A Randomized, Double-blind, Multicenter, 24-week Study of Subcutaneous Secukinumab to Assess Anti-interleukin-17A Treatment in Plaque Psoriasis Patients With Coexisting Non-alcoholic Fatty Liver Disease (pINPOINt)
Phase: PHASE3
Conditions: Plaque Psoriasis, Non-alcoholic Fatty Liver Disease
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development 
AIN457/secukinumab 
Clinical Trial Protocol CAIN457ADE15 / NCT04237116
A randomized, double-blind, multicenter, 24-week study of 
subcutaneous secukinumab to assess anti-interleukin-17A 
treatment in plaque psoriasis patients with coexisting 
 non-alcoholic fatty liver disease (pINPOINt) 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
2019-003168-37 
Version number: 
01 (Amendment 1) 
Clinical trial phase: 
Phase 3b 
Release date: 
05-Jun-2020
Property of Novartis. Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 2.0 (01-Aug-2018) 

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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 
Amendment 1 .................................................................................................................... 10 
Protocol summary .............................................................................................................. 12 
1 
Introduction ....................................................................................................................... 17 
1.1 
Background ............................................................................................................ 17 
1.2 
Purpose .................................................................................................................. 18 
2 
Objectives and endpoints ................................................................................................... 18 
3 
Study design ...................................................................................................................... 20 
4 
Rationale ............................................................................................................................ 21 
4.1 
Rationale for study design ..................................................................................... 21 
4.2 
Rationale for dose/regimen and duration of treatment .......................................... 21 
4.3 
Rationale for choice of control drug (placebo) ...................................................... 21 
4.4 
Purpose and timing of primary analysis/design adaptations .................................. 21 
4.5 
Risks and benefits .................................................................................................. 22 
5 
Population .......................................................................................................................... 23 
5.1 
Inclusion criteria .................................................................................................... 23 
5.2 
Exclusion criteria ................................................................................................... 23 
6 
Treatment ........................................................................................................................... 26 
6.1 
Study treatment ...................................................................................................... 26 
6.1.1 
Investigational and control drug ............................................................ 26 
6.1.2 
Additional study treatments .................................................................. 26 
6.1.3 
Treatment arms/group ........................................................................... 27 
6.1.4 
Treatment duration ................................................................................ 27 
6.2 
Other treatments ..................................................................................................... 27 
6.2.1 
Concomitant therapy ............................................................................. 27 
6.2.2 
Prohibited medication ........................................................................... 27 
6.2.3 
Rescue medication ................................................................................ 29 
6.2.4 
Dietary restrictions ................................................................................ 29 
6.3 
Patient numbering, treatment assignment, randomization ..................................... 29 
6.3.1 
Patient numbering ................................................................................. 29 
6.3.2 
Treatment assignment, randomization .................................................. 30 

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6.4 
Treatment blinding ................................................................................................. 31 
6.5 
Dose escalation and dose modification .................................................................. 31 
6.5.1 
Follow-up for toxicities ......................................................................... 31 
6.6 
Additional treatment guidance ............................................................................... 32 
6.6.1 
Treatment compliance ........................................................................... 32 
6.6.2 
Emergency breaking of assigned treatment code .................................. 32 
6.7 
Preparation and dispensation ................................................................................. 33 
6.7.1 
Handling of study treatment and additional treatment .......................... 33 
6.7.2 
Instruction for prescribing and taking study treatment ......................... 34 
7 
Informed consent procedures ............................................................................................ 35 
8 
Visit schedule and assessments ......................................................................................... 35 
8.1 
Screening ............................................................................................................... 41 
8.1.1 
Information to be collected on screening failures ................................. 41 
8.2 
Patient demographics/other baseline characteristics ............................................. 41 
8.2.1 
Smoking history .................................................................................... 41 
8.2.2 
Tuberculosis screening .......................................................................... 42 
8.2.3 
Relevant medical history/current medical conditions ........................... 42 
8.2.4 
Prior and concomitant medications ....................................................... 42 
8.2.5 
Serum pregnancy test ............................................................................ 42 
8.2.6 
Other baseline characteristics ................................................................ 43 
8.3 
Efficacy .................................................................................................................. 43 
8.3.1 
Psoriasis area severity index ................................................................. 43 
 
 45 
8.3.3 
Liver function tests and liver and/or systemic inflammation 
markers .................................................................................................. 45 
 
 46 
 
 46 
 
 46 
8.3.7 
Appropriateness of efficacy assessments .............................................. 47 
8.4 
Safety ..................................................................................................................... 47 
8.4.1 
Anthropometric assessments ................................................................. 47 
8.4.2 
Physical examination ............................................................................ 48 
8.4.3 
Vital signs.............................................................................................. 48 
8.4.4 
Laboratory evaluations .......................................................................... 49 
8.4.5 
Pregnancy and assessments of fertility ................................................. 50 
8.4.6 
Appropriateness of safety measurements .............................................. 50 
8.5 
Additional assessments .......................................................................................... 50 

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8.5.1 
Alcohol use disorders identification test (AUDIT) ............................... 50 
8.5.2 
Patient reported outcomes ..................................................................... 51 
 
 52 
9 
Study discontinuation and completion .............................................................................. 52 
9.1 
Discontinuation ...................................................................................................... 52 
9.1.1 
Discontinuation of study treatment ....................................................... 52 
9.1.2 
Withdrawal of informed consent ........................................................... 54 
9.1.3 
Lost to follow-up ................................................................................... 54 
9.1.4 
Early study termination by the sponsor ................................................. 54 
9.2 
Study completion and post-study treatment .......................................................... 55 
10 Safety monitoring and reporting ........................................................................................ 55 
10.1 
Definition of adverse events and reporting requirements ...................................... 55 
10.1.1 
Adverse events ...................................................................................... 55 
10.1.2 
Serious adverse events .......................................................................... 57 
10.1.3 
SAE reporting........................................................................................ 58 
10.1.4 
Pregnancy reporting .............................................................................. 58 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 59 
10.2 
Additional safety monitoring ................................................................................. 59 
10.2.1 
Liver safety monitoring ......................................................................... 59 
10.2.2 
Renal safety monitoring ........................................................................ 59 
10.2.3 
Steering committee ................................................................................ 60 
11 Data collection and database management ........................................................................ 60 
11.1 
Data collection ....................................................................................................... 60 
11.2 
Database management and quality control ............................................................ 60 
11.3 
Site monitoring ...................................................................................................... 61 
12 Data analysis and statistical methods ................................................................................ 61 
12.1 
Analysis sets .......................................................................................................... 61 
12.2 
Subject demographics and other baseline characteristics ...................................... 62 
12.3 
Treatments ............................................................................................................. 62 
12.4 
Analysis of the primary endpoint .......................................................................... 62 
12.4.1 
Definition of primary endpoint ............................................................. 62 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 63 
12.4.3 
Handling of missing values/censoring/discontinuations ....................... 63 
12.4.4 
Sensitivity and supportive analyses ...................................................... 63 
12.5 
Analysis of secondary endpoints ........................................................................... 64 
12.5.1 
Safety endpoints .................................................................................... 64 
 
 65 

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12.7 
Interim analyses ..................................................................................................... 65 
 
 66 
13 Ethical considerations and administrative procedures ...................................................... 67 
13.1 
Regulatory and ethical compliance ........................................................................ 67 
13.2 
Responsibilities of the Investigator and IRB/IEC ................................................. 67 
13.3 
Publication of study protocol and results............................................................... 67 
13.4 
Quality control and quality assurance .................................................................... 67 
14 Protocol adherence ............................................................................................................ 68 
14.1 
Protocol amendments ............................................................................................. 68 
15 References ......................................................................................................................... 69 
16 Appendices ........................................................................................................................ 72 
16.1 
Appendix 1: Clinically notable laboratory values ................................................. 72 
16.2 
Appendix 2: The American Heart Association (AHA) Recommended Diet ........ 73 
16.3 
Appendix 3: Liver event definitions and follow-up requirements ......................... 74 
List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 18 
Table 6-1 
Investigational and control drug ............................................................ 26 
Table 6-2 
Prohibited medication ........................................................................... 28 
Table 8-1 
Assessment schedule ............................................................................. 37 
Table 8-2 
PASI scoring system ............................................................................. 43 
 
 45 
Table 8-4 
Laboratory assessments ......................................................................... 49 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 59 
Table 14.1 
Liver Event Definitions ......................................................................... 74 
Table 14-2 
Liver Event Follow Up Requirements .................................................. 75 
List of figures 
Figure 3-1 
Study design .......................................................................................... 20 
 

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List of abbreviations 
AE 
Adverse Event 
AIDS 
Autoimmune Deficiency Syndrome 
 
 
ALT 
Alanine Aminotransferase 
APTT 
Activated Partial Thromboplastin Time 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chemical  
AUDIT 
Alcohol Use Disorders Identification Test 
BMI 
Body Mass Index 
BUN 
Blood Urea Nitrogen 
 
 
CFR 
US Code of Federal Regulations  
CI 
Confidence Interval 
CRF 
Case Report Form  
CRO 
Contract Research Organization 
CRP 
C-Reactive Protein 
DBP 
Diastolic Blood Pressure 
DLQI 
Dermatology Life Quality Index 
DMC 
Data Monitoring Committee 
DNA 
Deoxyribonucleic Acid 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
 
 
EMA 
European Medicines Agency 
 
 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
 
 
FSH 
Follicle Stimulating Hormone 
GCP 
Good Clinical Practice 
GCS 
Global Clinical Supply 
 
 
  
 
Hb 
Hemoglobin 
HbA1c 
Glycated Hemoglobin 
HBsAg 
Hepatitis B Surface Antigen 
HCC 
Hepatocellular Carcinoma 
HCV 
Hepatitis C Virus 
hCG 
Human Chorionic Gonadotropin 
HDL 
High Density Lipoprotein 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 

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ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IFG 
Increased Fasting Glucose 
 
 
IL 
Interleukin  
INR 
International Normalized Ratio 
IQR 
Interquartile range 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
LDL 
Low Density Lipoprotein 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MedDRA 
Medical Dictionary for Regulatory Activities  
MRI 
Magnetic Resonance Imaging 
NAFL 
Non-Alcoholic Fatty Liver 
NAFLD 
Non-Alcoholic Fatty Liver Disease 
NASH 
Nonalcoholic Steatohepatitis 
NSAIDs 
Nonsteroidal Anti-inflammatory Drugs 
NYHA 
New York Heart Association 
OR 
Odds Ratio 
PASI 
Psoriasis Area and Severity Index  
PCR 
Protein-Creatinine Ratio 
PFS 
Prefilled Syringe 
 
 
PRO 
Patient Reported Outcomes 
PT 
Preferred Term 
QMS 
Quality Management System 
RAS 
Randomized Analysis Set 
RBC 
Red Blood Cell 
RNA 
Ribonucleic Acid 
SAE 
Serious Adverse Event 
SAF 
Safety Set 
SBP 
Systolic Blood Pressure 
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
T2DM 
Type-2 Diabetes Mellitus 
TB 
Tuberculosis 
TBL 
Total Bilirubin 
TEAE 
Treatment-Emergent Adverse Event 
 
 
TNFα 
Tumor Necrosis Factor Alpha 

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Tregs 
T Regulatory 
UDCA  
Ursodeoxycholic Acid  
ULN 
Upper Limit Normal 
 
 
WBC 
White Blood Cells 
WHO 
World Health Organization  
WoC 
Withdrawal of Study Consent 
Glossary of terms 
 
Assessment 
A procedure used to generate data required by the study. 
Biologic samples 
A biological specimen including, for example, blood (plasma, serum), saliva, 
tissue, urine, stool, etc. taken from a study patient. 
Cohort 
A specific group of patients fulfilling certain criteria and generally treated at 
the same time. 
Control drug 
A  study drug (active or placebo) used as a comparator to reduce assessment 
bias, preserve blinding of investigational drug, assess internal study validity, 
and/or evaluate comparative effects of the investigational drug. 
Dosage 
Dose of the study treatment given to the patient in a time unit 
Electronic data 
capture  
Electronic data capture (EDC) is the electronic acquisition of clinical study 
data using data collection systems, such as Web-based applications, 
interactive voice response systems and clinical laboratory interfaces. EDC 
includes the use of Electronic Case Report Forms (eCRFs) which are used to 
capture data transcribed from paper source forms used at the point of care 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last patient or at a 
later point in time as defined by the protocol  
Enrollment 
Point/time of patient entry into the study at which informed consent must be 
obtained  
Investigational drug/ 
treatment 
The drug whose properties are being tested in the study 
Medication number 
A unique identifier on the label of medication kits 
Mis-randomized 
patients 
Mis-randomized patients are those who were not qualified for randomization 
and who did not take study treatment, but have been inadvertently 
randomized into the study  
Other treatment 
Treatment that may be needed/allowed during the conduct of the study (i.e. 
concomitant or rescue therapy) 
Period 
The subdivisions of the trial design (e.g. Screening, Treatment, Follow-up) 
which are described in the Protocol. Periods define the study phases and will 
be used in clinical trial database setup and eventually in analysis 
Personal data 
Patient information collected by the Investigator that is transferred to Novartis 
for the purpose of the clinical trial. This data includes patient identifier 
information, study information and biological samples.  
Premature patient 
withdrawal 
Point/time when the patient exits from the study prior to the planned 
completion of all study drug administration and/or assessments; at this time 
all study drug administration is discontinued and no further assessments are 
planned 

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Randomization 
number 
A unique identifier assigned to each randomized patient 
Screen failure 
A patient who did not meet one or more criteria that were required for 
participation in the study 
Source 
data/document 
Source data refers to the initial record, document, or primary location from 
where data comes. The data source can be a database, a dataset, a 
spreadsheet or even hard-coded data, such as paper or eSource 
Start of the clinical 
trial 
The start of the clinical trial is defined as the signature of the informed 
consent by the first patient. 
Study treatment 
Any single drug or combination of drugs or intervention administered to the 
patient as part of the required study procedures 
Study treatment 
discontinuation 
When the patient permanently stops taking any of the study drug(s) prior to 
the defined study treatment completion date (if any) for any reason; may or 
may not also be the point/time of study discontinuation  
Patient number 
A unique number assigned to each patient upon signing the informed 
consent. This number is the definitive, unique identifier for the patient and 
should be used to identify the patient throughout the study for all data 
collected, sample labels, etc. 
Treatment arm/group  
A treatment arm/group defines the dose and regimen or the combination, and 
may consist of 1 or more cohorts. 
Variable 
A measured value or assessed response that is determined from specific 
assessments and used in data analysis to evaluate the drug being tested in 
the study 
Withdrawal of study 
consent (WoC) 
Withdrawal of consent from the study occurs only when a patient does not 
want to participate in the study any longer and does not allow any further 
collection of personal data  
 

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• Section 8.4 – Laboratory evaluations: Removal of parameters that will no longer be 
assessed during the study from table 8-4. 
• Section 8.5.1 – Alcohol use disorder identification test (AUDIT): Instead of the patients 
completing the questionnaire on their own, the site staff will perform the AUDIT together 
with the patient in the form of an interview. Consequently, AUDIT was removed from 
section 8.5.2 – Patient reported outcomes.  
 
Additionally, this protocol amendment includes changes to increase clarity and consistency of 
the text. Consequently, changes were incorporated directly into the protocol with track 
changes, even if not listed specifically in this section. 
The changes herein do not affect the Informed Consent. None of the changes described in this 
amended protocol are made due to newly emerged safety considerations. 
 

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Protocol summary 
 
Protocol number 
CAIN457ADE15 
Full title 
A randomized, double-blind, multicenter, 24-week study of subcutaneous 
secukinumab to assess anti-Interleukin-17A treatment in Plaque Psoriasis 
patients with coexisting NAFLD (pINPOINt) 
Brief title 
A study of secukinumab treatment in patients with plaque psoriasis and 
coexisting non-alcoholic fatty liver disease (NAFLD) 
Sponsor and 
clinical phase 
Novartis, Phase 3b 
Investigation type 
Drug 
Study type 
Interventional 
Purpose and 
rationale 
The aim of this study is to assess the therapeutic efficacy of secukinumab on 
the psoriatic skin and to explore the anti-inflammatory (reduction of hepatic 
inflammation and cell damage), anti-steatotic (reduction of hepatic triglyceride 
content) and anti-fibrotic (reduction of hepatic fibrosis) effects of secukinumab 
in patients with psoriasis and coexisting NAFLD. 
Primary objective  
To demonstrate superiority of secukinumab compared to placebo in patients 
with moderate to severe chronic plaque-type psoriasis and NAFLD with respect 
to psoriasis area and severity index (PASI)90 response at Week 12. 
Secondary 
objectives 
• 
To evaluate the effect of secukinumab compared to placebo on 
hepatic inflammation in patients with moderate to severe psoriasis and 
NAFLD with respect to serum alanine aminotransferase (ALT) levels at 
Week 12. 
• 
To evaluate the effect of secukinumab in patients with moderate to 
severe psoriasis and NAFLD compared to placebo on quality of life 
with respect to dermatology life quality index (DLQI) at Week 12. 

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Study design 
This is a randomized, placebo-controlled, double-blind, parallel-group, 
interventional, multicenter study in patients with moderate to severe plaque 
psoriasis and coexisting NAFLD. This study consists of a Screening Period (up 
to 4 weeks) and 2 Treatment Periods (covering 24 weeks in total).  
Treatment period 1 
Patients will be randomized 2:1 to either receive secukinumab 300 mg s.c. (in 
2 × 150 mg PFS) or placebo (2 × PFS) at Baseline, Week 1, Week 2, Week 3, 
Week 4 and Week 8. 
Treatment period 2 
Starting from Week 12, all patients will receive secukinumab 300 mg s.c. up to 
Week 20.  
Patients who were randomized to placebo during Treatment Period 1 will 
receive secukinumab 300 mg s.c. at Week 12, Week 13, Week 14, Week 15, 
Week 16, and Week 20.  
Patients who were randomized to secukinumab during Treatment Period 1 will 
receive secukinumab 300 mg s.c. at Week 12, Week 16, and Week 20, and 
placebo at Week 13, Week 14 and Week 15 to maintain the blind. 
Population 
Patients with moderate to severe plaque psoriasis and coexisting NAFLD who 
are candidates for systemic psoriasis therapy will be included in this study.  
Inclusion criteria 
1. Patient must be able to understand and communicate with the 
investigator and comply with the requirements of the study, and must 
provide written, signed and dated informed consent before any study 
assessment is performed . 
2. Men and women ≥ 18 years of age at the time of consent. 
3. Moderate to severe plaque-type psoriasis diagnosed for at least 
6 months prior to Screening with a PASI of >10 at baseline. 
4. Candidate for systemic therapy, defined as a subject having moderate 
to severe chronic plaque-type psoriasis that is inadequately controlled 
by: 
• 
Topical treatment and/or, 
• 
Phototherapy and/or, 
• 
Previous systemic therapy. 
5. Diagnosis of NAFLD by either ultrasound at Screening or liver 
histology within 6 months before Baseline. 
6. Obesity with BMI > 25 kg/m2 at Screening. 
7. Elevation of ALT 1.2 to 3.0 × ULN. 
8. Liver fat ≥ 8% at Screening as determined by the reading of the central 
MRI vendor of locally produced images. Note: the MRI assessment 
should only be performed after eligibility has been confirmed for all 
other Screening assessments. 

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Exclusion criteria 
1. Forms of psoriasis other than chronic plaque-type psoriasis at 
Screening. 
2. Drug-induced psoriasis (i.e. new onset or current exacerbation from 
beta-blockers, calcium channel inhibitors or lithium) at Screening and 
baseline. 
3. Ongoing use of prohibited treatments (see Section 6.2.2 of main 
protocol). Respective washout periods detailed in this section have to 
be adhered to. 
4. History of hypersensitivity to any of the study drug constituents. 
5. Pregnant or nursing (lactating) women. 
6. Women of childbearing potential, defined as all women physiologically 
capable of becoming pregnant, unless they are using effective 
methods of contraception during the study or longer if required by 
locally approved prescribing information (e.g., 20 weeks in the 
European Union).  
7. Previous treatment with biological drug targeting IL-17 or the IL-17 
receptor (including prior treatment with secukinumab, ixekizumab, or 
brodalumab).  
8. Past medical history record of infection with human immunodeficiency 
virus (HIV), hepatitis B or hepatitis C prior to screening.  
9. Active systemic infections during the last two weeks (exception: 
common cold) prior to randomization or any infection that reoccurs on 
a regular basis. 
10. History of an ongoing, chronic or recurrent infectious disease, or 
evidence of tuberculosis infection as defined by a positive 
QuantiFERON-TB-Gold Plus (QFT) test 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 randomization and establishes 
conclusively that the subject has no evidence of active tuberculosis. If 
presence of latent tuberculosis is established, then treatment 
according to local guidelines must have been completed prior to 
screening. During treatment of latent tuberculosis, ALT had to remain 
below 2x compared to pre-treatment ALT value.  
11. Significant medical problems, including but not limited to:  
• 
Congestive heart failure [New York Heart Association status of 
class III or IV]. 
• 
Severely reduced kidney function (estimated glomerular filtration 
rate (eGFR) ≤ 29 mL/min/1.73 m2). 
12. Unstable weight (± 5%) over the last 6 months prior to Screening. 
13. Type I diabetes or uncontrolled Type II diabetes (defined as HbAlc ≥ 
10% at Screening.) 
14. Total white blood cell (WBC) count < 2500/μL, or neutrophils < 
1500/μL or hemoglobin < 8.5 g/dL at Screening. 
15. Evidence of hepatic decompensation or severe liver impairment or 
cirrhosis, as defined by the presence of any of the following 
abnormalities: 
• 
Serum albumin < 3.2 mg/dL 
• 
INR > 1.3 
• 
Total bilirubin > 1.3 mg/dL 
• 
AST > 5 × ULN [for elevation of ALT refer to inclusion criterion 7] 

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• 
Alkaline phosphatase > 300 IU/L 
• 
Platelets outside of normal reference range (± 5%) 
• 
History of esophageal varices, ascites, or hepatic encephalopathy 
• 
Splenomegaly 
16. History of liver transplantation or planned liver transplant. 
17. History of biliary diversion. 
18. Presence or history of other liver disease (including but not limited to 
autoimmune hepatitis, hereditary hemochromatosis, alpha-1-
antitrypsin deficiency, Wilson’s disease, drug-induced liver disease). 
19. Current, or history of, significant alcohol consumption for a period of 
more than 3 consecutive months within 1 year prior to screening 
(significant alcohol consumption is defined as more than 20 g/day in 
females or more than 30 g/day in males, on average) or a score on the 
modified alcohol use disorders identification test (AUDIT) 
questionnaire ≥ 8. 
20. History of bariatric surgery or intention to have bariatric surgery during 
study conduct. 
21. History of lymphoproliferative disease or any known malignancy or 
history of malignancy of any organ system treated or untreated within 
the past 5 years, regardless of whether there is evidence of local 
recurrence or metastases (except for skin Bowen’s disease, or basal 
cell carcinoma or actinic keratosis that have been treated with no 
evidence of recurrence in the past 12 weeks; carcinoma in situ of the 
cervix or non-invasive malignant colon polyps that have been 
removed). 
22. Underlying conditions (including, but not limited to metabolic, 
hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal) which in the opinion of the 
Investigator significantly immunocompromise the patient and/or places 
the patient at unacceptable risk for receiving an immunomodulatory 
therapy. 
23. Current severe progressive or uncontrolled disease, which in the 
judgment of the clinical investigator renders the subject unsuitable for 
the trial or puts the subject at increased risk. 
24. 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.  
25. Inability or unwillingness to undergo MRI of the abdomen (e.g., 
patients with pacemakers, or metal fragments / foreign objects in the 
body that are not compatible with performing an MRI of the abdomen, 
weight in excess of MRI machine capacity).  
26. Inability or unwillingness to undergo repeated venipuncture (e.g., 
because of poor tolerability or lack of access to veins). 
27. Ongoing participation (including safety follow-up period) in other 
interventional studies. 
 

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Study treatment 
Study treatment 
Dose form 
Route and frequency of 
administration 
Investigational arm 
 
 
Secukinumab 300 mg 
2 × 150 mg 
PFS  
s.c. weekly in first 4 weeks, 
followed by q4w up to 
Week 20. 
Placebo  
2 × Placebo 
PFS  
s.c. at Week 13, 14, and 15. 
Control arm  
 
 
Placebo  
2 x Placebo 
PFS  
s.c. weekly in the first 
4 weeks followed by q4w up 
to Week 8 
Secukinumab 300 mg 
2 x 150 mg 
PFS  
s.c. weekly for 4 weeks 
starting at Week 12, followed 
by q4w up to Week 20 
PFS = prefilled syringe, q4w = every 4 weeks, s.c. = subcutaneous 
 
Efficacy 
assessments 
• 
PASI 
• 
Hepatic inflammation (assessed via liver enzyme levels) 
Key safety 
assessments 
• 
Adverse events (AEs) 
• 
Vital signs 
• 
Laboratory assessments (e.g. hematology, chemistry, urine tests) 
• 
Physical examinations 
Other 
assessments 
• 
Alcohol use disorders identification test (AUDIT) 
• 
Dermatology Life Quality Index (DLQI) 
 
 
 
 
Data analysis 
The primary analysis will be performed comparing treatments with respect to 
the primary efficacy variable in a logistic regression model with the factors 
treatment group and center as factors and PASI score at Baseline (Day 1) as 
covariates. The odds ratio and its 95 % confidence interval (CI) and p-value will 
be given. The primary analysis will be based on the Full Analysis Set (FAS) and 
will be performed when all patients have completed the Week 12 assessment. 
Key words 
Plaque psoriasis, DLQI, 
, NAFLD, NASH, PASI, secukinumab  

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1 
Introduction 
1.1 
Background 
Psoriasis is a chronic, immune-mediated, inflammatory skin disease that affects 
approximately 2% to 3% of adults in the general population of Western countries (Mantovani 
et al 2016). Psoriasis is also frequently associated with multiple metabolic co-morbidities, 
including non-alcoholic fatty liver disease (NAFLD), obesity, type 2 diabetes, and metabolic 
syndrome (Boehncke and Schön 2015, Warnecke et al 2011). NAFLD affects up to 33% of 
the Western World population, where it has become an important public health problem due 
to its potential progression to severe liver disease (Weiss et al 2014). The pathogenesis of 
NAFLD is described by “multiple hits” on a non-alcoholic fatty liver (NAFL) which is a 
central feature of non-alcoholic steatohepatitis (NASH) (Jahn et al 2016). Histologically, 
NAFLD is defined by a spectrum of lesions, ranging from bland hepatic steatosis (defined as 
intrahepatic triglyceride content of more than 5% of the liver volume or liver weight) without 
inflammation or fibrosis (NAFL) to steatohepatitis (NASH), which involves hepatic 
inflammatory changes and apoptosis leading to liver injury and fibrosis. 
The prevalence rate of hepatic steatosis is approximately 20-30% in non-obese patients but up 
to 75% in obese patients. Remarkably, in a cross-sectional study involving 103 United States 
middle-aged adult patients with psoriasis or psoriatic arthritis (Roberts et al 2015), the 
prevalence of ultrasound-diagnosed NAFLD was 47%, whereas that of NASH was 22% 
among those (n = 52) who underwent a liver biopsy. Recent studies document the prevalence 
of NAFLD to be around 50% in psoriasis patients (e.g. Gisondi et al 2009). A recent 
meta-analysis confirmed that psoriatic patients had a 2-fold increased rate of prevalent 
NAFLD compared with non-psoriatic control individuals, and that this risk was higher among 
those with either more severe psoriasis or psoriatic arthritis (Candia et al 2015). These data 
clearly indicate a prevalence of NAFLD in psoriasis patients, which is far above the general 
population. In addition, the psoriasis severity and systemic inflammatory load has been shown 
to be higher in patients with both psoriasis and NAFLD compared to psoriasis patients 
without NAFLD (Gisondi et al 2009). 
Treatment options for psoriasis are classified as topical, phototherapy, conventional systemic 
or biologic therapy. Systemic drugs such as methotrexate, cyclosporine, fumarates, acitretin, 
apremilast and biologics such as tumor necrosis factor alpha (TNFα) antagonists (etanercept, 
adalimumab and infliximab), the anti-IL-12/23 monoclonal antibody ustekinumab, and the 
anti-IL-17 monoclonal antibody secukinumab are established therapies of moderate-to-severe 
psoriasis (Boehncke & Schön 2015, Nast et al 2015, Nast et al 2017). Secukinumab was 
shown to be effective in moderate to severe psoriasis in a large Phase 2/3 clinical trial 
program, validating IL-17A as a therapeutic target for psoriasis (Langley et al 2014). 
Secukinumab was approved in 2015 by the United States federal Food and Drug 
Administration (FDA) and the European Medicines Agency (EMA) for the treatment of adults 
with moderate-to-severe plaque psoriasis who are candidates for systemic therapy. 
No medical therapy has been established or licensed for NAFLD at this time. Different T-cell 
populations such as T regulatory (Tregs), Th1 and Th17 cells play a central role in the 
immunopathogenesis of fatty liver disease (Vonghia et al 2013). Th17 cells lead to tissue 

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inflammation by the secretion of various cytokines such as IL-17, IL-21, IL-22 and TNFα 
(Ouyang and Valdez 2008). Following the recruitment of macrophages and release of 
pro-inflammatory cytokines in early NASH, induction of hepatic Th17 cell infiltration has 
recently been described as a pathophysiological hallmark in human NASH (Tang et al 2011, 
Rau et al 2016, Harley et al 2014). The pathophysiological relevance of IL-17 becomes 
evident from studies in IL-17RA-/- mice, which are resistant to the development of 
steatohepatitis, whereas wild-type mice show progression from NAFL to NASH by induction 
of the IL-17 axis (Harley et al 2014, Kisseleva et al 2014). Moreover, in a murine high 
fat-induced NAFLD model IL-17 blockade with monoclonal IL-17 antibody showed an 
improved liver function, attenuated hepatic lipid accumulation, suppressed Kupffer cell 
activation and decreased proinflammatory cytokine levels (Xu et al 2013). IL-17, therefore, 
represents an attractive therapeutic target for NAFLD (Giles et al 2015). 
Given the frequent co-incidence of NAFLD and psoriasis, and the higher psoriasis severity 
and increased inflammatory load in patients with both psoriasis and NAFLD compared with 
patients with psoriasis only (Gisondi et al 2009), the efficacy of secukinumab in psoriasis 
patients with coexisting NAFLD remains to be further investigated. With IL-17 being a shared 
pathophysiological hallmark of both psoriasis and NAFLD, this study will further explore 
whether patients with psoriasis and NAFLD additionally benefit from a treatment with 
secukinumab beyond their skin. 
1.2 
Purpose 
The aim of this study is to assess the therapeutic efficacy of secukinumab on the psoriatic skin 
and to explore the anti-inflammatory (reduction of hepatic inflammation and cell damage), 
anti-steatotic (reduction of hepatic triglyceride content) and anti-fibrotic (reduction of hepatic 
fibrosis) effects of secukinumab in patients with psoriasis and coexisting NAFLD. 
2 
Objectives and endpoints 
Table 2-1 
Objectives and related endpoints  
Objectives 
Endpoints 
Primary objectives 
Endpoints for primary objectives 
• 
To demonstrate superiority of 
secukinumab compared to placebo in 
patients with moderate to severe 
chronic plaque-type psoriasis and 
NAFLD with respect to PASI90 
response at Week 12. 
• 
Proportion of patients achieving PASI90 response at 
Week 12. 
Secondary objectives 
Endpoints for secondary objectives 
• 
To evaluate the effect of secukinumab 
compared to placebo on hepatic 
inflammation in patients with moderate 
to severe psoriasis and NAFLD with 
respect to serum ALT levels at 
Week 12. 
• 
Serum ALT level at Week 12. 
• 
To evaluate the effect of secukinumab 
compared to placebo on quality of life 
• 
Proportion of patients achieving DLQI 0/1 at 
Week 12. 

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4 
Rationale 
4.1 
Rationale for study design 
The randomized, double-blind, parallel-group design of this study is aligned with previous 
studies performed in the indication of plaque psoriasis and registration secukinumab studies. 
The double-blind design will be maintained throughout the study to ensure reliable efficacy 
and safety measures are obtained for both treatment groups in patients with moderate to 
severe plaque psoriasis and coexisting NAFLD. This study involves 2 treatment periods, 
which will allow exploration of efficacy and safety effects of secukinumab 300 mg up to 
Week 12 in a placebo-controlled manner and additionally from Week 12 up to Week 24 (with 
last dose at Week 20) with active treatment only. 
4.2 
Rationale for dose/regimen and duration of treatment 
Secukinumab 300 mg s.c. with an initial weekly induction schedule up to 4 weeks followed 
by a s.c. administration of every 4 weeks up to Week 20 is based on the secukinumab Phase 3 
registration program. 
The 12-week placebo-controlled Treatment Period 1 will allow indirect comparisons to 
placebo-controlled pivotal studies regarding skin-related endpoints which also had their 
primary endpoint at Week 12 and assessment of effects on NAFLD related endpoints 
exceeding typically observed placebo effects (Neuschwander-Tetri et al 2015, Ratziu et al 
2008, Harrison et al 2018a, Harrison et al 2018b).  
In previous proof-of-concept studies in NASH patients, 12 weeks has been a standard 
treatment length to demonstrate reduction of hepatic inflammation, steatosis and fibrosis 
markers, and effects have been observed as early as after 4 weeks of treatment 
(Neuschwander-Tetri et al 2015, Ratziu et al 2008, Harrison et al 2018a, Harrison et al 2018b). 
As due to ethical reasons, the placebo-controlled period needs to be limited to 12 weeks in 
patients with moderate to severe psoriasis, Treatment Period 2 will enable this study to 
explore the longitudinal effects of secukinumab up to 24 weeks. Moreover, with Treatment 
Period 2, all patients enrolled in the study will be able to benefit from secukinumab treatment.  
4.3 
Rationale for choice of control drug (placebo) 
A placebo control has been selected for the first 12 weeks in this study in order to assess the 
safety and effectiveness of secukinumab 300 mg in a double-blind, unbiased manner in 
patients with moderate to severe psoriasis and concomitant NAFLD. Patients assigned to 
placebo will switch to active treatment with secukinumab 300 mg for Treatment Period 2 
(Week 12 up to Week 20). Furthermore, patients will be allowed to use concomitant potent 
topical corticosteroids and/or vitamin D analogues as needed at the discretion of the 
investigator. 
4.4 
Purpose and timing of primary analysis/design adaptations 
The primary analysis for this study will be conducted after all patients have completed 
Treatment Period 1. Following an evaluation of these data by a Study Steering Committee, it 

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according to the label represents a convenient and safe intervention in patients with plaque 
psoriasis, the conduction this study in psoriasis patients with concomitant NAFLD is justified 
to treat a frequently coinciding disease of global socioeconomic impact and disease burden 
with life-threatening complications of end stage disease. 
The risk to patients in this trial may be minimized by compliance with the eligibility criteria 
and study procedures, as well as close clinical monitoring.  
Women of childbearing potential must be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study, and agree that 
in order to participate in the study they must adhere to the contraception requirements outlined 
in the exclusion criteria. If there is any question that the patient will not reliably comply, they 
should not be entered or continue in the study. 
5 
Population 
Approximately 90 patients with moderate to severe plaque psoriasis and coexisting NAFLD 
who are candidates for systemic psoriasis therapy will be included in this study.  
5.1 
Inclusion criteria 
Patients eligible for inclusion in this study must meet all of the following criteria: 
1. Patient must be able to understand and communicate with the investigator and comply 
with the requirements of the study, and must provide written, signed and dated informed 
consent before any study assessment is performed. 
2. Men and women ≥ 18 years of age at the time of consent. 
3. Moderate to severe plaque-type psoriasis diagnosed for at least 6 months prior to 
Screening with a PASI of >10 at baseline. 
4. Candidate for systemic therapy, defined as a subject having moderate to severe chronic 
plaque-type psoriasis that is inadequately controlled by: 
• Topical treatment and/or, 
• Phototherapy and/or, 
• Previous systemic therapy. 
5. Diagnosis of NAFLD by either ultrasound at Screening or liver histology within 6 months 
before Baseline. 
6. Obesity with BMI > 25 kg/ m 2 at Screening. 
7. Elevation of ALT 1.2 to 3.0 × ULN. 
8. Liver fat ≥ 8% at Screening as determined by the reading of the central MRI vendor of 
locally produced images. Note: the MRI assessment should only be performed after 
eligibility has been confirmed for all other Screening assessments. 
5.2 
Exclusion criteria 
Patients meeting any of the following criteria are not eligible for inclusion in this study. 
1. Forms of psoriasis other than chronic plaque-type psoriasis at Screening. 

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2. Drug-induced psoriasis (i.e. new onset or current exacerbation from beta-blockers, 
calcium channel inhibitors or lithium) at screening and baseline. 
3. Ongoing use of prohibited treatments (see Section 6.2.2). Respective washout periods 
detailed in this section have to be adhered to. 
4. History of hypersensitivity to any of the study drug constituents. 
5. Pregnant or nursing (lactating) women. 
6. Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during the 
study or longer if required by locally approved prescribing information (e.g., 20 weeks in 
the European Union). Effective contraception methods include: 
• Total abstinence (when this is in line with the preferred and usual lifestyle of the 
patient). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
• Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy) total hysterectomy or tubal ligation at least 6 weeks before taking study 
treatment. In case of oophorectomy alone, only when the reproductive status of the 
woman has been confirmed by follow-up hormone level assessment. 
• Male sterilization (at least 6 months prior to Screening). For female patients on the 
study, the vasectomized male partner should be the sole partner for that patient. 
• Barrier methods of contraception: condom or occlusive cap (diaphragm or 
cervical/vault caps). For countries where applicable, the use of spermicidal 
foam/gel/film/cream/vaginal suppository will be allowed. 
• Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of 
contraception or placement of an intrauterine device or intrauterine system or other 
forms of hormonal contraception that have comparable efficacy (failure rate < 1 %), 
for example hormone vaginal ring or transdermal hormone contraception. 
In case of use of oral contraception, women should have been stable on the same pill 
for a minimum of 12 weeks before taking study treatment. 
Women are considered post-menopausal and not of childbearing potential if they have 
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile (e.g. age appropriate history of vasomotor symptoms) or have had surgical 
bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal 
ligation at  least 6 weeks ago. In the case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by follow-up hormone level 
assessment, is she considered not of childbearing potential. 
7. Previous treatment with biological drug targeting IL-17 or the IL-17 receptor (including 
prior treatment with secukinumab, ixekizumab, or brodalumab).  
8. Past medical history record of infection with human immunodeficiency virus (HIV), 
hepatitis B or hepatitis C prior to screening.  
9. Active systemic infections during the last two weeks (exception: common cold) prior to 
randomization or any infection that reoccurs on a regular basis. 
10. History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis 
infection as defined by a positive QuantiFERON-TB Gold Plus (QFT) test at screening. 

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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 randomization and establishes conclusively that the subject has no 
evidence of active tuberculosis. If presence of latent tuberculosis is established, then 
treatment according to local guidelines must have been completed prior to screening. 
During treatment of latent tuberculosis, ALT had to remain below 2x compared to pre-
treatment ALT value. 
11. Significant medical problems, including but not limited to:  
• Congestive heart failure [New York Heart Association status of class III or IV].  
• Severely reduced kidney function (estimated glomerular filtration rate (eGFR) 
≤ 29 mL/min/1.73m2). 
12. Unstable weight (± 5%) over the last 6 months prior to Screening. 
13. Type I diabetes, or uncontrolled Type II diabetes (defined as HbAlc ≥ 10 % at screening). 
14. Total white blood cell (WBC) count < 2500/μL, or neutrophils < 1500/μL or hemoglobin 
< 8.5 g/dL at Screening. 
15. Evidence of hepatic decompensation or severe liver impairment or cirrhosis, as defined 
by the presence of any of the following abnormalities: 
• Serum albumin < 3.2 mg/dL 
• INR > 1.3 
• Total bilirubin > 1.3 mg/dL 
• AST > 5x ULN [for elevation of ALT refer to inclusion criterion 7] 
• Alkaline phosphatase > 300 IU/L 
• Platelets outside of normal reference range (± 5%) 
• History of esophageal varices, ascites, or hepatic encephalopathy 
• Splenomegaly  
16. History of liver transplantation or planned liver transplant. 
17. History of biliary diversion. 
18. Presence or history of other liver disease (including but not limited to autoimmune 
hepatitis, hereditary hemochromatosis, alpha-1-antitrypsin deficiency, Wilson’s disease, 
drug-induced liver disease). 
19. Current, or history of, significant alcohol consumption for a period of more than 
3 consecutive months within 1 year prior to screening (significant alcohol consumption is 
defined as more than 20 g/day in females or more than 30 g/day in males, on average) or 
a score on the modified alcohol use disorders identification test (AUDIT) questionnaire 
≥ 8. 
20. History of bariatric surgery or intention to have bariatric surgery during study conduct. 
21. History of lymphoproliferative disease or any known malignancy or history of 
malignancy of any organ system treated or untreated within the past 5 years, regardless of 
whether there is evidence of local recurrence or metastases (except for skin Bowen’s 
disease, or basal cell carcinoma or actinic keratosis that have been treated with no 
evidence of recurrence in the past 12 weeks; carcinoma in situ of the cervix or non-
invasive malignant colon polyps that have been removed). 

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22. Underlying conditions (including, but not limited to metabolic, hematologic, renal, 
hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which 
in the opinion of the Investigator significantly immunocompromise the patient and/or 
places the patient at unacceptable risk for receiving an immunomodulatory therapy. 
23. Current severe progressive or uncontrolled disease, which in the judgment of the clinical 
investigator renders the subject unsuitable for the trial or puts the subject at increased risk. 
24. 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.  
25. Inability or unwillingness to undergo MRI of the abdomen (e.g., patients with 
pacemakers, or metal fragments / foreign objects in the body that are not compatible with 
performing an MRI of the abdomen, weight in excess of MRI machine capacity).  
26. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor 
tolerability or lack of access to veins). 
27. Ongoing participation (including safety follow-up period) in other interventional studies. 
No additional exclusions may be applied by the Investigator in order to ensure that the study 
population will be representative of all eligible patients. 
6 
Treatment 
6.1 
Study treatment 
6.1.1 
Investigational and control drug 
The investigational and control arm regimens are presented in Table 6-1. 
Table 6-1 
Investigational and control drug 
Study treatment 
(Name and strength) 
Pharmaceutical 
dosage form 
Route and frequency  
of administration 
Supply type 
Sponsor 
(global or 
local) 
Investigational arm 
 
 
 
 
Secukinumab 300 mg 
2 × PFS 
s.c. weekly in first 
4 weeks, followed by 
q4w up to Week 20 
Double-blind 
supply; PFS 
Sponsor 
(local)  
Placebo  
2 × PFS 
s.c. at Week 13, 14, 15 
to maintain the blind 
Double-blind 
supply; PFS 
Sponsor 
(local)  
Control arm 
 
 
 
 
Placebo  
2 x PFS 
s.c. weekly in the first 
4 weeks followed by 
q4w up to Week 8 
Double-blind 
supply; PFS 
Sponsor 
(local)  
Secukinumab 300 mg 
2 x PFS  
s.c. weekly for 4 weeks 
starting at Week 12, 
followed by q4w up to 
Week 20 
Double-blind 
supply; PFS 
Sponsor 
(local)  
6.1.2 
Additional study treatments 
No other treatment beyond investigational drug and control drug are included in this trial. 

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6.1.3 
Treatment arms/group 
Treatment period 1 
Patients will be randomized 2:1 to either receive secukinumab 300 mg s.c. (in 2 × 150 mg 
PFS) or placebo at randomization, Week 1, Week 2, Week 3, Week 4 and Week 8. 
Treatment period 2 
Starting from Week 12, all patients will receive secukinumab 300 mg s.c. up to Week 20. 
Patients who were randomized to receive placebo during Treatment Period 1 will receive 
secukinumab 300 mg s.c. at Week 12, Week 13, Week 14, Week 15, Week 16 and Week 20 
Patients who were randomized to receive secukinumab during Treatment Period 1 will receive 
secukinumab 300 mg s.c. at Week 12, Week 16 and Week 20, and placebo at Week 13, 
Week 14 and Week 15 to maintain the blind. 
6.1.4 
Treatment duration 
This is a 24-week study. Patients will receive either secukinumab or placebo (2:1 ratio) for the 
first 12 weeks of the study (last study drug injection at Week 8), then secukinumab or 
secukinumab with intermittent placebo (placebo only at Week 13, 14 and 15 in patients 
randomized to receive secukinumab during Treatment Period 1) for the next 12 weeks of the 
study (last study drug injection at Week 20).   
6.2 
Other treatments 
6.2.1 
Concomitant therapy 
All medications, procedures and significant non-drug therapies (including physical therapy 
and blood transfusions) administered after the patient is enrolled into the study must be 
recorded on the appropriate CRFs. 
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. If the patient is already 
enrolled, contact Novartis to determine if the patient should continue participating in the study. 
Patients will be permitted to take concomitant potent topical corticosteroids and/or vitamin D 
analogues as needed at the discretion of the investigator over the course of the study, 
according to the respective approved label. 
6.2.2 
Prohibited medication 
Use of any treatments displayed in Table 6-2 that could confound the efficacy and safety of 
the study treatment are NOT allowed during the study after Baseline (Day 1) for any 
indication; wash-out periods for these treatments are indicated in the table. If the use of these 
treatments is required, then the patient should NOT be randomized into the study. 
The Investigator should instruct the patient to notify the study site about any new treatments 
he/she takes after the start of study treatment. All prohibited medications and significant 

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non-drug therapies administered after the patient starts treatment with study treatment must be 
listed on the CRF.  
If a prohibited treatment listed in Table 6-2 is used during the study, the patient should 
discontinue use of the prohibited treatment if he/she wishes to continue in the study.  
At the discretion of the Investigator, if the patient’s use during the study of a prohibited 
treatment listed in Table 6-2 presents undue safety risk for the patient, the patient should be 
discontinued from study treatment as per Section 9.1.1.  
If the patient received a live virus vaccination during the study, the patient must discontinue 
study treatment. 
Table 6-2 
Prohibited medication 
Prohibited treatments †, ‡  
Wash-out period (before first 
study drug administration)  
Biological drug targeting IL-17 or the IL-17 receptor (other than 
secukinumab e.g. ixekizumab, brodalumab)  
No prior use allowed 
Secukinumab 
No prior use allowed 
Biological immunomodulating agents other than above (e.g. 
etanercept, infliximab, adalimumab, alefacept, briakinumab, 
ustekinumab)  
12 weeks 
Methotrexate 
8 weeks 
Other systemic immunomodulating treatments (e.g. cyclosporine 
A, corticosteroids*§, cyclophosphamide).  
4 weeks 
Other systemic psoriasis treatments§ (e.g. retinoids, fumarates, 
apremilast). 
4 weeks 
Photochemotherapy (e.g. PUVA) 
4 weeks 
Phototherapy (e.g. UVA, UVB)  
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) 
Potent topical corticosteriods and/or vitamin D analogues are 
allowed after baseline as needed at the discretion of the 
investigator. 
2 weeks 
Live virus vaccinations (including nasal-spray flu vaccine) 
6 weeks 
Any other investigational treatment  
4 weeks or 5 half-lives 
(whichever is longer)  
Obeticholic acid 
4 weeks 
Pharmacologically-active weight loss medications (for example; 
lorcaserin, phentermine/topiramate, bupropion-naltrexone HCl, 
orlistat) 
4 weeks 
Anti-diabetic medications, insulin, beta-blockers, thiazide diuretics, 
fibrates, statins, niacin, ezetimibe, thyroid hormone, psychotropic 
Not allowed UNLESS on stable 
dosing for at least 3 months 

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medications, estrogen or estrogen containing birth control. 
before randomization 
Vitamin E, if doses > 200 IU/day (≤ 800 IU/day)  
Not allowed UNLESS on stable 
dosing for at least 3 months 
before randomization. 
Vitamin E doses > 800 IU/day 
3 months 
Glitazone, liraglutide or ursodeoxycholic acid (UDCA) therapy 
Not allowed if initiated within 3 
months before baseline 
UVA = ultraviolet A, UVB = ultraviolet B, MTX = methotrexate, PUVA = psoralen and UVA 
† If the prohibited treatment was used during the study, the subject must discontinue use of the prohibited 
treatment if he/she wishes to continue in the study. 
‡ In case of undue safety risk for the subject, the subject should discontinue study treatment at the discretion of 
the investigator and after consultation with Novartis. If the subject received a live virus vaccination during the 
study, the subject must discontinue study treatment. 
* Inhaled corticosteroids with only a topical effect (e.g. to treat asthma) are not considered “systemic 
immunomodulating treatments” and are therefore acceptable as a co-treatment. 
§ There is no restriction on the use of anti-histamines or of corticosteroid drops used in the eye or ear if dose 
regimen is stable for at least 4 weeks before the first study treatment administration.  
6.2.3 
Rescue medication 
Rescue medication for psoriasis is not permitted in this study. 
6.2.4 
Dietary restrictions  
No alcohol consumption is allowed for 8 hours before each dose of study medication. Alcohol 
should also not be consumed for 8 hours before each study visit. 
To keep the fat intake as constant as possible, patients participating in this study will be 
instructed to carefully adhere to American Heart Association (AHA) diet or local equivalent if 
there is a country specific recommended diet (Appendix 2). Patients will be asked about 
dietary compliance to the AHA diet (or local equivalent) as outlined in Table 8-1.  
6.3 
Patient numbering, treatment assignment, randomization 
6.3.1 
Patient numbering 
Germany 
Each patient is identified in the study by a Patient ID (Patient ID) that is assigned when the 
patient is first enrolled for screening and is retained as the primary identifier for the patient 
throughout his/her entire participation in the trial. The Patient ID consists of the Center 
Number (Center No.) (ascending numbers starting with 1001, as assigned by Novartis to the 
investigative site) with a sequential Patient Number (Patient No.) suffixed to it, so that each 
patient is numbered uniquely across the entire database. Upon signing the ICF, the patient is 
assigned to the next sequential Patient No. available in this center by the investigator. At each 
site the first patient is assigned Patient No. 1, and subsequent patients are assigned 
consecutive numbers (e.g. the second patient is assigned Patient No. 2, the third patient is 
assigned Patient No. 3). Once assigned to a patient, a Patient No. 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. 

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Spain 
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 ICF, the patient is assigned to the next sequential Patient No. available in 
this center by the investigator. At each site the first patient is assigned Patient No. 1, and 
subsequent patients are assigned consecutive numbers (e.g. the second patient is assigned 
Patient No. 2, the third patient is assigned Patient No. 3). The subject number (patient ID) is 
assigned, at Screening Visit 1, via Interactive Response Technology (IRT). 
The Patient ID consists of the Center Number (Center No.) (ascending numbers starting with 
2001, as assigned by Novartis to the investigative site) with a sequential Patient Number 
(Patient No.) suffixed to it, so that each patient is numbered uniquely across the entire 
database. 
Once assigned to a patient, a Patient No. 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. 
6.3.2 
Treatment assignment, randomization 
Germany 
At Baseline (Randomization Visit/Day 1), all patients who meet the inclusion criteria and do 
not fulfill any of the exclusion criteria will be given the lowest available number of the 
randomization block assigned to each site. This number assigns them to one of the treatment 
arms. The investigator will enter the randomization number on the eCRF. 
The randomization numbers will be generated using the following procedure to insure that 
treatment assignment is unbiased and concealed from patients and investigator staff. A 
randomization list will be produced by or under the responsibility of Novartis using a 
validated system that automates the random assignment of treatment arms to randomization 
numbers in the specified ratio. 
The randomization scheme will be reviewed by a Biostatistics Quality Assurance Group and 
locked by them after approval. 
Spain 
At Baseline (Randomization visit /Day 1), all patients who meet the inclusion criteria and do 
not fulfill any of the exclusion criteria will be randomized via IRT and a treatment will be 
assigned to individual subjects by way of a randomization number. The randomization 
number is only used to identify which treatment the patient has been randomized to receive. 
The patient number assigned to a patient at screening remains the unique identifier for the 
patient throughout the study.  
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from subjects and investigator staff.  
A subject randomization list will be produced by the IRT provider using a validated system 
that automates the random assignment of subject numbers to randomization numbers.  

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These randomization numbers are linked to the different treatment arms, which in turn are 
linked to medication numbers. A separate medication list will be produced by or under the 
responsibility of Novartis Drug Supply Management using a validated system that automates 
the random assignment of medication numbers to packs containing the investigational drug. 
The randomization scheme for subjects will be reviewed and approved by a member of the 
Randomization Office. 
6.4 
Treatment blinding 
Patients, Investigator staff, persons performing the assessments, and the Clinical Trial Team 
will remain blind to the identity of the treatment from the time of randomization until 
database lock, using the following methods:  
1. Randomization data are kept strictly confidential until the time of unblinding, and will not 
be accessible by anyone else involved in the study.  
2. The identity of the treatments will be concealed by the use of study treatment that are all 
identical in packaging, labeling, schedule of administration, appearance, taste and odor. 
Unblinding will occur in the case of patient emergencies and at the conclusion of the study. 
A selected Novartis clinical team will be unblinded to the Week 12 results at the time of 
primary analysis. Details will be specified in a separate document.  
6.5 
Dose escalation and dose modification 
Study treatment dose adjustments are not permitted. Study treatment interruption should be 
avoided with the following exceptions: 
Study treatment interruption is only permitted if, in the opinion of the investigator, a patient is 
deemed to be placed at a significant safety risk unless dosing is temporarily interrupted. In 
such cases study treatment should be interrupted only during the time that this risk is present 
and ongoing. Study treatment can be restarted at the next scheduled visit after resolution of 
the safety risk. 
Any study treatment interruption must be recorded on the corresponding CRF page. 
6.5.1 
Follow-up for toxicities 
Not applicable. 

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6.6 
Additional treatment guidance 
6.6.1 
Treatment compliance 
All doses of study treatment administration will be recorded on the appropriate Dosage 
Administration Record CRF. Compliance to the planned administration schedule is expected 
to be high since the administrations of study treatment will be done in the presence of the 
Investigator or study personnel. Compliance will also be assessed by means of site and 
patient-specific drug accountability by Novartis study personnel during the site monitoring 
visits using medication pack numbers, Drug Label Form information. 
6.6.2 
Emergency breaking of assigned treatment code 
Emergency unblinding should only be done when necessary in order to treat the patient. Most 
often, study drug discontinuation and knowledge of the possible treatment assignments are 
sufficient to treat a study patient who presents with an emergency condition. Two complete 
sets of emergency code break cards are provided by Novartis. One set of emergency code 
break cards is provided by Novartis and is to be distributed to the investigators. They must be 
stored in a secure place but accessible in case of emergency. The investigator will receive a 
blinded code break card for each patient, with the details of drug treatment covered by a 
sealed tear-off cover. In an emergency, the tear-off cover can be removed to determine the 
treatment. The tear-off covers are not to be removed for any reason other than an emergency. 
When the investigator removes the tear-off cover he/she must note the date, time, and reason 
for removing it and retain this information with the case report form documentation. The 
unblinded treatment code should not be recorded on the eCRF. The investigator must also 
immediately inform the Novartis monitor that the code has been broken. 
It is the investigator’s responsibility to ensure that there is a procedure in place to allow access 
to the code break cards in case of emergency. The investigator will inform the patient how to 
contact his/her backup in cases of emergency when he/she is unavailable. The protocol 
number, study drug name if available, patient number, and instructions for contacting the 
German Novartis affiliated company (or any entity to which it has delegated responsibility for 
emergency code breaks) will be provided to the patient in case emergency unblinding is 
required at a time when the investigator and backup are unavailable. 
Spain 
Emergency treatment code breaks are performed using the IRT. When the investigator 
contacts the system to break a treatment code for a subject, he/she must provide the requested 
subject identifying information and confirm the necessity to break the treatment code for the 
subject. The investigator will then receive details of the investigational drug treatment for the 
specified subject and a fax or email confirming this information. The system will 
automatically inform the Novartis monitor for the site and the study team that the code has 
been broken. 
It is the investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT at any time in case of emergency. The investigator will provide: 

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• protocol number 
• subject number 
In addition, oral and written information on how to contact his/her backup in cases of 
emergency, or when he/she is unavailable, must be provided to the subject to ensure that un-
blinding can be performed at any time. 
The unblinded treatment code should not be recorded on the eCRF. The investigator must also 
immediately inform the Novartis monitor that the code has been broken. 
6.7 
Preparation and dispensation 
Each study site will be supplied with study drug in packaging as described under 
investigational and control drugs section. 
Germany 
The randomization number will be printed on the study medication label.  
As per the treatment assigned to the patient, investigator staff will select the study treatment to 
dispense to the patient. The study medication has a 2-part label (base plus tear-off label), 
immediately before dispensing the package to the patient, site personnel will detach the outer 
part of the label from the package and affix it to the patient’s source document. 
Two treatment packages (i.e. 1 package for Treatment Period 1 and 1 package for Treatment 
Period 2) will be supplied for each patient, with each package containing sufficient study 
treatment for all visits in each period (i.e. 2 × PFS labelled for each treatment visit).  
Spain 
Investigator staff will identify the study medication kits to dispense to the participant by 
contacting the IRT and obtaining the medication number(s). The study medication has a 2-part 
label (base plus tear-off label), immediately before dispensing the medication box to the 
participant, site personnel will detach the outer part of the label from the packaging and affix 
it to the source document. 
6.7.1 
Handling of study treatment and additional treatment 
6.7.1.1 
Handling of study treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secure location to which only the Investigator and 
designated site personnel have access. Upon receipt, all study treatment must be stored 
according to the instructions specified on the labels and in the Investigator’s Brochure. 
Clinical supplies are to be dispensed only in accordance with the protocol. Technical 
complaints are to be reported to the respective Novartis Country Organization Quality 
Assurance. 
Medication labels will be in the local language and comply with the local legal requirements.  

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For Germany, they will include storage conditions for the study treatment but no information 
about the patient except for the randomization number. For Spain, they will include storage 
conditions for the study treatment and medication number. 
The Investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
monitors during site visits or remotely and at the completion of the trial. Note: all injections of 
secukinumab/placebo will be administered by site staff or under supervision of site staff at the 
scheduled treatment visits. 
At the conclusion of the study, and as appropriate during the course of the study, the 
Investigator will return all unused study treatment, packaging, drug labels, and a copy of the 
completed drug accountability log to the Novartis monitor or to the Novartis address provided 
in the Investigator folder at each site. 
6.7.1.2 
Handling of additional treatment 
Not applicable. 
6.7.2 
Instruction for prescribing and taking study treatment 
Secukinumab solution for s.c. injection or placebo solution will be provided in PFS as 
described in Section 6.7. 
Each patient will require 1 box (containing 2 × PFS) for each treatment visit throughout the 
study, i.e. 
• Two secukinumab 150 mg PFS OR  
• Two secukinumab placebo 150 mg PFS. 
Patients assigned to the investigational arm will receive secukinumab 300 mg weekly for the 
first 4 weeks, followed by q4w up to Week 20, and placebo to secukinumab at Week 13, 14 
and 15.  
Patients assigned to the control arm will receive placebo to secukinumab weekly for the first 
4 weeks, then at Week 8, followed by secukinumab 300 mg weekly for 4 weeks starting from 
Week 12, then q4w up to Week 20.  
For German sites all study treatment kits assigned to the patient during the study will be 
captured in the eCRF. For Spanish sites, no kit numbers will be captured. 
Administration 
All doses of study treatment that are administered at the study site should be performed after 
the study assessments for the visit, including blood sampling and PRO questionnaires, have 
been completed.  
The first study treatment administration will occur at the Baseline Visit, after all study 
scheduled assessments have been performed (and inclusion/exclusion criteria confirmed) and 
only after the scheduled blood samples have been drawn.  

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Prior to administration, the boxes containing the PFS with study treatment solution should be 
allowed to come to room temperature unopened. Used PFS should be disposed immediately 
after use in a sharps container OR according to local regulations.  
The study treatment solution must be injected s.c. in non-affected areas of the skin. If possible 
throughout the trial, the study treatment should be administered to one of the following body 
regions, rotating the injection site from visit to visit: right thigh, left thigh, right stomach, left 
stomach, upper outer arm (when assisted by attendant). 
All dates and times of injections during the study must be recorded on the appropriate CRF. 
7 
Informed consent procedures 
Eligible patients may only be included in the study after providing, Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC)-approved informed consent. 
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 an ICF that complies with the 
ICH GCP guidelines and local regulatory requirements and is considered appropriate for this 
study.  
Information about common side effects already known about the investigational drug can be 
found in the Investigator's Brochure (and/or Core Data Sheet for marketed drugs). This 
information will be included in the patient informed consent and should be discussed with the 
patient during the study as needed. Any new information regarding the safety profile of the 
investigational drug that is identified between Investigator's Brochure updates will be 
communicated as appropriate, for example, via an Investigator notification or an aggregate 
safety finding. New information might require an update to the informed consent and then 
must be discussed with the patient. 
Women of childbearing potential must be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirements. 
8 
Visit schedule and assessments 
The Assessment Schedule (Table 8-1) lists all of the assessments when they are performed. 
All data obtained from these assessments must be supported in the patient’s source 
documentation. 
Patients should be seen for all visits/assessments as outlined in the assessment schedule 
(Table 8-1) or as close to the designated day/time as possible. Missed or rescheduled visits 
should not lead to automatic discontinuation. Recommended study visit windows are ± 2 days 
for Week 1, 2, 3, 4, 8, 12, 13, 14, 15, and 16, ± 3 days for Week 20 and 24.
 

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Patients who prematurely discontinue the study treatment (s.c. secukinumab or placebo) are 
encouraged to remain in the study to continue the study-related assessments until completion 
of the study. 
Patients who prematurely discontinue completely from the study for any reason should return 
for the final visit to undergo the EOT assessments (4 weeks after the last study treatment 
administration of secukinumab). This will be EOT1 (Week 12) for patients who prematurely 
discontinue during Treatment Period 1 and EOT2 (Week 24) for patients who prematurely 
discontinue during Treatment Period 2. See Section 9.1.1 for further details.  
At this visit, all dispensed investigational product should be reconciled, and the AE and 
concomitant medications recorded on the CRF. 
If a patient refuses to return for these assessments or are unable to do so, every effort should 
be made to contact them or a knowledgeable informant by telephone or by sending 
appropriate correspondence (i.e. certified letter) immediately. At this contact, the safety (e.g. 
potential occurrence of AE or SAE) and the primary reason for a patient’s premature 
withdrawal should be determined. 
At a minimum, patients who prematurely discontinue the treatment will be contacted for 
safety evaluations during the 4 weeks following the last dose of study treatment, including 
final contact at the 4 week point. Documentation of attempts to contact the patient should be 
recorded in the subject record. 
 

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Table 8-1 
Assessment schedule 
 
Screening§ 
Baseline 
Treatment Period 1 
Treatment Period 2 
 
Week (relative to baseline) 
-4 to -1 
BSL 
1 
2 
3 
4 
8 
12 
EOT1 
13 
14 
15 
16 
20 
24 
EOT2 
Uns§§ 
Day 
-28 to -7 
1 
8 
15 
22 
29 
57 
85 
92 
99 
106 
113 
141 
169 
 
§ The second screening visit can be 
conducted as soon as eligibility has been 
confirmed for all assessments from the 
first screening visit. 
§§ Unscheduled visits might be required 
e.g. if patients observe symptoms 
between scheduled visits or for safety 
reasons. The safety assessments listed 
herein may be performed at the 
discretion of the Investigator as needed 
to resolve the reason for the unscheduled 
visit. (S)AE assessment and concomitant 
medications are mandatory for all 
unscheduled visits. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Obtain informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria: 
These assessments are supported by 
and stored within the source 
documentation. Data relating to 
inclusion/exclusion criteria are 
captured in the corresponding CRF 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Smoking history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psoriasis medical history / Previous 
psoriasis therapies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Other medical history and prior 
treatments 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant medications 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Screening§ 
Baseline 
Treatment Period 1 
Treatment Period 2 
 
Week (relative to baseline) 
-4 to -1 
BSL 
1 
2 
3 
4 
8 
12 
EOT1 
13 
14 
15 
16 
20 
24 
EOT2 
Uns§§ 
Day 
-28 to -7 
1 
8 
15 
22 
29 
57 
85 
92 
99 
106 
113 
141 
169 
 
Alcohol history (AUDIT)/compliance 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Physical examination 
S 
 
S 
 
 
 
 
 
 
 
 
 
 
 
S 
S 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
X 
X 
X 
X 
Body mass index 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Waist and hip circumference 
X 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Blood collection for: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Routine laboratory assessments 
including analysis of liver enzymes 
(
, ALT, 
 
) 
C 
 
C 
 
C 
 
C 
C 
C 
 
 
 
C 
C 
C 
C 
Coagulation (INR) 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERON-TB Gold Plus test 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C 
Serum pregnancy test for females 
of childbearing potential 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
C 
Follicle stimulating hormone (FSH) 
test (if applicable) 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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Screening§ 
Baseline 
Treatment Period 1 
Treatment Period 2 
 
Week (relative to baseline) 
-4 to -1 
BSL 
1 
2 
3 
4 
8 
12 
EOT1 
13 
14 
15 
16 
20 
24 
EOT2 
Uns§§ 
Day 
-28 to -7 
1 
8 
15 
22 
29 
57 
85 
92 
99 
106 
113 
141 
169 
 
Urine pregnancy test (local) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
Urinalysis (local) 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
X 
PASI/BSA 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Screening§ 
Baseline 
Treatment Period 1 
Treatment Period 2 
 
Week (relative to baseline) 
-4 to -1 
BSL 
1 
2 
3 
4 
8 
12 
EOT1 
13 
14 
15 
16 
20 
24 
EOT2 
Uns§§ 
Day 
-28 to -7 
1 
8 
15 
22 
29 
57 
85 
92 
99 
106 
113 
141 
169 
 
DLQI 
X 
 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
X 
X 
(S)AE assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Study treatment or dispensing 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Drug accounting 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
AHA diet review 
 
 
S 
 
 
 
S 
 
S 
 
 
 
S 
 
S 
 
Diet compliance 
 
 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
, ALT = alanine aminotransferase, 
, BSA = body surface area, EOT = end of treatment 
period;
 PASI = psoriasis area and severity index 
C = centrally analyzed laboratory or MRI; X = assessment to be recorded on clinical database; S = assessment to be recorded on source documentation  
 

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8.1 
Screening 
Patient’s eligibility for the study will be assessed during Screening period (Day -28 to -7) 
including Screening Visit 1, Screening Visit 2 and at the Baseline Visit (see Table 8-1). 
It should be noted that for each patient, results from Screening Visit 1 must be available and 
indicate primary eligibility before the patient can proceed to Screening Visit 2.  
Patients who fail screening for any reason may be rescreened. If the reason for screen failure 
is regarded as a transient constraint for study participation, then there will be no restriction on 
the number of times a potential patient may be rescreened or on how much time must pass 
from the date of screen failure and the date of rescreening. Patients who are rescreened must 
sign a new ICF and be issued a new Patient No. before any study-related assessment is 
performed or any data for the Screening Period are collected for the patient under the new 
Patient No. 
The Investigator or qualified site staff will record all rescreenings on the Rescreening eCRF 
page and any applicable screening numbers the patient was issued prior to the current 
screening number. The date of the new informed consent signature must be entered on the 
Informed Consent eCRF page to correspond with the new screening Patient No. 
The Withdrawal of Consent eCRF page must be completed if consent was withdrawn during 
the Screening Period before the patient was randomized. 
8.1.1 
Information to be collected on screening failures 
Patients who sign an ICF and subsequently are found to be ineligible prior to randomization 
will be considered screen failures. The reason for screen failure should be recorded on the 
appropriate 
eCRF 
page. 
The 
demographic 
information, 
informed 
consent, 
and 
inclusion/exclusion pages must also be completed for screen failures. No other data will be 
entered into the clinical database for screen failures, unless the patient experienced an SAE 
during the Screening Period (see Section 10.1.3 for reporting details). If the patient fails to be 
randomized, Novartis (Germany) / the IRT (Spain) must be notified within 2 days. 
8.2 
Patient demographics/other baseline characteristics 
Baseline assessments will occur during Screening Visits or the Baseline Visit depending on 
the assessment as indicated in Table 8-1.  
Patient demographics and Baseline characteristics to be collected for all patients include: year 
of birth, age, sex, race, height, weight. 
8.2.1 
Smoking history 
The current and/or previous use of tobacco products will be recorded, as well as the estimated 
number of pack-years based on the approximate consumption per year. Non-smokers will be 
advised not to start smoking during the study. 

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8.2.2 
Tuberculosis screening 
A central laboratory immunological test (QuantiFERON-TB Gold Plus) must be performed 
at Screening to screen the patient population for latent tuberculosis infection. The results 
must be known prior to randomization to determine the patient’s eligibility for the study. 
Patients with a positive test may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that: 
The patient has no evidence of active tuberculosis. 
If presence of latent tuberculosis is established then treatment according to local country 
guidelines must have been completed before screening. 
The QuantiFERON-TB Gold Plus test will be analyzed by the central laboratory. Details 
on the collection, processing and shipment of samples and reporting of results by the central 
laboratory are provided in the laboratory manual. 
8.2.3 
Relevant medical history/current medical conditions 
Relevant medical history and current medical conditions, not including psoriasis or psoriatic 
arthritis, prior to signing of the informed consent will be recorded in the Medical History 
eCRF page. Whenever possible, diagnoses and not symptoms will be recorded. 
Patients with inflammatory bowel disease will be eligible for the study but should be closely 
followed when (possibly) treated with secukinumab. 
8.2.3.1 
Psoriasis medical and treatment history 
Disease history will be collected at Screening Visit 1. The information to be collected and 
entered in the Psoriasis History eCRF page and Prior Psoriasis Therapies eCRF page will 
include the following: 
• Date of first diagnosis of plaque psoriasis. 
• Previous treatments of psoriasis (including previous use of biologic therapies, as well as 
phototherapy and/or photo-chemotherapy) and the reason for discontinuation of each 
therapy. 
• Presence of psoriatic arthritis or ankylosing spondylitis (including questions on signs and 
symptoms captured in the eCRF) and the date of the first diagnosis by a physician.  
8.2.4 
Prior and concomitant medications 
Concomitant medications and prior non-psoriasis medications taken within the 6 months 
preceding study enrollment will be captured at Screening Visit 1, and updated at the Baseline 
Visit or subsequent visits. 
8.2.5 
Serum pregnancy test 
A serum pregnancy test will be performed for females of childbearing potential at Screening 
Visit 1.  

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8.2.6 
Other baseline characteristics 
Other Baseline characteristics will be collected as described in Section 8.3 and Section 8.4.  
8.3 
Efficacy 
• PASI 
• Hepatic inflammation (assessed via liver enzyme levels) 
8.3.1 
Psoriasis area severity index 
The Investigator or trained qualified designee will complete the PASI assessment as indicated 
in Table 8-1. Whenever possible, the same evaluator should perform this PASI 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 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 4 percentages will be added up to estimate the 
total BSA affected by plaque-type psoriasis. The PASI scoring system is further described in 
Table 8-2.  
A PASI score (Fredriksson and Pettersson 1978, Weisman et al 2003, Gottlieb et al 2006) will 
be derived as indicated in Table 8-2. 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 help the 
assessment: 
1. The neck is assessed as part of the head. 
2. The axillae and groin are assessed as part of the trunk. 
3. The buttocks are assessed as part of the lower limbs. 
When scoring the severity of erythema, scales should not be removed. 
Table 8-2 
PASI scoring system 
Body region Erythema (E) 
Thickening 
(plaque elevation, 
induration, I) 
Scaling 
(desquamation, D) 
Area score 
(based on true 
area %, A)* 
Head (H)† 
0=none  
1=slight  
2=moderate  
3=severe 
0=none  
1=slight  
2=moderate  
3=severe 
0=none  
1=slight  
2=moderate  
3=severe 
0=no 
involvement 
1=>0-<10% 
2=10-<30% 

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4=very severe 
4=very severe 
4=very severe 
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 CRF 
† 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.  
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 8-2.  
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 following definitions will be used in this study based on the EMA guideline on clinical 
investigation 
of 
medicinal 
products 
indicated 
for 
the 
treatment 
of 
psoriasis 
(CHMP/EWP/2454/02 corr): 
• PASI 50 response (partial response): patients achieving ≥ 50% improvement (reduction) 
in PASI score compared to Baseline are defined as PASI 50 responders. 
• PASI 75 response: patients achieving ≥ 75% improvement (reduction) in PASI score 
compared to Baseline are defined as PASI 75 responders. 

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• PASI 90 response: patients 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). 
8.3.3 Liver function tests and liver and/or systemic inflammation markers 
Hepatic inflammation markers (i.e. ALT, 
 
, 
) will be assessed as 
indicated in Table 8-1. The methods for assessment and recording are specified in the 
laboratory manual. 
Some of the liver function tests will be completed as part of the blood chemistry panel (see 
Section 8.4.4). 

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8.3.7 
Appropriateness of efficacy assessments 
Psoriasis area severity index scores measures the severity of symptoms and the extent to 
which the patient’s body area is affected by the disease; it is mandated by the EMA for the 
clinical 
investigation 
of 
medicinal 
products 
for 
the 
treatment 
of 
psoriasis 
(CHMP/EWP/2454/02). 
8.4 
Safety 
Safety assessments are specified below with the assessment schedule detailing when each 
assessment is to be performed. For details on AE collection and reporting, refer to Section 10. 
8.4.1 
Anthropometric assessments  
Height, body weight (to the nearest 0.1 kilogram [kg] in indoor clothing, but without shoes), 
and waist and hip circumference in centimeters (cm), will be measured as indicated in 
Table 8-1.  
For the assessment of the waist and hip circumference, the patient should be standing upright 
during the measurements, with arms relaxed at the side, feet evenly spread apart and body 
weight evenly distributed.  
The waist circumference should be measured on bare skin at the end of several consecutive 
natural breaths, at a level parallel to the floor, midpoint between the top of the iliac crest and 
the lower margin of the last palpable rib in the mid axillary line. The hip circumference 
should be measured on bare skin at a level parallel to the floor, at the largest circumference of 
the buttocks. For both measurements it is advised to use a stretch-resistant tape that is 
wrapped snugly around the patient, but not to the point that the tape is constricting (World 

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Health Organization Dec 2008). It is recommended that waist and hip circumference 
measurements are performed by the same person throughout the study.  
Waist-to-hip ratio (WHR) will be calculated using the following formula: 
• WHR = Waist circumference (cm) / Hip circumference (cm) 
Body mass index (BMI) will be calculated using the following formula: 
• BMI = Body weight (kg)/[height (m2)] 
8.4.2 
Physical examination 
Physical examinations will be performed as indicated in Table 8-1. 
A complete physical examination will include the examination of general appearance, skin, 
neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, 
extremities, vascular, and neurological. If indicated based on medical history and/or 
symptoms, rectal, external genitalia, breast, and pelvic exams will be performed. In particular, 
the examination will include recognition of enthesitis, dactylitis, and the patterns of joint, or 
nail involvement. 
Information for all physical examinations must be included in the source documentation at the 
study site. Clinically relevant findings that are present prior to signing informed consent must 
be recorded on the appropriate CRF that captures medical history. Significant findings made 
after signing informed consent which meet the definition of an AE must be recorded as an AE. 
8.4.3 
Vital signs 
Vital signs will be measured as indicated in Table 8-1. Vital signs include systolic blood 
pressure (SBP), diastolic blood pressure (DBP), and pulse measurements. After the patient has 
been sitting for 5 minutes, with back supported and both feet placed on the floor, SBP and 
DBP will be measured 3 times using an automated validated device, e.g. OMRON, with an 
appropriately sized cuff. The repeat sitting measurements will be made at 1 to 2 minute 
intervals and the mean of the 3 measurements will be used. The results of all measurements, 
including the mean measurement, should be recorded in the source data. In case the cuff sizes 
available are not large enough for the patient’s arm circumference, a sphygmomanometer with 
an appropriately sized cuff may be used. 
If possible, assessments should be performed by the same study site staff member throughout 
the study. 
Normal blood pressure will be defined as SBP of 90 to < 120 mmHg, and diastolic blood 
pressure of 60 to < 80 mmHg under the measurement conditions outlined above. Notable 
blood pressure findings will be hypertension (SBP of ≥ 140 mmHg and/or DBP of ≥ 90 
mmHg) or hypotension (SBP of < 90 mmHg and/or a DBP of < 60 mmHg). A blood pressure 
indicative of prehypertension (SBP of 120 to < 140 mmHg and/or DBP of 80 to < 90 mmHg) 
will not be regarded as notable (Whelton et al 2017). 
A normal pulse rate will be defined as a rate of 60 to 100 beats per minute (bpm) under the 
measurement conditions outlined above. Notable pulse rate will be a rate below 60 bpm 
(bradycardia) or above 100 bpm (tachycardia). 

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Whether action needs to be taken to address notable vital signs will be decided by the 
Investigator, taking into account the overall status of the patient. No specific action is foreseen 
as part of the study protocol. 
8.4.4 
Laboratory evaluations 
Laboratory evaluations will be performed as indicated in Table 8-1. A central laboratory will 
be used for the analysis of all specimens collected except for urine dipstick and pregnancy 
tests, which will be analysed locally. Details on the collection, shipment of samples and 
reporting of results by the central laboratory will be provided to Investigators in the laboratory 
manual. Clinically notable laboratory findings are defined in Appendix 1. 
Table 8-4 
Laboratory assessments 
Test category 
Test name 
Hematology 
Hematocrit, Hemoglobin, Mean Corpuscular Hemoglobin (MCH), Mean 
Corpuscular Hemoglobin Concentration (MCHC), Mean Corpuscular Volume 
(MCV), Platelets*, Red Blood Cells (RBCs), White Blood Cells (WBCs), , 
Differential (Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils, 
Bands) 
Chemistry 
Albumin*, Alkaline Phosphatase, Alanine Amino Transferase (ALT*)
 
 
 Lactate 
Dehydrogenase (LDH), Bicarbonate, Calcium, Magnesium, Phosphorus, 
Chloride, Sodium, Potassium, Creatinine, Creatine Kinase, Direct Bilirubin, 
Indirect Bilirubin, Total Bilirubin*, Total Cholesterol*, Low Density Lipoprotein 
(LDL), High Density Lipoprotein (HDL), Total Protein, Triglycerides*, Blood Urea 
Nitrogen (BUN) or Urea, Uric Acid, Amylase, Lipase, Glycated Hemoglobin 
(HbA1c), Glucose (fasting)* 
Urinalysis 
The central laboratory will provide dipsticks to the sites for local analysis of urine. 
Dipstick analysis will measure specific gravity, protein, glucose and blood. 
Microscopy and white blood cell count and red blood cell count sediments will 
be assessed in case of an abnormal dipstick test. Only samples with abnormal 
dipstick will be assessed by the central laboratory and the results provided in 
loaded data and reported to the investigator. 
Study sites should record the results in the source documentation 
Coagulation 
International normalized ratio (INR) 
Pregnancy test 
A serum β-hCG test will be performed for all pre-menopausal women at 
Screening Visit 1. 
Any woman with a confirmed positive pregnancy test (hCG > 5 mIU/mL) during 
Screening will not be eligible for randomization. Urine pregnancy tests will be 
performed thereafter as shown in Table 8-1. 
Women of childbearing potential should use an effective method of contraception 
while on treatment, or longer if required by locally-approved prescribing 
information (e.g. 20 weeks after the last dose in the European Union and 
countries where applicable for secukinumab.  
Fertility test 
A follicle stimulating hormone (FSH) test will be performed if required for fertility 
testing in the absence of other records of fertility (see Section 8.4.5) 
* These parameters will be used as part of the study efficacy analyses described in Section 8.3.3 and 

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Test category 
Test name 
Section 8.3.4.  
8.4.5 
Pregnancy and assessments of fertility 
Pregnancy testing 
Secukinumab must not be given to pregnant women; therefore, effective methods of birth 
control must be used for women of childbearing potential (see Exclusion Criteria definitions, 
Section 5.2). 
A serum β-hCG test will be performed in all women of child-bearing potential at Screening. 
All pre-menopausal women who are not surgically sterile at Screening will have local urine 
pregnancy tests as indicated in Table 8-1. A positive urine pregnancy test requires immediate 
interruption of study treatment until serum β-hCG is performed and found to be negative. If 
positive, the patient must be discontinued from the trial. Additional pregnancy testing might 
be performed if requested per local requirements. Refer to Section 10.1.4 for details on 
reporting of pregnancy. Pregnancy test results are kept in the eCRF. 
Assessments of fertility 
Refer to Section 5.2 for criteria to determine women that are not of childbearing potential. 
Medical documentation of oophorectomy, hysterectomy, or tubal ligation must be retained as 
source documents. Subsequent hormone level assessment to confirm the woman is not of 
childbearing potential must also be available as source documentation in the following cases: 
1. Surgical bilateral oophorectomy without a hysterectomy 
2. Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile. 
In the absence of the above medical documentation, follicle stimulating hormone (FSH) 
testing is required of any female patient who states that they are of non-childbearing potential 
regardless of reported reproductive/menopausal status at Screening/Baseline. 
8.4.6 
Appropriateness of safety measurements 
The safety assessments selected are standard for this indication/patient population. 
8.5 
Additional assessments 
8.5.1 
Alcohol use disorders identification test (AUDIT) 
Any history of alcohol use will be recorded in the CRF. Further, the Alcohol Use Disorders 
Identification Test (AUDIT) will be performed at Screening Visit 1 and as indicated in Table 
8-1. For this purpose, the patients will be interviewed by the site staff. At Screening Visit 1, a 
10-item questionnaire will be used, whereas at the following visits, the shortened version 
(AUDIT-C), a 3-item questionnaire will be used. 
 
 

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8.5.2 
Patient reported outcomes 
The impact of psoriasis on various aspects of patients’ health will be assessed by the 
following measures: 
• Dermatology life quality index  
 
 
 
 
These QoL assessments should be completed by the patient (in the language he/she is most 
familiar with) at the scheduled visit before the patient sees the Investigator (or designee) for 
clinical assessments. The patient should be given sufficient space and time to complete the 
questionnaires. The study coordinator should check the questionnaires for completeness and 
encourage the respondent to complete any missing responses. Prior to clinical examination, 
the Investigator should review the completed questionnaires for responses that may indicate 
potential AEs or SAEs.  
If AEs or SAEs are confirmed, the Investigator must record the events as per the instructions 
Section 10 of the protocol. The Investigator should not encourage the patient to change the 
responses reported in the completed questionnaires.  
8.5.2.1 
Dermatology life quality index 
The DLQI is a 10-item general dermatology disability index designed to assess health-related 
quality of life in adult patients with skin diseases such as eczema, psoriasis, acne, and viral 
warts (Finlay and Khan 1994, Basra et al 2008).  
This measure is self-administered and includes domains of daily activities, leisure, personal 
relationships, symptoms and feelings, treatment, and work/school. The measure is widely 
used: it has been tested across 32 different skin conditions and is available in 85 languages. 
The DLQI is the most frequently used instrument in studies of randomized controlled trials in 
dermatology. 
The recall period is the last week, and the instrument requires 1 to 2 minutes for completion. 
Each item has 4 response categories, ranging from 0 (not at all) to 3 (very much). “Not 
relevant” is also a valid response and is scored as 0. The DLQI total score is a sum of the 
10 questions. Scores range from 0 to 30 and higher scores indicate greater health-related 
quality-of-life impairment. Additionally, each subscale of the DLQI may be analyzed 
separately.  
The DLQI questionnaire will be completed by the patient as indicated in Table 8-1.  

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9 
Study discontinuation and completion 
9.1 
Discontinuation 
9.1.1 
Discontinuation of study treatment 
Discontinuation of study treatment for a patient occurs when study treatment 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 for a given patient if he/she believes that 
continuation would negatively impact the patient's well-being. 
Study treatment must be discontinued under the following circumstances: 
• Withdrawal of informed consent 
• Emergence of the following AEs: 

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• Any severe or SAE that is not compatible with administration of study medication, 
including AEs that require treatment with an unacceptable concomitant medication. 
• Onset of lymphoproliferative disease or any malignancy, except for treated basal cell 
carcinoma, treated actinic keratoses, treated in situ carcinoma of the cervix or non- 
invasive malignant colon polyps which are being or have been removed. 
• Life-threatening infection. 
• Severe hypersensitivity reaction or anaphylactic reaction. 
• Any laboratory abnormalities that in the judgment of the investigator are clinically 
significant and are deemed to place the patient at a safety risk for continuation in the study 
(A general guidance on clinically notable laboratory values is provided in Appendix 1). 
• Pregnancy. 
• Use of any biologic immunomodulating agent except secukinumab. 
• Any protocol deviation that results in a significant risk to the patient’s safety. 
• Disease worsening unacceptable at the Investigator’s discretion 
• Use of prohibited treatment as per recommendations in the prohibited treatment section. 
If discontinuation of study treatment occurs, the Investigator should make a reasonable effort 
to understand the primary reason for the patient’s premature discontinuation of study 
treatment and record this information. 
If study treatment discontinuation occurs because of study treatment unblinding, please refer 
to Section 6.2.2.  
Discontinuation of study treatment does not require the patient to be discontinued from the 
study and all ongoing visit assessments except in case of withdrawal of informed consent 
(see Section 9.1.2). Refer to Section 8 for the visit schedule and assessments. 
Patients who prematurely discontinue the study treatment (s.c. secukinumab or placebo) are 
encouraged to remain in the study to continue the study-related assessments until completion 
of the study. 
Patients who prematurely discontinue completely from the study for any reason should return 
for the final visit to undergo the EOT assessments (4 weeks after the last study treatment 
administration of secukinumab). This will be EOT1 (Week 12) for patients who prematurely 
discontinue during Treatment Period 1 and EOT2 (Week 24) for patients who prematurely 
discontinue during Treatment Period 2.  
If they fail to return for these assessments for unknown reasons, every effort (e.g. telephone, 
e-mail, letter) should be made to contact the patient/ pre-designated contact as specified in the 
lost to follow-up section. This contact should preferably be done according to the study visit 
schedule. 
If the patient cannot or is unwilling to attend any visit(s), the site staff should maintain regular 
telephone contact with the patient, or with a person pre-designated by the patient. This 
telephone contact should preferably be done according to the study visit schedule. 
After study treatment discontinuation, at a minimum, in abbreviated visits, the following data 
should be collected at clinic visits or via telephone/email contact: 

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• New/concomitant treatments. 
• Adverse events/SAEs. 
9.1.2 
Withdrawal of informed consent 
Patients may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent occurs only when a patient: 
• Does not want to participate in the study anymore, and 
• Does not allow further collection of personal data. 
In this situation, the Investigator should make a reasonable effort (e.g. telephone, e-mail, 
letter) to understand the primary reason for the patient’s decision to withdraw his/her consent 
and record this information. 
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the patient’s study withdrawal should be made as detailed in the 
assessment table. 
Novartis will continue to keep and use collected study information (including any data 
resulting from the analysis of a patient’s samples until the time of withdrawal) according to 
applicable law. 
All biological samples not yet analyzed at the time of withdrawal will no longer be used, 
unless permitted by applicable law. They will be stored according to applicable legal 
requirements. 
9.1.3 
Lost to follow-up 
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the Investigator must show "due diligence" by 
documenting in the source documents steps taken to contact the patient, e.g. dates of 
telephone calls, registered letters, etc. A patient should not be considered as lost to follow-up 
until due diligence has been completed or until the end of the study. 
9.1.4 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time. Reasons for early termination may 
include: 
• Unexpected, significant, or unacceptable safety risk to patients enrolled in the study 
• Decision based on recommendations from applicable board(s) after review of safety and 
efficacy data  
• Discontinuation of study drug development 
In taking the decision to terminate, Novartis will always consider patient welfare and safety. 
Should early termination be necessary, patients must be seen as soon as possible and treated 

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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 or Novartis depending on local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial. 
9.2 
Study completion and post-study treatment 
Study completion is defined as when the last patient finishes their Final Visit (Week 24/Early 
Withdrawal) and any repeat assessments associated with this visit have been documented and 
followed-up appropriately by the Investigator or, in the event of an early study termination 
decision, the date of that decision (e.g. each patient will be required to complete the study in 
its entirety and thereafter no further study treatment will be made available to them). 
All randomized and/or treated patients should have a safety follow-up conducted 30 days after 
the last administration of study treatment. This will be performed at Week 24 for patients who 
complete the study (last administration received at Week 20). The information collected is 
kept as source documentation. All SAEs reported during this period must be reported as 
described in Section 10.1.3. Attempts to contact the patient should be recorded in the source 
documentation. 
10 
Safety monitoring and reporting 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign 
(including abnormal laboratory findings), symptom or disease) in a patient or clinical 
investigation patient after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. 
The Investigator has the responsibility for managing the safety of individual patient and 
identifying AEs. 
Novartis qualified medical personnel will be readily available to advise on trial related 
medical questions or problems. 
The occurrence of AEs must be sought by non-directive questioning of the patient at each 
visit during the study. Adverse events also may be detected when they are volunteered by the 
patient during or between visits or through physical examination findings, laboratory test 
findings, or other assessments. 
Adverse events must be recorded under the signs, symptoms, or diagnosis associated with 
them, accompanied by the following information (as far as possible) (if the event is serious 
refer to Section 10.1.2): 
1. The severity grade: 
• Mild: usually transient in nature and generally not interfering with normal activities. 
• Moderate: sufficiently discomforting to interfere with normal activities. 

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• Severe: prevents normal activities. 
2. Its relationship to the study treatment (suspected: yes or no). If the event is due to lack of 
efficacy or progression of underlying illness (i.e. progression of the study indication) the 
assessment of causality will usually be “not suspected.” The rationale for this guidance is 
that the symptoms of lack of efficacy or progression of underlying illness are not caused 
by the study treatment, they happen in spite of its administration and/or both lack of 
efficacy and progression of underlying disease can only be evaluated meaningfully by an 
analysis of cohorts, not on a single patient. 
3. Its duration (start and end dates) or if the event is ongoing, an outcome of not 
recovered/not resolved must be reported. 
4. Whether it constitutes a SAE (see Section 10.1.2 for definition of SAE) and which 
seriousness criteria have been met. 
5. Action taken regarding the study treatment. 
All AEs must be treated appropriately. Treatment may include one or more of the 
following: 
• Dose not changed. 
• Dose reduced/increased. 
• Drug interrupted/withdrawn. 
6. Its outcome. 
Conditions that were already present at the time of informed consent should be recorded in 
medical history of the patient. 
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Adverse event monitoring should be continued for at least 30 days following the last dose of 
study treatment. 
Once an AE is detected, it must be followed until its resolution or until it is judged to be 
permanent (e.g. continuing at the end of the study), and assessment must be made at each visit 
(or more frequently, if necessary) of any changes in severity, the suspected relationship to the 
interventions required to treat it, and the outcome. 
Information about adverse drug reactions for the investigational drug can be found in the 
Investigator’s Brochure. 
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria: 
• They induce clinical signs or symptoms. 
• They are considered clinically significant. 
• They require therapy. 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
Baseline or the previous visit, or values which are considered to be non-typical in patients 

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with the underlying disease. Clinically notable laboratory values and vital signs are presented 
in Appendix 1.  
10.1.2 
Serious adverse events 
An SAE is defined as any AE (appearance of (or worsening of any pre-existing) undesirable 
sign(s), symptom(s) or medical conditions(s)) which meets any one of the following criteria: 
• Fatal 
• Life-threatening 
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 the ICH-E2D Guidelines). 
• Results in persistent or significant disability/incapacity. 
• Constitutes a congenital anomaly/birth defect. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:  
• Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition. 
• 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. 
• Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition. 
• Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission. 
• Is medically significant, e.g. defined as an event that jeopardizes the patient or may 
require medical or surgical intervention to prevent one of the outcomes listed above. 
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. Such 
events should be considered as “medically significant”. Examples of such events are intensive 
treatment in an emergency room or at home for allergic bronchospasm, blood dyscrasias or 
convulsions that do not result in hospitalization or development of dependency or 
abuse (please refer to the ICH-E2D Guidelines). 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.  
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All reports of intentional misuse and abuse of the product are also considered SAEs 
irrespective if a clinical event has occurred (Section 10.1.5).  

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10.1.3 
SAE reporting 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 30 days after the last study visit must be reported to 
Novartis safety within 24 hours of learning of its occurrence. Detailed instructions regarding 
the submission process and requirements are to be found in the Investigator folder provided to 
each site. 
Serious adverse events occurring after the patient has provided informed consent until the 
time the patient is deemed a Screen Failure must be reported to Novartis. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up 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. 
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 CMO&PS 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. 
Any SAEs experienced after the 30-day period following the last administration of study 
treatment should only be reported to Novartis Safety if the Investigator suspects a causal 
relationship to study treatment. 
10.1.4 
Pregnancy reporting 
To ensure patient safety, each pregnancy occurring after signing the informed consent must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications. 
Pregnancy should be recorded on a Clinical Trial Pregnancy Form and reported by the 
Investigator/qualified study center staff to the Novartis CMO&PS. Pregnancy follow-up 
should be recorded on the same form and should include an assessment of the possible 
relationship to the study treatment of any pregnancy outcome. Any SAE experienced during 
pregnancy must be reported. 
Pregnancy outcomes should be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes 
should be obtained from the mother ((please confirm)). 

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10.1.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, 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. 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate CRF 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 within 24 hours of 
Investigator’s awareness (Table 10-1). 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error type 
Document in dosing 
CRF (Yes/No) 
Document in 
AE eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated 
with an AE 
Only if associated with 
an SAE 
Misuse/Abuse 
Yes 
Yes 
Yes, even if not 
associated with a SAE 
For more information on AE and SAE definition and reporting requirements, please see the 
respective sections. 
10.2 
Additional safety monitoring 
10.2.1 
Liver safety monitoring 
There has been no safety signal for liver toxicity with secukinumab to date in approximately 
13000 patients and healthy subjects exposed, and from a mechanism of action standpoint 
there is no known effect of blocking IL-17a on the liver. Standard liver function tests will be 
obtained at regular intervals, but special measures for liver safety monitoring are not planned 
over and above those collected for the study endpoints (see Section 8.3.3, Section 8.3.4 and 
Section 8.4.4). For further information on standard liver function tests, see Appendix 1.  
10.2.2 
Renal safety monitoring 
There has been no safety signal for nephrotoxicity with secukinumab to date in approximately 
13000 patients and healthy subjects exposed, and from a mechanism of action standpoint 
there is no known effect of blocking IL-17a on the kidney. All patients with laboratory tests 
containing clinically significant abnormal values (see Appendix 1 for notable laboratory 
values) are to be followed until the values return to normal ranges or until a valid reason, 
other than treatment related AE, is defined. Standard renal function tests (BUN, serum 
creatinine) will be obtained at regular intervals, but special measures for renal safety 
monitoring are not planned. 

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10.2.3 
Steering committee 
The Steering Committee will be established comprising investigators participating in the trial, 
i.e. not being Novartis/sponsor representatives from the Clinical Trial Team. 
The Steering Committee will ensure transparent management of the study according to the 
protocol through recommending and approving modifications as circumstances require. The 
Steering Committee will review protocol amendments as appropriate. Together with the 
clinical trial team, the Steering Committee will also develop recommendations for 
publications of study results including authorship rules. The details of the role of the Steering 
Committee will be defined in the steering committee charter. 
11 
Data collection and database management 
11.1 
Data collection 
Designated Investigator staff will enter the data required by the protocol into electronic case 
report forms (eCRFs). The eCRFs will be built using fully validated secure web-enabled 
software that conforms to 21 CFR Part 11 requirements, Investigator site staff will not be 
given access to the EDC system until they have been trained. Automatic validation programs 
check for data discrepancies in the eCRFs, allow modification and/or verification of the 
entered data by the Investigator staff. 
The Investigator/designee is responsible for assuring that the data (recorded on CRFs) 
(entered into eCRF) is complete, accurate, and that entry and updates are performed in a 
timely manner. The Investigator must certify that the data entered are complete and accurate 
After final database lock, the Investigator will receive copies of the patient data for archiving 
at the investigational site. 
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
11.2 
Database management and quality control 
Novartis personnel (or designated clinical research organization (CRO)) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated 
Investigator site staff are required to respond promptly to queries and to make any necessary 
changes to the data. 
Concomitant treatments and prior medications entered into the database will be coded using 
the World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions and 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology. 
Each occurrence of a code break will be reported to the clinical team and monitor. The code 
break functionality will remain available until study shut down or upon request of Novartis. 

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Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked and the treatment codes will be unblinded and 
made available for data analysis/moved to restricted area to be accessed by independent 
programmer and statistician.  Any changes to the database after that time can only be made 
after written agreement by Novartis development management. 
11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an Investigator’s meeting, a 
Novartis/delegated CRO representative will review the protocol and data capture requirements 
(i.e. eCRFs) with the Investigators and their staff. During the study, Novartis employs several 
methods of ensuring protocol and GCP compliance and the quality/integrity of the sites’ data. 
The field monitor will visit the site to check the completeness of patient records, the accuracy 
of data capture / data entry, the adherence to the protocol and to GCP, the progress of 
enrollment, and to ensure that study treatment is being stored, dispensed, and accounted for 
according to specifications. Key study personnel must be available to assist the field monitor 
during these visits. Continuous remote monitoring of each site’s data may be performed by a 
centralized Novartis/delegated CRO. Additionally, a central analytics organization may 
analyze data and identify risks and trends for site operational parameters, and provide reports 
to Novartis clinical teams to assist with trial oversight. 
The Investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, 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 ICF 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 will be disclosed. 
12 
Data analysis and statistical methods 
The data will be analyzed by Novartis and/or a designated CRO. 
The analyses will be conducted on all patient data after database lock for the study. Any data 
analysis carried out independently by the Investigator should be submitted to Novartis before 
publication or presentation. 
12.1 
Analysis sets 
The following analysis sets will be used in this study: 
Randomized Analysis Set (RAS): The RAS is defined as all patients who were randomized. 
Unless otherwise specified, miss-randomized patients will be excluded from the RAS. 

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Full Analysis Set (FAS): The FAS comprises all patients to whom study treatment/reference 
treatment has been assigned by randomization. According to the intent to treat principle, 
patients will be analyzed according to the treatment they have been assigned to during the 
randomization procedure. 
Safety Set: The Safety Set includes all patients who received at least one dose of study 
treatment/reference treatment. Patients will be analyzed according to the study treatment 
received, where treatment received is defined as the randomized treatment if the patient took 
at least one dose of that treatment or the first treatment received if the randomized treatment 
was never received.  
12.2 
Subject demographics and other baseline characteristics 
Demographic and other Baseline data including disease characteristics will be listed and 
summarized descriptively by treatment group and in total for the FAS and Safety Set. 
Categorical data will be presented as frequencies and percentages. For continuous data, mean, 
standard deviation, median, minimum, and maximum will be presented.  
Relevant medical histories and current medical conditions at Baseline will be summarized by 
system organ class and preferred term (PT), and by treatment group. 
12.3 
Treatments 
The Safety Set will be used for the analyses below. Categorical data will be summarized as 
frequencies and percentages. For continuous data, mean, standard deviation, median, 
minimum, and maximum will be presented. 
The duration of exposure to study treatment by treatment group will be summarized by means 
of descriptive statistics using the Safety Set. In addition, the number of patients with exposure 
of certain thresholds will be displayed. Compliance will be calculated based on documented 
study drug administrations and syringe counts and displayed by treatment group and study 
phase. 
Concomitant medications and significant non-drug therapies received prior to and after the 
start of the study treatment will be listed and summarized according to the anatomical 
therapeutic chemical (ATC) classification system, by treatment group. Prior treatments are 
defined as treatments taken and stopped prior to first dose of study treatment. Any treatment 
given at least once between the day of first dose of randomized study treatment and the last 
day of study visit will be a concomitant treatment, including those which were started pre-
Baseline and continued into the treatment period. Treatments will be presented in alphabetical 
order, by ATC codes and grouped by anatomical main group. Tables will also show the 
overall number and percentage of patients receiving at least one treatment of a particular ATC. 
12.4 
Analysis of the primary endpoint 
12.4.1 
Definition of primary endpoint 
The primary aim of this study will be to demonstrate the superiority of secukinumab 
compared to placebo in patients with moderate to severe chronic plaque-type psoriasis and 
NAFLD with respect to PASI90 response at Week 12. 

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The primary endpoint variable is the PASI90 response at Week 12.  
The analysis of the primary variable will be based on the following estimand: 
• Analysis set: FAS 
• Variable of interest: PASI 90 response at Week 12 
• Intercurrent event: study discontinuation – effect between secukinumab versus placebo in 
patients with moderate to severe chronic plaque-type psoriasis and NAFLD irrespective of 
adherence to treatment. Patients who discontinue the trial prematurely will be counted as 
non-responders. 
• Summary measure: Odds ratio (OR) 
12.4.2 
Statistical model, hypothesis, and method of analysis 
The null hypothesis to be rejected is that the OR of a PASI90 response for patients with 
secukinumab vs. patients with placebo are ≥ 1 after 12 weeks. 
Let pj denote the probability of a PASI90 response at 12 weeks for treatment group j, j=0,1 
where 
• 0 corresponds to placebo 
• 1 corresponds to secukinumab 300 mg 
The following hypotheses will be tested: 
H0: (p0 / 1-p0)) / (p1 / 1-p1)) ≥ 1 versus HA: (p0 / 1-p0)) / (p1 / 1-p1)) < 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 group and center as 
factors and PASI score at Baseline (Day 1) as covariates. The OR and its 95% confidence 
interval (CI) and p-value will be given. The primary analysis will be based on the FAS and 
will be performed when all patients have completed the Week 12 assessment. 
12.4.3 
Handling of missing values/censoring/discontinuations 
For the analysis of the primary endpoint PASI90 response at Week 12, all patients of the FAS 
will be included. A patient with a missing assessment will be considered as a non-responder. 
Missing values of secondary endpoints or other outcomes (e.g. quality of life, safety or 
laboratory measurements) will not be replaced. 
12.4.4 
Sensitivity and supportive analyses 
A “while on treatment” estimand will be calculated as a sensitivity analysis. It will be based 
on the following estimand: 
• Analysis set: FAS 
• Variable of interest: PASI 90 response at Week 12 
• Intercurrent event: study discontinuation – effect between secukinumab versus placebo in 
patients with moderate to severe chronic plaque-type psoriasis and NAFLD. A patient 
with a missing assessment will be considered as a responder if he/she has met the response 
criterion already at the time of drop out. Otherwise, he/she will be considered as a 
non-responder. Summary measure: OR.  

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12.5 
Analysis of secondary endpoints 
Serum ALT level at Week 12 
The analysis of historic data from non-NAFLD patients suggests that the distribution of ALT 
values might be highly skewed to the left; however, after a log-transformation the distribution 
appeared quite symmetric, bell-shaped and could be well approximated by a normal 
distribution. Therefore, the log-transformed ALT-values will be used for the analysis.  
For this secondary objective, this study is meant as a Proof-of-Concept study, i.e. to evaluate 
if there is any evidence for a beneficial effect on this endpoint and to provide the basis for the 
planning of further, confirmatory studies; therefore a Bayesian methodology seems adequate 
for the analyses of possible drug effects on ALT. 
A sample from the posterior distribution of the difference between treatments of the log(ALT) 
levels will be produced using the BAYES-option is SAS PROC GENMOD (with the default, 
non-informative prior). These posterior samples will be re-transformed (exponentiated) and 
the percentage of samples  < 1, < .9, <.8 and <.7 (corresponding to the posterior probabilities 
of any reduction resp. reductions of at least 10%, 20% or 30% of ALT levels under 
secukinumab compared to placebo) will be calculated. The study will suggest to continue the 
development of secukinumab for hepatic inflammation, if the posterior probability of any 
effect (significance) is at least 90% and if the posterior probability of a relevant effect (> 20% 
reduction) is at least 50%. 
DLQI at Week 12 
The DLQI measures functional disability of adult patients with dermatological disorders and 
had been utilized as a relevant clinical measure in a range of dermatology clinical trials. The 
DLQI is a simple, validated, self-administered 10-item questionnaire. The instrument contains 
6 functional scales (i.e. symptoms and feeling, daily activities, leisure, work and school, 
personal relationships, treatment).  
Each question is answered with the following response: “not at all,” “a little,” “a lot,” or “very 
much”. Seven scores will be derived from the DLQI: the total score of each of the six 
dimensions as well as the total score over all items. The higher the score, the more quality of 
life is impaired.  
For total DLQI as well as for each of its 7 sub-dimensions the percentage change from 
baseline will be derived. Descriptive summary statistics will be provided for absolute values 
as well as for the percentage change by visit and treatment group. Additionally, the percentage 
of patients achieving a DLQI-score of 0 or 1 (DLQI 0/1) will be tabulated. 
12.5.1 
Safety endpoints 
For all safety analyses, the Safety Set will be used. All listings and tables will be presented by 
treatment group. 
Safety summaries (tables, figures) will include only data from the on-treatment period with 
the exception of Baseline data, which will also be summarized where appropriate (e.g. change 
from Baseline summaries). In addition, a separate summary for deaths including on-treatment 
and post-treatment deaths will be provided. In particular, summary tables for AEs will 

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summarize only on-treatment events, with a start date during the on-treatment period (i.e. 
treatment-emergent AEs as defined below).  
Adverse events 
All information obtained on AEs will be displayed by treatment group and patient. 
The number (and percentage) of patients with treatment-emergent AEs will be summarized in 
the following ways: 
• By treatment group, primary SOC and PT. 
• By treatment group, primary SOC, PT and maximum severity. 
Separate summaries will be provided for study medication related AEs, death, serious AEs, 
other significant AEs leading to discontinuation. 
A patient with multiple AEs within a primary SOC is only counted once towards the total of 
the primary SOC.  
Vital signs 
All vital signs data will be listed by treatment group, patient, and visit/time, and if ranges are 
available, abnormalities will be flagged. Analysis of the vital sign measurements using 
summary statistics for the change from Baseline for each post-Baseline visit will be 
performed. These descriptive summaries will be presented by vital sign and treatment group. 
Change from Baseline will only be summarized for patients with both Baseline and 
post-Baseline values. 
Clinical laboratory evaluations 
All laboratory data will be listed by treatment group, patient, and visit and if normal ranges 
are available abnormalities will be flagged. Summary statistics will be provided by treatment 
and visit. Change from baseline will only be summarized for patients with both Baseline and 
post-baseline values. Baseline to the worst on-treatment value. 
12.7 
Interim analyses 
No interim analysis will be performed. However, the final analysis of the data of Treatment 
Period 1 (including the primary endpoint) may already be conducted before all patients have 

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finished Treatment Period 2. Details about access to these data and about the maintenance of 
the blind while Treatment Period 2 is still ongoing will be specified in a separate document. 

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13 
Ethical considerations and administrative procedures 
13.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in 
accordance with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with 
applicable local regulations (including European Directive 2001/20/EC, US CFR 21), and 
with the ethical principles laid down in the Declaration of Helsinki. 
13.2 
Responsibilities of the Investigator and IRB/IEC 
Before initiating a trial, Novartis must obtain approval/favorable opinion from the IRB/IEC 
for the trial protocol, written ICF, consent form updates, patient recruitment procedures (e.g. 
advertisements) and any other written information to be provided to patients. Prior to study 
start, the Investigator is required to sign a protocol signature page confirming his/her 
agreement to conduct the study in accordance with these documents and all of the instructions 
and procedures found in this protocol and to give access to all relevant data and records to 
Novartis monitors, auditors, Novartis Quality Assurance representatives, designated agents of 
Novartis, IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site 
is requested by a regulatory authority, the Investigator must inform Novartis immediately that 
this request has been made. 
13.3 
Publication of study protocol and results 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required in EudraCT. In addition, after study completion (defined as last patient last visit) 
and finalization of the study report the results of this trial will be submitted for publication 
and posted in a publicly accessible database of clinical trial results, such as the Novartis 
clinical trial results website and all required Health Authority websites (e.g. Clinicaltrials.gov, 
EudraCT etc.). 
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the trial 
Investigator meetings. 
13.4 
Quality control and quality assurance 
Novartis maintains a robust Quality Management System (QMS) that includes all activities 
involved in quality assurance and quality control, to ensure compliance with written Standard 
Operating Procedures (SOPs) as well as applicable global/local GCP regulations and ICH 
Guidelines. 
Audits of Investigator sites, vendors, and Novartis systems are performed by auditors, 
independent from those involved in conducting, monitoring or performing quality control of 
the clinical 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. 

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14 
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected 
on study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances including 
incidental collection is an Investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the Investigator shall immediately disclose it to 
Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
Investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be 
implemented. 
14.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. 
Only amendments that are required for patient safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the Investigator is 
expected to take any immediate action required for the safety of any patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis 
should be notified of this action and the IRB/IEC at the study site should be informed 
according to local regulations. 

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15 
References 
References are available upon request 
Basra MK, Fenech R, Gatt RM et al (2008) The Dermatology Life Quality Index 1994-2007: 
a comprehensive review of validation data and clinical results. Br J Dermatol;159(5): 
997-1035. 
Bissonnette R, Luger T, Thaçi D, et al (2015) Secukinumab demonstrates high sustained 
efficacy and a favorable safety profile in patients with moderate to severe psoriasis through 
5 years of treatment (SCULPTURE Extension Study). Journal of the European Academy of 
Dermatology and Venereology;32(9): 1507-1514. 
Blauvelt A, Lebwohl MG, Bissonette R (2015) IL-23/IL-17A dysfunction phenotypes inform 
possible clinical effects from anti-IL-17A therapies. J Invest Dermatol;135: 1946-1953. 
Boehncke WH, Schön MP (2015) Psoriasis. Lancet;386(9997): 983-94. 
Candia R, Ruiz A, Torres-Robles R, et al (2015) Risk of non-alcoholic fatty liver disease in 
patients with psoriasis: a systematic review and meta-analysis. J Eur Acad Dermatol 
Venereol;29(4): 656-62. 
Committee for medicinal products for human use (CHMP), European Medicines Agency for 
the Evaluation of Medicines for Human Use (2004) Guideline on clinical investigation of 
medicinal products indicated for the treatment of psoriasis. CHMP/EWP/2454/02 corr. 
document. London, UK. 
Dolan P (1997) Modeling valuations for EuroQol health states. Med Care 35(11): 1095-108. 
Finlay AY, Khan GK (1994). Dermatology Life Quality Index (DLQI): A simple practical 
measure for routine clinical use. Clin Exp Dermatol; 19: 210-216. 
Fredriksson T, Pettersson U (1978) Severe psoriasis-oral therapy with a new retinoid. 
Dermatologica; 157: 238-44. 
Giles DA, Moreno-Fernandez ME, Divanovic S (2015) IL-17 Axis Driven Inflammation in 
Non-Alcoholic Fatty Liver Disease Progression. Curr Drug Targets;16(12): 1315-23. 
Gisondi P, Targher G, Zoppini G (2009) Non-alcoholic fatty liver disease in patients with 
chronic plaque psoriasis. J Hepatol;51(4): 758-64.  
Gottlieb AB, Hamilton T, Ivor C, et al (2006) Long-term continuous efalizumab therapy in 
patients with moderate to severe chronic plaque psoriasis: updated results from an ongoing 
trial for the Efalizumab Study Group. J Am Acad Dermatol; 54(4): S154-S163. 
Harley IT, Stankiewicz TE, Giles DA, et al (2014) IL-17 signaling accelerates the progression 
of nonalcoholic fatty liver disease in mice. Hepatology;59(5): 1830-9.  
Harrison SA, Rinella ME, Abdelmalek MF, et al (2018a) NGM282 for treatment of non-
alcoholic steatohepatitis: a multicentre, randomised, double-blind, placebo-controlled, phase 2 
trial. Lancet;391(10126): 1174-1185.  
Harrison SA (2018) Overview of Current and Emerging Therapeutic Approaches to 
Nonalcoholic Steatohepatitis. Gastroenterol Hepatol (NY);14(6): 380-383. 

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ICH E2D (2004) Clinical Safety Data Management: Definitions and Standards for expedited 
reporting. Accessed from: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC5
00002807.pdf Accessed on: 02Dec2016. 
Jahn D, Rau M, Wohlfahrt J, et al (2016) Non-alcoholic steatohepatitis: from pathophysiology 
to novel therapies. Digestive diseases (Basel, Switzerland);34: 356-63. 
Kisseleva T (2014) Does interleukin-17 play the villain in nonalcoholic steatohepatitis? 
Hepatology;59(5): 1671-2. 
Langley RG, Elewski BE, Lebwohl M, et al (2014) Secukinumab in plaque psoriasis – results 
of two phase 3 trials. N Engl J Med;371: 326-38. 
Mantovani A, Gisondi P, Lonardo A, et al (2016) Relationship between non-alcoholic fatty 
liver disease and psoriasis: a novel hepato-dermal axis? Int J Mol Sci. 5;17(2): 217. 
McInnes IB, Mease PJ, Kirkham B, et al (2015) Secukinumab, a human anti-interleukin-17A 
monoclonal antibody, in patients with psoriatic arthritis (FUTURE 2): a randomised, double-
blind, placebo-controlled, phase 3 trial. Lancet;386: 1137-46. 
Mease PJ, McInnes I, Kirkham B, et al (2015) Secukinumab inhibition of interleukin-17a in 
patients with psoriatic arthritis. New England Journal of Medicine;373: 1329-1339. 
Nast A, Gisondi P, Ormerod AD, et al (2015) European S3-Guidelines on the systemic 
treatment of psoriasis vulgaris--Update 2015--Short version--EDF in cooperation with EADV 
and IPC. J Eur Acad Dermatol Venereol;29(12): 2277-94.  
Nast A, Spuls PI, van der Kraaij G, et al (2017) European S3-Guideline on the systemic 
treatment of psoriasis vulgaris - Update Apremilast and Secukinumab - EDF in cooperation 
with EADV and IPC. J Eur Acad Dermatol Venereol;31(12): 1951-1963.  
Neuschwander-Tetri BA, Van Natta ML, Tonascia J, et al (2015) Trials of obeticholic acid for 
non-alcoholic steatohepatitis – Authors’ reply. Lancet;386(9988): 28-29. 
Ouyang W, Valdez P (2008) IL-22 in mucosal immunity. Mucosal Immunol;1(5): 335-8.  
Paul C, Lacour JP, Tedremets L, et al (2015) Efficacy, safety and usability of secukinumab 
administration by autoinjector/pen in psoriasis: a randomized, controlled trial (JUNCTURE). J 
EU Acad Dermatol Venereol;29: 1082-90. 
Ratziu V, Giral P, Jacqueminet S, et al (2008) Rosiglitazone for nonalcoholic steatohepatitis: 
one-year results of the randomized placebo-controlled Fatty Liver Improvement with 
Rosiglitazone Therapy (FLIRT) Trial. Gastroenterology;135(1): 100-10.  
Rau M, Schilling AK, Meertens J (2016) Progression from nonalcoholic fatty liver to 
nonalcoholic steatohepatitis is marked by a higher frequency of Th17 cells in the liver and an 
increased th17/resting regulatory t cell ratio in peripheral blood and in the liver. 
J Immunol;196(1): 97-105.  
Roberts KK, Cochet AE, Lamb PB, et al (2015) The prevalence of NAFLD and NASH among 
patients with psoriasis in a tertiary care dermatology and rheumatology clinic. Aliment 
Pharmacol Ther;41(3): 293-300. 
Sanyal A, Charles ED, Neuschwander-Tetri B, et al (2017) BMS-986036 (pegylated FGF21) 
in patients with non-alcoholic steatohepatitis: a phase 2 study. J Hepatol Suppl, 66(1), p. S89-
S90. 

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Tang Y, Bian Z, Zhao L, et al (2011) Interleukin-17 exacerbates hepatic steatosis and 
inflammation in non-alcoholic fatty liver disease. Clin Exp Immunol;166(2): 281-90. 
Thaçi D, Humeniuk J, Frambach Y, et al (2015) Secukinumab in psoriasis: randomized, 
controlled phase 3 trial results assessing the potential to improve treatment response in partial 
responders (STATURE). Br J Dermatol;173: 777-87. 
The EuroQol Group (1990) EuroQol-a new facility for the measurement of health-related 
quality of life. Health Policy 16(3): 199-208. 
Van de Kerkhof PC, Griffiths CE, Reich K, et al (2016) Secukinumab long-term safety 
experience: A pooled analysis of 10 phase II and III clinical studies in patients with moderate 
to severe plaque psoriasis. Journal of the American Academy of Dermatology;75: 83-98. 
Vonghia L, Michielsen P, Francque S (2013) Immunological mechanisms in the 
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Warnecke C, Manousaridis I, Herr R, et al (2011) Cardiovascular and metabolic risk profile in 
German patients with moderate and severe psoriasis: a case control study. Eur J 
Dermatol;21(5): 761-70.  
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comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat; 14: 158-165. 
Weiss J, Rau M, Geier A (2014) Non-alcoholic fatty liver disease: epidemiology, clinical 
course, investigation, and treatment. Dtsch Arztebl Int;111(26): 447-52.  
Whelton PK, Carey RM, Aronow WS et al (2017) 
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practice guidelines. J Am Coll Cardiol; S0735-1097(17): 41519-1. 
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Xu R, Tao A, Zhang S (2013) Neutralization of interleukin-17 attenuates high fat diet-induced 
non-alcoholic fatty liver disease in mice. Acta Biochim Biophys Sin (Shanghai);45(9):726-33.  
Zuniga LA, Shen WJ, Joyce-Shaikh B (2010) IL-17 regulates adipogenesis, glucose 
homeostasis, and obesity. Journal of Immunology;185:6947-59. 

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16 
Appendices 
16.1 
Appendix 1: Clinically notable laboratory values  
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 8.4.3. 
No specific action is pre-defined within this protocol to respond to specific abnormal 
laboratory values, 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 patient. For additional information please refer to the laboratory 
manual.  
Liver function and related variables  
ALT (SGPT):  
 
 
 
> 3 x upper limit of normal (ULN) 
AST (SGOT):  
 
 
 
> 3 x ULN 
Total bilirubin: 
 
 
 
> 1.5 x ULN 
Alkaline phosphatase:  
 
 
> 2 x ULN 
Renal function and electrolyte variables 
Creatinine (serum): 
 
 
 
> 1.5 x ULN 
Hematology 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 
Urinalysis variable 
Protein urine dipstick:  
 
 
++* (* ++ is ≥ 100 mg/dL) 

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16.2 
Appendix 2: The American Heart Association (AHA) 
Recommended Diet 
Optimization of diet can result in a marked triglyceride-lowering effect that ranges between 
20% and 50%. Good practices include weight loss, reducing simple carbohydrates at the 
expense of increasing dietary fiber, eliminating industrial-produced trans fatty acids, 
restricting fructose and saturated fatty acids, implementing a Mediterranean-style diet, and 
consuming marine-derived omega-3 PUFA.  
AHA recommends the following: 
Eat a variety of fruit and vegetable servings every day. Dark green, deep orange, or yellow 
fruits and vegetables are especially nutritious. Examples include spinach, carrots, peaches, 
and berries. Eat a variety of grain products every day. Include whole-grain foods that have 
lots of fiber and nutrients. Examples of whole grains include oats, whole wheat bread, and 
brown rice. Eat fish at least 2 times each week. Oily fish, which contain omega-3 fatty acids, 
are best for your heart. These fish include tuna, salmon, mackerel, lake trout, herring, and 
sardines. Stay at a healthy weight by balancing the amount of calories you eat with the 
activity you do every day. If you want to lose weight, increase your activity level to burn 
more calories than you eat.  
Eat foods low in saturated fat and cholesterol. Try to choose the following foods: 
• Lean meats and meat alternatives like beans or tofu 
• Fish, vegetables, beans, and nuts 
• Nonfat and low-fat dairy products 
• Polyunsaturated or monounsaturated fats, like canola and olive oils, to replace saturated 
fats, such as butter  
Read food labels and limit the amount of Trans fat you eat. Trans fat is found in many 
processed foods made with shortening or with partially hydrogenated or hydrogenated 
vegetable oils. These foods include cookies, crackers, chips, and many snack foods.  
Limit sodium intake to less than 2,300 mg of sodium a day (about one teaspoon). Choose and 
prepare foods with little or no salt.   
Limit alcohol intake to 2 drinks a day for men and 1 drink a day for women.  
Limit drinks and foods with added sugar. 

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16.3 
Appendix 3: 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 
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 

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Criteria 
Event type 
Actions required 
Follow-up monitoring 
≤ 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.