A Randomized, Double-blind, Placebo- and Active Controlled Multicenter Trial to Demonstrate Efficacy of Subcutaneous Secukinumab Compared to Placebo and Etanercept (in a Single-blinded Arm) After Twelve Weeks of Treatment, and to Assess the Safety, Tolerability, and Long-term Efficacy in Subjects From 6 to Less Than 18 Years of Age With Severe Chronic Plaque Psoriasis
Phase: PHASE3
Conditions: Chronic Severe Plaque-type Psoriasis
Sponsor: Novartis Pharmaceuticals

Clinical Development - General Medicine
Secukinumab/AIN457
Clinical Trial Protocol CAIN457A2310 / NCT02471144
A randomized, double-blind, placebo- and active controlled 
multicenter trial to demonstrate efficacy of subcutaneous 
secukinumab compared to placebo and etanercept (in a 
single-blinded arm) after twelve weeks of treatment, and to 
assess the safety, tolerability, and long-term efficacy in 
subjects from 6 to less than 18 years of age with severe 
chronic plaque psoriasis
Document type:
Amended Protocol Version 
EUDRACT number:
2014-005663-32
Version number:
v04 (clean)
Development phase:
III
Release date:
18-Sep-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, November, 2013

Novartis
Confidential
Page 2
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Table of contents
Table of contents .................................................................................................................2
List of tables ........................................................................................................................6
List of figures ......................................................................................................................6
List of abbreviations............................................................................................................7
Glossary of terms...............................................................................................................10
Amendment 4 (18-Sep-2020)............................................................................................11
Amendment 3 ....................................................................................................................14
Amendment 2 ....................................................................................................................15
Amendment 1 ....................................................................................................................17
Protocol summary..............................................................................................................18
1
Introduction .......................................................................................................................21
1.1
Background............................................................................................................21
1.2
Purpose ..................................................................................................................23
2
Study objectives.................................................................................................................24
2.1
Primary objective(s)...............................................................................................24
2.2
Secondary objectives .............................................................................................24
24
3
Investigational plan ...........................................................................................................25
3.1
Study design...........................................................................................................25
3.2
Rationale of study design.......................................................................................29
3.3
Rationale of dose/regimen, route of administration and duration of treatment.....29
3.4
Rationale for choice of comparator .......................................................................30
3.5
Purpose and timing of interim analyses/design adaptations..................................31
3.6
Risks and benefits..................................................................................................31
4
Population..........................................................................................................................33
4.1
Inclusion criteria ....................................................................................................33
4.2
Exclusion criteria...................................................................................................33
5
Treatment...........................................................................................................................35
5.1
Protocol requested treatment .................................................................................35
5.1.1
Investigational treatment.......................................................................35
5.1.2
Additional study treatment....................................................................36
5.2
Treatment arms......................................................................................................36
5.3
Treatment assignment, randomization...................................................................39
5.4
Treatment blinding.................................................................................................39
5.5
Treating the subject................................................................................................41

Novartis
Confidential
Page 3
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
5.5.1
Patient numbering .................................................................................41
5.5.2
Dispensing the investigational treatment ..............................................42
5.5.3
Handling the study treatment ................................................................44
5.5.4
Instructions for prescribing and taking study treatment........................44
5.5.5
Permitted dose adjustments and interruptions of study treatment ........46
5.5.6
Rescue medication ................................................................................47
5.5.7
Prior and Concomitant treatment ..........................................................47
5.5.8
Prohibited Treatment.............................................................................48
5.5.9
Discontinuation of study treatment and of treatment-free period .........50
5.5.10
Withdrawal of consent ..........................................................................51
5.5.11
Loss to follow-up ..................................................................................52
5.5.12
Emergency breaking of assigned treatment code..................................52
5.5.13
Study completion and post-study treatment..........................................53
5.5.14
Early study termination.........................................................................53
6
Visit schedule and assessments .........................................................................................53
6.1
Information to be collected on screening failures..................................................64
6.2
Subject demographics/other baseline characteristics.............................................64
6.2.1
Demographics .......................................................................................64
6.2.2
Psoriasis medical history / Previous psoriasis therapy..........................64
6.2.3
Relevant medical history / current medical conditions.........................64
6.2.4
Chest X-ray (optional)...........................................................................65
6.2.5
Determination of Tuberculosis status....................................................65
6.2.6
Other baseline characteristics................................................................68
6.3
Treatment exposure and compliance .....................................................................68
6.4
Efficacy..................................................................................................................68
6.4.1
Investigator Global assessment (IGA mod 2011) .................................68
6.4.2
Assessment of total body surface area (BSA) and psoriasis area 
safety index (PASI)...............................................................................69
72
6.4.4
Appropriateness of efficacy assessments..............................................72
6.5
Safety.....................................................................................................................72
6.5.1
Physical examination ............................................................................72
73
6.5.3
Vital signs..............................................................................................73
6.5.4
Height and weight .................................................................................73
6.5.5
Laboratory evaluations..........................................................................74

Novartis
Confidential
Page 4
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
6.5.6
Electrocardiogram (ECG) .....................................................................75
76
6.5.8
Pregnancy and assessments of fertility .................................................76
6.5.9
Appropriateness of safety measurements..............................................78
6.6
Other assessments..................................................................................................78
6.6.1
Health related Quality of Life ...............................................................78
6.6.2
Resource utilization...............................................................................79
80
81
7
Safety monitoring..............................................................................................................82
7.1
Adverse events.......................................................................................................82
7.2
Serious adverse events...........................................................................................84
7.2.1
Definition of SAE .................................................................................84
7.2.2
SAE reporting........................................................................................84
7.3
Liver safety monitoring .........................................................................................86
7.4
Renal safety monitoring.........................................................................................87
7.5
Pregnancy reporting...............................................................................................89
8
Data review and database management.............................................................................89
8.1
Site monitoring ......................................................................................................89
8.2
Data collection.......................................................................................................90
8.3
Database management and quality control............................................................90
8.4
Data Monitoring Committee..................................................................................91
8.5
Adjudication Committee........................................................................................91
9
Data analysis......................................................................................................................91
9.1
Analysis sets ..........................................................................................................92
9.2
Subject demographics and other baseline characteristics......................................92
9.3
Treatments .............................................................................................................93
9.4
Analysis of the primary variable(s) .......................................................................93
9.4.1
Variable(s).............................................................................................93
9.4.2
Statistical model, hypothesis, and method of analysis..........................93
9.4.3
Handling of missing values/censoring/discontinuations.......................94
9.4.4
Supportive analyses...............................................................................95
9.5
Analysis of secondary variables ............................................................................95
9.5.1
Efficacy variables..................................................................................95
9.5.2
Other Efficacy variables........................................................................96
9.5.3
Safety variables .....................................................................................97

Novartis
Confidential
Page 5
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
9.5.4
Resource utilization...............................................................................99
9.5.5
Health-related Quality of Life...............................................................99
100
100
9.5.8
Biomarkers..........................................................................................100
9.5.9
PK/PD .................................................................................................100
9.6
Interim analyses...................................................................................................100
9.7
Sample size calculation........................................................................................101
10 Ethical considerations......................................................................................................102
10.1
Regulatory and ethical compliance......................................................................102
10.2
Informed consent procedures...............................................................................102
10.3
Responsibilities of the investigator and IRB/IEC................................................103
10.4
Publication of study protocol and results.............................................................104
11 Protocol adherence ..........................................................................................................104
11.1
Protocol Amendments .........................................................................................104
12 References .......................................................................................................................104
13 Appendix 1: Clinically notable laboratory values and vital signs...................................107
14 Appendix 2: Liver event and Laboratory trigger Definitions and Follow-up 
Requirements...................................................................................................................110
112
16 Appendix 4: Weight and recommended blood volumes .................................................113
114
18 Appendix 6:  CDLQI questionnaire ................................................................................115
19 Appendix 7: CHAQ Questionnaire .................................................................................117

Novartis
Confidential
Page 6
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
List of tables
Table 5-1
Secukinumab/Placebo treatment arms and injections at each visit 
during Induction and maintenance epoch .............................................37
Table 5-2
Prohibited treatment..............................................................................49
Table 6-1
Visit and assessment schedule for the Blinded Epoch..........................56
Table 6-2
Visit and Assessment schedule for the Extended treatment epoch.......60
Table 6-3
IGA mod 2011 scale..............................................................................69
Table 6-4
PASI scoring system .............................................................................70
Table 7-1
Specific Renal Alert Criteria and Actions.............................................88
Table 9-1
Treatment groups for analyses ..............................................................91
Table 13-1
Notable Pediatric ranges for vital signs* ............................................109
Table 13-2
Recommended Dimensions for Blood Pressure Cuff Bladders ..........109
Table 14-1
Liver Event and Laboratory Trigger Definitions ................................110
Table 14-2
Follow Up Requirements for Liver Events and Laboratory Triggers.110
112
112
Table 16-1
Total blood volume, 1% and 3% of total blood volume by weight 
assuming 85mL per kg total blood volume.........................................113
114
List of figures
Figure 3-1
Study design..........................................................................................26
Figure 3-2
Average concentration for the proposed low dose and high dose 
secukinumab arms.................................................................................30
Figure 6-1
Tuberculosis screening flowchart .........................................................67
Figure 9-1
Testing strategy.....................................................................................96

Novartis
Confidential
Page 7
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
List of abbreviations
AE
adverse event
ACR
American college of Rheumatology
ALT
alanine aminotransferase
ANCOVA
Analysis of covariance
AST
aspartate aminotransferase
BDR
Bioanalytical Data Report
b.i.d.
twice a day
BUN
Blood Urea Nitrogen
CFR
US Code of Federal Regulations
CDLQI
Children’s Dermatology Life Quality Index
CHAQ©
Childhood Health Assessment Questionnaire
COVID-19
Coronavirus disease of 2019
CRF
Case Report/Record Form (paper or electronic)
CPO
Country Pharma Organization
CRO
Contract Research Organization
CS
Corticosteroids
CT
Computerized Tomography
CTC
Common Toxicity Criteria
DLQI
Dermatology Life Quality Index
DMC
Data Monitoring Board
DNA
Deoxyribonucleic acid
DS&E
Drug Safety & Epidemiology
ECG
Electrocardiogram
e.g.
Example
EOI
End of Induction
EOM
End of Maintenance
EOT
End of Treatment
EOF
End of Follow up
eCRF
electronic Case Report/Record Form
EDC
Electronic Data Capture
EDTA
Ethylenediaminetetraacetic acid
ELISA
Enzyme-Linked Immunosorbent Assay
eGFR
Estimated Glomerular Filtration Rate
EU
European Union
FAS
Full Analysis Set

Novartis
Confidential
Page 8
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
FDA
United States Food and Drug Administration
GCP
Good Clinical Practice
GDPR
General Data Protection Regulation
GGT
Gamma –glutamyl transferase
GTD
Global Trial Director
GWA
genome-wide association
HA
Health Authorities
hCG
Human chorionic gonadotropin
HCP
Health Care Professional
HRQoL
health-related quality of life
HIV
Human Immunodeficiency virus
IA
Interim Analysis 
IB
Investigator’s Brochure
ICH
International Council for Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use
ICF
Informed Consent Form
IEC
Independent Ethics Committee
IGA 
Investigator’s Global Assessment
IGA mod 2011
Novartis Investigator’s Global Assessment modified 2011
IgG
Immunoglobulin G
IL
interleukin
i.v.
intravenous
IN
Investigator Notification
IQS
Integrated Quantitative Sciences
IRB
Institutional Review Board
IRT
Interactive Response Technology
IVRS
Interactive Voice Response System 
IWRS
Interactive Web Response System
IUD
Intrauterine device
IUS
Intrauterine System
LFT
Liver function test (raised serum transaminases and/or bilirubin levels)
LLOQ
lower limit of quantification
MACE
Major Adverse Cardiovascular events
MAP
Meta-Analytic-Prediction
MedDRA
Medical dictionary for regulatory activities 

Novartis
Confidential
Page 9
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
MRI
Magnetic Resonance Imaging
OC/RDC
Oracle Clinical/Remote Data Capture
o.d.
once a day
 
p.o.
oral(ly)
PASI 
Psoriasis Area and Severity Index
PCR
Protein over Creatinine Ratio
PFS
Pre-filled Syringe  
PRO
Patient Reported Outcome
PT/INR
Prothrombin Time/International Normalized Ratio
PUVA 
Photo chemotherapy (e.g. psoralen + UVA treatment)
QFT 
QuantiFERON TB-Gold test
R
Randomization
RDC
Remote Data Capture
SAE
serious adverse event
s.c. 
Subcutaneous
SGOT
Serum Glutamic Oxaloacetic Transaminase
SGPT
Serum Glutamic Pyruvic Transaminase
SMQ
Standardized MedDRA queries
SST
Serum Separator Tube
SUSAR
Suspected Unexpected Serious Adverse Reactions
TB 
tuberculosis
TBL
Total Bilirubin
TCS 
Topical Corticosteroid
Th17
T helper 17 cells
TNF
Tumor necrosis factor
UV
Ultraviolet
UVA
Ultraviolet A, long wave 400 nm–315 nm
UVB
Ultraviolet B, medium wave 315 nm–280 nm
VAS
Visual Analog Scale
vs
Versus
WBC
White blood cells / leukocytes
WHO
World Health Organization

Novartis
Confidential
Page 10
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Glossary of terms
Assessment
A procedure used to generate data required by the study
Cohort 
A group of newly enrolled patients treated at a specific dose and regimen 
(i.e. treatment group) at the same time
Control drug
Any drug (an active drug or an inactive drug, such as a placebo) which is 
used as a comparator to the drug being tested in the trial
Dose level
The dose of drug given to the patient (total daily or weekly etc.)
Enrollment
Point/time of patient entry into the study at which informed consent must 
be obtained (i.e. prior to starting any of the procedures described in the 
protocol)
Epoch 
A portion of the study which serves a specific purpose. Typical Epochs 
are: screening/recruitment, wash-out, treatment, and follow-up
Investigational drug
The drug whose properties are being tested in the study; this definition is 
consistent with US CFR 21 Section 312.3 and is synonymous with 
“investigational new drug” or “investigational medicinal product.”
Investigational treatment
All investigational drug(s) whose properties are being tested in the study 
as well as their associated treatment controls. 
This includes any placebos, any active controls, as well as approved 
drugs used outside of their indication/approved dosage or tested in a fixed 
combination. 
Investigational treatment generally does not include protocol-specified 
concomitant background therapies when these are standard treatments in 
that indication.
Medication number
A unique identifier on the label of each investigational/study drug package 
in studies that dispense medication using an IRT system.
Personal Data
Subject information collected by the Investigator that is transferred to 
Novartis for the purpose of the clinical trial. This data includes subject 
identifier information, study information and biological samples.
Protocol
A written account of all the procedures to be followed in a trial, which 
describes all the administrative, documentation, analytical and clinical 
processes used in the trial.
Premature subject/patient 
withdrawal
Point/time when the patient exits from the study prior to the planned 
completion of all study treatment administration and/or assessments; at 
this time all study treatment administration is discontinued and no further 
assessments are planned, unless the patient will be followed for 
progression and/or survival
Randomization number
A unique identifier assigned to each randomized patient, corresponding to 
a specific treatment arm assignment
Study drug/ treatment
Any single drug or combination of drugs administered to the patient as 
part of the required study procedures; includes investigational drug (s), 
active drug run-ins or background therapy 
Study/investigational treatment 
discontinuation
Point/time when patient permanently stops taking study/investigational 
treatment  for any reason; may or may not also be the point/time of 
premature patient withdrawal
Subject Number 
A number assigned to each patient who enrolls into the study 
Variable
A measured value or assessed response that is determined in specific 
assessments and used in data analysis to evaluate the drug being tested 
in the study
Withdrawal of study consent
Withdrawal of consent from the study occurs only when a subject does not 
want to participate in the study any longer, and does not allow any further 
collection of personal data.

Novartis
Confidential
Page 11
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Amendment 4 (18-Sep-2020)
The rationale for this amendment is to introduce a level of flexibility in drug dispensation, 
protocol assessments and visit schedule if a major health care event like COVID-19 
(Coronavirus disease of 2019) pandemic requires it, thus allowing patients to remain in the trial 
and continue treatment while being monitored for safety.
The purpose of these changes, is to reduce the risk of exposure for patients and site staff and 
potentially the risk of transmission of infectious diseases (e.g. COVID-19).
These changes are limited to the duration of COVID-19 pandemic or of any other major health 
care event and must be done in accordance with the local rules and regulations relevant to 
pandemic containment measures.
In addition, renal and liver monitoring procedures will no longer be followed for subjects who 
reach adulthood (≥18 years). These procedures were introduced for the pediatric population in
this study but are no longer relevant once subjects reach adult age, considering that 
secukinumab has been approved for adults in all major markets since 2014 without any 
requirement for renal and liver safety monitoring. Review of the trial data by the independent 
DMC has not revealed any concern about renal or liver safety in pediatric subjects treated with 
secukinumab. Novartis will continue renal and liver safety monitoring in pediatric subjects 
(<18 years) in this study.  
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined for insertions. 
Changes to the protocol
The amendment includes changes: 

Due to COVID-19 pandemic or any other pandemic

Allowing shipment of study medication to the patient’s home (Section 5.5.2)

Alternative options to visits (Sections 6, 6.5)

Local laboratory testing for safety purposes (Section 6.5.5)

Home Pregnancy testing (Section 6.5.8)

Remote PRO collection (Section 6.6.1.1)

Informed consent procedures (Section 10.2)

To update safety monitoring

Discontinuation of liver monitoring in adults (Section 7.3)

Discontinuation of  renal monitoring in adults (Section 7.4)

Small modifications and clarifications on Specific Renal Alert Criteria and Actions in 
Table 7-1 of Section 7.4.

Added Inflammatory Bowel Disease as an example for discontinuation of study 
treatment in Section 5.5.9.

To manage inconsistencies in the original protocol

Added age stratum (Section 9.4.2, 9.5.2) 

Novartis
Confidential
Page 12
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

For handling of missing values/censoring/discontinuations, modified non-responder 
imputation was replaced with pure non-responder imputation. This change was in line 
with HA recommendation and the pivotal adult studies (Section 9.4.3)

Added age stratum and replaced modified non responder imputations with pure non-
responder imputations (Section 9.4.4)

For Health-related Quality of Life, CDLQI 0 or 1 related text was added. The Van-
Elteren testing and Hodges-Lehmann estimates for CDLQI total score were removed 
as relevant CDLQI 0 or 1 analysis was already included to compare with controls 
(Section 9.5.5)

As well as other miscellaneous minor corrections and clarifications.
IRBs/IECs
A copy of this amended protocol will be sent to the Institutional Review Boards
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.
This protocol 
amendment is considered substantial. The changes described in this amended protocol require 
IRB/IEC and Health Authority approval according to local regulations prior to implementation. 
COVID-19 related measures may/will be implemented immediately and prior to IRB/IEC and
HA approvals. Submission for review and approval to IRB/IEC and Health Authorities should 
occur as early as possible.
The changes herein affect the Informed Consent.  Sites are required to update and submit a
revised Informed Consent for approval that takes into account the changes described in this 
protocol amendment. 

Novartis
Confidential
Page 13
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Summary of previous amendments 
Amendment 3 (April 2018)
Amendment 2 (February 2016)
Amendment 1 (April 2015)

Novartis
Confidential
Page 14
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Amendment 3
Amendment rationale 
The main purpose of this amendment is to include an additional Interim Analysis prior to the 
Week 24 analysis once sufficient safety 
 have been collected.  This 
analysis aligned with the efficacy extrapolation principle, is expected to provide the basis for a 
submission package to health authorities (HA), with the intent to allow earlier availability of 
secukinumab to pediatric patients in countries which accept a submission of clinical data with 
use of extrapolation methodology. This analysis may be performed before all subjects have 
reached the primary endpoint. 
In addition to that, some clarifications, as well as editorial changes were undertaken in the 
protocol.
At the time of the protocol amendment finalization, a total of 120 subjects have been enrolled. 
The changes resulting from this amendment will not impact the study population or the study 
design.
Changes to the protocol
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined for insertions.
Changes to the protocol include the following:

Section 3.5, Purpose and Timing of Interim Analyses and Section 9.6 Interim Analyses 
were revised with the additional interim analysis information

Information for blinding relevant to the additional interim analysis was provided in 
Section 5.4

The changes were made in data analysis Section 9.6 to reflect the additional interim 
analysis. Moreover, following changes have been made in Section 9:

Clarification regarding one-sided p-values for hypothesis testing but two-sided for the 
others in Section 9. 

In Section 9.4.3, clarification regarding the definition of non-responder imputation 
and emphasizing a modified approach to be used.

In Section 9.4.4, one of the sensitivity analyses was changed to analysis using 
modified non-responder imputation for missing data.
 

Section 5.5.10, language related to Withdrawal of Consent was updated as per European 
Economic Area’s General Data Protection Regulation (GDPR) requirement

In Section 5.5.7.2 and Section 5.5.8 it is clarified that corticosteroid topical treatment 
during screening period is also allowed for hands and feet, which is aligned with what is 
stated in Table 5-2.

Clarification regarding the timing of screening visit was provided,  in form of footnote in
Table 6-1

Novartis
Confidential
Page 15
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

Following clarification related to drug self-administration has been added to Section 5.2, 
Section 5.5.2, Table 6-1 and Table 6-2: 

Subjects <12 years of age must not self-administer. However, adolescents (aged 12 to 
<18 years) can self-administer while under supervision by Health Care Professional 
(HCP) or caregiver/guardian 

In Table 7-1, clarification added regarding Protein Creatinine Ratio (PCR) analysis 
following estimated Glomerular Filtration Rate (eGFR) decrease from baseline

In Section 5.5.7, a clarification was added regarding prior medications

Clarification that Children’s Dermatology Life Quality Index (CDLQI) will no longer be 
completed once the subject reaches 18 years of age was provided in , Section 6.6.1.1 and 
Table 6-1

In  Section 6 in  the order of assessment paragraph it is mentioned that the CHAQ 
questionnaire must  be reviewed by the investigator 

Assessment schedule Table 6-1 was corrected to indicate that the optional X-ray is part of 
the screening procedure 

In Section 7.2.2 SAE reporting, a sentence was added to explain that SAEs after 20 wks 
since last dose should be reported to Novartis only if the investigator suspects a causal 
relationship to study treatment 
 

A footnote was added in Table 13-1 for vital signs, to indicate that values outside the 
provided ranges are considered notable 
Amendment 2 
Amendment rationale 
One key purpose for Amendment 2 is to modify inclusion criterion 5 to align with the text 
agreed with the Pediatric Committee (PDCO) of the European Medicines Agency (EMA).The 
inclusion criterion will now read: 
Patient being regarded by the investigator to be a candidate for systemic therapy because of: 
(1) inadequate control of symptoms with topical treatment, or 
(2) failure to respond to or tolerate previous systemic treatment and/or UV therapy 
As of today only 4 patients have been randomized, thus the impact of this update to the subject 
population is very limited. 
Another key purpose of this Amendment, is to include the Childhood Health Assessment 
Questionnaire (CHAQ©) for those subjects with History of Psoriatic Arthritis. This addition is 
made following a request by the Japanese Health Authority. Further to that, some protocol text 
changes were undertaken following requests from IRBs.
Changes to the protocol
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined for insertions.

Novartis
Confidential
Page 16
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
As mentioned in the rationale of Amendment 2 the inclusion criterion 5 was revised in the 
protocol Section 4.1 and in the Protocol Summary. Subsequently the purpose of the study 
Section 1.2 was also updated to reflect this revision.
Regarding addition of the CHAQ© the following protocol sections were revised or newly 
created:
Secondary objectives in Section 2.2 were revised. Section 6, order of assessments and Table 6-
1 were revised. Section 6.6.1.2 was created. Section 9.5.5 was revised. Appendix 7 was created 
to describe the CHAQ© questionnaire.  
Additionally other changes to the protocol include the following:

 

In Section 4.1 Inclusion Criteria and Synopsis text was corrected to state IGA of 4 

In Section 4.2 Exclusion Criteria, previous exclusion criteria 18 and 19 were merged into 
one. They were previously separate due to a typing error

In Section 5.2 Treatment Arms, clarifications were provided

In Section 5.2 , high dose group paragraph a correction was made stating that last dose in 
the extension treatment period occurs at Week 232 and not at EOT

In Section 5.4 Treatment Blinding, clarifications were provided

A phrase was added in the beginning of Section 5.5 to indicate availability of sponsor 
medical personnel to advise on trial related medical questions or problems

In Section 5.5.4, the number of overall injections was corrected to 92 from 86 and text was 
added explaining that the removable caps of the secukinumab pre-filled syringes and the 
needle covers of the etanercept pre-filled syringes contain latex

In Section 5.5.9 Treatment Discontinuation,  subject’s wish, withdrawal of consent, renal 
events and live virus vaccinations were added to the list

In Section 5.5.12, a clarification was provided concerning emergency unblinding

In Table 6-2 Assessment schedule: Added height, weight and physical examination at the 
8 Weeks follow up visit

In Table 6-4 PASI scoring system, some typographical errors were corrected

A sentence was added in Section 6.5.8 to reiterate the responsibility of the sites to start 
performing urine pregnancy testing during the study once female subjects reach menarche 
or 12 years of age

In Section 7.4 Renal Safety Monitoring, for better clarity <49% of eGFR was replaced by 
<50%; also “abnormal serum glucose” was replaced by “normal serum glucose”.

In Section 8.3 Data Base Management and Quality Control, clarifications were provided

Clarifications were provided and text improvements were done in Section 9.4, analysis of 
the primary variables and in Section 9.5, analysis of secondary variables. 

Section 9.4.3 Handling of missing values, was updated

Section 12 References, was updated with two references for CHAQ©

Novartis
Confidential
Page 17
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

 

Other minor changes like text revisions or improvements were done throughout the 
protocol, as needed
The changes described in this amended protocol require IRB/IEC approval prior to 
implementation. In addition, certain changes herein affect the Informed Consent, which will be 
updated take into account the changes described in this amended protocol. 
Amendment 1
Amendment rationale
This amendment has been generated in order to provide more details and clarification on the 
duration of contraception requested during the study and to give option to align the duration on 
local label requirements.
The protocol has not been submitted to any Health Authorities or any Institutional Review 
Boards (IRBs)/Independent Ethics Committees (IECs). This study has not yet started and no
patients have been enrolled. Therefore, this amendment will not influence the study population 
or results.
Changes to the protocol
Section 4.2 (Exclusion criteria 9) has been updated with regard to the duration of use of effective 
contraception and to reflect that females of child-bearing potential can only enter the study if 
they are willing to prevent pregnancy during the indicated duration.
Section 6.5.8 was updated with regard to the duration of use of effective contraception and to 
reflect that if females of child-bearing potential do not agree to abstinence and who are or might 
become sexually active they must be informed of the need to use effective contraception during 
the indicated duration.
All changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined for insertions.
The changes described in this amended protocol require IRB/IEC approval prior to 
implementation. This amended protocol serves as the initial protocol, therefore a copy of this 
amended protocol will be sent to the Institutional Review Boards (IRBs)/Independent Ethics 
Committees (IECs) and Health Authorities. In addition, the changes herein affect the Informed 
Consent, which take into account the changes described in this amended protocol.

Novartis
Confidential
Page 18
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Protocol summary
Protocol number
CAIN457A2310
Title
A randomized, double-blind, placebo- and active controlled multicenter 
trial to demonstrate efficacy of subcutaneous secukinumab compared to 
placebo and etanercept (in a single-blinded arm) after twelve weeks of 
treatment, and to assess the safety, tolerability, and long-term efficacy in 
subjects from 6 to less than 18 years of age with severe chronic plaque 
psoriasis. 
Brief title
Study of efficacy and safety of secukinumab in pediatric patients with 
severe plaque psoriasis. 
Sponsor and Clinical 
Phase
Novartis 
Phase 3
Investigation type
Biological
Study type
Interventional
Purpose and rationale
The efficacy and safety of secukinumab has been demonstrated in 
adults in a comprehensive phase II/III program. It is now appropriate that 
a similar assessment is made in the pediatric population with a dosing 
regimen that can be extrapolated from the adult efficacious dose. The 
purpose of this trial is to demonstrate the efficacy and safety of 
secukinumab compared to placebo and etanercept in children and 
adolescents aged 6 to less than 18 years with severe plaque psoriasis.
Primary Objective(s) 
To demonstrate the superiority of secukinumab in pediatric subjects with 
severe chronic plaque psoriasis with respect to both PASI 75 and IGA 
mod 2011 0 or 1 response (co-primary endpoints) at Week 12, 
compared to placebo.
Secondary Objectives
To demonstrate superiority of secukinumab (low and high dose) in 
subjects with severe chronic plaque psoriasis with respect to PASI 90 
response at Week 12, compared to placebo.
To assess efficacy of secukinumab in subjects with severe chronic 
plaques psoriasis with respect to PASI 50 and PASI 100 at Week 12, 
compared to placebo.
To assess efficacy of secukinumab in subjects with severe chronic 
plaque psoriasis with respect to PASI 50, PASI 75, PASI 90 , PASI 100 
and IGA mod 2011 0 or 1 at Week 16 and over time up to Week 52.
To assess the efficacy of secukinumab with respect to changes in PASI 
score and IGA mod 2011 score at Week 12, compared to placebo, and 
over time up to Week 52.
To investigate the effects of treatment with secukinumab with respect to 
changes in CDLQI at Week 12, compared to placebo, and over time up 
to Week 52.
To investigate the effects of treatment of secukinumab with respect to 
CDLQI 0 or 1 achievement at Week 12, compared to placebo, and over 
time up to Week 52.
To evaluate the effects of treatment of secukinumab on disability at 
Week 12 and over time up to Week 52 by use of the Childhood Health 
Assessment Questionnaire (CHAQ©), for subjects with history of 
psoriatic arthritis
To investigate the clinical safety and tolerability of secukinumab as 
assessed by growth, weight gain, tolerability of s.c. injections, vital 

Novartis
Confidential
Page 19
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
signs, clinical laboratory variables, ECGs, and adverse events 
monitoring, compared to placebo.
Study design
Multicenter, randomized, double-blind, parallel group, placebo- and 
active (etanercept)-controlled study.
12 week induction treatment period followed by a 40 week maintenance 
treatment period, a 184 week open-label extension treatment period and 
a 16 week follow-up off treatment period. 
Population
Pediatric subjects aged 6 years to less than 18 years with severe 
chronic plaque psoriasis. 
Approximately 160 subjects aged 6 years to <18 years will be enrolled, 
of which at least 30 will be 6 years to <12 years old. 
Inclusion criteria

Patient must be 6 to less than 18 years of age at the time of 
randomization (Subjects 12 to less than 18 years enrolled from 
beginning of trial; Subjects 6 to less than 12 years enrolled after 
positive external DMC recommendation following review of data 
from the first 80 adolescents)

Severe plaque psoriasis, defined as a PASI score ≥ 20, and IGA 
mod 2011 score of  4, and BSA involvement of ≥10%, at 
randomization

History of plaque psoriasis for at least 3 months 

Patient being regarded by the investigator to be a candidate for 
systemic therapy because of: 

(1) inadequate control of symptoms with topical treatment, or 

(2) failure to respond to or tolerate previous systemic treatment 
and/or UV therapy 
Exclusion criteria

Forms of psoriasis other than chronic plaque-type or drug-induced 
psoriasis, active at randomization

Female patients of childbearing potential (menarchal or become 
menarchal during the study) who do not agree to abstinence or, if 
sexually active, do not agree to the use of contraception

Active ongoing inflammatory diseases other than psoriasis that 
might confound the evaluation of the benefit of secukinumab therapy

Underlying condition (including, but not limited to metabolic, 
hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal) which in the opinion of the 
investigator significantly immunocompromises the subject and/or 
places the subject at unacceptable risk for receiving an 
immunomodulatory therapy

Ongoing infections as evidenced by chest X-ray, CT  scan or MRI , 
obtained within 12 weeks prior to randomization, and evaluated by a 
qualified physician

History of an ongoing, chronic or recurrent infectious disease, or 
evidence of tuberculosis infection

History of lymphoproliferative disease or any known malignancy or 
history of malignancy of any organ system within the past 5 years 
prior to screening
Investigational and 
reference therapy
Secukinumab tested at low dose and high dose will be available in 
prefilled syringes as a 150 mg in 1.0 mL syringe and a 75 mg in a 0.5 
mL syringe

Novartis
Confidential
Page 20
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Secukinumab placebo will be available in prefilled syringes in a form to 
match secukinumab syringes
Etanercept active comparator will be provided centrally or as available in 
local markets
Efficacy assessments

Psoriasis Area and Severity Index (PASI) score

PASI 50 response: subjects achieving ≥ 50% improvement 
(reduction) in PASI score compared to baseline

PASI 75 response: subjects achieving ≥ 75% improvement 
(reduction) in PASI score compared to baseline 

PASI 90 response: subjects achieving ≥ 90% improvement 
(reduction) in PASI score compared to baseline 

PASI 100 response / remission: complete clearing of psoriasis 
(PASI=0)
 
 

Investigator’s Global Assessment (IGA mod 2011; scale from 0 – 4)

Children’s Dermatology Life Quality Index

Childhood Health Assessment Questionnaire (CHAQ ©)
Safety assessments

Adverse Events

Physical exam

Vital signs

Height and weight

Laboratory evaluations (hematology, clinical chemistry, urinalysis)

ECG

Pregnancy and assessments of fertility
Other assessments
Data analysis
The statistical hypotheses for PASI 75 response at Week 12 and IGA 0 
or 1 response at Week 12 being tested is that there is no difference in 
the proportion of subjects with PASI 75 response and IGA 0 or 1 
response at Week 12 in any of the secukinumab groups versus placebo.
The secondary variable of PASI 90 response of subjects with severe 
chronic plaque-type psoriasis at Week 12 will be analyzed for superiority 
comparison of secukinumab doses versus placebo. The PASI 90 
response of subjects with severe chronic plaque-type psoriasis at Week 
12 will be analyzed in the same way as the primary variables. 
The co-primary efficacy variables and secondary efficacy variable will be 
analyzed using the FAS
Key words
Severe plaque psoriasis, pediatric, secukinumab

Novartis
Confidential
Page 21
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
1
Introduction
1.1
Background 
Psoriasis is a chronic relapsing inflammatory skin disease with an estimated prevalence of 0.32% 
in children under the age of 18 in 1996 (National Center for Health Statistics of the Centers for 
Disease Control and Prevention 1996). Since then, more epidemiologic studies have provided 
estimates on the prevalence of psoriasis in children in Europe and the USA. 

In the United Kingdom, prevalence of psoriasis was 0.55% in children aged 0 to 9 years 
and 1.37% in children and adolescents aged 10 to 19 years, with a higher prevalence in 
girls than in boys (Gelfand 2005). 

In Germany, 0.71% of children were affected by psoriasis and the prevalence increased 
from 0.12% at the age of 1 year to 1.2% at the age of 18 years (Augustin 2010). 

Results from a survey among dermatologists and general practitioners in the Netherlands 
suggested a prevalence of 0.37% in children aged 0 to 10 years, and 1.09% in children 
aged 11 to 19 years (de Jager 2009). 

In the USA, a Southern California study in children enrolled in an integrated health plan 
reported a 0.30% prevalence of psoriasis in children aged 2 to 19 years. The prevalence 
increased consistently after 5 years of age and was higher in females than in males. 
Stratification by gender (males vs. females) and age group yielded an overall prevalence 
of 0.17 % vs 0.21%; ages 2-5 years, 0.03% vs. 0.04%; ages 6-11 years, 0.16% vs. 0.15%; 
ages 12-19 years, 0.25% vs. 0.33% (Wu 2011). 
The incidence of psoriasis in childhood in the US has been shown to increase with increasing 
age but also in recent years. Incidence of psoriasis in children increased significantly from 29.6 
per 100,000 in 1970-1974 to 62.7 per 100,000 in 1995-1999 (Tollefson 2010).
Plaque psoriasis affects 80 to 90% of all psoriasis subjects of all age-groups (Griffiths 2007;
Pariser 2007) and hence is the most common variant in pediatric subjects. Most children 
manifest with plaque psoriasis in patterns similar to adult subjects, with lesions localized to the 
scalp, post auricular region, elbows, and knees; however, lesions in children are often smaller, 
thinner, and less scaly than those seen in adults. Involvement of the face and flexural regions is 
more common in children than adults, and psoriatic lesions in the diaper area are prevalent 
during infancy. 
As in adults, pediatric psoriasis is frequently associated with significant co-morbidities like 
diabetes mellitus, Crohn’s disease, obesity, hypertension, high cholesterol, psychological and 
psychiatric impact. The overall rate of comorbid conditions in psoriasis subjects under 20 years 
of age is double that of their peers who do not have psoriasis (Augustin 2010). A pediatric study 
using an international cohort of psoriasis subjects found that a significantly higher percentage 
of children with psoriasis showed excess adiposity (37.9% vs. 20.5%) or obesity (20.2% vs 
7.3%), significantly higher than the general pediatric population (Paller 2013).
The psychological impact of psoriasis can be particularly traumatic to children and adolescents. 
In children with at least one of 12 different skin diseases, children with psoriasis reported the 
greatest impairment to quality of life. Itch or pain was reported in the same study as the most 
significant problem affecting their health-related quality of life (Beattie 2006). Psoriasis, a 

Novartis
Confidential
Page 22
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
debilitating and disfiguring skin condition, is an independent risk factor for psychiatric 
comorbidities in children and adolescents. Compared with a matched psoriasis-free control 
cohort in a study based on health services claims data in the USA, pediatric subjects had 
approximately 25% to 30% greater risks of being given a diagnosis of any psychiatric disorder, 
depression, or anxiety subsequent to the psoriasis diagnosis (Kimball 2012).
Due to the higher prevalence of plaque psoriasis in children compared to other types and the 
significant physical and psychological burden it carries in the pediatric population, Novartis 
plans to study secukinumab in the treatment of plaque psoriasis in patients from 6 to less than 
18 years of age.
The treatments for psoriasis have expanded over the past decade though in children treatment 
is frequently off-label. The use of topical therapy in childhood is the first line of treatment for 
skin-limited disease. With chronicity of illness and in more severe cases, phototherapy and 
systemic therapy are added to help induce remission (Silverberg 2009). 
Topical therapies represent the vast majority of prescriptions (57 to 91%), while systemic agents 
are rarely used (4%), and biologics being even more rarely used (0.4%) (Wu 2011, Kimball 
2012). Commonly used topical treatments for psoriasis include corticosteroids, coal tar, 
anthralin, calcipotriol either alone or in combination with topical steroids, tazarotene and 
calcineurin inhibitors (Burden 1999, Farber 1999, Benoit 2007). None of these treatments have 
been approved for the treatment of psoriasis in children below 12 years of age. Phototherapy is 
extensively used in adults and is a treatment option for some children with widespread plaques. 
Narrow-Band-UVB is considered the first-line phototherapy because it is similarly effective as 
Psoralen + UVA (PUVA), more convenient, and less carcinogenic (Van Weelden 1990). PUVA 
therapy is not generally recommended in children, but may be used with caution in adolescents 
(Burden 1999).
Systemic therapy is usually considered if the disease is moderate to severe in intensity, and not 
adequately controlled by topical therapies. Systemic treatments approved for use in adult 
psoriasis include acitretin, methotrexate, cyclosporine, and biologics. Acitretin is approved for 
subsets of psoriatic pediatric patients in some EU countries and Switzerland. However 
cyclosporine and methotrexate are not currently approved for the treatment of 
children/adolescents suffering from psoriasis. While there is no biologic approved for the 
treatment of psoriasis in subjects below the age of 18 years in the USA, etanercept, adalimumab 
and infliximab are tumor necrosis factor-alpha inhibitors that are used for the treatment of 
pediatric autoimmune diseases and have been used off-label to treat pediatric subjects with 
psoriasis (de Jager 2010, Luu  2013). In Europe, Enbrel (etanercept) was approved in 2011 for 
“Treatment of chronic severe plaque psoriasis in children and adolescents from the age of 6 
years who are inadequately controlled by, or are intolerant to, other systemic therapies or 
phototherapies”. Approval was based on a double-blind, placebo controlled study in moderate 
to severe pediatric subjects (Paller 2008); a retrospective analysis of results in severe subjects 
aged from 8 to 17 years showed that PASI 75 at Week 12 was achieved in 54.7% of subjects 
receiving etanercept vs. 11.3% of subjects receiving placebo, p<0.001 (Landells 2010).
Use of methotrexate, cyclosporine, retinoids (particularly acitretin), and, with a much lower 
frequency, dapsone and hydroxyurea has been reported in the literature (Zappel 2004; Benoit 
2007). Most experience has been reported with retinoids, but the potential effect on bone growth 

Novartis
Confidential
Page 23
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
and teratogenicity limit their use in children and adolescents. Use of cyclosporine and 
methotrexate is limited by their adverse event (AE) profile (kidney dysfunction, hypertension 
and liver dysfunction, respectively). Reports on the use of biologics in pediatric patients are 
scarce (Benoit 2007).
In summary, a very limited number of systemic drugs for the treatment of psoriasis are approved 
for children, and the few approved drugs all have severe limitations. There is a high medical 
need to evaluate the treatment of psoriasis in patients less than 18 years of age where controlled 
studies are mostly missing (Burden 1999; Farber 1999; Benoit 2007; Paller 2008). 
Secukinumab (AIN457) is a recombinant high-affinity fully human monoclonal anti-human 
Interleukin-17A (IL-17A) antibody of the IgG1/κ-class. Secukinumab binds to human IL-17A 
and neutralizes the bioactivity of this cytokine. IL-17A is the central lymphokine of a newly 
defined subset of inflammatory T cells, the Th17 cells which, in several animal models, are 
pivotal in several autoimmune and inflammatory processes. IL-17A is mainly produced by 
memory effector CD4+ and CD8+ T lymphocytes. IL-17A is being recognized as one of the 
principal pro-inflammatory cytokines in immune mediated inflammatory diseases. Its 
neutralization is expected to treat the underlying pathophysiology of immune mediated disease, 
and as a consequence provide relief of symptoms.
In adult phase II/III studies, secukinumab 300 mg and 150 mg has been shown to be efficacious 
with an acceptable safety profile, with secukinumab 300 mg comparable to 150 mg and both 
doses comparable to placebo over 12 weeks and etanercept over 52 weeks of treatment (Langley 
2014).
Based on the natural history of psoriasis and the similar clinical features and histology in adults 
and pediatric population (Burden 1999; Farber 1999; Benoit 2007), it is expected that a human 
monoclonal antibody such as secukinumab will have an identical mode of action in children 
and would be metabolized similarly when compared to adults. Now that efficacy and safety 
have been demonstrated in adults in a comprehensive phase II/III program, it seems appropriate 
that the pediatric population can be exposed to secukinumab in long term studies with a dosing 
regimen that is extrapolated from the adult efficacious dose.
1.2
Purpose 
The purpose of this study is to demonstrate superior efficacy of secukinumab versus placebo at 
Week 12, based on both PASI 75 and IGA mod 2011 0 or 1 response rates in children and 
adolescents aged 6 to less than 18 years with severe chronic plaque psoriasis who are candidates 
for systemic therapy because of: (1) inadequate control of symptoms with topical treatment, or 
(2) failure to respond to or tolerate previous systemic treatment and/or UV therapy. Moreover, 
this study will assess the long term safety and tolerability of secukinumab in this pediatric age 
group 
 
 

Novartis
Confidential
Page 24
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
2
Study objectives
2.1
Primary objective(s)
To demonstrate the superiority of secukinumab (low and high dose) in pediatric subjects with 
severe chronic plaque psoriasis with respect to both PASI 75 and IGA mod 2011 0 or 1 response 
(co-primary endpoints) at Week 12, compared to placebo.
2.2
Secondary objectives

To demonstrate superiority of secukinumab (low and high dose) in subjects with severe 
chronic plaque psoriasis with respect to PASI 90 response at Week 12, compared to 
placebo.

To assess efficacy of secukinumab in subjects with severe chronic plaques psoriasis with 
respect to PASI 50 and PASI 100 at Week 12, compared to placebo.

To assess efficacy of secukinumab in subjects with severe chronic plaque psoriasis with 
respect to PASI 50, PASI 75, PASI 90 , PASI 100 and IGA mod 2011 0 or 1 at Week 16 
and over time up to Week 52.

To assess the efficacy of secukinumab with respect to changes in PASI score and IGA 
mod 2011 score at Week 12, compared to placebo, and over time up to Week 52.

To investigate the effects of treatment with secukinumab with respect to changes in 
CDLQI at Week 12, compared to placebo, and over time up to Week 52.

To investigate the effects of treatment of secukinumab with respect to CDLQI 0 or 1 
achievement at Week 12, compared to placebo, and over time up to Week 52.

To evaluate the effects of treatment of secukinumab on disability at Week 12 and over 
time up to Week 52 by use of the Childhood Health Assessment Questionnaire (CHAQ©), 
for subjects with history of psoriatic arthritis.

To investigate the clinical safety and tolerability of secukinumab as assessed by growth, 
weight gain, tolerability of s.c. injections, vital signs, clinical laboratory variables, ECGs, 
and adverse events monitoring, compared to placebo.

Novartis
Confidential
Page 25
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
3
Investigational plan
3.1
Study design
This is a multicenter, randomized, double-blind, placebo- and active-controlled (etanercept in 
single blinded arm) study in pediatric subjects aged 6 years to less than 18 years with severe 
chronic plaque psoriasis. Approximately 160 subjects aged 6 years to <18 years will be enrolled, 
of which at least 30 will be 6 years to <12 years old. It is expected that subjects will be enrolled 
at approximately 70 study sites worldwide.
Two age subgroups will be studied in a staggered approach within this clinical study: 12 to less 
than 18 years of age, and 6 to less than 12 years of age (age for the subgroups determined at the 
time of randomization). Enrolment of children aged 6 to less than 12 years will begin after a 
favorable recommendation by an independent external Data Monitoring Committee (DMC) 
who will review data of approximately 80 (approximately 40 treated with secukinumab) 
enrolled adolescents (aged 12 to less than 18 years) treated for 28 weeks. Adolescents will 
continue to be recruited while the data from the first 80 subjects are being collected and 
analyzed.
Subjects will be randomized using a 1:1:1:1 ratio into one of the treatment arms: secukinumab 
low dose, secukinumab high dose, etanercept or placebo. Subjects randomized to secukinumab 
treatment arms (high dose and low dose) will receive dose based on the weight category (<25 
kg, 25 to <50kg, ≥50 kg). If a subject moves into a higher or lower weight group at two 
consecutive visits with weight measurements during the maintenance (from Week 12 onwards 
as assessed at monthly visits, i.e. Week 13, 14, 15 will not be taken into account) or during 
extension treatment period (as assessed at scheduled site visits), the subject will receive dosing 
according to the new (higher or lower) weight group respectively. 

Novartis
Confidential
Page 26
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Figure 3-1
Study design
The study consists of 5 Epochs: screening (up to 4 weeks), induction (of 12 weeks), 
maintenance (of 40 weeks), extension treatment epoch (open-label of 184 weeks) and post-
treatment follow-up epoch (of 16 weeks). An outline of the visits is presented in Figure 3-1, 
while a detailed visit and assessment schedule can be found in Table 6-1, Table 6-2.
Screening Epoch
The screening epoch of up to 4 weeks will be used to assess eligibility of the subjects and to 
taper subjects off prohibited medications.
Induction Epoch
The induction epoch is defined as randomization through Week 12 (prior to dose). In this epoch 
the study is both active and placebo-controlled and at its completion the primary endpoint is 
assessed (Week 12). 
At the start of the induction epoch, eligible subjects will be randomized in a 1:1:1:1 ratio into 
one of four treatment groups (etanercept, secukinumab low dose group, secukinumab high dose 
group, or placebo group). The randomization will be stratified by age (<12 years or ≥12 years) 
and weight (<25, 25-<50, ≥50) at randomization; Subjects randomized to the secukinumab 
treatment group will receive respective high and low doses according to their weight category. 
Subjects randomized to the placebo group will be pre-assigned to either the low- or high-dose 
group of secukinumab, at the Randomization visit, in case they are not achieving a PASI 75 
response as assessed at Week 12.  During the induction epoch, all subjects will be visiting the 
study site at Randomization and Weeks 1, 2, 3, 4, 8, and 12. The secukinumab and placebo 
treatment groups will receive s.c. study treatment and/or s.c. placebo weekly for four weeks 
(randomization and Weeks 1, 2, and 3) and then one dose of study treatment and/or placebo at 

Novartis
Confidential
Page 27
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Weeks 4 and 8 (last dose during the induction epoch). Secukinumab will be administered at site. 
Subjects in the etanercept arm will receive weekly s.c. dose of 0.8 mg/kg (up to a maximum of 
50 mg) of open-label etanercept. Etanercept will be administered at site during site visits and at 
home or at the site for the remaining weekly visits based on the visit schedule (Table 6-1 and 
Table 6-2).
Assessments for the primary endpoint will be done at Week 12 for all treatment arms prior to 
the dose at Week 12.
For subjects who discontinue study treatment for any reason before the end of the induction 
epoch, an EOI Visit (Week 12 Visit) should be performed approximately four weeks after their 
last dose of study drug and then the subject will enter the post-treatment follow-up period and 
perform F4, F8, F12 and F16 visits. If subjects start another systemic anti psoriatic treatment 
during follow up, they do not need to continue with the remaining follow-up visits but they will 
be expected to return to site after the start of the systemic treatment and perform End of Follow-
up (EOF) visit.
Placebo PASI 75 responders at Week 12, at the completion of the Induction epoch, cannot 
continue into the Maintenance epoch but must enter the post treatment follow-up epoch instead, 
perform first visit F4 and four weeks later perform visit EOF and complete the study. If subjects 
start another systemic anti psoriatic treatment during follow up, they do not need to perform the 
remaining follow-up visits but they will be expected to return to site after the start of the 
systemic treatment and perform End of Follow-up (EOF) visit.
Maintenance Epoch 
The maintenance epoch is defined as Weeks 12 (from dosing) through Week 52. In this epoch 
the study is active-controlled and the objectives focus on the maintenance of the response 
observed at Week 12.   
Subjects who were receiving secukinumab or etanercept during induction will continue in 
maintenance with the same treatment. 
Subjects who were on placebo during induction and at Week 12 were PASI 75 responders 
cannot continue into maintenance epoch but will need to move into the follow-up epoch and 
terminate the study.
Subjects who were on placebo during induction and at Week 12 were PASI 75 non-responders 
will be switched to either secukinumab low dose or secukinumab high dose treatment group in 
maintenance epoch according to their baseline randomization. 
The dose given at Week 12 for the placebo and the secukinumab arms is the first dose of the 
maintenance epoch and is followed by doses of secukinumab study treatment and / or placebo 
weekly up to Week 15, and every four weeks starting at Week 16 and up to Week 48.
Assessments for all the treatment arms will be done at Week 52 prior to dose at Week 52.
The Week 52 visit is the planned End of Maintenance epoch (EOM) visit. The EOM visit is 
considered complete when week 52 assessments are finished.

Novartis
Confidential
Page 28
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
At the end of the maintenance epoch, subjects on secukinumab will enter the open-label 
extension treatment epoch of the study whereas subjects on etanercept will enter the post-
treatment follow-up epoch and thereafter will complete the study.
For subjects who discontinue study treatment for any reason before the end of the maintenance 
epoch, the Week 52 Visit (planned End of Maintenance Period (EOM) visit) should be 
performed approximately 4 weeks after their last dose of study drug in the maintenance epoch 
and then the subject will enter the post-treatment follow-up epoch and perform F4, F8, F12 and 
F16 (EOF) visits. If subjects start another systemic anti psoriatic treatment during follow up, 
they do not need to continue with the remaining follow-up visits but they will be expected to 
return to site after the start of the systemic treatment and perform End of Follow-up (EOF) visit.
Extension Treatment Epoch
The extension treatment epoch is defined as Week 52 (from dosing) until Week 236. At this 
epoch the subjects are all treated with secukinumab and the purpose is the collection of long 
term safety and efficacy data.  
At the end of the maintenance epoch, all subjects on secukinumab will enter the extension 
treatment epoch of the study and will continue to receive the same dose of secukinumab they 
had received at completion of maintenance epoch. 
Subjects who participated in the maintenance epoch but prematurely discontinued the study will 
not be able to enter the extension treatment epoch of the study. Patients receiving etanercept 
will not be eligible to enter the extension treatment epoch. Instead, at Week 52, they will 
complete an EOM visit and then enter the post-treatment follow-up epoch. The first 
secukinumab dose of the Extension Treatment epoch is administered at Week 52. Subsequent 
doses of secukinumab will be administered every four weeks until the End of Treatment (EOT). 
For subjects who discontinue study treatment for any reason before the end of the extension 
treatment epoch, the End of Extension Treatment (EOT) visit should be performed 
approximately 4 weeks after their last dose of secukinumab. The subject will then enter the 
post-treatment follow-up epoch (perform F4, F8, F12 and F16 visits). If subjects start another 
systemic anti psoriatic treatment during follow up, they do not need to continue with the 
remaining follow-up visits but they will be expected to return to site after the start of the 
systemic treatment and perform End of Follow-up (EOF) visit.
Follow-up Epoch 
The treatment-free follow-up visits will be at Week 240 (Post-treatment Follow-up visit F4, 
which is 4 weeks post EOT and 8 weeks post last dose of secukinumab), Week 244 (Post-
treatment Follow-up visit F8, which is 8 weeks post EOT and 12 weeks post last dose of 
secukinumab), Week 248 (Post-treatment follow-up visit F12) and Week 252 (Post-treatment 
follow-up visit F16 (i.e. EOF, End of follow -up)). Subjects who complete or discontinue the 
treatment are expected to perform the complete treatment-free follow up period unless they start 
another systemic anti psoriatic treatment. In this case they do not need to continue with the 
remaining follow up visits but they will be expected to return to site after the start of the 
systemic treatment and perform End of Follow-up (EOF) visit.    

Novartis
Confidential
Page 29
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Subjects who completed the extension treatment epoch will enter the treatment-free follow up 
epoch. In addition, the following subjects will enter the treatment-free follow up epoch:

Subjects randomized to placebo that were PASI 75 responders at the End of Induction 
(EOI) epoch and completed the End of Induction (EOI) visit. These subjects are not 
eligible to continue to maintenance. These subjects are expected to do F4 (Post-treatment
Follow-up visit F4, which is 4 weeks post EOI and 8 weeks post last study treatment) and 
four weeks later perform the End of Follow-up (EOF) visit and complete the study. 

Subjects who discontinued prematurely from the induction epoch. (Subjects should be
scheduled for the EOI visit approximately 4 weeks after their last treatment dose and then 
enter the treatment-free follow up epoch.)  

Subjects on secukinumab who completed the maintenance epoch and the EOM visit and 
do not want to continue into the extension treatment l epoch. 

Subjects on etanercept arm who completed the maintenance epoch and the EOM visit.  
These subjects are not eligible to continue into extension treatment epoch.

Subjects who discontinued prematurely from the maintenance epoch. (Subjects should be 
scheduled for the EOM visit approximately 4 weeks after their last treatment dose and 
then enter the treatment-free follow up epoch).  

Subjects who discontinued prematurely from the extension treatment epoch. (Subjects 
should be scheduled for the EOT visit approximately 4 weeks after their last treatment 
dose and then enter the treatment-free follow up epoch). 
3.2
Rationale of study design
The double-blind, randomized, parallel-group, placebo controlled design used in this study is 
aligned with adult phase III trials with secukinumab. The primary endpoint of the trial at Week 
12 will allow for assessment of efficacy at a point in time for which efficacy data from all 
currently approved systemic therapies for pediatric psoriasis as well as phase III adult data for 
secukinumab are available. The blinding in the secukinumab arms is maintained beyond the 
primary endpoint so as to ensure reliable efficacy measures beyond the induction epoch of 12 
weeks.
This is the first pediatric study in psoriasis for secukinumab. The sequential planning of the 
study recruitment allows to first assess an initial benefit-risk evaluation in adolescents before 
enrolling children 6 to less than 12 years of age while also capturing a subject population 
representative of those with highest unmet medical need. The lower age of enrollment has been 
limited to 6 years since the prevalence of psoriasis in the 0 to less than 6 age group is very low 
(with the highest prevalence published of 0.3%) and the proportion of children with a severe 
condition in need of a systemic treatment is 4%, giving a final prevalence of the condition to be 
about 1 per 10,000 in this age group. 
3.3
Rationale of dose/regimen, route of administration and duration 
of treatment
The dose selection for secukinumab in pediatric psoriasis subjects is based on the recently 
completed phase III program in adults as well as modeling and simulation based on the results 
from adult phase II/III studies. Secukinumab 300 mg and 150 mg are selected based on evidence 

Novartis
Confidential
Page 30
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
from adult phase III studies that demonstrated both doses to be safe and effective in treating 
moderate to severe plaque psoriasis. 
The proposed doses for the high dose and low dose secukinumab arms are based on a 
population-PK model that has been built based on the pool of key phase II/III trials to predict 
exposure of secukinumab according to various body weights (Figure 3-2). This dosing rationale 
assumes that the concentration-response relationship and disease characteristics (onset, severity, 
progression) in children are similar to adults with no major differences in target expression of 
IL-17A. Therefore, similar PK concentration profiles across the adult and pediatric populations 
will achieve comparable response.
Figure 3-2
Average concentration for the proposed low dose and high dose 
secukinumab arms     
                 
Extrapolation of the exposure in children / adolescents in a bodyweight range down to 20 kg to 
allow maintaining exposure levels similar to those observed in adults with 50 kg body weight 
led to selection of 75mg, 150 mg and 300 mg within weight categories as follows:
Subjects ≥50 kg: 150 mg (low dose group) or 300 mg (high dose group)
Subjects 25 kg to < 50 kg: 75 mg (low dose group) or 150 mg (high dose group)
Subjects < 25 kg: 75 mg (for both dose groups in order to ensure no overly high exposures in 
this sub-population).
The dosing regimen used is consistent with that of adults and the total study duration including 
one year of blinded treatment plus the open-label extension treatment epoch and follow-up 
epoch (>5 drug half-lives) will allow for assessment of long term safety and efficacy.
3.4
Rationale for choice of comparator
The use of placebo is in accordance with health authority guidelines (FDA Guidance E10, and 
EMEA/CPMP Position Statement (EMEA/17424/01) and the Declaration of Helsinki Item 32.  
Etanercept was chosen as an active comparator, since it is the first biologic medication approved 
for use in children and adolescents with severe psoriasis in the European Union and elsewhere 
High dose

Novartis
Confidential
Page 31
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
and is in accordance with Health Authority feedback. However there will be no formal 
comparison between secukinumab and etanercept treatment groups.  
The placebo arm is double blinded and the etanercept arm is single (efficacy assessor) blinded 
to prevent observer bias, and not subject-blinded because the dosing regimens of the two 
products are so different that double blinding is considered inappropriate in children due to the 
number of additional placebo injections needed in order to achieve a true double-blind 
administration. Site personnel performing the efficacy assessments, will be blinded to all 
treatment allocation, whilst site personnel performing the remaining assessments will be 
blinded to the secukinumab/secukinumab placebo allocation only (see also Section 5.4).
3.5
Purpose and timing of interim analyses/design adaptations
An interim analysis for the sole purpose of evaluating safety and efficacy in the adolescent 
population will be conducted once at least 80 adolescents complete 28 weeks of treatment 
(dosed up to Week 24). Enrollment of the pediatric population aged 6 to less than 12 years will 
begin only if there are no serious efficacy and/or safety concerns based on DMC’s 
recommendation. No conclusions regarding demonstration of efficacy affecting the conduct of 
the study will be made.
A full analysis, including the primary endpoint (at week 12) analysis will be conducted when 
all subjects have completed the Week 24 visit. Another full analysis will be performed when all 
subjects have completed the Week 52 visit.
An additional interim analysis will be performed prior to the Week 24 analysis. Under the 
provision that sufficient safety 
 data have been collected, this analysis, 
aligned with efficacy extrapolation principle, is expected to provide the basis for a submission 
package to health authorities (HA). The intention of this interim analysis is to potentially make 
secukinumab available to pediatric patients sooner, by way of an earlier HA approval based on 
this analysis, in countries which accept a submission of clinical data with use of extrapolation 
methodology. This analysis may be performed before all subjects have reached the primary 
endpoint. It is expected that data from at least approximately 100 patient years of secukinumab 
treatment will be included in this analysis.
Efficacy and safety data collected during the extension treatment epoch (until the end of study) 
may be reported yearly in separate reports.
If requested by Health Authorities, additional interim analyses may be performed for instance 
on 
 data to confirm modeling assumptions. For these occasions 
 
will share data with 
 in a blinded fashion. Overall, should such requests 
occur during the blinded portion of the study, they will be performed without unblinding of 
Novartis personnel. Unblinded data will only be made available to independent Novartis/CRO 
individuals involved in the preparation of the interim analyses and who are not directly involved 
in the study conduct.
3.6
Risks and benefits
Biologics like secukinumab are an attractive option for treating psoriasis in the pediatric 
population as they are convenient to use, requiring less frequent dosing than traditional systemic 

Novartis
Confidential
Page 32
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
agents such as methotrexate, cyclosporine, and acitretin. In addition, they lack many of the 
potential end-organ toxicities of traditional agents because of their targeted action. 
Non-clinical studies and phase II and III clinical studies in adults have not shown any 
impediment to using secukinumab subcutaneously in man. In adult studies, secukinumab has 
shown a very good efficacy profile in the treatment of moderate to severe chronic plaque 
psoriasis. The safety data from the completed and ongoing studies including AE and SAE data, 
laboratory parameters and immunogenicity data demonstrate a good safety profile which 
included an observed risk of infections in particular candida infections and neutropenia or 
hypersensitivity reactions that can be seen with administration of foreign proteins. Most of the 
infections were non-serious, mild to moderate in severity, clinically easily manageable and did 
not lead to treatment discontinuation. Cases of neutropenia were uncommon, generally mild to 
moderate and transient and did not lead to treatment discontinuation, and only a few cases were 
timely associated with non-serious infections.
Potential risks for subjects on secukinumab include malignancies, major adverse cardiovascular 
events (MACE), Crohn’s disease, immunogenicity, and interactions with live vaccines.
Since the immune system was shown to reach adult levels of maturation by 6 years of age 
(Comans-Bitter 1997), no adverse effects of secukinumab on development of this system are 
expected in this trial’s pediatric population (age 6 to <18years). Consequently, no additional 
risks of infections, malignancies, or impact on peripheral competent immune cells over those 
described for adults are anticipated for this pediatric group.
A potential for increased exposure of secukinumab at lower body weights has been suggested 
by the analysis of population pharmacokinetic data. Consequently, weight category based 
dosing has been instituted to ensure that exposure levels of secukinumab are comparable across 
all weight groups in the study population.
No adverse effects are anticipated with respect to linear bone growth and development given 
the absence of bone findings in knock-out mice (Kokubu 2008) and in toxicology studies with 
secukinumab. Height to measure linear growth will be monitored all through the study. 
Potential risks for subjects on etanercept could include common side effects of etanercept 
namely injection site reactions, upper respiratory infections, and headache. Injection site 
reactions such as redness, rash, swelling, itching, or bruising usually subside within 3 to 5 days. 
The subjects may also be at increased risk for infections and possibly cancer, as etanercept is a 
medication that has the potential to suppress the immune system.
Prior to participating in a clinical trial with secukinumab, participants should consider 
completion of all age appropriate immunizations according to immunization guidelines. 
Subjects treated with secukinumab should not receive live vaccines. Non-live vaccinations 
received during secukinumab treatment may not elicit an immune response sufficient to prevent 
disease.

Novartis
Confidential
Page 33
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
4
Population
The study population will consist of male and female subjects age 6 to less than 18 years of age 
(at the start of study treatment) with severe plaque psoriasis who are candidates for systemic 
treatment.
The investigator must ensure that all subjects being considered for the study meet the following 
eligibility criteria. No additional exclusions should be applied by the investigator, in order that 
the study population will be representative of all eligible subjects.
4.1
Inclusion criteria
Subjects eligible for inclusion in this study have to fulfill all of the following criteria:
1. Written informed assent and parental permission (age as per local law) obtained at 
screening before any assessment is performed. Of note, that if subjects reach age of 
consent (age as per local law) during the study, they will need to also sign the 
corresponding study Informed Consent(s). 
2. Must be 6 to less than 18 years of age at the time of randomization
a. Subjects 12 to less than 18 years enrolled from beginning of trial 
b. Subjects 6 to less than 12 years enrolled after positive DMC recommendation 
following review of data from the first 80 adolescents 
3. Severe plaque psoriasis, defined as a PASI score ≥ 20, and IGA mod 2011 score of 4, and 
BSA involvement of ≥10%, at randomization
4. History of plaque psoriasis for at least 3 months 
5. Patient being regarded by the investigator to be a candidate for systemic therapy because 
of: 
(1) inadequate control of symptoms with topical treatment, or 
(2) failure to respond to or tolerate previous systemic treatment and/or UV therapy 
4.2
Exclusion criteria
Subjects fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible subjects.
1. Forms of psoriasis other than chronic plaque-type (e.g., pustular, erythrodermic and 
guttate psoriasis), active at randomization
2. Drug-induced psoriasis (i.e., new onset or current exacerbation from beta-blockers, 
calcium channel blockers or lithium)
3. Ongoing use of prohibited treatments as mentioned in Table 5-2 (Washout periods as 
detailed in Table 5-2 have to be adhered to). 
4. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or 
the IL-17 receptor, or to etanercept 
5. Use of any other investigational treatment within 4 weeks before randomization, or within 
a period of 5 half-lives of the investigational treatment, whichever is longer.

Novartis
Confidential
Page 34
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
6. History of severe hypersensitivity reaction or anaphylaxis to any biological agents (human 
monoclonal antibody or soluble receptor)
7. Pregnant or nursing (lactating) females, where pregnancy is defined as the state of a 
female after conception and until the termination of gestation, confirmed by a positive 
hCG laboratory test
8. Female patients (< 18 years of age) of childbearing potential (menarchal or becoming 
menarchal during the study) who do not agree to abstinence or, if sexually active, do not 
agree to the use of contraception as defined in Section 6.5.8  
9. Female patients (who become ≥18 years of age during the study) of child-bearing 
potential, defined as all women physiologically capable of becoming pregnant, unless they 
are using effective methods of contraception during dosing of study treatment and for a 
minimum of 16 weeks after stopping study treatment or longer if local label requires it 
(e.g. in EU 20 weeks). Effective contraception methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the 
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception

Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy) or tubal ligation at least six weeks before taking study treatment.  In 
case of oophorectomy alone, only when the reproductive status of the woman has 
been confirmed by follow up hormone level assessment

Male sterilization (at least 6 months prior to screening). For female subjects on the 
study, the vasectomized male partner should be the sole partner for that subject

Barrier methods of contraception: 
a. Male or female condom with or without spermicide 
b. Cap, diaphragm or sponge with spermicide 

Use of oral, injected or implanted hormonal methods of contraception or other forms 
of hormonal contraception that have comparable efficacy (failure rate <1%), for 
example hormone vaginal ring or transdermal hormone contraception

Placement of an intrauterine device (IUD) or intrauterine system (IUS)
In case of use of oral contraception women should have been stable on the same pill for a 
minimum of 3 months before taking study treatment
10. Active ongoing inflammatory diseases other than psoriasis that might confound the 
evaluation of the benefit of secukinumab and/or etanercept therapy
11. Underlying condition (including, but not limited to metabolic, hematologic, renal, hepatic, 
pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal) which in the 
opinion of the investigator significantly immunocompromises the subject and/or places the 
subject at unacceptable risk for receiving an immunomodulatory therapy
12. Investigator discretion should be used for subjects with preexisting or recent-onset central 
or peripheral nervous system demyelinating disorders
13. Subjects with a Glomerular Filtration Rate (eGFR), estimated by the Schwartz equation, 
of  < 60 mL/min/1.73 m2 at screening. Assessment may be repeated once, two or more 

Novartis
Confidential
Page 35
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
days later, and if eGFR value 60, subject may be included at the discretion of the 
investigator.  
14. Subjects with total WBC count <2,500/μL, or platelets <100,000/μL or neutrophils 
<1,500/μL or hemoglobin <8.5 g/dL at screening
15. Ongoing infections and in particular tuberculosis. If warranted for a subject and based on 
the investigator’s judgment, an X-ray or MRI (at pre specified sites) may be performed as 
part of the screening procedure.  
16. Active systemic infections during the last two weeks (exception: common cold) prior to 
randomization and any infections that reoccur on a regular basis.
17. Investigator/qualified site staff discretion should be used regarding subjects who have 
traveled or resided in areas of endemic mycoses, such as histoplasmosis, 
coccidioidomycosis or blastomycosis and for subjects with underlying conditions that may 
predispose them to infection, such as advanced or poorly controlled diabetes
18. History of an ongoing, chronic or recurrent infectious disease, or evidence of tuberculosis 
infection as defined by a positive QuantiFERON TB-Gold test (QFT) at screening.
Subjects with a positive QFT test may participate in the study if further work up 
(according to local practice/guidelines) establishes conclusively that the subject has no 
evidence of active tuberculosis. If presence of latent tuberculosis is established, then 
treatment must have been initiated and maintained according to local country guidelines 
prior to randomization. 
19. Known infection with HIV, hepatitis B or hepatitis C at screening 
20. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system within the past 5 years prior to screening
21. Plans for administration of live vaccines during the study period or within 6 weeks prior to 
randomization.
22. 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.
23. Hypersensitivity or allergy to any of the ingredients of study treatments, including 
etanercept.
24. History or evidence of ongoing alcohol or drug abuse, within the last 24 weeks before 
randomization.
25. Subjects not willing to limit UV light exposure (e.g., sunbathing and/or the use of tanning 
devices) during the course of the study.
26. Unwillingness to undergo repeated venipuncture or subcutaneous injections.
5
Treatment
5.1
Protocol requested treatment
5.1.1
Investigational treatment
The following study treatments will be used:
Investigational drug

Novartis
Confidential
Page 36
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

Secukinumab prefilled syringes, available as a 150 mg in 1.0 mL and as a 75 mg in 0.5 
mL syringes. Provided by Novartis.
Reference therapies

Secukinumab placebo: secukinumab placebo available as 1 mL and 0.5 mL prefilled 
syringes, provided by Novartis in a form to match secukinumab prefilled syringes.

Etanercept active comparator (not a biosimilar): 
a. as provided centrally by a CRO or
b. as available and purchased locally 
All study treatments will be labelled appropriately.
5.1.2
Additional study treatment
No additional treatment beyond investigational treatment is requested for this trial.
5.2
Treatment arms 
Subjects will be randomized using a 1:1:1:1 ratio into one of the treatment arms mentioned 
below. Subjects randomized to secukinumab treatment arms (high dose and low dose) will 
receive dose according to the weight category (<25 kg, 25-
<50kg, ≥50 kg). 
Subjects in the two secukinumab arms weighing ≥50kg will receive 150 mg (low dose group) 
and 300 mg (high dose group), 25 to <50 kg will receive 75mg (low dose group) and 150 mg 
(high dose group) and <25kg will receive 75mg for both dose groups. In order to maintain the 
treatment blind, all subjects in secukinumab or placebo arms will receive 2 s.c. injections at 
each dose, except for subjects <25kg weight category who will receive only 1 injection of either 
75 mg secukinumab or matching placebo (Table 5-1).

Novartis
Confidential
Page 37
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Table 5-1
Secukinumab/Placebo treatment arms and injections at each visit 
during Induction and maintenance epoch 
Weight category at 
randomization
Treatment arms 
Blinded Dose (PFS)
Number of 
injections at each 
visit during 
Induction Epoch 
Number of 
injections at each 
visit during 
Maintenance 
Epoch
<25 kg 
AIN high dose
75mg/0.5mL  AIN 
1
1
AIN low dose 
75mg/ 0.5mL AIN 
1
1
Placebo high 
dose(pre 
assigned at 
randomization)
75mg/0.5mL AIN PBO 
1
1*
Placebo low dose 
(pre-assigned at 
randomization)
75mg/0.5mL AIN PBO 
1
1*
25 to <50kg
AIN high dose
2x75mg/0.5mL AIN 
2
2
AIN low dose 
75mg/0.5mL AIN 
+75mg/0.5mL AIN PBO
2
2
Placebo high 
dose(pre 
assigned at 
randomization)
2x75mg/0.5mL AIN 
PBO
2
2*
Placebo low dose 
(pre-assigned at 
randomization)
2x75mg/0.5mL AIN 
PBO
2
2*
≥50kg
AIN high dose
2x150mg/1.0ml  AIN
2
2
AIN low dose 
150mg/1.0mL 
AIN+150mg/1.0mL AIN 
PBO
2
2
Placebo high 
dose(pre 
assigned at 
randomization)
2x150mg/1.0mL AIN 
PBO 
2
2*
Placebo low dose 
(pre-assigned at 
randomization)
2x150mg/1.0 mL AIN 
PBO 
2
2*
*Placebo PASI 75 non responders will start receiving at Week 12 active treatment (secukinumab) high or low, as 
preassigned at randomization

Etanercept active comparator group: S.C. etanercept 0.8 mg/kg (up to a maximum 
dose of 50 mg) once per week, for 51 weeks administered at home (self-injected or by 
caregiver) or at the study site. No subject blinding will be introduced for this arm, but 
the efficacy assessor will be blinded as regards to treatment assignment. 

Secukinumab low dose group: According to the weight category, s.c. secukinumab 
75 mg (in <25 kg and 25 to <50 kg) or 150 mg (≥50 kg) injections at Randomization, 
Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab 
at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 
and every 4 weeks during the extension treatment epoch until Week 232. Subjects and 
all site staff will be blinded as regards to treatment assignment and secukinumab dose 
levels during the induction and maintenance epochs. After data base lock for Week 52 

Novartis
Confidential
Page 38
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
analysis has been performed, the placebo injection will no longer be administered and 
the study will become open label. In the extension treatment epoch, between the site 
visits, subjects will be expected to perform the study treatment administrations at home. 
This can be self-administered by subject or by caregiver. Subjects <12 years of age 
must not self-administer. However, adolescents (aged 12 to <18 years) can self-
administer while under supervision of HCPs or caregiver/guardian. If subject/parent do 
not feel confident in performing treatment administration at home they are still allowed 
to receive study treatment administration at site.

Secukinumab high dose group: According to the weight category , s.c. secukinumab 
75mg (in <25 kg), 150mg (25 to <50 kg), 300 mg (≥50 kg) injections at Randomization, 
Weeks 1, 2, 3, 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, and 48, and Placebo secukinumab 
at Weeks 13, 14 and 15 during the blinded phase of the study; thereafter at Week 52 
and every 4 weeks during the extension treatment epoch until Week 232. Subjects and 
all site staff will be blinded as regards to treatment assignment and secukinumab dose 
levels during the induction and maintenance epochs. After data base lock for Week 52 
analysis has been performed, the placebo injection will no longer be administered and 
the study will become open label. In the extension treatment epoch, between the site 
visits, subjects will be expected to perform the study treatment administrations at home. 
This can be self-administered by subject or by caregiver. Subjects <12 years of age 
must not self-administer. However, adolescents (aged 12 to <18 years) can self-
administer while under supervision of HCPs or caregiver/guardian. If subject/parent do 
not feel confident in performing treatment administration at home they are still allowed 
to receive study treatment administration at site.

Placebo group: Placebo secukinumab (one/two s.c. injections per dose) once per week 
for four weeks (at Randomization, Weeks 1, 2 and 3), followed by dosing every four 
weeks (Weeks 4 and 8). Subjects and the efficacy assessor will be blinded as regards to 
treatment assignment. At Week 12, subjects in the placebo group based on their PASI 
75 response status at Week 12 will proceed as follows:

PASI 75 responders on placebo will discontinue study treatment at Week 12 and 
enter the treatment-free follow-up epoch for 8 weeks or until systemic therapy 
begins 

PASI 75 non-responders on placebo will receive high dose or low dose 
secukinumab, according to the pre-assignment at the Randomization visit, and 
receive their treatment according to the weight category based on the weight 
measured at Week 12 visit (<25 kg, 25- <50kg, ≥50 kg), on Weeks 12, 13, 14, 15, 
and then every four weeks starting at Week 16 until Week 48 during the 
maintenance epoch; thereafter Week 52 and every 4 weeks during the extension 
treatment epoch until week 232. After data base lock for Week 52 analysis has 
been performed, the placebo injection will no longer be administered and the study 
will become open label. In the extension treatment epoch, between the site visits, 
subjects will be expected to perform the study treatment administrations at home. 
This can be self-administered by subject or by caregiver. Subjects <12years of age 
must not self-administer. However, adolescents (aged 12 to <18 years) can self-
administer while under supervision of HCPs or caregiver/guardian. If 

Novartis
Confidential
Page 39
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
subject/parent do not feel confident in performing treatment administration at 
home they are still allowed to receive study treatment administration at site.
5.3
Treatment assignment, randomization 
At Randomization (Visit 2), all eligible patients will be randomized via Interactive Response 
Technology (IRT) to one of the treatment arms. The qualified site personnel will contact the 
IRT after confirming that the patient fulfills all the inclusion/exclusion criteria. The subject 
number, the weight of the subject and the age will be entered. The IRT will assign a 
randomization number to the patient. For the subjects who will receive secukinumab or 
secukinumab placebo, this number will be used to link the patient to a treatment arm and will 
specify a unique medication number for the package or packages of investigational treatment 
to be dispensed to the patient. Each subject will receive one or two packages per dispensing 
visit, depending on the treatment group and treatment epoch. For those subjects who will be 
randomized to etanercept, medication will be provided centrally (by a CRO) or purchased from 
the local market. The randomization number will not be communicated to the caller or other 
site members.
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from patients and investigator staff. A patient 
randomization list will be produced by the IRT provider using a validated system that automates 
the random assignment of patient numbers to randomization numbers. These randomization 
numbers are linked to the different treatment arms, which in turn are linked to medication 
number (for the secukinumab and the secukinumab placebo treatment arms). 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(s). 
Stratification
Randomization will be stratified by age and body weight collected at Randomization Visit. This 
stratification ensures balanced allocation of subjects to treatment groups within the age and 
weight strata. 
The age strata is “age < 12” or “age ≥12”. The weight strata will be “body weight < 25 kg”, 
“25 kg ≤body weight < 50 kg” or “body weight ≥50 kg”. Stratification by age and body 
weight will occur at Randomization Visit. For the randomization at Randomization Visit, it will 
be targeted to have at least approximately 30% of the subjects in each weight stratum.
The randomization scheme for subjects will be reviewed and approved by a member of the IQS 
Randomization Group.
Within each weight stratum, subjects will be assigned to the high dose or the low dose treatment 
group for secukinumab or placebo (see Table 5-1). 
5.4
Treatment blinding 
The secukinumab and the placebo arms are double blind (patient, investigator and assessor) 
until the data base lock for Week 52 analysis. However, for placebo PASI 75 responders 

Novartis
Confidential
Page 40
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
unblinding will occur at Week 12, since these subjects cannot continue into the Maintenance 
period but need to enter the post treatment follow-up period. 
The etanercept arm is single (assessor) blind until the moment subjects complete the Week 52 
visit and enter the follow-up period. Site staff (with the exception of the efficacy assessor), 
subject and sponsor are not blinded to the Etanercept arm for the entire treatment duration with 
Etanercept.
Any interim data analyses for the DMC or any other interim analyses which may be requested 
by health authorities during the blinded portion of the study will be performed without 
unblinding of Novartis personnel. Unblinded data will only be made available to independent 
Novartis/CRO individuals involved in the preparation of the interim analyses and who are not 
directly involved in the study conduct. 
Secukinumab and placebo treatment arms 
Subjects, investigator staff, and data analysts will remain blinded to the identity of the treatment 
from the time of randomization, using the following methods: (1) Randomization data will be 
kept strictly confidential until the time of unblinding, and will not be accessible by anyone else 
involved in the study, (2) the identity of the placebo and secukinumab  in prefilled syringes will 
be concealed by the use of study drugs that are all identical in packaging, labeling, schedule of 
administration, appearance, and odor. 
Subjects on secukinumab arms, or those who were on placebo arm in induction and PASI 75 
non-responders at Week 12, will remain blinded until Week 52 database lock.
Subjects who were on placebo arm in induction and PASI 75 responders at Week 12 will be 
unblinded to their treatment at Week 12, since they cannot continue into the maintenance epoch
of the protocol and must enter the treatment-free follow-up. However the unblinding occurs 
after the primary endpoint assessments at Week 12 will have been completed. 
An interim analysis will be performed before the planned IA at Week 24 and possibly before 
all subjects have reached the primary endpoint. In order to maintain the blind, the sponsor study 
team which will be directly involved in this analysis will no longer be part of the study conduct. 
The sponsor team members who will be involved in the study conduct after the interim data 
base lock, will not have access to any patient-level unblinded interim data until at least the data 
base lock for the next interim analysis at Week 24. The detailed procedures will be described 
in a separate charter. 
After the interim database lock for the analysis at Week 24, designated Sponsor team members 
will be unblinded, whereas as mentioned earlier the subjects, investigator staff and persons 
performing the assessments will remain blinded until the database lock at Week 52.
Etanercept arm
Person(s) performing efficacy assessments will remain blind to the identity of the treatment 
from the time of randomization until Week 52 visit of a patient, using the following methods: 
(1) Randomization data will be strictly confidential until the time of unblinding and will not be 
accessible by anyone else involved in the study, (2) etanercept treatment will be dispensed and 
administered by qualified site personnel other than the efficacy assessor (3) the efficacy assessor 

Novartis
Confidential
Page 41
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
will not speak to the subject or parent or other site personnel for study matters other than those 
associated directly with the performed efficacy assessments.
All treatment arms
For all treatment groups, unblinding of site personnel during the induction and the maintenance 
epochs other than described above will only occur in the case of subject emergencies.
At the time of the interim evaluation of the data from the first 80 adolescent subjects by the 
external Data Monitoring Committee (DMC), designated Sponsor personnel (other than the 
study team) involved with the interim analyses will be unblinded.
After the Week 52 database lock (start of open label extension treatment), all subjects, sponsor 
team members, site personnel and persons performing the assessments will be unblinded for all 
treatment arms. 
 
 
The appropriate personnel from the study site and Novartis will assess whether study treatment 
should be discontinued for any subject whose treatment code has been broken inadvertently for 
any reason. Study treatment must be discontinued after emergency unblinding.
5.5
Treating the subject
Sponsor qualified medical personnel will be readily available to advise on trial related medical 
questions or problems
5.5.1
Patient numbering
Each subject is uniquely identified by a Subject Number which is composed by the site number 
assigned by Novartis and a sequential number assigned by the investigator. Once assigned to a 
subject, the Subject Number will not be reused. 
Upon signing the informed consent form, the subject is assigned the next available sequential 
number by the investigator. At each study site, the first subject is assigned subject number 1, 
and subsequent subjects are assigned consecutive numbers (e.g. the second subject is assigned 
subject number 2; the third subject is assigned subject number 3). The investigator or his/her 
staff will contact the IRT and provide the requested identifying information for the subject to 
register them into the IRT. The site should select the CRF book with a matching Subject 
Number from the OC/RDC system to enter data.
If the patient fails to be treated for any reason, the IRT must be notified within 2 days that the 
patient was not treated. The reason for not being treated will be entered on the Screening Epoch 
Study Disposition CRF.

Novartis
Confidential
Page 42
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
5.5.2
Dispensing the investigational treatment
Secukinumab and Secukinumab placebo
Each study site will be supplied by Novartis with secukinumab active and placebo treatment in 
packaging of identical appearance. The secukinumab active and placebo treatment packaging 
has a 2-part label. A unique medication number is printed on each part of this label. 
At all visits where secukinumab active and/or placebo is dispensed, the IRT system will allocate 
a medication number which will be transmitted to the pharmacist (or other qualified site 
personnel) responsible for dispensation of study treatments. The pharmacist (or other qualified 
site personnel) will then identify the study treatment package(s) to administer to the subject 
corresponding to the medication number(s). Immediately before preparation of the study 
treatment, the pharmacist (or other qualified site personnel) will detach the outer part of the 
label from the packaging and affix it to the source document (Drug Label Form) for that 
subject’s unique subject number. These documents will be kept in a secured location as 
appropriate. The study treatment will be administered by study nurse/ qualified site personnel 
individual.  
During the COVID-19 pandemic or similar major health care disruption that limits or prevents 
on-site study visits, delivery of study drug directly to a subjects’s home is generally permitted 
in the event the Investigator has decided that an on-site visit by the subject is no longer 
appropriate or possible, and that it is in the interest of the subject’s health to administer the 
study treatment even without performing an on-site visit. The dispatch of study drug from the 
site to the subject’s home remains under the accountability of the Investigator.  
At the site level, the agreement with approval of the Principal Investigator, Independent Ethics 
Committee/ Institutional Review Board (IEC/IRB) and any other Board as appropriate should 
be in place to implement home delivery.
Home administration of secukinumab and secukinumab placebo
After Week 52, subjects will be expected to perform home administrations of secukinumab or 
secukinumab placebo Pre-filled Syringe (PFS) at the protocol specified time points, when they 
are not visiting the site for other trial related procedures. Subjects/custodians will be previously 
trained by site staff regarding the administration of secukinumab, secukinumab/placebo. Only 
adolescent subjects ≥ 12 years and <18 of age are allowed to self-inject under HCPs or 
caregiver/guardian supervision. 
If the subject or custodian is not confident to administer medication at home he/she should visit 
the site every 4 weeks and according to the visit schedule, to have the administrations performed 
there by the site staff. Alternatively, if possible, local arrangements can be done for a trained 
nurse to administer medication to the subject at home. This person must be sufficiently trained 
before.
For these cases the pharmacist/ qualified site personnel will dispense, via IRT, an appropriate 
number of investigational treatment packages for home administrations and detach outer part 
of the label from the packaging as indicated above. The subjects will record the date(s) of 
administration at home and will return the used PFS and packaging at their next visit to the site. 

Novartis
Confidential
Page 43
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Site staff are to transcribe this information into the appropriate Dosage Administration Record 
eCRF.
The used PFS should be disposed immediately after use in a sharps container OR according to 
the requirements of the respective countries and brought back to site. Subjects will be asked to 
return all unused medication the latest at the completion of the study or at the time of 
discontinuation of the investigational treatment. Detailed instructions will be provided 
separately.
Etanercept (Enbrel®)
Etanercept (Enbrel®) will be either provided centrally via a CRO or by purchase from local 
markets. Etanercept will be provided locally with support as needed by Novartis Country 
Pharma Organization (CPO). 
Etanercept should be dispensed as described in the Instructions for use/package leaflet. As per 
label, the quantity of the etanercept to be administered to pediatric subjects is dependent on 
their weight. Subjects will receive weekly s.c. dose of 0.8 mg/kg (up to a maximum of 50 mg) 
The pharmacist will receive from the study coordinator / study nurse the weight of etanercept 
subjects in all study visits where the weight assessment is performed. Based on the weight of 
the patient, the pharmacist will prepare a dispensation sheet containing at a minimum, study 
identification, subject number, the weight of the subject, the etanercept form to be administered, 
date and the amount of drug (volume) the patient will need to receive. It will be dated and signed 
by the Pharmacist. This sheet will be filed in a secure place with other drug related 
documentation. A copy of it will be provided together with the etanercept medication to the site 
staff, who is going to administer the medication to the subject. Alternatively if etanercept 
administration will occur at home a copy of it will be handed to the subject/custodian or trained 
nurse/caregiver. Detailed instructions will be provided separately.
Home administration of Etanercept (Enbrel®)
Alternatively, outside of the scheduled site visits, weekly etanercept medication can be 
administered at home by subject, trained custodian or trained nurse /caregiver. The first dose of 
etanercept should be administered at the site under the instruction/supervision of the qualified 
site staff. Qualified site staff will provide the subjects/custodians trained nurse/caregiver with 
appropriate training and necessary instructions as applicable to their local regulations.
Etanercept administration must follow the instructions for use as described in the package 
leaflet and the volume administered will be stated in the etanercept dispensation sheet, as 
prepared by the pharmacist. Each dose, taken home will be documented appropriately by the 
subject/custodian or trained nurse/caregiver. Site staff will transcribe this information into the 
appropriate Dosage Administration Record eCRF. Detailed instructions will be provided 
separately.
Subjects should be instructed on proper storage, transport of the treatment, as well as about the 
disposal of used syringes. Sharps containers will be provided for subjects to transport the used 
syringes back to the site at frequent intervals for proper disposal. Detailed instructions will be 
provided separately.  

Novartis
Confidential
Page 44
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
5.5.3
Handling the study treatment
The pharmacist or site personnel must maintain an accurate record of the shipment and 
dispensing of all study treatments in a drug accountability log. Monitoring of drug 
accountability will be performed by field monitors during site visits or remotely and at the 
completion of the trial. Patients will be asked to return all used study treatment and packaging 
at frequent intervals and all unused study treatment and packaging the latest at the end of the 
study or at the time of discontinuation of study treatment.
5.5.3.1
Handling of investigational treatment 
Investigational treatment (secukinumab and secukinumab placebo prefilled syringes) must be 
received by designated personnel at the study site, handled and stored safely and properly, and 
kept in a secured location. Upon receipt, all investigational treatment should be stored according 
to the instructions specified on the labels. Clinical supplies are to be dispensed only in 
accordance with the protocol. Technical complaints are to be reported to the respective Novartis 
CPO Quality Assurance.
Medication labels for secukinumab and secukinumab placebo prefilled syringes will be in the 
local language and comply with the legal requirements of each country. They will include 
storage conditions for the investigational treatment but no information about the patient except 
for the medication number. They must be stored in a secured refrigerator at 2-8°C (36-46°F), 
and must be carefully controlled in accordance with regulations governing investigational 
medicinal products and local regulations. Study treatments should not be frozen. 
5.5.3.2
Handling of other study treatment 
Etanercept will be provided either centrally or obtained from local market and will be stored 
and handled according to the conditions mentioned in the package leaflet by the manufacturer. 
It must be carefully controlled in accordance with regulations governing investigational 
medicinal products and local regulations. 
Any labelling of etanercept for use by study subjects will be done according to local 
requirements.
5.5.4
Instructions for prescribing and taking study treatment 
All study treatments will be administered subcutaneously throughout the study. All doses of 
study treatments at scheduled site visits will be administered at the study site after the study 
assessments for the visit have been completed. Prior to administration to the subject, the study 
treatment will be dispensed by the qualified site personnel appointed at the study site. 
For home administrations the processes described earlier must be followed.
It needs to be noted that site staff other than efficacy assessor(s) will be unblinded regarding 
which subject receives investigational drug (secukinumab or secukinumab placebo) which 
receives active comparator (etanercept). They will not be aware regarding who is receiving 
active secukinumab and who is receiving placebo.  
The first study treatment administration will occur at the Randomization Visit, after all study 
scheduled assessments have been performed (and inclusion/exclusion criteria confirmed) and 

Novartis
Confidential
Page 45
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
only after the scheduled blood samples have been drawn. Similarly, at each other visit, all study 
assessments should be completed prior to the administration of study treatment.
During the induction epoch for the secukinumab or secukinumab placebo treatment groups the 
number of injections in total will be:

For the weight group <25 kg:  6 injections 

For the weight groups 25 to <50kg and ≥50kg : 12 injections
During the maintenance epoch for the secukinumab treatment group the number of injections 
in total will be:

For the weight group <25 kg: 13 injections 

For the weight groups 25 to <50kg and ≥50kg : 26 injections
During the extension epoch for the secukinumab treatment group the number of approximate 
injections in total will be:

For the weight group <25 kg:  46 injections 

For the high dose weight groups 25 to <50kg and ≥50kg: 92 injections 

For the low dose weight groups 25 to <50kg and ≥50kg: between 46-92 injections*
* 92 injections is only the theoretical maximum. After the week 52 interim data base lock the 
study will become open label and the placebo injection that the low dose group was taking to 
maintain the double blind will no longer be administered. Thus a subject in this treatment group 
will be receiving only one injection instead of previously two. 
During the induction, for the etanercept treatment group the total number of injections will 
depend on the etanercept forms available centrally or in the local markets and on the weight of 
the subject and will be between 12 and 24. Always, every effort should be done for a subject to 
receive the minimal amount of injections aligned with the required etanercept dose to be 
administered.
During the maintenance, for the etanercept treatment group the amount of injections will depend 
on the etanercept forms available centrally or in the local markets and on the weight of the 
subject and will be between 40 and 80. Always, every effort should be done for a subject to 
receive the minimal amount of injections aligned with the required etanercept dose to be 
administered
All kits of investigational treatment assigned by the IRT (for secukinumab and secukinumab 
placebo) will be recorded/data-based in the IRT.
The investigator should promote compliance by instructing the subject to attend visits as 
planned so that the study treatment can be administered as foreseen in the study protocol. 
Similarly, for home administration of study drugs (etanercept; secukinumab or secukinumab 
placebo in extension treatment epoch) compliance can be promoted by instructing the subject 
to take the study treatment exactly as prescribed and by stating that compliance is necessary for 
the subject’s safety and the validity of the study. The subject should be instructed to contact the 
investigator if he/she is unable for any reason to take the study treatment as prescribed. 

Novartis
Confidential
Page 46
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Administration of secukinumab/secukinumab placebo
Secukinumab Solution for Subcutaneous Injection (active or placebo, respectively) will be 
provided in Prefilled syringes (75 mg/0.5 mL and 150 mg/mL). 
The study treatment solution must be injected into non-affected areas of the skin.
If possible, throughout the trial, the study treatment should be administered to body regions, 
changing the injection site from visit to visit, for example: right thigh, left thigh, right abdominal 
area, left abdominal area.
Single prefilled syringes will be packed in individual boxes. The boxes containing the syringes 
with study treatment solution should be kept at 2 to 8°C (36°F and 46°F) and protected from 
light. They should not be frozen or shaken. Prior to administration the boxes containing the 
syringes with study treatment solution should be allowed to come to room temperature 
unopened for about 15-30 minutes before administration. Used syringes should be disposed 
immediately after use in a sharps container or according to the requirements of the respective 
countries. For home administration please refer to Section 5.5.2.  
Note: The removable cap of the secukinumab pre-filled syringe 1 mL and 0.5mL form contains 
a derivative of natural rubber latex. Although no natural rubber latex is detected in the cap, the 
safe use of the secukinumab 1 mL or 0.5 mL pre-filled syringe in latex-sensitive individuals has 
not been studied.
Administration of Etanercept
Etanercept medication will be administered as described in the local instructions for 
use/package leaflet (see also Section 5.5.2)
Etanercept medication can be administered either at site or at home. The preferred option would 
be the home administration and should be encouraged and facilitated by the site. The decision 
nevertheless remains with subject/custodian. Depending on local capabilities, study personnel 
or trained nurse /caregiver should also be considered to administer the Etanercept medication 
at the subject’s home. Qualified site staff will discuss all options with the subject/custodian and 
support their decision.
For subjects who opt for home administration, at each site visit commercially available 
etanercept medication will be handed. The amount of medication should be sufficient to cover 
the time period until the next scheduled site visit with surplus medication to cover for eventual 
misuse or malfunctioning of etanercept syringe or for delay in presenting to the next visit.
For more information about home administration refer to Section 5.5.2.
Note: The needle cover of the pre-filled Etanercept syringe and pens contains latex (dry natural 
rubber) that may cause hypersensitivity reactions when handled by, or when Etanercept is 
administered to, persons with known or possible latex sensitivity. The majority of Etanercept 
patients in this study are expected to use the 25 mg powder for solution for injection rather than 
the prefilled syringe or pen. 
5.5.5
Permitted dose adjustments and interruptions of study treatment
No dose adjustments or interruptions are permitted.

Novartis
Confidential
Page 47
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
5.5.6
Rescue medication 
Rescue medication for psoriasis is not permitted in this study.
5.5.7
Prior and Concomitant treatment 
Relevant treatments (excluding those for psoriasis) taken within 6 months from screening date 
must be entered in the Prior and Concomitant Medications eCRF.
All treatments ongoing or starting at screening or at any point in the study and for any reason 
NOT including psoriasis will be entered in the Prior and Concomitant Medications eCRF or the 
Procedures and Significant Non-drug Therapies eCRF. 
Any psoriasis treatments used from the time subject started to treat psoriasis will be reported 
on the Prior psoriasis therapy eCRF and not in the Prior and Concomitant Medications eCRF. 
This includes all topical treatments, systemic treatments and phototherapies for psoriasis 
administered prior to Randomization Visit (Section 6.2.2). Any treatment used to treat a 
symptom of psoriasis but not the condition itself should not be entered on the Prior Psoriasis 
Therapies CRF (e.g., enter antihistamine or bland emollient in the concomitant medications 
eCRF and enter any non-medicated intervention in the Procedures and Non-drug therapies 
eCRF). 
Topical corticosteroids (TCS) must be recorded in the concomitant medications TCS eCRF. 
Start date, end date, dose, unit, frequency, route and reason for administration or change are to 
be recorded (see Section 5.5.7.1.).
The investigator should instruct the patient to notify the study site about any new medications 
he/she takes after the patient was enrolled into the study. All medications, procedures and 
significant non-drug therapies (including physical therapy and blood transfusions) administered 
after the patient was enrolled into the study must be recorded
5.5.7.1
Permitted concomitant medications (not for psoriasis or psoriatic 
arthritis)
Concomitant medications are allowed if not listed in Table 5-2. Dose adjustments of these 
medications should be avoided during the study. If a dose adjustment of these medications does 
occur, they must be recorded on the Prior and Concomitant medications eCRF or the Procedures 
and Significant non-drug therapies eCRF.
Subjects who are receiving treatments known to worsen psoriasis (e.g. beta-blockers) must be 
on stable dose for at least 4 weeks before Randomization Visit.
TCS and other topical treatments will be allowed from Week 12 visit and until the end of study 
only if:

medication was started after the week 12 visit was completed;

medication was used for 14 consecutive calendar days or less;

medication was used for an indication other than psoriasis and not on the area affected with 
psoriasis.  
Use of these TCS must be recorded on the Concomitant medications TCS eCRF. 

Novartis
Confidential
Page 48
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
There is no restriction on the use of anti-histamines or of corticosteroid drops used in the eye 
or ear during the study
5.5.7.2
Permitted concomitant medication for psoriasis
After the screening period, the use of concomitant medication for psoriasis in all body regions 
is restricted to bland emollients (not supplied by Novartis) and other non-medicated 
interventions (not listed in Table 5-2). Use of bland emollients must be recorded on the Prior 
and Concomitant medications eCRF. Use of any other non-medicated interventions must be 
recorded on the Procedures and Significant non-drug therapies eCRF.
The definition of “bland” excludes all topical medications that contain pharmacologically active 
ingredients such as (but not limited to) lactic acid, salicylic acid, urea, α-hydroxy acids or fruit 
acids.
Once the subject is screened and if the subject has intolerable scaling and/or itching, the use of 
bland emollients is permitted. The use of bland emollients should be avoided during the 12 
hours preceding a scheduled study visit. 
A topical corticosteroid (CS) treatment of mild or moderate activity is allowed for the face, 
scalp, hands, feetand genitoanal area during the screening period, but not after the subject has 
been randomized. These topical CS must not be used during the 12 hours preceding the 
Randomization study visit. Use of these topical CS must be recorded on the Prior psoriasis 
therapy eCRF if used to treat psoriasis. If not used to treat psoriasis it should be entered in the 
TCS eCRF (Section 5.5.7.1).
5.5.8
Prohibited Treatment 
Use of any treatments displayed in Table 5-2 that could confound the efficacy are NOT allowed 
during the study for any indication and wash-out periods for these treatments prior to 
randomization are indicated in the table. If the use of these treatments is required, then the 
subject should NOT be randomized into the study
The investigator should instruct the subject to notify the study site about any new treatments 
he/she takes after the start of the study treatment. All prohibited medications and significant 
non-drug therapies administered after the subject starts treatment with study treatment must be 
listed on the Prior and Concomitant medications eCRF or the Procedures and Significant non-
drug therapies eCRF or Concomitant medications TCS eCRF for any TCS used by subjects 
after randomization.  
If a prohibited treatment listed in Table 5-2 was used during the study, the subject must 
discontinue use of the prohibited treatment if he/she wishes to continue in the study. At the 
discretion of the investigator, if the subject’s use during the study of a prohibited treatment 
listed in Table 5-2 presents undue safety risk for the subject, the subject should be discontinued 
from study treatment as per Section 5.5.9. If the subject received a live virus vaccination during 
the study, the subject must discontinue study treatment.
During the screening period, subjects will be allowed to use some active topical treatments for 
any indication in the following body regions: face, scalp, hands, feet and genitoanal area. The 

Novartis
Confidential
Page 49
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
active topical treatments are limited to: mild or moderate potency CS. The subject must stop 
use of these topical CS at least 12 hours preceding the Randomization visit. 
For all other body regions, a washout period of 2 weeks applies for all active topical treatments 
for any indication (Table 5-2).
The Sponsor will be notified if a prohibited treatment is taken while the subject is on study.
Table 5-2
Prohibited treatment
Prohibited Treatment 
Wash-out period up 
to Randomization
Induction 
Epoch1,2
Maintenance 
Epoch1,2
Open label Epoch1,2
Alefacept, briakinumab, 
efalizumab, ustekinumab
26 weeks
Not allowed 
Not allowed
Not allowed
Biological immunomodulating 
agents other than above (e.g., 
adalimumab, infliximab)
12 weeks
Not allowed 
Not allowed 
Not allowed 
Etanercept 
No prior use 
allowed 
Other systemic 
immunomodulating treatments
(e.g., MTX, cyclosporine A 
[CSA], corticosteroid, 
cyclophosphamide)
4 weeks
Not allowed 
Not allowed 
Not allowed 
Photochemotherapy (e.g., 
PUVA) 
4 weeks
Not allowed
Not allowed
Not allowed
Other systemic therapy for 
psoriasis (e.g., retinoids, 
fumarate)
4 weeks
Not allowed
Not allowed
Not allowed
Any other investigational 
treatment or participation in 
any interventional trial
4 weeks or 5 half-
lives (whichever is 
longer)
Not allowed
Not allowed
Not allowed
Phototherapy (e.g., UVA, UVB)
2 weeks
Not allowed
Not allowed
Not allowed
Topical treatment3 for psoriasis 
or any other skin condition 
(e.g., corticosteroids, vitamin D 
analogues, pimecrolimus, 
retinoids, salicylvaseline, 
salicylic acid, lactic acid, 
tacrolimus, tar, urea, α-hydroxy 
or fruit acids), except on the 
face, scalp, hand and feet and 
genitoanal area during 
screening
2 weeks4
Not allowed 
Not allowed5
Not allowed5
Live virus vaccinations
6 weeks
Not allowed 6
Not allowed 6
Not allowed 6
Killed virus vaccinations
None 
Allowed
Allowed 
Allowed 
1.
If a prohibited treatment of psoriasis is used during the study, the subject must discontinue use of the 
prohibited treatment if he/she wishes to continue in the study. 
2.
In case of undue safety risk for the subject, the subject should discontinue study treatment at the discretion of 
the investigator. 
3.
Including intra-articular or peri-articular injections. Note that inhaled corticosteroids as well as corticosteroid 
drops in the eye or ear or nasal sprays are permitted. 
4.
Mild to moderate topical corticosteroids are allowed only during the screening period if used only on the face, 
scalp, hands and feet and/or genitoanal area and if not used during the 12 h preceding the randomization 
visit

Novartis
Confidential
Page 50
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
5.
Topical corticosteroids and other topical treatments will be allowed during maintenance and extension 
treatment epoch only if (all must apply):

medication was started after the Week 12 visit was completed;

medication was used for 14 consecutive calendar days or less;

medication was used for an indication other than psoriasis and not on the area affected with psoriasis
6.
If the subject received a live virus vaccination during the study, the subject must discontinue study treatment.
Exposure to light
Subjects need to be advised to limit exposure to ultraviolet (UV) light (including sunbathing 
and/or use of UV tanning devices) during the study to avoid possible effect on psoriasis
5.5.9
Discontinuation of study treatment and of treatment-free period
Discontinuation of study treatment
Subjects may voluntarily discontinue study treatment for any reason at any time. 
Study treatment must be discontinued under the following circumstances: 

Subject’s wish 

Withdrawal of consent

If the investigator/qualified site staff believe that for a given subject continuation of the 
study treatment would be detrimental to the subject’s well-being.

Emergence of the following AEs: AEs that in the judgment of the investigator/qualified 
site staff, taking into account the subject’s overall status, prevent the subject from 
continuing study treatment for example sepsis or newly occurring or worsening 
Inflammatory Bowel Disease, including Crohn’s disease and ulcerative colitis. 

Any laboratory abnormalities that in the judgment of the investigator/qualified site staff, 
and taking into consideration the subject’s overall status, prevents the subject from 
continuing study treatment. 

Any requirements met for liver events or liver laboratory value triggers as described in 
Appendix 2, Table 14-2

Any requirement met for renal events as described in Section 7.4

Live virus vaccination

Pregnancy (see Section 6.5.8 and Section 7.5) 

Ongoing use of prohibited treatment as per recommendations in Section 5.5.8. 

Emergency unblinding.

Any protocol deviation that results in a significant risk to patient’s safety
If discontinuation occurs for any reason in a treatment epoch, the investigator/qualified site staff 
must make every effort to determine the primary reason for a subject’s discontinuation from the 
study.  This information will then be recorded by investigator/qualified site staff on the 
applicable end of study epoch eCRF.
Subjects discontinued from study treatment will NOT be considered discontinued from the 
study. On the applicable end of treatment epoch eCRF (EOI, EOM, and EOT completion 

Novartis
Confidential
Page 51
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
eCRFs), the investigator/qualified site staff must record the date and primary reason for 
stopping study treatment. 
At the time of the study treatment discontinuation visit, if it has been approximately 4 weeks 
post last dose of study treatment then the assessments described EOI Visit Week 12 (for early 
discontinuation during induction epoch) or EOM Visit Week 52 (for early discontinuation 
during maintenance epoch) or EOT Visit Week 236 (for early discontinuation during extension 
epoch) should be completed at this visit. 
If it has not been approximately 4 weeks post last dose of study treatment at the time of the 
study treatment discontinuation visit, then the subject should be scheduled to return 4 weeks 
post last dose for their EOI, EOM or EOT visit as appropriate.
The investigator/qualified site staff must contact the IRT when the subject performs the EOI, 
EOM, EOT Visits as appropriate, to register the subject’s early completion of the study due to 
study treatment discontinuation. 
See Section 6 for the required assessments of these subjects after study treatment 
discontinuation. 
Discontinuation from a treatment-free period
If premature withdrawal occurs for any reason in the treatment-free period (follow up epoch, 
Week 240-Week 252), the investigator must make every effort to determine the primary reason 
for a subject’s premature withdrawal from the study and record this information on the 
applicable end of study period eCRF (Follow up  epoch completion eCRF EOF, Visit Week 
252 (F16)). Of note, if subjects start another systemic anti psoriatic treatment during follow up, 
they do not need to continue with the remaining follow-up visits but they will be expected to 
return to site after the start of the systemic treatment and perform End of Follow-up (EOF) visit.
See Section 6 for the required assessments of these subjects who discontinue from the Follow 
up period.
5.5.10
Withdrawal of consent 
Subjects may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent occurs only when a subject:

Does not want to participate in the study anymore, and

Does not 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 subject’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 subject are not allowed unless safety findings require 
communicating or follow-up.

Novartis
Confidential
Page 52
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the subject’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 subject’s samples until their time of withdrawal) according to applicable 
law.
For US and Japan: All biological samples not yet analyzed at the time of withdrawal may still 
be used for further testing/analysis in accordance with the terms of this protocol and of the 
informed consent form.
For EU and RoW: 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.
5.5.11
Loss to follow-up 
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to withdraw, the investigator should show "due diligence" by contacting the patient, 
family or family physician as agreed in the informed consent and by documenting in the source 
documents steps taken to contact the patient, e.g. dates of telephone calls, registered letters, etc.
5.5.12
Emergency breaking of assigned treatment code 
Emergency treatment code breaks should only be undertaken when it is essential to treat the 
patient safely and efficaciously. Most often, study treatment discontinuation and knowledge of 
the possible treatment assignments are sufficient to treat a study patient who presents with an 
emergency condition. Emergency treatment code breaks are performed using the IRT. When 
the investigator contacts the system to break a treatment code for a patient, he/she must provide 
the requested patient identifying information and confirm the necessity to break the treatment 
code for the patient. The investigator will then receive details of the investigational drug 
treatment for the specified patient and a fax or email confirming this information. The system 
will automatically inform the Novartis monitor for the site and the Global Trial Director (GTD) 
that the code has been broken.
It is the investigator’s responsibility to ensure that there is a procedure in place to allow access 
to the IRT/code break cards at any time in case of emergency. The investigator will inform the 
patient orally and in written how to contact his/her backup in cases of emergency or when he/she 
is unavailable, to ensure that un-blinding can be performed at any time. The investigator will 
provide protocol number, study treatment name if available and patient number.
The appropriate personnel from the study site and Novartis will assess whether study treatment 
should be discontinued for any subject whose treatment code has been broken inadvertently for 
any reason.
Study treatment must be discontinued after emergency unblinding. 
Subjects, who are prematurely unblinded and are discontinued from study treatment, will be 
requested to return for the applicable end of period visit (EOI Visit Week 12 or the EOM Visit 
Week 52 or Week 236 EOT) and the four follow-up visits (Visits Week 240, Week 244, Week 

Novartis
Confidential
Page 53
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
248 and Week 252). If subjects start another systemic anti psoriatic treatment during follow up, 
they do not need to continue with the remaining follow-up visits but they will be expected to 
return to site after the start of the systemic treatment and perform End of Follow-up (EOF) visit. 
5.5.13
Study completion and post-study treatment
Study completion for each individual subject occurs when the End of Follow-up visit (EOF) 
has been performed as per protocol. For a discontinued subject study completion corresponds 
to the last study visit of the patient or contact of the site with him/her.  Study completion for the 
study will occur when all subjects who have been randomized will have completed the study as 
stated above. 
The investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care. 
5.5.14
Early study termination 
The study can be terminated at any time for any reason by Novartis. Should this be necessary, 
the patient should be seen as soon as possible and be treated as a prematurely discontinued 
patient (see Section 5.5.9). The investigator may be informed of additional procedures to be 
followed in order to ensure that adequate consideration is given to the protection of the patient’s 
interests. The investigator will be responsible for informing the Institutional Review 
Board/Independent Ethics Committee (IRBs/IECs) of the early termination of the trial.
Subjects who prematurely discontinue study treatment for any reason should be scheduled for 
an End of Induction (EOI) or End of Maintenance (EOM) or End of treatment (EOT) visit as in 
Table 6-1 and Table 6-2. If the subject is unable to return for the EOI or EOM or EOT visits, 
every effort should be made to contact the patient by telephone to obtain safety related 
information (primarily AEs) during the 20 weeks following the last dose of study drug. 
Documentation of attempts to contact the patient should be recorded in the source documents.
6
Visit schedule and assessments
Subjects should be seen for all visits on the designated day or as closely as possible to the 
original planned visit schedule.
During the COVID-19 pandemic or similar major health care disruption which limits or 
prevents on-site study visits, alternative methods of providing continuing care may be 
implemented such as phone calls, virtual contacts (e.g. teleconsult) or visits by site staff or a 
home nursing service to the subject´s home depending on local regulations and capabilities, that 
can partially replace on-site study visits, for the duration of the pandemic until it is safe for the 
subject to visit the site again. These contacts should occur on or around the scheduled visit dates 
(or more frequently if needed). Every effort should be made to complete all study visit 
assessments feasible per protocol. Special effort should be made to conduct the scheduled EOT 
and EOF visits on site. If it is not feasible to conduct these visits on-site, at least phone contact 
or if possible, visits to the subject´s home by site staff as mentioned previously should be 
attempted.

Novartis
Confidential
Page 54
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Screening will be flexible in duration and will last up to a maximum of 4 weeks. During this 
time, the subject will sign the informed consent form, be evaluated for eligibility and will have 
all screening visit assessments done as indicated in Table 6-1. 
Table 6-1, Table 6-2 lists all of the assessments and indicates with an “x” at which visits the 
assessments are performed. 
If for any reason the subject is a screen failure, the subject may be rescreened. There is no 
restriction on the number of times a potential subject may be rescreened or on how much time 
must pass from the date of screen failure and the date of rescreening.
If a subject rescreens for the study, then the subject must sign a new ICF and be issued a new 
subject number prior to any screening assessment being conducted for the subject under the 
new screening subject number. For all subjects, the investigator/qualified site staff will record 
if the subject was rescreened on the rescreening CRF and any applicable screening numbers the 
subject was issued prior to the current screening number.
The date of the new informed consent signature must be entered on the Informed consent CRF 
to correspond to the new screening subject number. Informed Consent for a rescreened subject 
must be obtained prior to performing any study related assessment or collecting any data for the 
Screening Visit. For rescreening, all screening assessments must be performed as per protocol, 
except for the tuberculosis (TB) work up, if applicable, if performed not more than 12 weeks 
before randomization. 
If the date of a TB work up is less than 12 weeks from the projected randomization date, then 
it is not required that the TB work up be repeated. However, the subject must repeat the 
QuantiFERON test performed by the central laboratory.
At the discretion of the investigator, laboratory assessments at randomization visit need not to 
be performed if screening laboratory assessments were performed within 7 days from 
randomization.
During the treatment epochs, subjects may be seen at an unscheduled visit, e.g. if they 
experience deterioration of psoriasis, or AEs that in the opinion of the investigator need 
intervention or repeated laboratory testing. During these unscheduled visits, study treatment 
will NOT be administered. The assessment(s) performed at an unscheduled visit are at the 
investigator’s discretion. 
Suggested order of assessments:
Suggested guidelines for conduct of the visit assessments are below:

Subject to complete CDLQI at the study site prior to any study assessments 

Parent/custodian (or together with subject if subject is of 18 years of age or older) to 
complete childhood health assessment questionnaire, CHAQ©

Efficacy assessor to complete efficacy assessments.
1. IGA mod 2011 (all visits)
2. PASI (all visits)

Investigator to complete investigator assessments
1. Review CDLQI and CHAQ data (at applicable visits)

Novartis
Confidential
Page 55
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
2. Physical exam (at applicable visits)

All remaining study visit procedures (e.g., laboratory sample collection, vital signs 
measurements) must be completed prior to study treatment dosing.

Enter PASI data into the source data worksheets and perform calculations as needed 
BEFORE contacting IRT at randomization and Week 12 Visit.

Contact IRT to register the subject visit, as applicable

Administration of study treatment, as applicable

Novartis
Confidential
Page 56
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Table 6-1
Visit and assessment schedule for the Blinded Epoch
Epoch
Scr
Induction Epoch
Maintenance Epoch
Visit
1
2
3
4
5
6
7
8a
E
OI
9
10
11
12
13
14
15
16
17
18
19
20
21b
EO
M
Week
-4-R*
R
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
Day
-28-R*
1
8
15
22
29
57
85
92
99
106
113
141
169
197
225
253
281
309
337
365
Obtain informed consent 1 
x
Subject demographics
x
Inclusion/exclusion2
S
S
Psoriasis history/prior therapies
x
Medical history and prior 
medications
x
Concomitant medications3
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
Surgeries and  non-drug 
procedures
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
Physical Exam
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Height4
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
Weight 
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
Vital signs (BP & pulse)
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
Labs: Hematology6
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
Blood chemistry6, Urinalysis 
(local) 
x
x
x
x
x
X
x
x
x
x

Novartis
Confidential
Page 57
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Epoch
Scr
Induction Epoch
Maintenance Epoch
Visit
1
2
3
4
5
6
7
8a
E
OI
9
10
11
12
13
14
15
16
17
18
19
20
21b
EO
M
Week
-4-R*
R
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
Day
-28-R*
1
8
15
22
29
57
85
92
99
106
113
141
169
197
225
253
281
309
337
365
Renal monitoring (conditional) 
Urinalysis, Urine Microscopy, 
Fasting Glucose. 6, 7
x
x
x
X
x
x
x
x
x
x
x
x
x
Tuberculosis test8
x
Pregnancy test (in females of 
childbearing potential) 6,9
x
x
x
x
x
x
Chest X ray (optional) 10
x
ECG (standard 12-lead)
x
x
x
x
PASI
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
IGA mod 2011 
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
CDLQI 12
x
x
x
x
x
x
x
CHAQ© (for subjects with History 
of Psoriatic Arthritis only)
x
x
x
x
x
x
x
Adverse event assessment 
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
SAE assessment 
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
Randomization via IRT 13
x
Data entry of weight into IRT14
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x

Novartis
Confidential
Page 58
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Epoch
Scr
Induction Epoch
Maintenance Epoch
Visit
1
2
3
4
5
6
7
8a
E
OI
9
10
11
12
13
14
15
16
17
18
19
20
21b
EO
M
Week
-4-R*
R
1
2
3
4
8
12
13
14
15
16
20
24
28
32
36
40
44
48
52
Day
-28-R*
1
8
15
22
29
57
85
92
99
106
113
141
169
197
225
253
281
309
337
365
Administration of study drug 
(double blind: secuk/placebo)
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
Dispense etanercept 15
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
End of induction eCRF 
completion 
x
End of maintenance eCRF 
completion
x
Contact IVRS/IWRS
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
R=Randomization, 
ECG=Electrocardiograms, CDLQI= children’s dermatology life quality index, SAE=serious adverse events, 
IRT=Interactive response technology, EOI- End of induction, EOM- End of Maintenance.
X=assessment entered or transferred into the clinical database. S= assessment only recorded in source.
*Before randomizing the subject, the site must ensure that all assessments of the screening visit have been performed, all lab results are available and 
subject is eligible. Special attention must be given to tuberculosis testing as results take longer to be available.
a During Week 12 visit subjects will have their last assessment performed for the induction epoch prior to the dose at this visit.
 
b During Week 52 visit subjects will have their last assessments performed for the maintenance epoch (EOM) and will enter the open-label extension 
treatment epoch.
 
1 There are two types of informed consent for this study, the general informed consent/assent 
 
2 These assessments are supported by and are stored with the source documentation. However, data regarding to which inclusion/exclusion criteria are 
met are captured on the Inclusion/Exclusion screen eCRF.

Novartis
Confidential
Page 59
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
3 Information on Topical Corticosteroid medication, that a subject may use, is entered in the Concomitant medications-topical corticosteroids eCRF
4  Measured standing and barefoot, using the same calibrated stadiometer. 
  
  
6 Samples will be shipped to and analyzed by the central lab. At the discretion of the investigator, laboratory assessments need not to be performed 
again at Randomization (R) visit if screening labs were performed within 7 days from randomization.
7As part of the renal safety monitoring (details in Section 7.4) certain alert conditions may be fulfilled based on biochemistry and urine dipstick results. As 
a follow up action urine samples (first morning void) must be shipped to central lab for quantitative urinalysis and/or urine microscopy. Similarly, fasting 
glucose analysis may be also be required based on glucose urine dipstick result.
8 If the first QuantiFERON® TB-Gold In-Tube test is indeterminate, the investigator may choose to perform a second QuantiFERON® TB-Gold In-Tube 
test (as part of an unscheduled visit) or refer the subject for tuberculosis workup per local guidelines.  If the result of any QuantiFERON® TB-Gold In-
Tube test is “positive” or the results of 2 sequential QuantiFERON® TB-Gold In-Tube tests are ”indeterminate”, the subject must be referred to have a 
tuberculosis workup per local guidelines (if no workup within 12 weeks prior to randomization is available).   The subject will not be eligible for 
randomization if “active tuberculosis is present “or if “latent tuberculosis is present and is untreated as per local guidelines.”  No QuantiFERON® TB-Gold 
In-Tube test is to be done at the central laboratory after the subject has been randomized.
9 Serum pregnancy tests will be performed at screening and urine pregnancy test at all other scheduled visits. If there is a positive urine pregnancy test, 
study treatment must be withheld and a serum pregnancy test done at the same visit. Pregnancy tests will be performed in female subjects of child 
bearing potential, i.e. those who have started menstruation and/or are of age 12 or older.
10 Optional assessment. Chest X-ray or chest MRI (at prespecified sites) may be performed based on the investigator’s judgment, to assess presence of 
infections or malignancies.
 
 
 
12 Text only version will be used in all subjects. Assessment will no longer be performed once subjects reach 18 years of age.
13 At visit 2 the PASI Score and BSA must be calculated by efficacy assessor/appropriate site staff prior to contacting IRT.  The investigator must ensure 
subject meets all eligibility criteria before contacting IRT to randomize the subject.  At Visit 8 (week12), the site should have the PASI 75 responder 
status calculated prior to contacting IRT to communicate it.
14 For every visit (including unscheduled), weight measured at that visit will be entered into IRT.
15 Etanercept will be administered weekly up to and including Week 51. Outside of site visits, administration should preferable occur at home by subject, 
or caregiver. Alternatively if subject/parent does not feel confident in performing study treatment administration at home, they are allowed to receive 
study treatment administration at site. 

Novartis
Confidential
Page 60
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Table 6-2
Visit and Assessment schedule for the Extended treatment epoch
Epoch
Extension Treatment Epoch
Follow-up Epoch
Unscheduled d
Visit
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
End of  
ext. 
treat. 
(EOT)b
F4c
F8c
F12c
F16c
EOF
Week
52a
64
76
88
104
116
128
140
156
168
180
192
208
220
232
236
240
244
248
252
Day
365
449
533
617
729
813
897
981
1093
1177
1261
1345
1457
1541
1625
1653
1681
1709
1737
1765
Concomitant 
medications1
x
x
x
x
x
x
x
x
X
x
X
x
x
x
x
x
x
x
x
x
Surgeries and non-
drug procedures
x
x
x
x
x
x
x
x
X
x
X
x
x
x
x
x
x
x
x
x
Physical Exam
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Height2
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
Weight 
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
Vital signs (BP & 
pulse)
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
Hematology4  
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
Blood Chemistry4 , 
Urinalysis (local) 
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
Renal monitoring 5 
(conditional) 
Urinalysis4 , Urine 
Microscopy4, Fasting 
Glucose4
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x

Novartis
Confidential
Page 61
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Epoch
Extension Treatment Epoch
Follow-up Epoch
Unscheduled d
Visit
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
End of  
ext. 
treat. 
(EOT)b
F4c
F8c
F12c
F16c
EOF
Week
52a
64
76
88
104
116
128
140
156
168
180
192
208
220
232
236
240
244
248
252
Day
365
449
533
617
729
813
897
981
1093
1177
1261
1345
1457
1541
1625
1653
1681
1709
1737
1765
Pregnancy test (in 
females of 
childbearing 
potential) 4,7
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
ECG (standard 12-
lead)
x
x
x
x
x
x
x
x
PASI
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
IGA mod 2011
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
CDLQI
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
Adverse event 
assessment 
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
SAE assessment 
x
x
x
x
x
x
x
x
x
x
X
x
x
x
x
x
x
x
x
x
Data entry of weight 
into IRT9
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
Contact IVRS/IWRS 
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x
Dispensing10
secukinumab
x
x
x
x
x
x
x
x
x
x
x
X
x
x
x

Novartis
Confidential
Page 62
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Epoch
Extension Treatment Epoch
Follow-up Epoch
Unscheduled d
Visit
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
End of  
ext. 
treat. 
(EOT)b
F4c
F8c
F12c
F16c
EOF
Week
52a
64
76
88
104
116
128
140
156
168
180
192
208
220
232
236
240
244
248
252
Day
365
449
533
617
729
813
897
981
1093
1177
1261
1345
1457
1541
1625
1653
1681
1709
1737
1765
End of Extension 
Treatment eCRF 
completion
x
End of Follow-up 
eCRF completion 
x
, ECG=Electrocardiogram, CDLQI= children’s dermatology life quality index, SAE=serious adverse events , IRT=Interactive 
response technology, EOI- End of induction, EOM- End of Maintenance, EOT- End of Extension Treatment ,  EOF- End of Follow-up
X=assessment entered or transferred into the clinical database. S= assessment only recorded in source
a Week 52 is the final visit in maintenance epoch and the first visit in the extension epoch. Assessments done for the EOM will be used for the extension 
treatment epoch.
b During EOT visit subjects will have their last assessments performed for extension treatment epoch
 
c Follow-up assessments are  to be conducted for subjects who complete extension treatment epoch and for subjects who discontinue study treatment 
early 
d The assessments performed at an unscheduled visit are at the investigator’s discretion 
1Information on Topical Corticosteroid medication, that a subject may use, is entered in the Concomitant medications-topical corticosteroids eCRF
2 Measured standing and barefoot, using the same calibrated stadiometer, 
 
  
4 Samples will be shipped to and analyzed by the central lab.
5As part of the renal safety monitoring (details in Section 7.4) certain alert conditions may be fulfilled based on biochemistry and urine dipstick results. As 
a follow up action urine samples (first morning void) must be shipped to central lab for quantitative urinalysis and/or urine microscopy. Similarly, fasting 

Novartis
Confidential
Page 63
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
glucose analysis by the central lab may also be required based on the glucose urine dipstick result. Once a subject reaches adulthood (≥18 years of age) 
this procedure no longer needs to be followed.
 
 
 
7 Serum pregnancy tests will be performed at screening and urine pregnancy test at all other scheduled visits. If there is a positive urine pregnancy test, 
study treatment must be withheld and a serum pregnancy test done at the same visit. Pregnancy tests will be performed in female subjects of child 
bearing potential, that is those who have started menstruation and/or are of age 12 or older.
 
 
 
9 For every visit weight measured at that visit will be entered into IRT
10 Secukinumab will be dispensed at site visits. In the extension treatment epoch, between site visits, it will be administered every 4 weeks at home, 
either by subject (self-injection only for adolescents of at least 12 years of age and under supervision) or by caregiver. In case subject or parent does not 
feel confident in performing home administrations they will be allowed to continue to perform administration at site. These administrations should occur at 
Wk 56, Wk 60, Wk 68, Wk 72, Wk 80, Wk 84, Wk 92, Wk 96, Wk 100, Wk 108, Wk 112, Wk 120, Wk 124, Wk 132, Wk 136, Wk 144, Wk 148, Wk 152, 
Wk 160, Wk 164, Wk 172, Wk 176, wk 184, Wk 188, Wk 196, Wk 200, Wk 204, Wk 212, Wk 216, Wk 224 and Wk 228.  

Novartis
Confidential
Page 64
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
6.1
Information to be collected on screening failures 
All subjects who sign the informed consent but discontinue prior to randomization at Visit 2 are 
considered to be screen failures. 
If a subject discontinues prior to randomization, the IRT provider must be notified within 5 
days, and the reason for the subject not being randomized will be entered on the Screening 
Phase Disposition eCRF. The Screening visit date, the Demography eCRF, the Informed 
Consent eCRF, the Inclusion/Exclusion eCRF, and the subject rescreening eCRF must be 
completed.  The AE eCRF should be completed for any SAEs that occurred during the screening 
period. Adverse events that are not SAEs will be followed by the investigator and collected only 
in the source data. The Death eCRF should be completed in the case of a death during the 
screening period. The withdrawal of consent eCRF must be completed if consent was 
withdrawn during the screening period before the subject was randomized.
For all subjects who sign the informed consent and entered into the next period of the study, all 
AEs occurring after the informed consent is signed will be recorded on the AE eCRF.
Investigators will have the discretion to record abnormal test findings on the medical history 
CRF whenever in their judgment, the test abnormality occurred prior to the informed consent 
signature.
6.2
Subject demographics/other baseline characteristics 
All Baseline assessments should be performed prior to first study treatment administration. 
These may be in the screening period (e.g. demographics) or at the Randomization Visit (e.g. 
PROs), depending on the assessment. 
6.2.1
Demographics
Data to be collected on all patients include: year of birth, age, sex, race, ethnicity, and child-
bearing potential (for females). 
6.2.2
Psoriasis medical history / Previous psoriasis therapy
Disease history will be collected at the screening visit. The information to be collected and 
entered in the Psoriasis History eCRF and Prior Psoriasis Therapies eCRF includes the 
following:

The date of first diagnosis of plaque psoriasis (by a physician)

The previous treatments of psoriasis (including previous use systemic therapies, biologic 
therapies, as well as phototherapy and/or photo chemotherapy or topical use) and the 
reason for discontinuation of each therapy

The presence of psoriatic arthritis and the date of first diagnosis (by a physician)
6.2.3
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. 
Whenever possible, diagnoses and not symptoms will be recorded.

Novartis
Confidential
Page 65
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Significant findings that are observed after the subject has signed the informed consent form 
and that meet the definition of an AE must be recorded in the AE eCRF.
Investigators will have the discretion to record abnormal test findings on the medical history 
CRF whenever in their judgment, the test abnormality occurred prior to the informed consent 
signature.
6.2.4
Chest X-ray (optional)
Chest X-ray is an optional assessment which can be performed in screening at the discretion of 
the investigator, if warranted for the subject. This is aimed to detect ongoing infection and 
particularly tuberculosis or malignancy.
A chest X-ray (or chest MRI at pre specified sites) must only be done after it is fairly certain 
that the subject meets the other inclusion/exclusion criteria, in order to minimize unnecessary 
exposure to X-ray radiation for subjects. 
If the chest X-ray or MRI evaluated by a qualified physician shows evidence of ongoing 
infections or malignancy and the subject was not treated subsequent to the X-ray (or MRI), the 
subject will not be eligible to enter the study.
6.2.5
Determination of Tuberculosis status
Determination of tuberculosis (TB) status will be required before administration of study 
treatment and should be performed as defined by local guidelines. TB status must be determined 
by medical history, signs, symptoms and TB testing (QuantiFERON-TB Gold assay). Any 
significant findings will be recorded in the TB assessment eCRF and the Medical History eCRF, 
as necessary.
QuantiFERON TB-Gold In-Tube assay
A QuantiFERON® TB-Gold In-Tube assay (QFT) will be performed to assess the TB status at 
screening for all subjects. This test will only be used to determine subject’s eligibility for the 
trial. The test will be used to screen the subject population for latent tuberculosis infection 
(Doherty 2008).
This blood-based assay is specific for Mycobacterium tuberculosis and is not influenced by 
previous Bacillus Calmette-Guérin vaccination or exposure to other Mycobacteria species. This 
test, in contrast to the purified protein derivative (PPD) skin test, is also insensitive to a booster 
effect since the subject is not exposed to the vaccine. The assay measures the production of 
interferon-gamma and presents it relative to a negative and a positive control sample. Further 
information is available in Manuel and Kumar (2008).
The QuantiFERON®-TB Gold assay test will be supplied by the central laboratory. Details on 
the collection, shipment of samples and reporting of results by the central laboratory are 
provided to investigators in the laboratory manual.
Refer to Figure 6-1 for guidance on subject eligibility with respect to TB testing. The results of 
a workup for a subject with a positive or indeterminate test must be recorded on the Tuberculosis 
assessment eCRF.

If the test result is negative, the subject may be randomized.

Novartis
Confidential
Page 66
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

If the test result is positive, the investigator should perform workup for the test result as 
per local procedures. If a TB workup was conducted prior to the screening the subject, 
results of the workup can be used to assess eligibility if the workup was conducted within 
12 weeks prior to randomization.

Subjects’ positive for latent TB per workup may be randomized to the trial if sufficient 
treatment has been initiated according to local routine clinical practice and will be 
maintained for the prescribed duration. Subjects positive for active TB per workup are not 
eligible for the study. Subjects negative for TB (no signs of latent or active TB) per 
workup may be randomized to the trial.

If the test result is indeterminate, the investigator may repeat the test once or may 
proceed directly to perform workup for the test result as per local procedures. This 
action is at the discretion of the investigator. If a TB workup was conducted prior to the 
screening the subject, results of the workup can be used to assess eligibility if the workup 
was conducted within 12 weeks prior to randomization. 

If the second test is negative, the subject may be randomized.

If the second test is positive, the investigator should perform workup as per local
guidelines. Subjects’ positive for latent TB per workup may be randomized to the trial if 
sufficient treatment has been initiated according to local routine clinical practice and will 
be maintained for the prescribed duration. Subjects positive for active TB per workup are 
not eligible for the study. Subjects negative for TB per workup (no signs of latent or 
active TB) may be randomized to the trial.

If the second test is again indeterminate, the investigator should perform follow-up for the 
test result as per local procedures. Subjects tested positive for latent TB per workup may 
be randomized to the trial if sufficient treatment has been initiated according to local 
routine clinical practice. Subjects positive for active TB per workup are not eligible for
the study. Subjects negative for TB per workup (no signs of latent or active TB) may be 
randomized to the trial if the workup was conducted 12 within weeks prior to 
randomization.
If eligibility is being assessed with only 1 test result and a TB workup (i.e., no second TB test 
will be performed), the TB test to assess eligibility must have been done via the central 
laboratory for the study within the screening period (within 4 weeks prior to randomization) 
and TB workup will only be considered if it was completed within 12 weeks prior to 
randomization. Subjects’ positive for latent TB per workup may be randomized to the trial if 
sufficient treatment has been initiated according to local routine clinical practice and will be 
maintained for the prescribed duration. Subjects positive for active TB per workup are not 
eligible for the study. Subjects negative for TB per workup (no signs of latent or active TB) 
may be randomized to the trial.

Novartis
Confidential
Page 67
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Figure 6-1
Tuberculosis screening flowchart

Novartis
Confidential
Page 68
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
6.2.6
Other baseline characteristics
Baseline characteristic data to be collected on all subjects include (all labs are central except 
where indicated): 
ECG, vital signs; hematology; clinical chemistry; local urinalysis; past medical history record 
of HIV, hepatitis B or hepatitis C status;
 PASI; IGA mod 2011; cDLQI. 
A serum pregnancy test will be performed for females of child bearing potential or of at least 
12 years of age.
6.3
Treatment exposure and compliance 
All doses of study treatment administration will be recorded on the appropriate Dosage 
Administration Record eCRF page (visit specific and summary pages). 
Information on drug dispensing, administration, accountability will be collected in drug 
accountability logs and other documents as appropriate. For drug administrations at home 
subject will record relevant information at home which will then be transcribed at the 
corresponding documents at site including Dosage Administration Record eCRF page (see also 
Section 5.5).
Compliance will also be assessed and confirmed by field monitor via drug accountability logs 
and via info documentation and information provided by IRT and by the qualified site personnel 
responsible for treatment dispensation, preparation, administration and accountability.  
6.4
Efficacy
All efficacy assessments should be performed prior to administration of study treatment. 
Qualified site personnel (efficacy assessors) other than those treating the subjects, blinded to 
the allocation, will perform the efficacy assessments.
There are two co-primary efficacy variables in this study: PASI 75 response and IGA mod 2011 
0 or 1 response.
The following order should be applied when performing the efficacy assessments during study 
visits:

Investigator’s Global Assessment (IGA mod 2011; scale from 0 – 4)

Psoriasis Area and Severity Index (PASI; score from 0 – 72)
6.4.1
Investigator Global assessment (IGA mod 2011)
An efficacy assessor other than the investigator treating the subject will perform IGA mod 2011 
assessment as indicated in Table 6-3. It is recommended that the same assessor conducts the 
efficacy assessment throughout the study whenever possible.
The IGA mod 2011 rating scale for overall psoriatic disease is shown in Table 6-3 below.
The IGA mod 2011 scale has been developed based on a previous version of the scale used in 
secukinumab phase II studies in collaboration with health authorities, in particular the FDA. 

Novartis
Confidential
Page 69
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
The explanations/descriptions of the points on the scale have been improved to ensure 
appropriate differentiation between the points.
The IGA mod 2011 used in this study is static, i.e., it refers exclusively to the subject’s disease 
state at the time of the assessments, and does not attempt a comparison with any of the subject’s 
previous disease states, whether at baseline or at a previous visit.
The IGA mod 2011 score will be recorded in the eCRF.
Table 6-3
IGA mod 2011 scale
0
Clear, No signs of psoriasis. Post-inflammatory hyperpigmentation may be present
1
Almost clear- Normal to pink coloration of lesions; no thickening; no to minimal focal scaling
2
Mild- Pink to light red coloration; just detectable to mild thickening; predominantly fine scaling
3
Moderate -Dull bright red, clearly distinguishable erythema; clearly distinguishable to moderate 
thickening; moderate scaling
4
Severe- Bright to deep dark red coloration; severe thickening with hard edges; severe / coarse 
scaling covering almost all or all lesions
Based on this scale, a subject will be eligible to participate in the study if the subject has an IGA 
mod 2011 score at baseline of 4. 
Based on this scale, a subject will be considered as IGA mod 2011 0 or 1 responder if the subject 
achieves a score of 0 or 1 and improved by at least 3 points on the IGA mod 2011 scale 
compared to baseline. The IGA score will be recorded in the study-specific paper source form 
then will be entered into the eCRF at all visits with exception of Randomization visit when it 
will be also entered into the IRT to assess eligibility based on IGA mod 2011 score.
6.4.2
Assessment of total body surface area (BSA) and psoriasis area safety 
index (PASI)
The efficacy assessor (other than the investigator treating the subject) will complete the PASI 
assessment as indicated in Table 6-1, Table 6-2. Whenever possible, the same assessor should 
perform this efficacy assessment at all visits.
The total BSA affected by plaque-type psoriasis will be estimated from the percentages of areas 
affected, including head, trunk, upper limbs and lower limbs (see below for full details of the 
PASI assessment). The following calculations will be done: Each reported percentage will be 
multiplied by its respective body region corresponding factor (head = 0.1, trunk = 0.3, upper 
limbs = 0.2, lower limbs = 0.4). The resulting four percentages will be added up to estimate the 
total BSA affected by plaque-type psoriasis.
A PASI score (Fredriksson 1978, Weisman 2003, Gottlieb 2005) will be derived as indicated 
in Table 6-4. 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:

The neck is assessed as part of the head.

Novartis
Confidential
Page 70
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

The axillae and groin are assessed as part of the trunk.

The buttocks are assessed as part of the lower limbs.

When scoring the severity of erythema, scales should not be removed.
Table 6-4
PASI scoring system 
Body region
Erythema (E)
Thickening (I)
(plaque 
elevation, 
induration)
Scaling (D)
(desquamation)
Area score (A)
(based on true area %)*
Head (H)†
0=none
0=none
0=none
0 = no involvement
1= slight
1= slight
1= slight
1 = >0-<10%
2= moderate
2= moderate
2= moderate
2 = 10-<30%
3= severe
3= severe
3= severe
3 = 30-<50%
4=very severe
4=very severe
4=very severe
4 = 50- <70%
5 = 70-<90%
6= 90 -100%
Trunk (T)‡
0=none
0=none
0=none
0 = no involvement
1= slight
1= slight
1= slight
1 = >0-<10%
2= moderate
2= moderate
2= moderate
2 = 10-<30%
3= severe
3= severe
3= severe
3 = 30-<50%
4=very severe
4=very severe
4=very severe
4 = 50- <70%
5 = 70-<90%
6= 90-100%
Upper limbs (U)
0=none
0=none
0=none
0 = no involvement
1=slight
1=slight
1=slight
1 = >0-<10%
2=moderate
2=moderate
2=moderate
2 = 10-<30%
3=severe
3=severe
3=severe
3 = 30-<50%
4=very severe
4=very severe
4=very severe
4 = 50- <70%
5 = 70-<90%
6 = 90-100%
Lower limb (L)§
0=none
0=none
0=none
0 = no involvement
1=slight
1=slight
1=slight
1 = >0-<10%
2=moderate
2=moderate
2=moderate
2 = 10-<30%
3=severe
3=severe
3=severe
3 = 30-<50%
4=very severe
4=very severe
4=very severe
4 = 50- <70%
5 = 70-<90%
6 = 90-100%
*   Percentage (not score) of body region (not whole body) affected will be entered in the eCRF
† Neck is assessed as part of the Head (H) body region.
‡ Axillae and groin are assessed as part of the Trunk (T) body region.
§ Buttocks are assessed as part of the Lower limbs (L) body region.
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

Novartis
Confidential
Page 71
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
The keys for the letters are provided in Table 6-4.
PASI scores can range from a lowest value of 0, corresponding to no signs of psoriasis, up to a 
theoretic maximum of 72.
The efficacy assessor is responsible for evaluating the subject and collecting the components, 
scoring signs and total regional area. The efficacy assessor/qualified site staff will record PASI 
data in the study-specific paper source worksheet at study visits and subsequently, 
investigator/qualified site staff will enter the data into PASI eCRF. 
Calculations based on collected PASI components (e.g. total PASI score, BSA, PASI 75 
responder status- as applicable) will be done by efficacy assessor/qualified site staff. These will 
also be entered in the PASI source worksheet and PASI eCRF as required.
At Visit 1 and Visit 2, the efficacy assessor/qualified site staff, after collecting the components 
of the PASI calculation, must calculate and verify (as indicated previously) the total PASI score 
and the total BSA.
Based on PASI, to be eligible, a subject must have a score of 20 or more at the Randomization 
Visit. 
Based on total BSA, to be eligible, a subject must have 10% or more total BSA involved at the 
Randomization Visit.
Only if the above eligibility criteria and all other eligibility criteria are fulfilled should site 
contact IRT at the Randomization Visit to randomize the subject.
At Visit 8 (Week 12), the efficacy assessor/qualified site staff, after collecting the components 
of the PASI calculation, must calculate (as indicated previously) the total PASI score. In 
addition the PASI 75 responder status of the subject must be calculated. Subjects achieving ≥ 
75% improvement (reduction) in PASI score compared to baseline (Randomization Visit) are 
defined as PASI 75 responders. Those achieving < 75% improvement are considered as PASI 
75 non-responders. These will also be entered in the PASI source worksheet and PASI eCRF.
Once this is calculated and verified the site can contact IRT and indicate whether the subject is 
PASI 75 responder on PASI 75 non responder. 
Definitions of efficacy variables based on PASI
The following definitions are used in this study (see CHMP guidelines for psoriasis 
(CHMP/EWP/2454/02 2004)):
PASI 50 response (partial response): subjects achieving ≥ 50% improvement (reduction) in 
PASI score compared to baseline are defined as PASI 50 responders
PASI 75 response: subjects achieving ≥ 75% improvement (reduction) in PASI score compared 
to baseline are defined as PASI 75 responders
PASI 90 response: subjects achieving ≥ 90% improvement (reduction) in PASI score compared 
to baseline are defined as PASI 90 responders
PASI 100 response / remission: complete clearing of psoriasis (PASI=0)

Novartis
Confidential
Page 72
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
6.4.4
Appropriateness of efficacy assessments 
The PASI score, the assessment of the severity of the psoriasis symptoms and the extent to 
which the subject’s body area is affected by the disease, is considered acceptable by health 
authorities (CHMP guideline on the treatment of psoriasis-CHMP/EWP/2454/02 2004) to 
assess efficacy in conjunction with Investigator’s Global Assessment  (IGA).
6.5
Safety 
All blood draws and safety assessments should be done prior to study treatment administration. 
Appropriate safety assessments (e.g., evaluation of AEs and SAEs including injection site 
reactions) should be repeated after the dose is administered.
During the COVID-19 pandemic or similar major health care disruption that limits or prevents 
on-site study visits, phone calls, virtual contacts (e.g. teleconsult), or visits by site staff or home 
nursing service depending on local regulations and capabilities may occur on or around 
scheduled protocol visit dates (or more frequently if needed). This will be done for safety 
monitoring and discussion of the subject´s health status until the subject can again visit the 
site. Case report forms (e.g. AEs, concomitant medications, procedures and non-drug therapies) 
should be updated as appropriate.
6.5.1
Physical examination 
A physical examination, including general appearance, skin, neck, eyes, ears, nose, throat, lungs, 
heart, abdomen, back, lymph nodes, and extremities, and vascular and neurological systems 
will be performed as indicated in Table 6-1, Table 6-2. Investigator should pay special attention 
to any signs or symptoms of potential skin or mucosal candida infections.
If indicated, based on medical history and/or symptoms, additional exams will be performed at 
the discretion of the investigator.
If possible, assessments for an individual subject should be performed by the same member of 
the study site staff throughout the study.
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present prior to the screening visit (Visit 1) must be 
included in the Medical History screen on the subject’s eCRF. Significant findings made after 

Novartis
Confidential
Page 73
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
the start of study (Visit 1) that meet the definition of an adverse event must be recorded on the 
Adverse Event screen of the subject’s eCRF.
 
 
 
 
 
 
 
 
6.5.3
Vital signs 
Vital signs (including blood pressure and pulse measurements) will be assessed at every 
scheduled visit as indicated in Table 6-1, Table 6-2. If possible, assessments should be 
performed by the same study site staff member throughout the study.
After the subject has been sitting for five minutes, with back supported and both feet placed on 
the floor, systolic and diastolic blood pressure will be measured twice (measurements 
separated by 1 to 2 minutes) using a validated device, with a cuff that is appropriately sized for 
the subject’s arm circumference. The average of the two measurements will be entered on the 
Vital Signs eCRF.
Whether action needs to be taken to address notable vital signs will be decided by the 
investigator/qualified site staff, taking into account the overall status of the subject. No specific 
action is foreseen as part of the study protocol. Notable values for vital signs are indicated in 
Appendix 1, Table 13-1. 
6.5.4
Height and weight 
Height and body weight will be measured at visits as in Table 6-1, Table 6-2. Height 
measurements (in indoor clothing, but without shoes, socks, hats or hair accessories interfering 
with assessment) will be made using a stadiometer that is calibrated on a regular basis. Height 
measurements will be performed twice and the reported height will be the mean of the 2 
measurements. 
If possible, body weight assessments (in indoor clothing, but without shoes) should be 
performed by the same study site staff member and using the same scale throughout the study. 
The body weight recorded at Randomization (Visit 2) will be used to categorize the subject 
population at randomization and placebo PASI 75 non-responders at Week 12 respectively, to 
receive the corresponding doses in the high dose and low dose secukinumab groups.

Novartis
Confidential
Page 74
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
6.5.5
Laboratory evaluations 
Subjects should avoid smoking within the hour preceding the blood draws.
A central laboratory will be used for analysis of all specimens listed below, unless noted 
otherwise. Details on the collections, shipment of samples and reporting of results by the central 
laboratory are provided to investigators in the laboratory manual. The blood volume drawn will 
be adjusted for pediatric patients and will be stated in the laboratory manual.
During the COVID-19 pandemic or a major health care disruption that limits or prevents on-site 
study visits and central lab sampling, performing the safety lab tests locally, will be allowed in 
case it is needed to check safety parameters. Depending on local regulations, technical 
capabilities and following any applicable training in the required process, qualified staff may 
visit the subject at home to draw blood/ urine samples if needed to check safety parameters.
Clinically notable values for key laboratory tests are defined in Section 13, Appendix 1. For 
identification of pediatric abnormal values for all parameters, the laboratory manual must also 
be consulted.
Whether action needs to be taken to address notable laboratory values will be decided by the 
investigator, taking into account the overall status of the subject. No specific action is foreseen 
as part of the study protocol.
6.5.5.1
Hematology
Hemoglobin, hematocrit, red blood cell count, white blood cell count with differential 
(neutrophils including bands, lymphocytes, monocytes, eosinophils, basophils) and platelet 
count will be measured at scheduled study visits, as specified in Table 6-1, Table 6-2.
6.5.5.2
Clinical chemistry
Serum chemistry will include urea or BUN, creatinine, total bilirubin, AST (SGOT), ALT 
(SGPT), GGT, alkaline phosphatase, sodium, potassium, bicarbonate, calcium, phosphorous, 
total protein, albumin, and uric acid.
Serum chemistry will be measured at scheduled study visits as specified in Table 6-1, Table 6-
2. 
Estimated GFR
In addition estimated Glomerular Filtration Rate (eGFR) as per Schwartz et al (Schwartz 2009) 
will be calculated and reported by the Central Laboratory, whenever a serum creatinine is 
performed.
The calculation is based on the following formula: 
eGFR (ml/min/1.73m2) = 0.413 x height (cm) / serum creatinine (mg/dl)
Height will be provided by the site to the central lab.
For eGFR, baseline value for the decrease from baseline criterion will be calculated as the 
average of values prior to the first dose (i.e. screening and baseline values).

Novartis
Confidential
Page 75
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Fasting glucose (conditional)
In case urine dipstick evaluation shows new glucosuria ≥ 1+, a fasting blood sample must be 
collected and sent to central lab for glucose analysis. More details can be found in Section 7.4. 
6.5.5.3
Urinalysis
Urine Dipstick (local) 
A midstream urine sample (approx. 30 mL) will be obtained, in order to avoid contamination 
with epithelial cells and sediments, and allow proper assessments.
A semi-quantitative ‘dipstick’ evaluation for the following parameters will be performed: 
specific gravity, pH, glucose, protein, bilirubin, ketones, leukocytes and blood, micro albumin. 
Urinalysis will be measured locally at scheduled study visits as specified in Table 6-1, Table 6-
2.
Quantitative Urinalysis (conditional) and Urine Microscopy (conditional)
If the dipstick result is positive for protein, glucosuria and/or blood, a urine sample will be sent 
to central laboratory for microscopic analysis which will include WBC, RBC, crystals, casts as 
indicated in the renal safety section (Section 7.4). 
Furthermore, whenever eGFR decrease meets alert values as indicated in renal safety section 
(Section 7.4) a urine sample must be sent to the central laboratory for quantitative urinalysis. 
This analysis will include protein and creatinine to calculate the protein over creatinine ratio 
(PCR) and other parameters like bilirubin, blood, color, glucose, ketones, leukocytes, esterase, 
nitrite, pH, protein, specific gravity, urobilinogen.
6.5.6
Electrocardiogram (ECG) 
A standard 12-lead ECG will be performed as indicated in Table 6-1, Table 6-2. When ECG is 
performed at scheduled visits, the investigator will review and initial tracing, and store with the 
subject’s source documentation. All ECGs must be performed on the ECG machines provided 
to the study site.
All ECGs will be independently reviewed by a central reader. Instructions for the collection and 
transmission of the ECGs to the independent reviewer will be provided in the ECG investigator 
manual.
Even though there is no exclusion criterion specifically based on the ECG, the ECG performed 
at screening (Visit 1) must be reviewed for major abnormalities before dosing at the 
randomization visit. If the ECG findings are clinically relevant and would prevent the subject 
from participating in the study (taking into account the subject's overall status including medical 
history and concomitant medications), the subject should not receive treatment and should exit 
the study. If a clinically relevant abnormality is noted on the screening ECG it should be 
reported in the Medical History eCRF. Clinically relevant abnormalities noted after the 
screening ECG (Visit 1) should be recorded as AEs.

Novartis
Confidential
Page 76
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
6.5.8
Pregnancy and assessments of fertility 
Females of child-bearing potential are defined as all females physiologically capable of 
becoming pregnant. This includes female pediatric patients who are menarchal or who become 

Novartis
Confidential
Page 77
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
menarchal during the study. In this study pregnancy tests will be performed in female subjects 
who are menarchal or become menarchal during the study and/or are 12 years of age or older at 
the beginning or at any point during the study. Sites must ensure that pregnancy testing 
commences once any of these conditions are fulfilled. 
Serum pregnancy test will be performed for all females of child-bearing potential according to 
the schedule in Table 6-1, Table 6-2.
During the COVID-19 pandemic or similar major health care disruption, that limits or prevents 
female subjects of childbearing potential or at least of 12 years of age to visit the site, urine 
pregnancy test kits may be shipped or provided directly to the subject. After appropriate 
instruction, subjects can perform the urine pregnancy test at home at the time points specified 
in the protocol and report the result to the site. It is important that subjects perform the 
pregnancy test first and only if the test result is negative should they then proceed with the 
administration of the study drug. A communication process should be established with the 
subject so that the site is informed of the pregnancy test results. In these communications the 
privacy of the subject should be considered in accordance with the local law and ethics.
All menarchal girls and their parents/caregivers should be informed about the potential risks of 
pregnancy and the need to prevent pregnancy during the study. It is important to be sensitive in 
introducing this issue, as understanding and comprehension of puberty, sexual activity, 
pregnancy and contraception is influenced by age, as well as factors such as precocity, socio-
educational economic and familial background. These discussions with the patient and her 
parents/caregivers are therefore best performed by investigators familiar with the pediatric 
subject and her family and should be guided by requirements of the local regulatory authorities. 
These discussions should take into account the socio-economic, cultural factors and religious 
beliefs of the adolescent participant and her family. The investigator should also discuss the 
management of the pregnancy test results with the patient and her parents/caregivers. The 
privacy of the patient should be considered in accordance with the local law and ethics.
Additional pregnancy tests may be performed at the investigator’s discretion during the study. 
Patients becoming pregnant must be discontinued from study drug. However, a patient may 
choose to remain in the study should she become pregnant, and be followed in the treatment-
free follow-up epoch as described in Table 6-1, Table 6-2.
Female patients of child-bearing potential who do not agree to abstinence and who are or might
become sexually active must be informed of the need to prevent pregnancy, by using effective 
methods of contraception during dosing of study treatment and for a minimum of 16 weeks 
after stopping study treatment or longer if local label requires it (e.g. in EU 20 weeks). At a 
minimum, the acceptable effective contraception is:

Barrier methods of contraception: 
a. Male or female condom  with or without spermicide 
b. Cap, diaphragm or sponge with spermicide 

Use of established oral, injected or implanted hormonal methods of contraception, 
intrauterine device (IUD) or intrauterine system (IUS)
The decision on the contraceptive method should be reviewed at least every 3 months to 
evaluate the individual need and compatibility of the method chosen.

Novartis
Confidential
Page 78
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
6.5.9
Appropriateness of safety measurements 
The safety measures used in this study are reliable and relevant standard measures for a biologic 
immunomodulating agent in psoriasis. 
6.6
Other assessments 
6.6.1
Health related Quality of Life 
The impact of psoriasis on various aspects of subject’s health-related quality of life (HRQoL) 
will be assessed by Children’s Dermatology Life Quality Index (CDLQI).
The impact of Psoriatic Arthritis, on those subjects who have reported History of Psoriatic 
Arthritis will be assessed by their parent/custodian via the use of the childhood health 
assessment questionnaire, CHAQ© .
Sufficient time must be allowed for completion of both questionnaires. Questionnaires must be 
completed in a quiet environment.
Completed questionnaires will be reviewed and examined by the site staff (not the investigator 
or evaluator of the subject for the physician assessments), before the clinical examination, for 
responses that may indicate potential AEs or SAEs. If AEs or SAEs are confirmed then the 
events must be recorded as per instructions given in Section 7 of the protocol. Study site staff 
should not encourage the subjects to change the responses reported in the completed 
questionnaire.
6.6.1.1
Children’s Quality of Life Index (CDLQI) 
The Children’s Dermatology Life Quality Index (Lewis Jones and Finlay, 1995) is a 10-item 
general dermatology disability index designed to assess health-related quality of life in pediatric 
subjects aged 4 to 16 years. It is self-explanatory and may be completed by the child with 
assistance from parents or caregivers as necessary. The 10 questions cover six areas of daily 
activities including symptoms and feelings, leisure, school or holidays, personal relationships, 
sleep and treatment. The questions are based on the preceding week to permit accurate recall. 
Each question is answered on a 4-point Likert scale scored from 0 to 3. These are added to give 
a minimum score of 0 and maximum score of 30. A higher CDLQI score indicated greater 
degree of QoL impairment.
CDLQI is available in two versions, text only and text with cartoons. The text only version will 
be used in this study. The mean completion time of the text version is 120 seconds.
The purpose of the CDLQI in this study is to investigate the effects of treatment of secukinumab 
with respect to CDLQI at Week 12, compared to placebo, and over time up to Week 52.
This questionnaire should be completed in the language the subject is most familiar with before 
any other clinical assessments, 
The questionnaire should be completed by the subject with the help of parent/custodian if and 
as needed. The site staff may help understand the questions, as necessary. The subject should 
be given sufficient space and time to complete the questionnaire. The study coordinator should 
check the questionnaire for completeness and encourage the subject to complete any missing 

Novartis
Confidential
Page 79
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
responses before the clinical examination. Once subjects reach 18 years of age CDLQI must no 
longer be completed.
The CDLQI questionnaire will be completed by the subject as indicated in Table 6-1, Table 6-
2.
During the COVID-19 pandemic or similar major health care disruption that limits or prevents 
on-site study visits, CDLQI questionnaire data may be collected remotely (e.g. via telephone 
interview of the subject) by qualified site personnel. This will depend on local regulations, 
technical capabilities and following any applicable training in the required process. 
Documentation of the procedure should follow the vendor emergency manual directives.
6.6.1.2
Childhood Health Assessment Questionnaire (CHAQ) for subjects with 
Psoriatic Arthritis
The childhood health assessment questionnaire CHAQ© (Singh et al 1994;Ruperto et al 2001), 
will be used to assess physical ability and functional status of patients as well as quality of life, 
for those children only who have reported History of Psoriatic Arthritis. A representative 
example of the questionnaire is provided in Appendix 7.
The disability dimension consists of 20 multiple choice items concerning difficulty in 
performing eight common activities of daily living; dressing and grooming, arising, eating, 
walking, reaching, personal hygiene, gripping and other “activities”. The person completing the 
questionnaire chooses from four response categories, ranging from ‘without any difficulty’ to 
‘unable to do’. 
The CHAQ© will be completed by a parent/custodian only if a validated version of the 
instrument is available in the language understandable to the parent at the visits indicated in 
Table 6-1. The same parent/custodian should preferably complete the questionnaire at all visits 
required per protocol. If patients turn 18 years of age during the study, the questionnaire will 
be completed together by the patient and the parent/custodian for the remaining visits.
6.6.1.2.1 Parent’s or patient’s global assessment of patient’s overall well-being (VAS)
The parent’s or patient’s global assessment of patient’s overall well-being will be assessed on 
the VAS that is part of the CHAQ©. The VAS scale ranges from 0-100 mm, from very well (0
mm) to very poor (100 mm).
Scores on the 100-mm linear scale will be measured to the nearest millimeter from the left.
6.6.1.2.2 Parent’s or patient’s assessment of pain (VAS)
The parent’s or patient’s assessment of pain will be assessed on the VAS that is part of the 
CHAQ©. The VAS scale ranges from 0-100 mm, from no pain (0 mm) to very severe pain (100 
mm).
Scores on the 100-mm linear scale will be measured to the nearest millimeter from the left.
6.6.2
Resource utilization 
Not applicable

Novartis
Confidential
Page 80
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

Novartis
Confidential
Page 81
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

Novartis
Confidential
Page 82
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
7
Safety monitoring 
7.1
Adverse events 
An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or 
clinical investigation subject after providing written informed consent for participation in the 
study. Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product.
The occurrence of adverse events should be sought by non-directive questioning of the patient 
at each visit or scheduled phone contact during the study. Adverse events also may be detected 
when they are volunteered by the patient during or between visits or through physical 
examination, laboratory test, or other assessments.
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria:

they induce clinical signs or symptoms, 

they are considered clinically significant, 

they require therapy. 
Clinically significant abnormal laboratory values or test results should be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in patient with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
patient and identifying adverse events. Notable ranges for labs values are included in Appendix 
1.
Adverse events should be recorded in the Adverse Events CRF under the signs, symptoms or 
diagnosis associated with them, accompanied by the following information.

the severity grade 

mild: usually transient in nature and generally not interfering with normal activities

moderate: sufficiently discomforting to interfere with normal activities

Novartis
Confidential
Page 83
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

severe: prevents normal activities. 

its relationship to the

study treatment (no/yes), or

investigational treatment (no/yes), or

the other study treatment (non-investigational) (no/yes), or

both or indistinguishable

Its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved should be reported.

whether it constitutes a serious adverse event (SAE - See Section 7.2 for definition of 
SAE)

action taken regarding [study/investigational] treatment (select as appropriate)
All adverse events should be treated appropriately. Treatment may include one or more of the 
following: 

no action taken (i.e. further observation only) 

study treatment dosage adjusted/temporarily interrupted 

study treatment permanently discontinued due to this adverse event 

concomitant medication given 

non-drug therapy given 

patient hospitalized/patient’s hospitalization prolonged 

its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown)
Once an adverse event is detected, it should be followed until its resolution or until it is judged 
to be permanent, and assessment should be made at each visit (or more frequently, if necessary) 
of any changes in severity, the suspected relationship to the study drug, the interventions 
required to treat it, and the outcome.
Worsening of psoriasis in this study is evaluated via the use of PASI, IGA mod 2011 and cDLQI 
assessments and is not expected to be captured as an AE in the eCRF. Exceptions include cases 
when a) a new type of psoriasis is diagnosed e.g. guttate psoriasis) or b) the worsening of 
psoriasis is so severe that a qualitatively different status is reached.
Information about common side effects already known about the investigational drug can be 
found in the Investigator’s Brochure (IB) or will be communicated between IB updates in the 
form of Investigator Notifications. This information will be included in the patient informed 
consent and should be discussed with the patient during the study as needed.
The investigator should also instruct each patient to report any new adverse event (beyond the 
protocol observation period) that the patient, or the patient’s personal physician, believes might 
reasonably be related to study treatment. This information should be recorded in the 
investigator’s source documents; however, if the AE meets the criteria of an SAE, it must be 
reported to Novartis.

Novartis
Confidential
Page 84
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
7.2
Serious adverse events 
7.2.1
Definition of SAE 
An SAE is defined as any adverse event (appearance of (or worsening of any pre-existing) 
undesirable sign(s), symptom(s) or medical conditions(s) which meets any one of the following 
criteria:

is fatal or life-threatening 

results in persistent or significant disability/incapacity

constitutes a congenital anomaly/birth defect

requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:

routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (specify what this includes)

elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent

treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 

social reasons and respite care in the absence of any deterioration in the patient’s 
general condition

is medically significant, i.e. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention.
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.
Life-threatening in the context of a SAE refers to a reaction in which the patient was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if more severe (see Annex IV, ICH-E2D Guideline).
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the patient or might 
require intervention to prevent one of the other outcomes listed above. Examples of such events 
are intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization or development of dependency or 
abuse (see Annex IV, ICH-E2D Guideline).
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
All AEs (serious and non-serious) are captured on the CRF; SAEs also require individual 
reporting to Drug Safety and Epidemiology (DS&E) as per section 7.2.2.
7.2.2
SAE reporting 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 20 weeks after last dose was taken or until 30 days after 

Novartis
Confidential
Page 85
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
the last study visit (whichever is later) must be reported to Novartis within 24 hours of learning 
of its occurrence. Any SAE reported until 20 weeks after last dose was taken or until End of 
study visit (whichever is later) must be recorded in the AE eCRF. SAEs beyond that date will 
only be recorded in the Novartis Drug Safety and Epidemiology database.
Any SAEs experienced after the 30 days from end of study visit or after the 20 weeks since last 
dose was taken (whichever is later), should only be reported to Novartis if the investigator 
suspects a causal relationship to study treatment. 
Recurrent episodes, complications, or progression of the initial SAE must be reported as follow-
up to the original episode, regardless of when the event occurs. This report must be submitted 
within 24 hours of the investigator receiving the follow-up information. An SAE that is 
considered completely unrelated to a previously reported one should be reported separately as 
a new event.
Information about all SAEs (either initial or follow up information) is collected and recorded 
in English on the paper Serious Adverse Event Report Form or the electronic Serious Adverse 
Event Form within the Oracle Clinical/Remote Data Capture (OC/RDC) system (where 
available). The Investigator must assess the relationship to each specific component of the study 
treatment (if the study treatment consists of several components). 
SAEs (initial and follow-up) that are recorded on the paper SAE form should be faxed within 
24 hours of awareness of the SAE to the local Novartis Drug Safety and Epidemiology 
Department.  The telephone and fax number of the contact persons in the local department of 
Drug Safety and Epidemiology, specific to the site, are listed in the investigator folder provided 
to each site.  The original copy of the SAE Report Form and the fax confirmation sheet must be 
kept with the case report form documentation at the study site. Follow-up information should 
be provided using a new paper SAE Report Form stating that this is a follow-up to a previously 
reported SAE  
SAEs (initial and follow-up) that are recorded electronically in the OC/RDC system should be 
entered, saved and e-signed within 24 hours of awareness of the SAE or changes to an existing 
SAE. These data will automatically be submitted to Novartis Drug Safety & Epidemiology 
immediately after investigator signature or 24 hours after entry, whichever occurs first. 
Follow- up information provided should describe whether the event has resolved or continues, 
if and how it was treated, whether the treatment code was broken or not and whether the patient 
continued or withdrew from study participation. Each re-occurrence, complication, or 
progression of the original event should be reported as a follow-up to that event regardless of 
when it occurs.
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert (new 
occurrence) and is thought to be related to the investigational treatment a Drug Safety and 
Epidemiology Department associate may urgently require further information from the 
investigator for Health Authority reporting. Novartis may need to issue an Investigator 
Notification (IN) to inform all investigators involved in any study with the same investigational 
treatment that this SAE has been reported. Suspected Unexpected Serious Adverse Reactions 
(SUSARs) will be collected and reported to the competent authorities and relevant ethics 

Novartis
Confidential
Page 86
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
committees in accordance with EU Guidance 2011/C 172/01 or as per national regulatory 
requirements in participating countries.
7.3
Liver safety monitoring 
To ensure patient safety and enhance reliability in determining the hepatotoxic potential of an 
investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events will be followed for pediatric subjects. The liver safety monitoring procedure is 
applicable until the subject reaches adulthood. Once a subject reaches adulthood (≥18 years of 
age) this procedure no longer needs to be followed. However, if a subject is followed up for a 
specific event with liver monitoring procedures while turning 18, follow-up should continue 
until the event stabilizes or resolves.
The following two categories of abnormalities / adverse events have to be considered during 
the course of the study:

Liver laboratory triggers, which will require repeated assessments of the abnormal 
laboratory parameter

Liver events, which will require close observation, follow-up monitoring and completion 
of the standard base liver CRF pages
Please refer to Table 14-1 in Appendix 2 for complete definitions of liver laboratory triggers 
and liver events. 
Every liver laboratory trigger or liver event as defined in Table 14-1 of Appendix 2 should be 
followed up by the investigator or designated personal at the trial site as summarized below. 
Detailed information is outlined in Table 14-2 of Appendix 2.
For the liver laboratory trigger:

Repeating the LFT within the next week to confirm elevation.
These LFT repeats should be performed using the central laboratory if possible. If this is not 
possible, then the repeats can be performed at a local laboratory to monitor the safety of the 
patient. Repeats laboratory should then be performed at central laboratory as soon as possible. 
If a liver event is subsequently reported, any local LFTs previously conducted that are 
associated with this event should be reported on the Liver CRF pages.

If the elevation is confirmed, close observation of the patient will be initiated, including 
consideration of treatment interruption if deemed appropriate.
For the liver events:

Repeating the LFT to confirm elevation as appropriate

Discontinuation of the investigational drug if appropriate

Hospitalization of the patient if appropriate

A causality assessment of the liver event via exclusion of alternative causes (e.g., disease, 
co-medications)

An investigation of the liver event which needs to be followed until resolution. 
These investigations can include serology tests, imaging and pathology assessments, 
hepatologist’s consultancy, based on investigator’s discretion. All follow-up information, and 

Novartis
Confidential
Page 87
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
the procedures performed should be recorded on appropriate CRF pages, including the liver 
event overview CRF pages.
7.4
Renal safety monitoring
To ensure patient safety and enhance reliability in determining the nephrotoxic potential of an 
investigational drug, a standardized process for identification, monitoring and evaluation of 
renal events will be followed for pediatric subjects. The renal safety monitoring procedure is 
applicable until the subject reaches adulthood. Once a subject reaches adulthood (≥18 years of 
age) this procedure no longer needs to be followed. However, if a subject is followed up for a 
specific event with renal monitoring procedures while turning 18, follow-up should continue 
until the event stabilizes or resolves. 
The following two categories of renal adverse events have to be considered during the course 
of the study:
1. Serum event:

confirmed decrease in estimated glomerular filtration rate (eGFR) of  ≥ 25% compared to 
baseline during normal hydration status as estimated by Schwartz equation :               
eGFR  (ml/min/1.73m2) = 0.413 x height (cm) / serum creatinine (mg/dl)
2. Urine event: New onset (≥1+) proteinuria, hematuria or glucosuria 

new onset of proteinuria should be confirmed by urinary protein creatinine ratio 
Every renal laboratory trigger or renal event as defined in Table 7-1 should be followed up by 
the investigator or designated personnel at the trial site as summarized below. 

Novartis
Confidential
Page 88
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Table 7-1
Specific Renal Alert Criteria and Actions
Serum Event
Estimated GFR decrease
25 – <50% compared to baseline and eGFR 
<90mL/min/1.73m2
Confirm1 25%-<50% decrease and eGFR <90mL/min/1.73m2 
after 24-48h, if possible. 
If it persists1 follow up with repeat, if possible, within 2-5 days 
and perform urinary PCR on a first morning urine collection.
Then do some frequent monitoring (preferably weekly) until 
event resolves2 or stabilizes3. 
If event does not resolve or stabilize consider consulting 
nephrologist and/or drug interruption.
Acute Kidney Injury: Serum Estimated GFR 
decrease 50 % compared to baseline
Follow up within 24-48h if possible.
If value persists, consider consulting nephrologist and/or drug 
interruption. 
Urine Event
New dipstick proteinuria ≥ 1+
Confirm1 value after 24-48h, if possible.
If dipstick value confirmed: 
a) perform1 urinary protein creatinine ratio (PCR) within 2-5 
days, if possible, on a first morning urine collection.
b) perform urine microscopy and evaluate.
If PCR > 0.2 g/g and/or urine microscopy has findings (e.g. 
crystals, casts, dysmorphic RBC, leukocytes) consider 
consulting nephrologist or drug interruption or discontinuation.
New dipstick glucosuria ≥ 1+ not due to 
diabetes
Confirm value after 24-48h, if possible.
If it persists: 
a) perform, blood glucose (fasting).
b) perform urinary protein/creatinine ratio. 
If PCR ratio > 0.2 g/g and blood glucose normal consider 
consulting nephrologist and /or drug interruption or 
discontinuation.
New dipstick hematuria ≥ 1+ not due to 
trauma or menses
Confirm1 value after 24-48h, if possible.
If it persists:
a) perform1 urinary protein creatinine ratio (PCR) within 2-5 
days if possible, on a first morning urine collection. 
b) perform urine microscopy and evaluate.
If PCR > 0.2 g/g and /or urine microscopy has findings (e.g. 
crystals, casts , dysmorphic RBC, leukocytes) consider 
consulting nephrologist or drug interruption or discontinuation.
For all renal events:
Urine samples for testing for renal monitoring, and particularly those for the PCR ratio determination, must be 
collected at the first morning void.
Document contributing factors in the CRF: co-medication, other co-morbid conditions, and additional 
diagnostic procedures performed 
1Investigator and subject may decide to perform urinary PCR already with the first repeat
Monitor patient regularly (frequency at investigator’s discretion) until either: 
2Event resolution: estimated GFR within 20% of baseline and >90mL/min/1.73m2 or PCR < 0.2 g/g (<22.6
mg/mmol). 
3Event stabilization: estimated GFR within 20% of baseline OR >90mL/min/1.73m2 or PCR < 0.3 g/g (<34 
mg/mmol).

Novartis
Confidential
Page 89
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
7.5
Pregnancy reporting 
To ensure patient safety, each pregnancy occurring while the patient is on study treatment must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications.
Pregnancy should be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the local Novartis Drug Safety and Epidemiology Department. Pregnancy 
follow-up should be recorded on the same form and should include an assessment of the 
possible relationship to the study treatment.
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form.
8
Data review and database management 
8.1
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and CRFs 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 entries on the (e)CRFs, the adherence to the protocol and to 
Good Clinical Practice, the progress of enrollment, and to ensure that study treatment is being 
stored, dispensed, and accounted for according to specifications. Key study personnel must be 
available to assist the field monitor during these visits. Continuous remote monitoring of each 
site’s data may be performed by a centralized Novartis CRA organization,   Additionally, a 
central analytics organization may analyse data & identify risks & trends for site operational 
parameters, and provide reports to Novartis Clinical Teams to assist with trial oversight.
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
patient's file. The investigator must also keep the original informed consent form signed by the 
patient (a signed copy is given to the patient).
The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the CRF entries. Novartis monitoring standards require full verification for the 
presence of informed consent, adherence to the inclusion/exclusion criteria, documentation of 
SAEs, and of data that will be used for all primary variables. Additional checks of the 
consistency of the source data with the CRFs are performed according to the study-specific 
monitoring plan. No information in source documents about the identity of the patients will be 
disclosed.

Novartis
Confidential
Page 90
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
8.2
Data collection 
Designated investigator staff will enter the data required by the protocol into the OC/RDC 
system. Designated investigator site staff will not be given access to the system until they have 
been trained. 
Automatic validation procedures within the system check for data discrepancies during and 
after data entry and, by generating appropriate error messages, allow the data to be confirmed 
or corrected online by the designated investigator site staff. The Investigator must certify that 
the data entered into the electronic Case Report Forms are complete and accurate. After 
database lock, the investigator will receive copies of the patient data for archiving at the 
investigational site. 
8.3
Database management and quality control 
Novartis staff or designee review the data entered into the CRFs by investigational staff for 
completeness and accuracy and instruct the site personnel to make any required corrections or 
additions. Queries are sent to the investigational site using an electronic data query. Designated 
investigator site staff is required to respond to the query and confirm or correct the data. 
Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system. 
Concomitant procedures, non-drug therapies and adverse events will be coded using the 
Medical dictionary for regulatory activities (MedDRA) terminology.
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated CRO).
ECG readings will be processed centrally and the results will be sent electronically to Novartis 
(or a designated CRO).
Randomization codes and data about all study drug(s) dispensed to the patient and all dosage 
changes will be tracked using an Interactive Response Technology (IRT). The system will be 
supplied by a vendor, who will also manage the database. The database will be sent 
electronically to Novartis (or a designated CRO).
Each occurrence of a code break via IRT will be reported to the clinical team and monitor.  The 
code break functionality will remain available until study shut down or upon request of Novartis. 
The occurrence of relevant protocol deviations will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 
locked and the treatment codes will be unblinded and made available for data analysis. Any 
changes to the database after that time can only be made after written agreement by Novartis 
Development management.
Subjects/custodians will use an electronic tablet device to enter PRO data (CDLQI) as indicated 
in Section 6.6.1. The data will be transmitted by the site, processed centrally by the vendor and 
the results will be sent electronically to Novartis (or designee). A tablet device Site Manual will 
be provided for instructions related to tablet data entry. There are no other source data for this 
questionnaire, the data are entered directly in the tablet. In case of a technical issue  related to 
the tablet use during a study visit with a CDLQI assessment and which cannot be resolved 

Novartis
Confidential
Page 91
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
during the visit, a paper CDLQI questionnaire can be used as an emergency back-up solution. 
Data captured via the paper questionnaire will be retrieved and managed by the PRO vendor 
and transferred to Novartis according to the vendor’s standard procedure.   
For CHAQ© the parents/custodians will complete the questionnaire. Questionnaire will be 
completed together with patient if the patient is 18 years of age or older. The completed 
questionnaire will be transmitted to the vendor. The data will then be processed centrally by the 
vendor and the results will be sent electronically to Novartis (or designee).
 
 
 
 
 
8.4
Data Monitoring Committee 
An external data monitoring committee (DMC) will be appointed to monitor the safety and 
efficacy of the study subjects.
The safety and efficacy data from the first 80 adolescent subjects will be evaluated before 
children ages 6 to < 12 years can be enrolled. Further to that, safety and efficacy data will be 
reviewed by the DMC during the study, as described in the Secukinumab DMC Charter. 
Details regarding the DMC process, responsibilities and membership will be available, as 
needed, in the relevant Secukinumab DMC charter. 
8.5
Adjudication Committee 
Not required.
9
Data analysis 
Treatment groups for analyses will include as shown in Table 9-1. 
Table 9-1
Treatment groups for analyses
Weight category
Up to Week 12
Low dose 
secukinumab
High dose 
secukinumab
Placebo
Etanercept
(max 50mg per 
dose)
<25kg
75mg
75mg
X
0.8mg/kg
25-<50kg
75mg
150mg
X
0.8mg/kg
>50kg
150mg
300mg
X
0.8mg/kg
Weight 
category
Week 12-52

Novartis
Confidential
Page 92
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Low dose 
secukinumab
High dose 
secukinumab
Placebo to Low 
dose 
secukinumab
Placebo to High 
dose 
secukinumab
Etanercept 
(max 50mg per 
dose)
<25kg
75mg
75mg
75mg
75mg
0.8mg/kg
25-<50kg
75mg
150mg
75mg
150mg
0.8mg/kg
>50kg
150mg
300mg
150mg
300mg
0.8mg/kg
Weight 
category
Entire Study
Low dose 
secukinumab
High dose 
secukinumab
Placebo
Etanercept
(max 50mg 
per dose)
Any Low 
dose 
secukinumab
Any High
dose 
secukinumab
<25kg
75mg
75mg
x
0.8mg/kg
75mg
75mg
25-<50kg
75mg
150mg
x
0.8mg/kg
75mg
150mg
>50kg
150mg
300mg
x
0.8mg/kg
150mg
300mg
Summary statistics for continuous variables will include n, mean, standard deviation, minimum, 
lower quartile, median, upper quartile, maximum. Summary statistics for discrete variables will 
be presented in contingency tables and will include absolute and relative frequencies.
If not otherwise specified, p-values will be presented as one-sided for hypothesis testings and 
as two-sided for other analysis. Two-sided 95% confidence intervals will be displayed.
9.1
Analysis sets 
The following analysis sets will be used in this trial:
Randomized set: The randomized set will be defined as all subjects who were randomized. 
Unless otherwise specified, mis-randomized subjects (mis-randomized in IRT) will be excluded 
from the randomized set. (Mis-randomized subjects are defined as cases where IRT contacts
were made by the site either prematurely or inappropriately prior to confirmation of the 
subject’s final randomization eligibility and double-blind treatment was not administered to the 
subject).
Full analysis set (FAS): The FAS will be comprised of all subjects from the randomized set to 
whom study treatment has been assigned. Following the intent-to-treat principle, subjects will
be analyzed according to the treatment assigned to at randomization. If the actual stratum is 
different to the assigned stratum in IRT, the actual stratum will be used in analyses.
Safety set: The safety set includes all subjects who took at least one dose of study treatment
during the treatment epoch. Subjects will be analyzed according to treatment received.
9.2
Subject demographics and other baseline characteristics 
Demographics and baseline characteristics
Summary statistics will be presented for continuous demographic and baseline characteristics
variables for each treatment group and for all subjects in the randomized set. The number and
percentage of subjects in each category will be presented for categorical variables for each
treatment group and all subjects.

Novartis
Confidential
Page 93
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Medical history
Any condition entered as medical history or current medical conditions at baseline will be coded 
using the MedDRA dictionary. They will be summarized by system organ class and preferred 
term of the MedDRA dictionary. Summaries for psoriasis specific medical history will be 
provided as well.
9.3
Treatments 
Study treatment
The analysis of study treatment data will be based on the safety set.
The number of active and placebo injections will be summarized by treatment group by means 
of contingency tables. The duration of exposure to study treatment will also be summarized by 
treatment group. In addition, the number of subjects with exposure of at least certain thresholds 
(e.g. any exposure, ≥ 1 week, ≥ 2 weeks, ≥ 3 weeks, ≥ 4 weeks, ≥ 8 weeks, etc.) will be displayed.
Prior and concomitant treatment
Prior and concomitant treatments will be summarized by treatment group in separate tables. 
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 epoch.
Treatments will be presented in alphabetical order, by Anatomical Therapeutic Classification 
(ATC) codes and grouped by anatomical main group. Tables will also show the overall number 
and percentage of subjects receiving at least one treatment of a particular ATC code and at least 
one treatment in a particular anatomical main group. Psoriasis specific prior treatments will be 
presented as well.
In addition, non-drug therapies will be summarized.
9.4
Analysis of the primary variable(s)
This section will detail the statistical analysis of the primary endpoints. Details of the hypothesis
testing strategy including primary and secondary endpoints to handle multiplicity are provided 
in Section 9.5.1.
9.4.1
Variable(s)
The co-primary efficacy variables are PASI 75 response at Week 12 and IGA 0 or 1 response
at Week 12. The analysis of the co-primary variables will be based on the FAS.
9.4.2
Statistical model, hypothesis, and method of analysis
The statistical hypotheses for PASI 75 response at Week 12 and IGA 0 or 1 response at Week 
12 being tested is that secukinumab (low or high dose) is not superior to placebo in the 
proportion of subjects with PASI 75 and IGA 0 or 1 response at Week 12.

Novartis
Confidential
Page 94
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Let  denote the proportion of PASI 75 responders at Week 12 for treatment group j and 
denote the proportion of IGA 0 or 1 responders at Week 12 for treatment group j, j=0, 1, 2,
where

0 corresponds to placebo,

1 corresponds to secukinumab low dose,

2 corresponds to secukinumab high dose.
The following hypotheses will be tested
H
: p
 – p ≤0 versusH
: p
 – p > 0,
H: p – p ≤0 versus H: p – p > 0,
H: r
 – r ≤0 versus H: r
 – r > 0,
H: r – r ≤0 versus H: r – r > 0.
In other words:
H
: Secukinumab low dose is not superior to placebo with respect to PASI 75 response at
Week 12
H: secukinumab high dose is not superior to placebo with respect to PASI 75 response at
Week 12
H: secukinumab low dose is not superior to placebo with respect to IGA 0 or 1 response at 
Week 12
H: secukinumab high dose is not superior to placebo with respect to IGA 0 or 1 response at 
Week 12
The primary analysis method will be the exact logistic regression with all 4 treatment groups 
(including etanercept); baseline bodyweight, age stratum and baseline PASI score as 
explanatory variables. Odds ratios will be computed for comparisons of secukinumab dose
regimens versus placebo utilizing the logistic regression model fitted. Confidence intervals for 
risk difference will be derived based on the exact method. 
9.4.3
Handling of missing values/censoring/discontinuations
The following imputation methods will apply to the missing data for analysis up to Week 52 
including primary W12 analysis:

Response variables based on PASI score and IGA mod 2011 categories will be imputed 
with multiple imputations (MI) method as primary imputation method. Multiple 
imputation (MI) is a simulation based approach where missing values are replaced by 
multiple Bayesian draws from the conditional distribution of missing data given the 
observed data and covariates, creating multiple completed data sets. These completed 
data sets can then be analyzed using standard methods. Within this analysis the PASI 
score or IGA mod 2011 categories will be imputed and response variables will be 
derived based on the imputed scores. In the multiple imputation analysis the response 
status will be imputed based on the individual treatment arm information.  

Novartis
Confidential
Page 95
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

(Pure) Non-responder imputation will be used as a sensitivity method: Missing values
with respect to response variables based on PASI score and IGA mod 2011 categories 
will be imputed with non-response regardless to the reason for missing data. Subjects 
with missing baseline or those with all post-baseline missing will be imputed with non-
response.
The following imputation methods will apply to the missing data for analysis of the long term 
 
 
9.4.4
Supportive analyses 
Sensitivity analyses will be performed as follows:

PASI 75 and IGA 0 or 1 response at Week 12 will be evaluated using an exact logistic 
regression model with treatment group, baseline bodyweight stratum, age stratum and 
baseline PASI as effects with pure non-responder imputations for missing values. 

Primary analysis will also be evaluated on the subset of adolescents
9.5
Analysis of secondary variables
9.5.1
Efficacy variables 
The secondary variable in testing strategy is the PASI 90 response of subjects with severe 
chronic plaque-type psoriasis at Week 12 (for superiority comparison of secukinumab doses 
versus placebo). The PASI 90 response of subjects with severe chronic plaque-type psoriasis at 
Week 12 will be analyzed in the same way as the primary variables. 
The secondary efficacy variable PASI 90 at Week 12, will be analyzed using the FAS unless 
otherwise specified.
Testing strategy
The family-wise type I error will be set to α=2.5% (one-sided). The graphical approach of Bretz 
(Bretz et al 2009) for sequentially rejective testing procedures is used to illustrate the 
hierarchical testing strategy. The procedure allows the type I error rate associated with a rejected 
hypothesis to be reallocated according to a set of pre-specified rules. The hypotheses associated 
to the primary and secondary variables are as below.
Co-primary variables: 
H1 to H4 (see Section 9.4.2)
Secondary variable:
H5: secukinumab low dose is not superior to placebo with respect to PASI 90 response at
Week 12

Novartis
Confidential
Page 96
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
H6: secukinumab high dose is not superior to placebo with respect to PASI 90 response at
Week 12
The graphical approach of (Bretz 2009) for sequentially rejective testing procedures is used to 
illustrate the testing strategy in Figure 9-1.
Figure 9-1
Testing strategy
One-sided p-values will be derived. The family-wise error will be set to α=2.5% (one-sided). 
The hypotheses are mapped into two sets (H1, H3 and H5) or (H2, H4 and H6) such that 
hypotheses within a set correspond to the same secukinumab (AIN457) dose regimen. In 
essence, the type-I-error probability will be equally split for both sets of hypotheses and within 
each set the hypothesis are tested sequentially as follows:
Within each pair, of hypotheses (H1 or H3) and (H2 or H4), each hypothesis is tested at α/2 (one-
sided). Only if both hypotheses of a pair are rejected, the testing sequence will continue.
In the next step of the sequence, the null hypotheses corresponding to the PASI 90 comparison 
of secukinumab (AIN457) versus placebo is tested. H5 and H6 will be tested at α/2 (one-sided).
If all hypotheses within a set referring to a secukinumab dose regimen have been rejected, i.e., 
either (H1, H3 and H5) or (H2, H4 and H6), the corresponding type I error probability can be 
passed on to the other set of hypotheses, and if needed, hypotheses can be retested at a higher 
significance level.
9.5.2
Other Efficacy variables
PASI 75, PASI 90, PASI 100 and IGA 0 or 1 response over time
Summary statistics for PASI 75, PASI 90, PASI 100 and IGA 0 or 1 response by visit will be 
presented in contingency tables and will include absolute and relative frequencies. Confidence 
intervals for response rates will be derived as well based on the exact method.  
For PASI 75, PASI 90, PASI 100 and IGA 0 or 1 response at each visit, each secukinumab dose 
regimen will be compared to placebo (up to Week 12 only) 
by exact logistic 

Novartis
Confidential
Page 97
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
regression with treatment group, baseline bodyweight stratum, age stratum and baseline PASI 
score as explanatory variables.
For PASI 75, PASI 90 and IGA 0 or 1 response the placebo-adjusted response rates including 
95% confidence interval (exact method) will be derived by visit up to Week 12. Similarly, 
estimates for the difference in response rates for secukinumab minus
 will be derived 
over time.
Figures will also be provided. 
PASI score over time
Summary statistics will be provided for absolute PASI scores as well as for percent change from 
baseline by visit and treatment group. Figures will also be provided.
IGA mod 2011 score over time
Summary statistics for the IGA mod 2011 score over time will be presented by visit and
treatment group in contingency tables.
 
 
 
 
 
9.5.3
Safety variables 
All safety evaluations will be performed on the Safety set.
Adverse events
Treatment emergent adverse events (events started after the first dose of study treatment and 
within 84 days after the last study treatment, or events present prior to the first dose of study 
treatment but increased in severity based on preferred term within 84 days after the last study 

Novartis
Confidential
Page 98
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
treatment) will be summarized. Only primary paths within MedDRA will be considered for 
adverse event reporting. 
AEs will be summarized by presenting, for each treatment group, the number and percentage
of subjects having any AE, having an AE in each primary system organ class and having each
individual AE (preferred term). Summaries will also be presented for AEs by severity and for
study treatment related AEs. If a subject reported more than one adverse event with the same
preferred term, the adverse event with the greatest severity will be presented. If a subject
reported more than one adverse event within the same primary system organ class, the subject
will be counted only once with the greatest severity at the system organ class level, where
applicable.
These summaries will be presented separately for induction period and entire treatment period.
Confidence intervals for relative frequencies will be derived as well according to the exact 
method.
Separate summaries will be provided for death, serious adverse event, other significant adverse 
events leading to discontinuation and adverse events leading to dose adjustment (including 
study treatment discontinuation).
A graphical display of relative frequencies within system organ classes will be presented.
In supplementary analyses, for selected adverse events exposure (or observation) time adjusted 
analyses in terms of incidence rate will be provided for the entire treatment period.
Laboratory data
The summary of laboratory evaluations will be presented for three groups of laboratory tests
(hematology, serum chemistry and urinalysis). Descriptive summary statistics for the change
from baseline to each study visit will be presented. These descriptive summaries will be
presented by test group, laboratory test and treatment group. Change from baseline will only be 
summarized for subjects with both baseline and post baseline.
For each parameter, the maximum change from baseline within each study period will be
analyzed analogously.
In addition, shift tables will be provided for all lab parameters to compare a subject’s baseline 
laboratory evaluation relative to the most extreme post-baseline laboratory test value. Shift 
tables with respect to Common Toxicity grade Criteria (CTC) and normal ranges will be 
provided by laboratory test and treatment group. 
Incidence rates of notable abnormalities (see Appendix 1) will be presented.
Vital signs
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

Novartis
Confidential
Page 99
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
by vital sign and treatment group. Change from baseline will only be summarized for subjects
with both baseline and post-baseline values.
All information collected will be listed by patient and abnormal values (see Appendix 1) will
be flagged.
ECG
Summary statistics will be presented for ECG variables by visit and treatment group.
Growth and weight gain
Growth and weight gain will be summarized descriptively.
9.5.4
Resource utilization 
Not Applicable.
9.5.5
Health-related Quality of Life
Children’s Dermatology Quality of Life Index (CDLQI)
The CDLQI measures functional disability of subjects with dermatological disorders that are
less than 18 years of age and had been utilized as a relevant clinical measure in atopic dermatitis, 
as well as other dermatitis clinical trials. The CDLQI is a simple, validated, self-administered
10-item questionnaire. The instrument contains six functional scales (i.e., symptoms and feeling, 
leisure, school or holidays, personal relationships, sleep and treatment). The questions are based 
on the preceding week to permit accurate recall. For the CDLQI, each question will be answered 
on a 4-point Likert scale scored from 0 to 3. Seven scores will be derived from the CDLQI: 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 each of the seven scores the percentage change from baseline will be derived. Summary
statistics will be provided for absolute values as well as for the percentage change by visit and
treatment group in contingency tables. The CDLQI 0 or 1 achievement will be analyzed by visit 
and treatment group.
Childhood Health Assessment Questionnaire (CHAQ©)
Changes in health-related quality of life for subjects with history of psoriatic arthritis will be 
measured using CHAQ©.
Descriptive statistics will be used to summarize patient responses on the CHAQ© Questionnaire 
by treatment, total score and by domain. 
For parent’s or patients global assessment of patient’s overall well-being and of pain (VAS 
score) summary statistics for the observed values and the change/percent change from baseline 
will be provided by visit.

Novartis
Confidential
Page 100
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
9.5.8
Biomarkers 
Not applicable
9.5.9
PK/PD 
Not applicable
9.6
Interim analyses 
An interim analysis will be conducted once at least 80 adolescents complete 24 weeks of 
treatment. The key efficacy and safety data will be reviewed by the DMC to ensure that no 
serious efficacy or safety concerns are observed with the study treatments. Enrollment of the 
pediatric population aged 6 to less than 12 years will begin only when the safety and efficacy 
evaluation is satisfactory based on the DMC’s recommendation. 
An additional interim analysis, will be conducted once sufficient safety 
 
data have been collected. This analysis, aligned with the efficacy extrapolation principle, is
expected to provide the basis for a submission package to health authorities (HA), with the 
intent to allow earlier availability of secukinumab to pediatric patients, in countries which 

Novartis
Confidential
Page 101
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
accept a submission of clinical data with use of extrapolation methodology. This analysis may
be performed before all subjects have reached the primary endpoint. It is expected that data 
from at least approximately 100 patient years of secukinumab treatment will be included in this 
analysis.
This interim analysis will consist of a Bayesian full extrapolation approach using adult efficacy 
data along with available pediatric 
, safety, and efficacy data to support a submission to 
Health Authorities for plaque type psoriasis in a pediatric population of ages 6 to 18 years. This 
analysis will use a Bayesian meta-analytic-prediction (MAP) approach (Neuenschwander 2010) 
to demonstrate the consistency of efficacy responses between adults and pediatric population. 
The MAP approach is based on a Bayesian random-effects meta-analysis and provides a 
prediction of adult efficacy response rates in a new trial. The prediction will take into account 
uncertainty due to sample size and due to between-trial heterogeneity.
The observed pediatric response rates at Week 12 for PASI 75, PASI 90 and IGA 0/1 in this 
study will be checked for consistency with predicted response rates based on Novartis adult 
studies (CAIN457A2302, CAIN457A2303, CAIN457A2308 and CAIN457A2309) using a 
predictive check method.
Since the planned hypothesis will not be tested at this interim, the type-I error probability will 
not be adjusted for this interim and full alpha will be kept for the hypothesis test in the final 
analysis. 
A full analysis of all data collected up to Week 24, including primary endpoint at Week 12 will 
be performed after all subjects have completed either the Week 24 visit or the premature 
treatment discontinuation visit (i.e., EOI (Week 12 visit) for subjects discontinuing during 
induction epoch or EOM (Week 52 visit) for subjects discontinuing during the maintenance 
epoch visit. Data from subjects who have completed the treatment-free follow-up visits up to 
this time point (after premature discontinuation from the induction or the maintenance epoch) 
will also be included in this analysis.
Another full analysis of all data collected up to Week 52, including primary endpoint at Week 
12 will be performed after all subjects have completed either the Week 52 visit or the premature 
treatment discontinuation visit (i.e., EOI (Week 12 visit) for subjects discontinuing during 
induction epoch or EOM (Week 52 visit) for subjects discontinuing during the maintenance 
epoch visit. Data from subjects who have completed the treatment-free follow-up visits up to 
this time point (after premature discontinuation from the induction or the maintenance epoch) 
will also be included in this analysis. 
Efficacy and safety data collected during the extension treatment epoch (until the end of study) 
may be reported yearly in separate reports.
9.7
Sample size calculation
Approximately 160 pediatric subjects from 6 to less than 18 years of age, with 2 subgroups: 6 
to less than 12 years of age, and 12 to less than 18 years of age.  
Stratification is planned for age (<12 years, >=12 years) and weight (<25kg, 25-<50kg 
and >50kg). It will be targeted to have at least 30 subjects in the <12 years subgroup at a 
minimum. Enrollment of children aged 6 to less than 12 years will proceed after efficacy and 

Novartis
Confidential
Page 102
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
safety data for approximately 80 (approximately 40 treated with AIN) enrolled adolescents 
(aged 12 to less than 18 years) treated for 28 weeks have been reviewed and deemed satisfactory 
by a Data Monitoring Committee.
Since two secukinumab dose regimens will be tested versus placebo with respect to the co-
primary endpoints (PASI 75 response and IGA 0 or 1 response at Week 12), the type-I-error
will be split to 1.25% one-sided for each comparison. With 40 subjects per group and assuming 
a response rate of 10% for PASI 75 response and IGA 0 or 1 response in the placebo group, the 
power to show a response rate of 65% for PASI 75 response and 45% for IGA 0 response in the 
secukinumab groups based on Fisher’s exact test (nQuery Advisor 7.0, two group Fisher’s-exact 
test of equal proportions) is approximately 99% for PASI 75 response and approximately 88% 
for IGA mod 2011 0 or 1 response. For the secondary endpoint of PASI 90 response at week 
12, assuming a response rate of 8% in the placebo group, the power to show a significant 
difference between a secukinumab dose and placebo, assuming a response rate of 39% in the 
secukinumab groups based on Fisher’s exact test (nQuery Advisor 7.0, two group Fisher’s-exact 
test of equal proportions) is approximately 82% for PASI 90 response. The assumed response 
rates for secukinumab are based on the confirmatory efficacy in severe patients in the adult 
phase III program. At Week 12, PASI 75 response rates of 11% and PASI 90 response rates of 
7% have been reported in the placebo group in Paller et al (2008) for children and adolescents 
aged 4-17 years.  
10
Ethical considerations 
10.1
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented and reported in accordance with the 
ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 
regulations (including European Directive 2001/20/EC, US CFR 21, and Japanese Ministry of 
Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of 
Helsinki.
10.2
Informed consent procedures 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if incapable of doing 
so, after such consent has been provided by a legally acceptable representative(s) of the patient. 
In cases where the patient’s representative gives consent, the patient should be informed about 
the study to the extent possible given his/her understanding. If the patient is capable of doing 
so, he/she should indicate assent by personally signing and dating the written informed consent 
document or a separate assent form. Informed consent must be obtained before conducting any 
study-specific procedures (i.e. all of the procedures described in the protocol). The process of 
obtaining informed consent should be documented in the patient source documents. 
Novartis will provide to investigators in a separate document a proposed informed consent form 
that complies with the ICH GCP guideline and regulatory requirements and is considered 
appropriate for this study. Any changes to the proposed consent form suggested by the 

Novartis
Confidential
Page 103
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
investigator must be agreed to by Novartis before submission to the IRB/ IEC, and a copy of 
the approved version must be provided to the Novartis monitor after IRB/IEC approval.
In pediatric patients (< 18 years of age) parental permission and, whenever possible, child assent 
is needed instead of the procedure for informed consent used for research involving adults. In 
general, one or both parents or a guardian must be provided with the information ordinarily 
required for informed consent, so that they may decide whether to allow the child to participate, 
and children capable of assent must also express their willingness to participate. These forms 
will be submitted for IRB/IEC/REB approval.
Women of child bearing potential should be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirement for the 
duration of the study. If there is any question that the patient will not reliably comply, they 
should not be entered in the study.
 
 
 
 
In the event that Novartis wants to perform testing on the samples that are not described in this 
protocol, additional Institutional Review Board and/or Ethics Committee approval will be 
obtained.
During the COVID-19 pandemic or similar major health care disruption that may challenge the 
ability to obtain a standard written informed consent due to limitations that prevent an on-site 
visit, the Investigator may conduct the informed consent discussion remotely (e.g. telephone, 
videoconference). Guidance issued by local regulatory bodies on this aspect prevails and must 
be implemented and appropriately documented (e.g. the presence of an impartial witness, 
sign/dating separate ICFs or assent forms by trial subject/ guardian and person obtaining 
informed consent, etc).
In case Home Nursing (other than study treatment administration) is implemented during the 
COVID-19 pandemic or similar major health care disruption, a separate Home Nursing 
informed consent document must be used in addition to the main ICF.
10.3
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution should obtain approval/favorable opinion 
from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial 
protocol, written informed consent form, consent form updates, subject recruitment procedures 
(e.g., advertisements) and any other written information to be provided to 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
Confidential
Page 104
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Novartis, IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site 
is requested by a regulatory authority, the investigator must inform Novartis immediately that 
this request has been made.
10.4
Publication of study protocol and results 
Novartis assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and 
finalization of the study report the results of this trial will be either submitted for publication 
and/or posted in a publicly accessible database of clinical trial results.
11
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances should an 
investigator collect additional data or conduct any additional procedures for any research related 
purpose involving any investigational drugs.
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be implemented. 
All significant protocol deviations will be recorded and reported in the CSR.
11.1
Protocol Amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, Health Authorities where required, and the IRB/IEC prior to 
implementation. Only amendments that are intended to eliminate an apparent immediate hazard 
to patients may be implemented immediately provided the Health Authorities are subsequently 
notified by protocol amendment and the reviewing IRB/IEC is notified. Notwithstanding the 
need for approval of formal protocol amendments, the investigator is expected to take any 
immediate action required for the safety of any patient included in this study, even if this action 
represents a deviation from the protocol. In such cases, the reporting requirements identified in 
Section 7 Safety Monitoring should be followed.
12
References
References are available upon request
Augustin M, Reich K, Glaeske G et al (2010). Co-morbidity and Age-related Prevalence of 
Psoriasis: Analysis of Health Insurance Data in Germany, Acta Derm Venereol 2010; 90: 
147–151.
Beattie PE and Lewis-Jones MS (2006). A comparative study of impairment of quality of life 
in children with skin disease and children with other chronic childhood diseases; Br J 
Dermatol 2006 Jul; 155(1), 145–151.
Benoit S, Hamm H, (2007) Childhood psoriasis. Clin Dermatol , 25, 555–562

Novartis
Confidential
Page 105
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
 
Bretz F, Maurer W, Brannath W, Posch M (2009). A graphical approach to sequentially 
rejective multiple test procedures. Statist. Med.; 28: 586-604.
Burden AD (1999); Management of psoriasis in childhood; CED, 24, 341–345.
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 
393document. London, UK.
Comans-Bitter WM et al (1997); Immunophenotyping of blood lymphocytes in childhood; J 
Pediatr Volume 130, Number 3, 388. 
De Jager MEA et al (2009); Epidemiology and prescribed treatments in childhood psoriasis: 
A survey among medical professionals, Journal of Dermatological Treatment. 2009; 20:254–
258.
De Jager MEA, De Jong EM, Van de Kerkhof PCM et al (2010); Efficacy and safety of 
treatments for childhood psoriasis: A systematic literature review, J Am Acad Dermatol 2010; 
62:1013-30.
Doherty SD, Van Voohees A, Lebwohl MG (2008) National psoriasis foundation consensus 
statement on screening for latent tuberculosis infection in patients with psoriasis treated with 
systemic and biologic agents. J. Am. Acad. Dermatol; 59 (2): 209 – 217.
Farber EM, Nall ML, (1999); Childhood Psoriasis; Cutis 1999 Nov; 64(5): 309 -14.
Feld LG and Corey H (2007) Hypertension in childhood. Pediatr in Rev.; 28: 283-98.
Fredriksson T, Pettersson U (1978) Severe psoriasis – oral therapy with a new retinoid. 
Dermatologica; 157:238–44.
Gelfand JM, Weinstein R, Porter SB et al (2005). Prevalence and Treatment of Psoriasis in the 
United Kingdom: A Population based Study; Arch Dermatol 2005; 141:1537-1541
Gottlieb A, Griffiths CEM, Ho VC, et al (2005) Efficacy and tolerability of oral pimecrolimus 
in the treatment of moderate to severe chronic plaque type psoriasis: a double-blind, 
multicenter, randomized dose-finding trial. Br J Dermatol; 152:1219-27.
Griffiths CEM, Barker JNWN (2007) Pathogenesis and clinical features of psoriasis. Lancet; 
370: 263 – 271.
Kimball AB et al (2012) Risks of developing psychiatric disorders in pediatric patients with 
psoriasis, J Am Acad Dermatol 2012; 67:651-7.
Kokubu T, et al (2008); Immunolocalization of IL-17A, IL-17B, and Their Receptors in
Chondrocytes during Fracture Healing; J Histochem Cytochem. Volume 56(2): 89–95.
Landells I, Paller AS, Pariser D et al (2010); Efficacy and safety of etanercept in children and 
adolescents aged ≥8 years with severe plaque psoriasis; Eur J Dermatol 2010; 20 (3): 323-8.
Langley RG, Elewski BE, Lebwohl M et al (2014) Secukinumab in plaque psoriasis-Results 
of two phase three trials. N Engl J Med. Jul 24; 371(4): 326-38
Lewis-Jones MS, Finlay AY. The Children's Dermatology Life Quality Index (CDLQI): 
initial validation and practical use. Br J Dermatol 1995; 132: 942-949.

Novartis
Confidential
Page 106
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Luu M, and Cordoro KM (2013). The Evolving Role of Biologics in the Treatment of 
Pediatric Psoriasis. Skin Therapy Lett. 2013 Feb; 18(2) 1 - 7
Manuel O, Kumar D (2008) QuantiFERON-TB Gold assay for the diagnosis of latent 
tuberculosis infection. Expert Rev Diagn; 8(3): 247-56.
Neuenschwander B, Capkun-Niggli G, Branson M, Spiegelhalter DJ (2010) Summarizing 
historical information on controls in clinical trials. Clin Trials; 7(1): 5–18.
Newcombe RG (1998) Two-sided confidence intervals for the single proportion: comparison 
of seven methods. Statist. Med.; 17: 857-872.
Paller AS et al (2008) Etanercept Treatment for Children and Adolescents with Plaque 
Psoriasis. N Engl J Med 2008; 358:241-51.
Paller AS et al (2013) Association of Pediatric Psoriasis Severity with Excess and Central 
Adiposity JAMA Dermatol. 2013; 149(2):166-176.
Pariser DM, Bagel J, Gelfand JM et al (2007) National Psoriasis Foundation Clinical 
Consensus on Disease Severity. Arch Dermatol.; 143: 239-242.
Ruperto et al (2001) Cross-cultural adaptation and psychometric evaluation of the Childhood 
Health Assessment Questionnaire (CHAQ©) and the Child Health Questionnaire (CHQ) in 32 
countries. Review of the general methodology. Clin Exp Rheumatol; 19 (Suppl 23):S1-S9.
Schwartz GJ, Munoz A, Schnei MF et al (2009). New equations to estimate GFR in children 
with CKD. J Am Soc Nephrol ; 20:629-637.
Silverberg NB (2009); Pediatric psoriasis; Ther Clin Risk Manag 2009;5 849–856.
.
Singh et al (1994) Measurement of Health Status in children with juvenile Rheumatoid 
Arthritis. Arthritis and Rheum; Vol 37, 12:1761-1769.
Tollefson et al (2010) Incidence of psoriasis in children: a population based study. J Am Acad 
Dermatol. 2010 Jun; 62(6):979-87.
Van Weelden H, Baart de la faille H, Young E and Van der leun J C (1990); Comparison of 
Narrow-band UV-B Phototherapy and PUVA Photo chemotherapy in the Treatment of 
Psoriasis; Acta Derm Ycnereol (Stockh) 1990; 70: 212-215.
Weisman S, Pollack CR, Gottschalk RW (2003) Psoriasis disease severity measures: 
comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat; 14: 158-165.
Wu JJ et al (2011) Low prevalence of psoriasis among children and adolescents in a large 
multiethnic cohort in southern California. J Am Acad Dermatol 2011; 65: 957-64.
Zappel K, Sterry W, Blume-Peytavi U (2004) Therapy options for psoriasis in childhood and 
adolescence. JDDG; 2004. 2:329 – 342.

Novartis
Confidential
Page 107
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
13
Appendix 1: Clinically notable laboratory values and vital 
signs 
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests and vital sign parameters. 
Unless otherwise indicated (e.g. liver and renal safety monitoring procedure, Section 7.3 and 
Section 7.4 respectively) no specific action is pre-defined within this protocol to respond to 
specific abnormal laboratory values, as it will be decided by the investigator whether & which 
specific action needs to be taken to respond to any abnormal values, taking into account the 
overall status of the subject.
Laboratory values
Newly occurring selected notable laboratory abnormalities in pediatric patients at the time of 
the assessment:
Biochemistry and Urinalysis

Alanine transaminase (ALT)(SGPT): 
Upper Limit of Normal (ULN)
≥3 x ULN
≥5 x ULN
≥8 x ULN
≥10 x ULN

Aspartate transaminase (AST) (SGOT): 

>ULN

≥3 x ULN
≥5 x ULN
≥8 x ULN
≥10 x ULN

Total Bilirubin (TBL)
>ULN, 
≥1.5xULN, 
≥ 2xULN

ALP 
>ULN
≥1.5xULN, 
≥2xULN, 
≥3x ULN 
≥5xULN

ALT and/or AST >3x-, 5x-, 10x ULN accompanied by TBL >2xULN

ALT or AST >3x ULN and TBL >2x-, and ALP >2 x ULN.

ALP >3x ULN and TBL >2x ULN

Novartis
Confidential
Page 108
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

Gamma-Glutamyltransferase (GGT): 
>ULN
≥3 x ULN
≥5 x ULN
Renal function
For the parameters related to renal function (e.g. eGFR according to Schwartz, urine protein, 
urine blood, glucosuria) the instructions provided in the renal safety monitoring section must 
be followed (Section 7.4). 
Hematology

Hemoglobin: ≥ 20 g/L decrease from baseline, 
or < 85 g/L for < 16 years of age
< 100 g/L for ≥ 16 years of age

Absolute neutrophils:
Grade 1: <LLN – 1.5 x 10E9/L
Grade 2: <1.5 – 1.0 x 10E9/L
Grade 3: <1.0 – 0.5 x 10E9/L
Grade 4: <0.5 x 10E9/L

Criteria based on CTC grades for platelet count:
Grade 1: <LLN – 75.0 x 10E9/L
Grade 2: <75.0 – 50.0 x 10E9/L
Grade 3: <50.0 – 25.0 x 10E9/L
Grade 4: <25.0 x 10E9/L

Criteria based on CTC grades for WBC:
G1:<LLN – 3.0 x10E9/L
G2:<3.0 – 2.0 x10E9/L
G3:<2.0 – 1.0 x10E9/L
G4: <1.0 x10E9/L

Absolute Lymphocytes: < LLN 

Absolute Eosinophils: ≥ 1.1 x ULN

Absolute Eosinophils: ≥0.45 x 109/L 
Vital Signs
The following notable criteria will be used for systolic and diastolic BP and pulse. The age 
indicated is the age at the time of the visit.

Novartis
Confidential
Page 109
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Table 13-1
Notable Pediatric ranges for vital signs*
Age
Systolic BP
Diastolic BP
Pulse (BPM)
6 yrs
91-125
53-84
60-130
7 yrs
92-126
55-86
60-130
8 yrs
94-127
56-88
60-130
9 yrs
95-129
57-89
60-110
10 yrs
97-130
58-90
60-110
11 yrs
99-132
59-90
60-110
12 yrs
101-135
59-91
60-110
13 yrs
104-137
60-91
60-110
14 yrs
106-140
60-92
60-110
15 yrs
107-142
61-93
60-110
16 yrs
108-145
63-94
60-110
17 yrs
108-147
64-97
60-100
18 yrs
-
-
60-100
Source: http://www.who.int/childgrowth/standards
*values outside the provided ranges are considered notable
The Recommendations for the dimensions of Blood Pressure Cuff Bladders are noted in the 
following table.
Table 13-2
Recommended Dimensions for Blood Pressure Cuff Bladders
`
Width [cm]
Length [cm]
Maximum Arm 
Circumference [cm]*
Newborn
4
8
10
Infant
6
12
15
Child
9
18
22
Small adult
10
24
26
Adult
13
30
34
Large adult
16
38
44
*calculated so that the bladder can encircle even the largest arm by at least 80%
Source: Feld and Corey H (2007): Hypertension in childhood, Pediatric in Review 28: 283-98

Novartis
Confidential
Page 110
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
14
Appendix 2: Liver event and Laboratory trigger Definitions 
and Follow-up Requirements
Table 14-1
Liver Event and Laboratory Trigger Definitions
Definition/ threshold
LIVER LABORATORY TRIGGERS
3 x ULN < ALT / AST 5 x ULN
1.5 x ULN < TBL 2 x ULN
LIVER EVENTS
ALT or AST > 5 × ULN
ALP > 2 × ULN (in the absence of known bone pathology)
TBL > 2 × ULN (in the absence of known Gilbert syndrome)
ALT or AST > 3 × ULN and INR > 1.5 
Potential Hy’s Law cases (defined as ALT or AST > 3 × ULN and 
TBL > 2 × ULN [mainly conjugated fraction] without notable 
increase in ALP to > 2 × ULN)
Any clinical event of jaundice (or equivalent term)
ALT or AST > 3 × ULN accompanied by (general) malaise, fatigue, 
abdominal pain, nausea, or vomiting, or rash with eosinophilia
Any adverse event potentially indicative of a liver toxicity * 
Table 14-2
Follow Up Requirements for Liver Events and Laboratory Triggers
Criteria
Actions required
Follow-up monitoring
Potential Hy’s Law 
casea

Discontinue the study drug immediately

Hospitalize, if clinically appropriate

Establish causality

Complete liver CRF
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion)
ALT or AST
> 8 × ULN

Discontinue the study drug immediately

Hospitalize if clinically appropriate

Establish causality

Complete liver CRF
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion)
> 3 × ULN and 
INR > 1.5

Discontinue the study drug immediately

Hospitalize, if clinically appropriate

Establish causality

Complete liver CRF
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion)
> 5 to ≤ 8 × ULN

Repeat LFT within 48 hours

If elevation persists, continue follow-up 
monitoring

If elevation persists for more than 2 
weeks, discontinue the study drug

Establish causality

Complete liver CRF
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion)

Novartis
Confidential
Page 111
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
Criteria
Actions required
Follow-up monitoring
> 3 × ULN 
accompanied by 
symptomsb

Discontinue the study drug immediately

Hospitalize if clinically appropriate

Establish causality

Complete liver CRF
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion)
> 3 to ≤ 5 × ULN 
(subject is 
asymptomatic)

Repeat LFT within the next week

If elevation is confirmed, initiate close 
observation of the subject
Investigator discretion
Monitor LFT within 1 to 4 weeks 
ALP (isolated)
> 2 × ULN (in the 
absence of known 
bone pathology)

Repeat LFT within 48 hours

If elevation persists, establish causality

Complete liver CRF
Investigator discretion
Monitor LFT within 1 to 4 weeks or at 
next visit
TBL (isolated)
> 2 × ULN (in the 
absence of known 
Gilbert syndrome)

Repeat LFT within 48 hours

If elevation persists, discontinue the 
study drug immediately

Hospitalize if clinically appropriate

Establish causality

Complete liver CRF
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion)
Test for hemolysis (e.g., reticulocytes, 
haptoglobin, unconjugated [indirect] 
bilirubin)
> 1.5 to ≤ 2 × ULN
(subject is 
asymptomatic)

Repeat LFT within the next week

If elevation is confirmed, initiate close 
observation of the subject 
Investigator discretion
Monitor LFT within 1 to 4 weeks or at 
next visit
Jaundice

Discontinue the study drug immediately

Hospitalize the subject

Establish causality

Complete liver CRF
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion)
Any AE potentially 
indicative of a liver 
toxicity*

Consider study drug interruption or 
discontinuation 

Hospitalization if clinically appropriate

Establish causality

Complete liver CRF
Investigator discretion
*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
aElevated ALT/AST > 3 × ULN and TBL > 2 × ULN but without notable increase in ALP to > 2 × ULN
b(General) malaise, fatigue, abdominal pain, nausea, or vomiting, or rash with eosinophilia 
cResolution is defined as an outcome of one of the following: (1) return to baseline values, (2) stable 
values at three subsequent monitoring visits at least 2 weeks apart, (3) remain at elevated level after a 
maximum of 6 months, (4) liver transplantation, and (5) death.

Novartis
Confidential
Page 112
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

Novartis
Confidential
Page 113
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
16
Appendix 4: Weight and recommended blood volumes 
European Medicines Agency (EMA) recommendations for trial related blood loss (including 
any losses in the maneuver) in pediatric populations are that no more than 3% of total blood 
volume should be taken during a four week period and not more than 1% of total blood volume 
at a single time-point. At a total blood volume estimated at 80 to 90ml per kilogram (kg) body 
weight, this equates to 2.4mL to 2.7mL blood per kg body weight during a four week period, 
or 0.8mL to 0.9mL blood per kg at any one time. 
These recommended volumes must not be exceeded for any patient. Please use the information 
below to ensure that the recommended volumes are adhered to.
Table 16-1
Total blood volume, 1% and 3% of total blood volume by weight 
assuming 85mL per kg total blood volume
Weight (Kg)
Total Blood Volume* 
(mL)
1% Blood Volume (mL)**
3% Blood Volume (mL)**
5
425
4
12
10
850
8
24
15
1275
12
36
20
1700
17
51
25
2125
21
63
30
2550
25
75
35
2975
29
87
40
3400
34
102
45
3825
38
114
50
4250
42
126
55
4675
46
138
60
5100
51
103
65
5525
55
165
70
5950
59
177
75
6375
63
186
80
6800
68
204
*all blood volumes are rounded down 

Novartis
Confidential
Page 114
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310

Novartis
Confidential
Page 115
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
18
Appendix 6:  CDLQI questionnaire
CHILDREN'S DERMATOLOGY LIFE QUALITY INDEX
The aim of this questionnaire is to measure how much your skin problem has affected you 
OVER THE LAST WEEK.  Please tick one box for each question.
1.
Over the last week, how itchy, "scratchy",
Very much
□
sore or painful has your skin been?
Quite a lot
□
Only a little
□
Not at all
□
2.
Over the last week, how embarrassed
Very much
□
or self-conscious, upset or sad have you 
Quite a lot
□
been because of your skin?
Only a little
□
Not at all
□
3.
Over the last week, how much has your 
Very much
□
skin affected your friendships?
Quite a lot
□
Only a little
□
Not at all
□
4.
Over the last week, how much have you changed
Very much
□
or worn different or special clothes/shoes
Quite a lot
□
because of your skin?
Only a little
□
Not at all
□
5.
Over the last week, how much has your 
Very much
□
skin trouble affected going out, playing,
Quite a lot
□
or doing hobbies?
Only a little
□
Not at all
□
6.
Over the last week, how much have you
Very much
□

Novartis
Confidential
Page 116
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
avoided swimming or other sports because
Quite a lot
□
of your skin trouble?
Only a little
□
Not at all
□
7.
Last week,
If school time: Over the
Prevented school
□ 
last week, how much did
Very much
□
Was it school time?  your skin problem affect your
Quite a lot
□
school work?
Only a little
□
OR
Not at all
□
was it holiday time?   If holiday time: How much
Very much
□
over the last week, has your
Quite a lot
□
skin problem interfered with
Only a little
□
enjoyment of the holiday?
Not at all
□
8.
Over the last week, how much trouble 
Very much
□
have you had because of your skin with
Quite a lot
□
other people calling you names, teasing,
Only a little
□
bullying, asking questions or avoiding you?
Not at all
□
9.
Over the last week, how much has your sleep
Very much
□
been affected by your skin problem?
Quite a lot
□
Only a little
□
Not at all
□
10. Over the last week, how much of a 
Very much
□
problem has the treatment for your 
Quite a lot
□
skin been?
Only a little
□
Not at all
□
Please check that you have answered EVERY question. Thank you

Novartis
Confidential
Page 117
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
19
Appendix 7: CHAQ Questionnaire
1990 Original version by Singh G et al. 1998 Cross-cultural adapted version by Woo P, Murray 
KJ, Nugent J for PRINTO
1
CHILDHOOD HEALTH ASSESSMENT QUESTIONNAIRE
2
In this section we are interested in learning how your child's illness affects his/her ability to function in daily life. Please feel free to 
add any comments on the back of this page. In the following questions, please tick the one response which best describes your 
child's usual activities OVER THE PAST WEEK. ONLY NOTE THOSE DIFFICULTIES OR LIMITATIONS WHICH 
ARE DUE TO ILLNESS. If most children at your child's age are not expected to do a certain activity, please mark it as "Not 
Applicable". For example, if your child has difficulty in doing a certain activity or is unable to do it because he/she is too 
young but not because he/she is RESTRICTED BY ILLNESS, please mark it as "NOT Applicable".
3
Without 
ANY 
Difficulty
With SOME 
Difficulty
With MUCH 
Difficulty
UNABLE 
To do
Not 
Applicable
4
DRESSING & PERSONAL CARE
5 Is your child able to: 
6 - Dress, including tying shoelaces and doing buttons?





7 - Shampoo his/her hair?





8 - Remove socks?





9 - Cut fingernails?





10
GETTING UP
11 Is your child able to:
12 - Stand up from a low chair or floor?





13 - Get in and out of bed or stand up in a cot?





14
EATING
15 Is your child able to:
16 - Cut his/her own meat?





17 - Lift up a cup or glass to mouth?





18 - Open a new cereal box?





19
WALKING
20 Is your child able to:
21 - Walk outside on flat ground?





22 - Climb up five steps?





23 * Please tick any AIDS or DEVICES that your child usually uses for any of the above activities:
24 - Walking stick

- Devices used for dressing (button hook, zip pull, long-
handled shoe horn, etc.)

25 - Walking frame

- Built up pencil or special utensils

26 - Crutches

- Special or built up chair

27 - Wheelchair

- Other (Specify:_____________________________)

28 * Please tick any categories for which your child usually needs help from another person BECAUSE OF ILLNESS:
29 - Dressing and personal care

- Eating

30 - Getting up

- Walking


Novartis
Confidential
Page 118
Amended Protocol v04 (clean)
Protocol No. CAIN457A2310
31
Without 
ANY 
Difficulty
With SOME 
Difficulty
With MUCH 
Difficulty
UNABLE 
To do
Not 
Applicable
32
HYGIENE
33 Is your child able to:
34 - Wash and dry entire body?





35 - Take a bath (get in and out of bath)?





36 - Get on and off the toilet or potty?





37 - Brush teeth?





38 - Comb/brush hair?





39
REACH
40 Is your child able to:
41 - Reach and get down a heavy object such as a large game or 
books from just above his/her head?





42 - Bend down to pick up clothing or a piece of paper from the 
floor?





43 - Pull on a jumper over his/her head?





44 - Turn neck to look back over shoulder?





45
GRIP
46 Is your child able to:
47 - Write or scribble with pen or pencil?





48 - Open car doors?





49 - Open jars which have been previously opened?





50 - Turn taps on and off?





51 - Push open a door when he/she has to turn a door knob?





52
ACTIVITIES
53 Is your child able to:
54 - Run errands and shop?





55 - Get in and out of a car or toy car or school bus?





56 - Ride bike or tricycle?





57 - Do household chores (e.g. wash dishes, take out rubbish, 
hoovering, gardening, make bed, clean room)?





58 - Run and play?





59 * Please tick any AIDS or DEVICES that your child usually uses for any of the above activities:
60 - Raised toilet seat

- Bathrail

61 - Bath seat

- Long-handled appliances for reach

62 - Jar opener (for jars previously opened)

- Long-handled appliances in bathroom

63 * Please tick any categories for which your child usually needs help from another person BECAUSE OF ILLNESS:
64 - Hygiene

- Gripping and opening things

65 - Reach

- Errands and chores

66
PAIN: We are also interested in learning whether or not your child has been affected by pain because of his or her illness. 
How much pain do you think your child has had because of his/her illness IN THE PAST WEEK?
Place a mark on the line below, to indicate the severity of the pain
67       No pain   0                                                                                                                     100 Very severe pain
68 GENERAL EVALUATION: Considering all the ways that arthritis affects your child, rate how he/she is doing by placing a single 
mark on the line below.
69     Very well 0                                                                                                                     100 Very poor