psoriasis 
symptoms and the extent to which the subject’s body area is affected by the disease, is mandated 
by the EMA for the clinical investigation of medicinal products for the treatment of psoriasis 
(CHMP/EWP/2454/02 2004). 
Biomarkers of glucose: HbA1c and fasting plasma glucose are standard parameters used in daily 
clinical practice to monitor glucose metabolism and recommended in German national 
guidelines for diagnosis of diabetes (Kerner et al., 2014). Fructosamine is not as widely used as 
HbA1c or fasting plasma glucose but offers the advantage of indicating the quality of glucose 
control during the last 2-3 weeks in contrast to HbA1c, which is an indicator of glucose control 
during the last 8-12 weeks (Ribeirio et al., 2016). 
Biomarkers of lipid metabolism: total cholesterol, triglycerides, HDL and LDL are standard 
parameters used in daily clinical practice to monitor lipid status and assess cardiovascular risk 
profile. They are recommended in European guidelines for diagnosis and management of 
dyslipidemias (Reiner et al., 2011). 
CRP is the most widely used blood marker of systemic inflammation. The detection method 
used for the hsCRP test allows more sensitive testing and was used in several psoriasis clinical 
trials as a marker of systemic inflammation (Puig et al., 2014; Gkalpakiotis et al., 2016).  
Weight, BMI and hip circumference are clinical routine parameters for the assessment of 
obesity. Measurement of systolic and diastolic blood pressure is clinical routine for the 
assessment of hypertension. 
6.5 
Safety  
Blood withdrawals and safety assessments should be done prior to study treatment 
administration. Appropriate safety assessments (e.g. evaluation of AEs and SAEs including 
injection site reactions) should be repeated after the dose is administered. Several of the safety 
parameters are used as efficacy parameters as well and are therefore already described in the 
section 6.4 above (e.g hsCRP, blood pressure, body weight). 
6.5.1 
Physical examination  
A physical examination, including general appearance, skin, neck, eyes, ears, nose, throat, 
lungs, heart, abdomen, back, lymph nodes, extremities, vascular and neurological systems will 
be performed as indicated in Table 6-1. 
If necessary, based on medical history and/or symptoms, additional exams will be performed at 
the discretion of the investigator. 
Whenever possible, assessments for an individual subject should be performed by the same 
member of the study site staff throughout the study. 

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6.5.2 
Vital signs  
Vital signs (blood pressure and pulse measurements) will be assessed at every scheduled visit 
as indicated in Table 6-1. Whenever possible, assessments should be performed by the same 
study site staff member throughout the study. Please see detailed description of blood pressure 
measurement in section 6.4.6. 
6.5.3 
Height and weight  
Height and body weight will be measured as listed in Table 6-1, height in centimeters (cm) and 
body weight in kilogram (kg) (to the nearest 0,1 kg). 
Measurement is described in detail in section 6.4.4. 
6.5.4 
Laboratory evaluations 
A central laboratory will be used for analysis of all specimens listed below, unless noted 
otherwise. Details on the collections, shipment of samples and reporting of results by the central 
laboratory are provided to investigators in the laboratory manual. Refer to the Laboratory 
Manual for identification of laboratory reference range values and the schema for notification 
of site staff and Novartis for out of range values.  
Except for liver and renal laboratory values, no specific action is pre-defined within this 
protocol to respond to specific abnormal laboratory values, as it will be decided by the 
investigator whether and which specific action needs to be taken to respond to any abnormal 
values, taking into account the overall status of the subject.  
6.5.4.1 
Routine laboratory  
Routine laboratory measurements include clinical chemistry and hematology. They will be 
measured at all time points specified in Table 6-1. 
Hematology: Hemoglobin, hematocrit, red blood cell count, white blood cell count with 
differential (neutrophils including bands, lymphocytes, monocytes, eosinophils, basophils) and 
platelet count. 
Clinical chemistry/ proteins: Urea, creatinine, total bilirubin, AST (SGOT), ALT (SGPT), 
GGT, alkaline phosphatase, creatinine, sodium, potassium, bicarbonate, calcium, 
phosphorous, total protein, albumin, uric acid, amylase, lipase, hsCRP, HbA1c (only at visits 
1, 2, 7, 9, 11, 12, E1, E2, E3 included), fructosamine (only at visits 1, 2, 6, 7, 8, 9, 10, 11, 12, 
E1, E2, E3 included). 
6.5.4.2 
Fasting laboratory 
Fasting laboratory measurements will be made at all time points specified in Table 6-1. Fasting 
for 8 hours duration with water ad libitum is required prior to blood draws. Subjects 
should avoid smoking within in the hours preceding the blood draws.  
Fasting laboratory: Total cholesterol, triglycerides, HDL, LDL, fasting plasma glucose. 

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6.5.4.3 
Urinalysis  
Dipsticks will be provided by the central laboratory to the study sites for local urinalysis 
assessments. Standard dipstick measurements for specific gravity, nitrite, protein, glucose, pH, 
blood, urine blood dipstick (non-hemolyzed), urine blood dipstick (hemolyzed), urobilinogen, 
bilirubin, ketones and WBC will be done at scheduled visits as indicated in Table 6-1. If needed 
conditional microscopy assessments will be optional and will be performed locally. 
6.5.5 
Electrocardiogram (ECG)  
Not applicable in this study. 
6.5.6 
Pregnancy and assessments of fertility  
In all women who are not sterilized or are of childbearing potential a serum pregnancy test (ß-
hCG) must be performed as indicated in Table 6-1.  
Any woman with a confirmed positive pregnancy test during Screening is not eligible for 
randomization. A positive serum pregnancy test during the treatment phases of the study 
requires immediate interruption of study treatment. 
6.5.7 
Appropriateness of safety measurements  
The safety assessments selected are standard measures for a biologic immunomodulating agent 
in Psoriasis. 
The safety assessments selected are standard for this indication/patient population. 
6.6 
Other assessments  
6.6.1 
Clinical Outcome Assessments (COAs)  
6.6.1.1 
Clinician Reported Outcomes (ClinRO) 
Not applicable. 
6.6.1.2 
Patient Reported Outcomes (PRO) 
Patient reported outcomes will be assessed by the following validated instruments, each of 
which will be performed as indicated in Table 6-1: 
• Dermatology Life Quality Index (DLQI©) 
• Self-assessed pain, itching, scaling 
• WHO-5 
All these quality of life assessments should be completed by the subject before they see the 
study physician (investigator or designee) who will perform the investigator assessments. 
All these quality of life assessments will be completed in German language. The subject 
should be given sufficient space and time to complete the questionnaires. The study coordinator 
should check the questionnaires for completeness and encourage the subject to complete any 
missing responses. Prior to clinical examination, the investigator should review the completed 

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questionnaires for responses that may indicate potential AEs or SAEs. If AEs or SAEs are 
confirmed, the investigator must record the events as per instructions given in Section 7 of the 
protocol. 
Investigators should not encourage subjects to change the responses reported in the completed 
questionnaires. 
Dermatology Life Quality Index (DLQI©) 
The DLQI© is a 10-item general dermatology disability index designed to assess Health-related 
quality of life (HRQoL) in adult subjects with skin diseases such as eczema, psoriasis, acne, 
and viral warts (Finlay and Khan, 1994; Basra et al., 2008).  
The measure is self-administered and includes domains of daily activities, leisure, personal 
relationships, symptoms and feelings, treatment, and work/school. The measure is widely used: 
it has been tested across 33 different skin conditions and is available in 85 languages. The DLQI 
is the most frequently used instrument in studies of randomized controlled trials in dermatology. 
The recall period is the previous week, and the instrument takes 1 to 2 minutes to complete. 
Each item has four response categories ranging from 0 (not at all) to 3 (very much). “Not 
relevant” is also a valid response and is scored as 0. The DLQI© total score is a sum of the 10 
questions. Scores range from 0 to 30, with higher scores indicating greater HRQoL impairment. 
Each subscale of the DLQI© may also be analyzed separately. 
Subject’s self-assessed pain, itching and scaling 
A self-administered, 11-point numeric rating scale (NRS, 0-10) will be used to evaluate the 
subject’s assessment of their current pain, itching and scaling. Respondents will answer the 
following questions for the assessment of  
Pain: Overall, how severe was your psoriasis-related pain over the past 24 hours 
Itching: Overall, how severe was your psoriasis-related itch over the past 24 hours 
Scaling: Overall, how severe was your psoriasis-related scaling over the past 24 hours 
Subjects have to rate their pain, itching, and scaling from 0 to 10 (11-point scale), with the 
understanding that the 0 represents the absence or null end of the pain, itching, or scale intensity 
(i.e., no pain, itching or scaling) and the 10 represents the other extreme of pain, itching, or 
scaling intensity (i.e., pain, itching or scaling as bad as it could be). The number that the patient 
selects represents his or her intensity score. 
WHO-5 
The 5-tem World Health Organization Well-Being Index (WHO-5) is a validated, short 
questionnaire consisting of 5 simple questions, assessing subjective psychological well-being 
of the respondents. It is among the most widely used questionnaires for the assessment of 
psychological well-being and has been successfully applied across a wide range of study fields. 
The measure is self-administered and takes approximately one minute to complete. The recall 
period is the previous two weeks. Each item has 6 response categories, ranging from 5 (“the 
whole time”) to 0 (“at no time point”). The WHO-5 total score is the sum of the 5 questions. 
Each subscale of the WHO-5 may also be analyzed separately. 

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6.6.1.3 
Performance Outcomes (PerfO) 
Not applicable. 
6.6.1.4 
Observer Reported Outcomes (ObsRO) 
Not applicable 
6.6.1.5 
Proxy Reported Outcomes 
Not applicable. 
6.6.2 
Resource utilization  
Not applicable. 
6.6.3 
Pharmacokinetics  
Not applicable. 
6.6.4 
DNA sampling  
Not applicable. 
Pharmacogenetics 
Not applicable. 
6.6.5 
Biomarker substudy  
A biomarker sub-study will be performed during the core study to explore the effect of 
Secukinumab (300 mg, 4-weekly s.c.) combined with lifestyle intervention in comparison to 
Secukinumab alone on biomarkers including but not limited to those linked to lipid, glucose, 
muscle and bone metabolism, liver fibrosis/steatosis, heart failure, as well as to inflammatory 
processes in a subgroup of 100 patients (50 treated with secukinumab and lifestyle intervention 
and 50 treated with Secukinumab alone). At baseline (week 0), week 16 and week 28 the 
following markers will be assessed using fasting blood samples: Free fatty acid serum profile, 
sThy-1, adiponectin, leptin, insulin, HOMA-IR, proinsulin, IL-6, TNF-alpha, M30 assay, IL-1 
beta, IL-1Ra, IL-18, IL-18bp, P1NP, CTX, RANKL, OPG, sclerostin, NT-proBNP, CD154, 
and a 30-panel multiplex inflammatory cytokine and chemokines panel. 
The markers will be assessed centrally. 
7 
Safety monitoring  
7.1 
Adverse events  
An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or 
clinical investigation subject after providing written informed consent for participation in the 
study until the end of study visit. Therefore, an AE may or may not be temporally or causally 
associated with the use of a medicinal (investigational) product. Medical conditions/ diseases 

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present before first intake of study drug are only considered adverse events if the worsen after 
study start. 
In addition, all reports of intentional misuse and abuse of the product are also considered an 
adverse event irrespective if a clinical event has occurred. 
The occurrence of adverse events must be sought by non-directive questioning of the patient at 
each visit during the study. Adverse events also may be detected when they are volunteered by 
the patient during or between visits or through physical examination findings, laboratory test 
findings, or other assessments. 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria: 
• they induce clinical signs or symptoms,  
• they are considered clinically significant,  
• they require therapy.  
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in patient with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
patient and identifying adverse events. Alert ranges for laboratory and other test abnormalities 
are included in Appendix 1. Clinically significant abnormal laboratory values will also be 
assessed for the following parameters of the biomarker sub-study (only for patients participating 
in the biomarker sub-study): Adiponectin, leptin, insulin, HOMA-IR, proinsulin, IL-6, TNF-
alpha, M30 assay, NT-proBNP. 
Adverse events must be recorded in the Adverse Events CRF under the signs, symptoms or 
diagnosis associated with them, accompanied by the following information: 
• the severity grade 
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 and/or to the lifestyle intervention 
o “No Relationship to study treatment and lifestyle intervention” or 
o “Relationship to study treatment” or 
o “Relationship to lifestyle intervention” or  
o “Relationship to both study treatment and lifestyle intervention 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 serious adverse event (SAE - See Section 7.2 for definition of 
SAE) and which seriousness criteria have been met. 
• action taken regarding study drug or lifestyle intervention 
• its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown) 

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All adverse events must be treated appropriately. The action taken to treat the adverse event 
should be recorded on the Adverse Event eCRF. Treatment may include one or more of the 
following:  
• no action taken (e.g. further observation only)  
• study treatment dosage increased/reduced 
• lifestyle intervention intensity increased/reduced 
• study treatment and/or lifestyle intervention interrupted/withdrawn 
• concomitant medication given 
• non-drug therapy given  
• patient hospitalized/patient’s hospitalization prolonged (see Section 7.2 for definition of 
SAE) 
Once an adverse event is detected, it must be followed until its resolution or until it is judged to 
be permanent, and assessment must be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the study drug, the interventions required 
to treat it, and the outcome. 
Information about common side effects already known about the investigational drug can be 
found in the Investigator Brochure (IB). This information will be included in the patient 
informed consent and should be discussed with the patient prior to and during the study as 
needed. Any new information regarding the safety profile of the medicinal product that is 
identified between IB updates will be communicated as appropriate, for example, via an 
Investigator Notification or an Aggregate Safety Finding. New information might require an 
update to the informed consent and has then to be discussed with the patient. 
The investigator must also instruct each patient to report any new adverse event (beyond the 
protocol observation period) that the patient, or the patient’s personal physician, believes might 
reasonably be related to study treatment. This information must be recorded in the investigator’s 
source documents; however, if the AE meets the criteria of an SAE, it must be reported to 
Novartis. 
7.2 
Serious adverse events 
7.2.1 
Definition of SAE 
An SAE is defined as any adverse event 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 (specify what this includes) 

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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 (please refer to Annex IV, ICH-E2D Guideline). 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the patient or might 
require intervention to prevent one of the other outcomes listed above. Examples of such events 
are intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization or development of dependency or 
abuse (please refer to Annex IV, ICH-E2D Guideline). 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
7.2.2 
SAE reporting 
To ensure patient safety, every SAE must be reported to Novartis safety within 24 hours of 
learning of its occurrence.  
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 Secukinumab 
treatment or lifestyle intervention, 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 

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resolved or continues, if and how it was treated, and whether the patient continued or withdrew 
from study participation. 
 
SAE reporting in the Extension Period: 
In the Extension Period, the treating physician is free to choose suitable psoriasis therapy for 
each patient. 
Therapy with marketed Secukinumab or another Novartis product:  
Any SAE occurring in the Extension Period should be notified to Novartis Patient Safety 
within 24 hours of learning of its occurrence, .regardless of causality assessment. 
Furthermore, any SAE occurring until 10 weeks (70 days) after the last study visit, or 12 
Weeks (84 days) following the last administration of marketed Secukinumab, or 30 days after 
the subject has stopped study participation (whichever is later) must be reported to Novartis.  
Also any non-serious adverse event needs to be documented in the Adverse Events CRF 
section during study participation.  
Therapy with non-Novartis products:  
Any SAE occurring in the Extension Period under therapy with a non-Novartis product is sent 
to Novartis Patient Safety regardless of causality, within 12 weeks after last administration of 
investigational drug Secukinumab or marketed Secukinumab (if switch is performed during 
the Extension Period). During the 12 weeks period, physician should clearly state on the SAE 
form which treatment (current non-Novartis therapy or previous Secukinumab treatment) has 
been assessed as suspected or not. After this 12 weeks period, only SAE need to be forwarded 
to Novartis for which causality was assessed as suspected for Secukinumab by investigator. 
Furthermore, any suspected SAE under a non-Novartis drug should be forwarded to the 
respective manufacturer or the regulatory authority by the investigator. 
 
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert (new 
occurrence) and is thought to be related to the study treatment a Novartis Patient Safety  
Department associate may urgently require further information from the investigator for health 
authority reporting. Novartis may need to issue an Investigator Notification (IN) to inform all 
investigators involved in any study with the same study treatment that this SAE has been 
reported. Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and 
reported to the competent authorities and relevant ethics committees in accordance with EU 
Guidance 2011/C 172/01 or as per national regulatory requirements in participating countries. 
7.3 
Liver safety monitoring 
To ensure patient safety and enhance reliability in determining the hepatotoxic potential of an 
investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed.  
The following two categories of abnormalities / adverse events have to be considered during 
the course of the study (irrespective of whether classified/reported as (S)AE): 

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• Liver laboratory triggers, which will require repeated assessments of the abnormal 
laboratory parameter 
• Liver events, which will require close observation, follow-up monitoring and completion of 
the standard base liver CRF pages 
Please refer to Table 14-1 in Appendix 2 for complete definitions of liver laboratory triggers 
and liver events.  
Every liver laboratory trigger or liver event as defined in Table 14-1 of Appendix 2 should be 
followed up by the investigator or designated personal at the trial site as summarized below. 
Detailed information is outlined in Table 14-2 in Appendix 2. 
For the liver laboratory trigger: 
• Repeating the liver function test (LFT) within the next week to confirm elevation. 
These LFT repeats must be performed using the central laboratory if possible. If this is not 
possible, then the repeats can be performed at a local laboratory to monitor the safety of the 
patient. Repeats laboratory must then be performed at central laboratory as soon as possible. If 
a liver event is subsequently reported, any local LFTs previously conducted that are associated 
with this event must be reported on the Liver CRF pages. 
• If the elevation is confirmed, close observation of the patient will be initiated, including 
consideration of treatment interruption if deemed appropriate. 
For the liver events: 
• Repeating the LFT to confirm elevation as appropriate 
• Discontinuation of the investigational drug if appropriate 
• Hospitalization of the patient if appropriate 
• A causality assessment of the liver event via exclusion of alternative causes (e.g., disease, 
co-medications) 
• An investigation of the liver event which needs to be followed until resolution.  
These investigations can include serology tests, imaging and pathology assessments, 
hepatologist’s consultancy, based on investigator’s discretion. All follow-up information, and 
the procedures performed must be recorded on appropriate CRF pages, including the liver event 
overview CRF pages. 
7.4 
Reporting of study treatment errors including misuse/abuse  
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, patient or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 

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Study treatment errors and uses outside of what is foreseen in the protocol will be collected in 
the DAR (dose administration record) eCRF irrespective of whether or not associated with an 
AE/SAE and reported to Safety only if associated with an SAE. Misuse or abuse will be 
collected and reported in the safety database irrespective of it being associated with an AE/SAE. 
 
Table 7-1  
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error 
type 
Document in Dose 
Administration 
(DAR) eCRF (Yes/No) 
Document in AE 
eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated with 
an AE 
Only if associated with an 
SAE 
Misuse/Abuse 
Yes 
Yes,  
Yes, even if not 
associated with a SAE 
 
7.5 
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 Patient Safety 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 form. 
8 
Data review and database management  
8.1 
Site monitoring  
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and data capture requirements (i.e. eSource or eCRFs) 
with the investigators and their staff. During the study, Novartis employs several methods of 
ensuring protocol and GCP compliance and the quality/integrity of the sites’ data. The field 
monitor will visit the site to check the completeness of patient records, the accuracy of data 
capture / data entry, the adherence to the protocol and to Good Clinical Practice, the progress 
of enrollment, and to ensure that study treatment is being stored, dispensed, and accounted for 
according to specifications. Key study personnel must be available to assist the field monitor 
during these visits.  Continuous remote monitoring of each site’s data may be performed by a 
centralized Novartis CRA organization. Additionally, a central analytics organization may 

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analyze data & identify risks & trends for site operational parameters, and provide reports to 
Novartis Clinical Teams to assist with trial oversight. 
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
patient's file. The investigator must also keep the original informed consent form signed by the 
patient (a signed copy is given to the patient). 
The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. Novartis monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the CRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
patients/subjects will be disclosed. 
8.2 
Data collection  
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms using fully validated software that conforms to US CFR 21Part 11 
requirements. Designated investigator site staff will not be given access to the EDC system until 
they have been trained. Automatic validation programs check for data discrepancies and, by 
generating appropriate error messages, allow the data to be confirmed or corrected before 
transfer of the data to the CRO working on behalf of Novartis. The Investigator must certify 
that the data entered into the Electronic Case Report Forms are complete and accurate. After 
database lock, the investigator will receive copies of the patient data for archiving at the 
investigational site.  
8.3 
Database management and quality control  
Novartis staff [or CRO working on behalf of Novartis] review the data entered into the CRFs 
by investigational staff for completeness and accuracy and instruct the site personnel to make 
any required corrections or additions. Queries are sent to the investigational site using an 
electronic data query. Designated investigator site staff is required to respond to the query and 
confirm or correct the data. If the electronic query system is not used, a paper Data Query Form 
will be faxed to the site. Site personnel will complete and sign the faxed copy and fax it back 
to Novartis staff that will make the correction to the database. The signed copy of the Data 
Query Form is kept at the investigator site. 
Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system. 
Concomitant procedures, non-drug therapies and adverse events will be coded using the 
Medical dictionary for regulatory activities (MedDRA) terminology. 
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated CRO). 

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The occurrence of relevant protocol deviations will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 
locked. Any changes to the database after that time can only be made after written agreement 
by Novartis Development management. 
8.4 
Data Monitoring Committee  
Not required. 
8.5 
Adjudication Committee  
Not required. 
9 
Data analysis  
The analysis will be conducted on all subject data at the time the trial ends. Any data analysis 
carried out independently by the investigator should be submitted to Novartis before publication 
or presentation. 
9.1 
Analysis sets  
The following analysis sets will be used in this study: 
The Enrolled Set will include all patients who provided informed consent. 
The Randomized Set will consist of all patients who were randomized into this study at 
Baseline. 
The Safety Set (SAF) will consist of all patients who received at least 1 dose of study treatment. 
The Full Analysis Set (FAS) will consist of all patients who were randomized into this study 
at Baseline and received at least one dose of study treatment. Data will be analyzed according 
to the treatment assigned at randomization.  
9.2 
Patient demographics and other baseline characteristics  
Summary statistics will be presented for continuous demographic and baseline characteristics 
for each treatment group and for all patients in the randomized set. The number and percentage 
of patients in each category will be presented for categorical variables for each treatment group 
and for all patients. 
9.3 
Treatments   
9.3.1 
Study treatment 
The analysis of study treatment data will be based on the Safety Set.  
The duration of exposure to study treatment will be summarized by treatment group. In addition, 
the number of patients with exposure of certain thresholds of study treatment will be displayed. 
Compliance will be calculated based on documented study drug administrations, syringe counts 
and documented participation in lifestyle intervention and displayed by treatment group. 

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9.3.2 
Prior and concomitant treatment 
Prior and concomitant treatments and non-drug therapies will be summarized by treatment 
group in separate tables. 
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 and the last study visit day will be a concomitant treatment, including those that were 
started pre-baseline and continued into the treatment period. 
Treatments will be presented in alphabetical order, by anatomical therapeutic classification 
(ATC) codes and grouped by anatomical main group. The overall number and percentage of 
patients receiving at least 1 treatment in a particular ATC will also be presented in summary 
tables. 
 
9.4 
Analysis of the primary variable(s) 
9.4.1 
Primary Variable(s) 
The primary variable is the percentage of patients achieving PASI90 at week 28 in both 
randomized treatment arms, Secukinumab alone and Secukinumab combined with lifestyle 
intervention. 
9.4.2 
Statistical model, hypothesis, and method of analysis 
The null hypothesis to be rejected is that the odds of response Week 28 are equal in both 
treatment groups. The corresponding alternative hypothesis is that the odds of response at 
Week 28 are higher under Secukinumab combined with lifestyle intervention compared to 
Secukinumab alone. 
Let pj denote the proportion of responders at Week 28 for treatment group j, j=0, 1, where 
• 0 corresponds to Secukinumab combined with lifestyle intervention 
• 1 corresponds to Secukinumab alone 
The following hypotheses will be tested: 
H0: (p1 / (1- p1)) / (p0 / (1- p0)) = 1 versus HA: (p1 / (1- p1)) / (p0 / (1- p0)) ≠ 1 
In other words: 
HA: The odds ratio of achieving a response at Week 28 for Secukinumab combined with 
lifestyle intervention vs Secukinumab alone is different from 1. 
The primary analysis will be performed comparing treatments with respect to the primary 
efficacy variable in a logistic regression model with the factors treatment, center and covariate 
baseline PASI. The odds ratio and its 95% confidence interval (CI) and p-value will be given. 
The null hypothesis of equal odds will be rejected if the 2-sided p-value from the logistic 
regression model for the factor “treatment” is < 0.05; however, superiority of Secukinumab 
combined with lifestyle intervention will be claimed only if the direction is correct, i.e. if the 
odds of response are larger under Secukinumab combined with lifestyle intervention. 

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9.4.3 
Handling of missing values/censoring/discontinuations 
Patients who do not have a valid PASI assessment at week 28 will be regarded as non-
responders for the primary analysis. Non-responder imputation will also be applied to all 
secondary response variables. For continuous secondary endpoints, all available measurements 
will be included in the MMRM. 
9.4.4 
Sensitivity analyses  
The primary endpoint will be analyzed by means of a Cochran-Mantel-Haenszel (CMH) test. 
This test will be stratified by center. Treatment groups will be compared with respect to the 
proportion of responders using the Cochran-Mantel-Haenszel test statistics. The corresponding 
p-values will be based on the CMH statistics which follows a Chi-square distribution with one 
degree of freedom. 
9.5 
Analysis of secondary variables 
9.5.1 
Efficacy variables  
PASI 75, 90 and 100 at weeks 1, 2, 3, 4, 8, 12, 16, 20, 24 and 28 will be analyzed analogous to 
the primary endpoint. Absolute PASI scores will be analyzed using a Mixed Model for Repeated 
Measurements (MMRM) with factors treatment, center, visit, visit*treatment interaction and 
covariate baseline PASI. The raw- as well as the adjusted (LS-) means and their differences 
between treatment groups will be calculated for each visit together with their corresponding 
95% confidence intervals and p-values. 
The same MMRM model will also be used for the analyses of the other continuous secondary 
endpoints hsCRP, HbA1c, fructosamine, fasting plasma glucose, LDL, HDL, cholesterol, 
triglycerides, waist circumference, body weight, BMI, systolic and diastolic blood pressure, 
absolute DLQI, relative change of DLQI, proportion of patients with DLQI 0/1, absolute WHO-
5, relative change in WHO-5, absolute self-assessed itch, pain, scaling, relative change in self-
assessed itch, pain, scaling in both treatment arms throughout the duration of the core study, 
and activity levels. 
9.5.2 
Safety variables 
9.5.2.1 
Adverse events 
Treatment emergent adverse events (events started after the first dose of study treatment or 
events present prior to the first dose of study treatment but increased in severity) will be 
summarized by preferred term up to 12 weeks (84 days) after the last dose. Non-treatment-
emergent AEs will be listed in a listing but not summarized. 
Adverse events will be summarized by presenting, for each treatment group, 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 adverse event 
with the same preferred term, the adverse event with the greatest severity will be presented. If 
a patient reported more than one adverse event within the same primary system organ class, the 

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the Secukinumab combined with lifestyle intervention arm compared to the Secukinumab alone 
arm. In case the true effect size would only be 7.5 %, this sample size would still provide a 
power of 75 %. To compensate for some expected drop out and/or premature discontinuations, 
380 patients per arm are planned to be recruited for this trial.  
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, IRB/IEC-approved 
informed consent. In cases where the patient’s representative gives consent, the patient must be 
informed about the study to the extent possible given his/her understanding. If the patient is 
capable of doing so, he/she must indicate assent by personally signing and dating the written 
informed consent document or a separate assent form. Informed consent must be obtained 
before conducting any study-specific procedures (e.g. all of the procedures described in the 
protocol). The process of obtaining informed consent must be documented in the patient 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 trial, the investigator/institution must obtain approval/favorable opinion from 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, 
written informed consent form, consent form updates, subject recruitment procedures (e.g., 
advertisements) and any other written information to be provided to patients/subjects. Prior to 
study start, the investigator is required to sign a protocol signature page confirming his/her 
agreement to conduct the study in accordance with these documents and all of the instructions 
and procedures found in this protocol and to give access to all relevant data and records to 
Novartis monitors, auditors, Novartis Quality Assurance representatives, designated agents of 
Novartis, IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site 
is requested by a regulatory authority, the investigator must inform Novartis immediately that 
this request has been made. 

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10.4 
Publication of study protocol and results  
The key design elements of this protocol will be posted in a publicly accessible database such 
as clinicaltrials.gov. In addition, upon study completion and finalization of the study report the 
results of this trial will be either submitted for publication and/or posted in a publicly accessible 
database of clinical trial results. 
10.5 
Quality Control and Quality Assurance  
Novartis maintains a robust Quality Management (QM) system that includes all activities 
involved in quality assurance and quality control, including the assignment of roles and 
responsibilities, the reporting of results, and the documentation of actions and escalation of 
issues identified during the review of quality metrics, incidents, audits and inspections. 
Audits of investigator sites, vendors, and Novartis systems are performed by Novartis Pharma 
Auditing and Compliance Quality Assurance, a group independent from those involved in 
conducting, monitoring or performing quality control of the clinical trial. The clinical audit 
process uses a knowledge/risk based approach. 
 
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal SOPs, and are performed according to written Novartis processes. 
11 
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of patients/subjects 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  
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. Only amendments that are intended to eliminate an apparent immediate hazard 
to patients/subjects may be implemented immediately provided the health authorities are 
subsequently notified by protocol amendment and the reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 7 Safety Monitoring must be followed. 

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12 
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13 
Appendix 1: Clinically notable laboratory values and vital 
signs  
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests.  Notable values for blood pressure and pulse are presented in section Error! 
Reference source not found.. 
No specific action is pre-defined within this protocol to respond to specific abnormal laboratory 
values except for the follow up requirement for liver events as specified in Appendix 2, as it 
will be decided by the investigator/qualified site staff whether and which specific action needs 
to be taken to respond to any abnormal values, taking into account the overall status of the 
subject.  
Liver Function and Related Variables  
ALT (SGPT):  
 
 
 
> 3 x Upper Limit of Normal (ULN) 
AST (SGOT):  
 
 
 
> 3 x ULN 
Total bilirubin: 
 
 
 
> 1.5 x ULN 
Alkaline phosphatase:  
 
 
> 2 x ULN 

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Renal Function and Electrolyte Variables 
Creatinine (serum): 
 
 
 
> 1.5 x ULN 
Hematology Variables 
Hemoglobin:  
 
 
 
≥ 20 g/dL 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 
 
14 
Appendix 2: Liver event definitions and follow-up 
requirements 
Table 14.1 
Liver Event Definitions 
 
Definition/ threshold 
Adverse event of special 
interest 
 
Laboratory values 
ALT or AST > 3 x ULN 
 
ALP > 2 x ULN 
 
TBL > 1.5 x ULN 
Medically significant event 
(SAE) 
 
Laboratory values 
ALT or AST > 5 x ULN (with or without TBL > 2 x ULN [mainly 
conjugated fraction]) 
 
ALP > 5 x ULN (with or without TBL > 2 x ULN [mainly conjugated 
fraction]) 
 
TBL > 3 x ULN 
 
Potential Hy’s Law cases (defined as ALT/AST > 3 x ULN and 
TBL > 2 x ULN [mainly conjugated fraction] without notable 
increase in ALP to > 2 x ULN) 
Adverse events 
Any clinical event of jaundice (or equivalent term) 
 
ALT or AST > 3 x ULN accompanied by general malaise, fatigue, 
abdominal pain, nausea, or vomiting, or rash with eosinophilia 
 
Any event that links to a preferred term (PT) in the MedDRA 
dictionary falling under the SMQ sub-module “Drug-related hepatic 
disorders – severe events only”* or any “Hy’s law case” PT 
* These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver damage-related 
conditions; the non-infectious hepatitis; the benign, malignant and unspecified liver neoplasms 

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Table 14-2 
Liver Event Follow Up Requirements 
Criteria 
Event type 
Actions required 
Follow-up monitoring 
Potential Hy’s Law 
casea 
Medically 
significant 
Discontinue the study drug 
immediately 
Hospitalize, if clinically 
appropriate 
Report to Novartis as an SAE 
Establish causality 
ALT, AST, TBL, Alb, PT, 
ALP and γGT until 
resolutionc (frequency at 
investigator discretion) 
 
ALT or AST 
> 8 x ULN 
Medically 
significant 
Repeat LFT within 48 hours 
If elevation persists, discontinue 
the study drug immediately 
Hospitalize if clinically 
appropriate 
Report to Novartis as an SAE 
Establish causality 
ALT, AST, TBL, Alb, PT, 
ALP and γGT until 
resolutionc (frequency at 
investigator discretion) 
> 5 to ≤ 8 x ULN 
Medically 
significant 
Repeat LFT within 48 hours 
If elevation persists for more 
than 2 weeks, discontinue the 
study drug 
Report to Novartis as an SAE 
Establish causality 
ALT, AST, TBL, Alb, PT, 
ALP and γGT until 
resolutionc (frequency at 
investigator discretion) 
> 3 x ULN 
accompanied by 
symptomsb 
Medically 
significant 
Discontinue the study drug 
immediately 
Hospitalize if clinically 
appropriate 
Report to Novartis as an SAE 
Establish causality 
ALT, AST, TBL, Alb, PT, 
ALP and γGT until 
resolutionc (frequency at 
investigator discretion) 
> 3 to ≤ 5 x ULN  
(patient is 
asymptomatic) 
AESI 
Central laboratory to report to 
Investigator & Novartis 
Repeat LFT once or twice in the 
week 
If elevation persists, establish 
causality 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
≤ 3 x ULN  
(patient is 
asymptomatic) 
N/A 
Repeat LFT at next visit 
 
ALP (isolated) 
> 5 x ULN 
Medically 
significant 
Repeat LFT within 48 hours 
If elevation persists, report to 
Novartis as an SAE 
Establish causality 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
> 2 to ≤5 x ULN  
(patient is 
asymptomatic) 
AESI 
Central laboratory to report to 
Investigator & Novartis 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 

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Criteria 
Event type 
Actions required 
Follow-up monitoring 
Repeat LFT once or twice in the 
weekIf elevation persists, 
establish causality 
≤ 2 x ULN  
(patient is 
asymptomatic) 
N/A 
Repeat LFT at next visit 
 
TBL (isolated) 
> 3 x ULN 
Medically 
significant 
Repeat LFT within 48 hours 
If elevation persists, discontinue 
the study drug immediately 
Hospitalize if clinically 
appropriate 
Report to Novartis as an SAE 
Establish causality 
ALT, AST, TBL, Alb, PT, 
ALP and γGT until 
resolutionc (frequency at 
investigator discretion) 
Test for hemolysis (e.g., 
reticulocytes, haptoglobin, 
unconjugated [indirect] 
bilirubin) 
> 1.5 to ≤ 3 x ULN 
(patient is 
asymptomatic) 
AESI 
Central laboratory to report to 
Novartis 
Repeat LFT once or twice in the 
weekIf elevation persists, 
establish causality 
investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
≤ 1.5 x ULN 
(patient is 
asymptomatic) 
N/A 
Repeat LFT at next visit 
 
Preferred terms 
Jaundice 
Medically 
significant 
Discontinue the study drug 
immediately 
Hospitalize the patient 
Report to Novartis as an SAE 
Establish causality 
ALT, AST, TBL, Alb, PT, 
ALP and γGT until 
resolutionc (frequency at 
investigator discretion) 
“Drug-related 
hepatic 
disorders - severe 
events only” SMQ 
AE 
Medically 
significant 
Discontinue the study drug  
hospitalization if clinically 
appropriate 
Report to Novartis as an SAE 
Establish causality 
Investigator discretion 
a Elevated ALT/AST > 3 x ULN and TBL > 2 x ULN but with no notable increase in ALP to > 2 x ULN 
b General malaise, fatigue, abdominal pain, nausea, or vomiting, rash with eosinophilia 
c 
Resolution is defined as an outcome of one of the following: return to baseline values, stable 
values at three subsequent monitoring visits at least 2 weeks apart, remain at elevated level after a 
maximum of 6 months, liver transplantation, and death.