Clinical trial NCT03769168
Conditions: Juvenile Psoriatic Arthritis Enthesitis Related Arthritis
Keywords: JIA JPsA ERA Secukinumab ILAR Juvenile Psoriatic Arthritis Enthesitis Related Arthritis
Sponsor: Novartis Pharmaceuticals
Start date: 2019-06-07; Completion date: 2024-11-07
Enrollment: 55 participants; Allocation: NON_RANDOMIZED; Intervention model: SINGLE_GROUP

Brief summary:
Optional open label, roll over extension study to investigate the efficacy and safety of secukinumab treatment in Juvenile Idiopathic Arthritis (JIA) subtypes of Juvenile Psoriatic Arthritis (JPsA) and Enthesitis Related Arthritis (ERA).

Detailed description:
This study is an extension of a previous core study (NCT03031782 \[CAIN457F2304\]) aiming to assess the long-term efficacy, safety, and tolerability of secukinumab treatment in patients who completed the core study and chose to participate in the extension study. The primary objective was to gather comprehensive data on the efficacy and safety of secukinumab over an extended period.

At Week 104 of the core study, all eligible patients could opt to roll over to the extension study and continue receiving secukinumab at either 75 mg or 150 mg, as they were at the Week 100 visit of the core study. The treatment involved subcutaneous injections using pre-filled syringes (PFS). The duration of patient participation could range from a minimum of one year to a maximum of four years, or until one of the following conditions was met: the drug was locally approved, marketed, and reimbursed, secukinumab could be provided free of charge to patients in compliance with local guidelines, or a maximum of 4 years study duration.

During the extension study (starting from Week 108), to maintain a high proportion of clinically meaningful response during the entire duration of the extension study, the dosing options available, at the Investigator's discretion, were as follows:

* The dose could be escalated from 75 mg to 150 mg for patients whose signs and symptoms were not fully controlled with the current dose of 75 mg and might improve with a higher dose as judged by the investigator
* Further, the dose could be escalated to 300 mg for patients weighing 50 kg and over currently on the 150 mg dose whose signs and symptoms were not fully controlled and might improve further with an increase in dose as judged by the investigator
* Dose escalation from secukinumab 75 mg to 300 mg had to be done in two steps (first 150 mg then 300 mg if the patient weighed 50 kg or over and based on the investigator's judgement), also considering the gap between the two escalations to review the response

Arms: arm 1: Participants initially received secukinumab 75mg subcutaneously once every four weeks in the extension study. If the signs and symptoms of the participants were not adequately controlled with the 75mg dose, as determined by the investigator, the dose could be escalated to 150mg subcutaneously. For patients weighing 50kg and over, the dose could further be escalated to 300mg subcutaneously every four weeks. The dose escalation from secukinumab 75mg subcutaneously to 300mg subcutaneously was to be implemented in two steps, with the first step being an increase to 150mg subcutaneously, followed by another escalation to 300mg subcutaneously, based on the judgement of the investigator. arm 2: Participants initially received secukinumab 150mg subcutaneously once every four weeks in the extension study. If the signs and symptoms of the participants were not adequately controlled with the 150mg dose, as determined by the investigator, the dose could be escalated to 300mg subcutaneously.
Interventions: intervention 1: Secukinumab
Intervention descriptions: intervention 1: Secukinumab solution for subcutaneous injections was provided in PFS. Initially, participants continued to receive secukinumab at either 75 mg (in 0.5mL) or 150 mg (in 1mL) every 4 weeks, consistent with their dosage at the Week 100 visit of the core study. The dose could be escalated from 75 mg to 150 mg for patients whose signs and symptoms were not fully controlled, as judged by the investigator, with the current 75 mg dose. Furthermore, the dose could also be escalated to 300 mg every 4 weeks for patients weighing 50kg and over who were currently on the 150 mg dose and whose signs and symptoms were not well-controlled, as judged by the investigator. The dose escalation from secukinumab 75 mg to 300 mg was to be implemented in two steps (first 150 mg and then 300 mg based on the investigator's judgment). At each study treatment time point, one or two subcutaneous injections in the form of PFS were administered.

Protocol documents:
Prot_000.pdf: 
Novartis Research and Development 
Secukinumab AIN457 
Clinical Trial Protocol CAIN457F2304E1 / NCT03769168
An extension study of subcutaneous secukinumab to evaluate the long-term efficacy, safety and 
tolerability up to 4 years in patients with Juvenile Idiopathic Arthritis subtypes of Juvenile 
Psoriatic Arthritis and Enthesitis Related Arthritis 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
2018-002521-30 
Version number: 
00 (Original Protocol) 
Clinical Trial Phase: 
III 
Release date: 
12-NOV-2018
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template version 1.0 dated (01-Dec-2017) 


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Table of contents 
Table of contents ...................................................................................................................................... 2 
List of tables............................................................................................................................................. 5 
List of figures ........................................................................................................................................... 5 
List of abbreviations ................................................................................................................................ 6 
Glossary of terms ................................................................................................................................... 10 
Protocol summary .................................................................................................................................. 11 
1 
Introduction ............................................................................................................................................ 14 
1.1 
Background .............................................................................................................................. 14 
1.2 
Purpose ..................................................................................................................................... 15 
2 
Objectives and endpoints ....................................................................................................................... 15 
3 
Study design ........................................................................................................................................... 16 
4 
Rationale ................................................................................................................................................ 17 
4.1 
Rationale for study design ........................................................................................................ 17 
4.2 
Rationale for dose/regimen and duration of treatment ............................................................. 18 
4.3 
Rationale for choice of control drugs (comparator/placebo) or combination drugs ................. 21 
4.4 
Purpose and timing of interim analyses/design adaptations ..................................................... 21 
4.5 
Risks and benefits ..................................................................................................................... 21 
5 
Population .............................................................................................................................................. 22 
5.1 
Inclusion criteria ....................................................................................................................... 22 
5.2 
Exclusion criteria ...................................................................................................................... 22 
6 
Treatment ............................................................................................................................................... 23 
6.1 
Study treatment ......................................................................................................................... 23 
6.1.1 
Investigational and control drugs ........................................................................... 23 
6.1.2 
Additional study treatments ................................................................................... 24 
6.1.3 
Treatment group .................................................................................................... 24 
6.1.4 
Treatment duration ................................................................................................ 24 
6.2 
Other treatment(s) ..................................................................................................................... 25 
6.2.1 
Concomitant therapy .............................................................................................. 25 
6.2.2 
Prohibited medication ............................................................................................ 26 
6.2.3 
Rescue medication ................................................................................................. 26 
6.3 
Patient numbering, treatment assignment, randomization ........................................................ 27 
6.3.1 
Patient numbering .................................................................................................. 27 
6.3.2 
Treatment assignment, randomization ................................................................... 27 
6.4 
Treatment blinding ................................................................................................................... 27 
6.5 
Dose escalation and dose modification .................................................................................... 27 
6.5.1 
Dose escalation guidelines ..................................................................................... 28 
6.5.2 
Dose modifications ................................................................................................ 28 
6.5.3 
Follow-up for toxicities ......................................................................................... 28 
6.6 
Additional treatment guidance ................................................................................................. 28 
6.6.1 
Treatment compliance ........................................................................................... 28 


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6.6.2 
Emergency breaking of assigned treatment code................................................... 29 
6.7 
Preparation and dispensation .................................................................................................... 29 
6.8 
Administration .......................................................................................................................... 29 
6.8.2 
Handling of study treatment .................................................................................. 29 
6.8.3 
Handling of additional treatment ........................................................................... 30 
6.9 
Instruction for prescribing and taking study treatment ............................................................. 30 
7 
Informed consent procedures ................................................................................................................. 32 
8 
Visit schedule and assessments .............................................................................................................. 32 
8.1 
Screening .................................................................................................................................. 47 
8.2 
Patient demographics/other baseline characteristics ................................................................ 47 
8.3 
Efficacy .................................................................................................................................... 47 
8.3.1 
JIA ACR response criteria ..................................................................................... 50 
8.3.2 
Inactive Disease Status .......................................................................................... 52 
8.3.3 
Juvenile Arthritis Disease Activity Score (JADAS) .............................................. 53 
8.3.4 
Assessment of duration of morning stiffness ......................................................... 53 
8.3.5 
Assessment of Uveitis due to JIA .......................................................................... 53 
8.3.6 
Total enthesitis count ............................................................................................. 53 
8.3.7 
Total dactylitis count ............................................................................................. 53 
 
 54 
8.3.9 
Appropriateness of efficacy assessments ............................................................... 54 
8.4 
Safety ........................................................................................................................................ 54 
8.4.1 
Physical examination ............................................................................................. 54 
8.4.2 
Vital signs .............................................................................................................. 54 
8.4.3 
Height and weight .................................................................................................. 55 
8.4.4 
Laboratory evaluations .......................................................................................... 55 
8.4.5 
Electrocardiogram (ECG) ...................................................................................... 56 
8.4.6 
Pregnancy and assessments of fertility .................................................................. 56 
8.4.7 
Tolerability of secukinumab .................................................................................. 57 
8.4.8 
Immunogenicity ..................................................................................................... 57 
8.4.9 
Other safety evaluations ........................................................................................ 58 
8.4.10 
Appropriateness of safety measurements .............................................................. 58 
8.5 
Additional assessments ............................................................................................................. 58 
8.5.1 
Pharmacokinetics ................................................................................................... 58 
9 
Study discontinuation and completion ................................................................................................... 59 
9.1 
Discontinuation ........................................................................................................................ 59 
9.1.1 
Discontinuation of study treatment ........................................................................ 59 
9.1.2 
Withdrawal of informed consent ........................................................................... 60 
9.1.3 
Lost to follow-up ................................................................................................... 61 
9.1.4 
Early study termination by the sponsor ................................................................. 61 
9.2 
Study completion and post-study treatment ............................................................................. 61 
10 Safety monitoring and reporting ............................................................................................................ 62 


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10.1 
Definition of adverse events and reporting requirements ......................................................... 62 
10.1.1 
Adverse events ....................................................................................................... 62 
10.1.2 
Serious adverse events ........................................................................................... 63 
10.1.3 
SAE reporting ........................................................................................................ 64 
10.1.4 
Pregnancy reporting ............................................................................................... 65 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................................. 65 
10.2 
Additional Safety Monitoring ................................................................................................... 66 
10.2.1 
Liver safety monitoring ......................................................................................... 66 
10.2.2 
Renal safety monitoring ......................................................................................... 67 
11 Data Collection and Database management ........................................................................................... 67 
11.1 
Data collection .......................................................................................................................... 67 
11.2 
Database management and quality control ............................................................................... 68 
11.3 
Site monitoring ......................................................................................................................... 68 
12 Data analysis and statistical methods ..................................................................................................... 69 
12.1 
Analysis sets ............................................................................................................................. 69 
12.2 
Patient demographics and other baseline characteristics .......................................................... 69 
12.3 
Treatments ................................................................................................................................ 70 
12.4 
Analysis of the primary endpoint(s) ......................................................................................... 70 
12.4.1 
Definition of primary endpoint(s) .......................................................................... 70 
12.4.2 
Variable(s) ............................................................................................................. 70 
12.4.3 
Statistical model, hypothesis, and method of analysis ........................................... 70 
12.4.4 
Handling of missing values/censoring/discontinuations ........................................ 71 
12.4.5 
Sensitivity and Supportive analyses ...................................................................... 71 
12.5 
Analysis of secondary endpoints .............................................................................................. 71 
12.5.1 
Efficacy variables .................................................................................................. 71 
12.5.2 
Safety endpoints .................................................................................................... 71 
12.5.3 
Pharmacokinetics ................................................................................................... 73 
12.6 
Interim analyses ........................................................................................................................ 73 
12.7 
Sample size calculation ............................................................................................................ 73 
13 Ethical considerations and administrative procedures ........................................................................... 73 
13.1 
Regulatory and ethical compliance ........................................................................................... 73 
13.2 
Informed consent procedures ................................................................................................... 73 
13.3 
Responsibilities of the investigator and IRB/IEC ..................................................................... 74 
13.4 
Publication of study protocol and results ................................................................................. 74 
13.5 
Quality Control and Quality Assurance .................................................................................... 75 
14 Protocol adherence ................................................................................................................................. 75 
14.1 
Protocol Amendments .............................................................................................................. 75 
15 References .............................................................................................................................................. 76 
16 Appendices............................................................................................................................................. 77 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs ............................................ 77 
16.2 
Appendix 2: Liver event and Laboratory trigger Definitions and Follow-up Requirements .... 80 




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List of abbreviations 
ACR 
American College of Rheumatology 
ACR 
Albumin-creatinine ratio 
ADA 
Anti-drug antibody  
AE 
adverse event 
AESI 
adverse event of special interest 
Alb 
Albumin 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
ANA 
antinuclear antibodies 
ANCOVA 
analysis of covariance 
AS 
Ankylosing Spondylitis 
ATC 
Anatomical Therapeutic Classification 
AST 
aspartate aminotransferase 
BDR 
Bioanalytical Data Report 
BMI 
Body Mass Index 
BP 
Blood pressure 
BSA 
body surface area 
BUN 
blood urea nitrogen 
Cavg 
average concentration of drug in blood 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CD-ROM 
compact disc – read only memory 
CDC 
Center of Disease Control 
CDS 
Core Data Sheet (for marketed drugs) 
CFR 
Code of Federal Regulation 
CHAQ© 
Childhood Health Assessment Questionnaire 
CK 
creatinine kinase 
CMO&PS 
Chief Medical Office & Patient Safety 
CO2 
carbon dioxide 
COAR 
Clinical Operations, Analytics & Regions 
COX-2 
cyclooxygenase-2 
CPO 
Country Pharma Organization 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CRA 
Clinical Research Associate 
CRP 
C-Reactive Protein 
CTC 
Common Toxicity Criteria 
CTCAE 
Common Terminology Criteria for Adverse Event  
CTRD 
Clinical Trial Results Database 
CTT 
Clinical Trial Team 
CV 
coefficient of variation 
DMARD 
Disease-modifying antirheumatic drugs 


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DMC 
Data Monitoring Committee 
eCRF 
electronic case record form 
EC 
Ethics committee 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
ELISA 
Enzyme-linked immunosorbent assay 
ERA 
Enthesitis Related Arthritis  
EMA 
European Medicines Agency 
eSAE 
Electronic Serious Adverse Event 
EOT 
End of Treatment 
EOS 
End of Study 
EU 
European Union 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GGT 
Gamma - Glutamyl transferase  
h 
Hour 
hCG 
Human chorionic gonadotropin 
β-hCG 
Beta Human chorionic gonadotropin 
HDL 
High-density lipoprotein 
HLA 
human leukocyte antigen 
i.v. 
Intravenous 
IA 
Interim Analysis 
IB 
Investigator’s brochure 
IBD 
Inflammatory Bowel Disease 
ICF 
Informed Consent Form 
ICH 
International Council for  Harmonization of Technical Requirements Pharmaceuticals 
for Human Use 
IEC 
Independent Ethics Committee 
IFU 
Instructions for use 
IG 
Immunogenicity 
IL 
Interleukin 
ILAR 
International League of Associations for Rheumatology 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IUD 
intrauterine device 
IUS 
intrauterine system 
JADAS 
Juvenile Arthritis Disease Activity Score 
JIA 
Juvenile Idiopathic Arthritis 
JPsA 
Juvenile Psoriatic Arthritis 
LDH 
lactate dehydrogenase 
LDL 
Low Density Lipoprotein 


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LFT 
Liver function test 
LLN 
lower limit of normal 
LLOQ 
lower limit of quantification 
mAbs 
Monoclonal antibodies 
MABEL 
minimum anticipated biological effect level 
MedDRA 
Medical Dictionary for Regulatory Activities 
MTX 
Methotrexate 
mg 
milligram(s) 
ml 
milliliter(s) 
mL 
milliliter(s) 
MRSD 
maximum recommended starting dose 
NCDS 
Novartis Clinical Data Standards 
NOVDD 
Novartis Data Dictionary 
NSAID 
Nonsteroidal anti-inflammatory drugs  
PA 
Posteroanterior 
PCR 
Protein-creatinine ratio 
PD 
pharmacodynamic 
PFS 
pre-filled syringes 
PIP 
pediatric investigation plan 
PK 
pharmacokinetic(s) 
PRN 
pro re nata 
PRO 
Patient Reported Outcome 
PsA 
Psoriatic Arthritis 
PSW 
premature patient/ withdrawal 
QMS  
Quality Management System 
QTcF 
QT interval corrected by Fridericia’s formula 
RBC 
red blood cell(s) 
RDC 
Remote Data Capture 
REB 
Research Ethics Board 
RF 
Rheumatoid Factor 
s.c. 
Subcutaneous 
SAE 
serious adverse event 
sCR 
serum creatinine 
SD 
standard deviation 
SGOT 
serum glutamic oxaloacetic transaminase 
SGPT 
serum glutamic pyruvic transaminase 
SJC 
Swollen Joint Count 
SOP 
Standard Operating Procedures 
SpA 
Spondyloarthropathy 
SOM 
Site Operations Manual 
SSZ 
sulfasalazine 
SUN 
Standardization of uveitis nomenclature 


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SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TBL 
total bilirubin 
TJC 
Tender Joint Count 
TP2 
Treatment Period 2  
TNF 
tumor necrosis factor 
UK 
United Kingdom 
ULN 
upper limit of normal 
ULQ 
upper limit of quantification 
US 
United States 
VAS 
Visual Analogue Score 
WBC 
white blood cell(s) 
WHO 
World Health Organization 
WoC 
Withdrawal of Consent 
 


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Glossary of terms 
Assessment 
A procedure used to generate data required by the study 
Dosage 
Dose of the study treatment given to the patient in a time unit (e.g. 100 mg once a 
day, 75 mg twice a day) 
Electronic Data 
Capture (EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical study data 
using data collection systems, such as web-based applications, interactive voice 
response systems and clinical laboratory interfaces. EDC includes the use of 
Electronic Case Report Forms (eCRFs) which are used to capture data transcribed 
from paper source forms used at the point of care. 
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) 
Investigational 
drug 
The study 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 
other treatments administered as concomitant background therapy required or 
allowed by the protocol when used within approved indication/dosage. 
Medication pack 
number 
A unique identifier on the label of each drug package in studies that dispense study 
treatment using an IRT system 
Patient 
An individual with the condition of interest 
Period 
A minor subdivision of the study timeline; divides phases into smaller functional 
segments such as screening, baseline, titration, washout, etc. 
Premature patient 
withdrawal 
Point/time when the patient exits from the study prior to the planned completion of all 
study drug administration and assessments; at this time all study drug administration 
is discontinued and no further assessments are planned. 
Randomization 
number 
A unique identifier assigned to each randomized patient, corresponding to a specific 
treatment arm assignment 
Study completion 
Point/time at which the patient came in for a final evaluation visit or when study drug 
was discontinued whichever is later. 
Study drug 
discontinuation 
Point/time when patient permanently stops taking study drug for any reason; may or 
may not also be the point/time of premature patient withdrawal. 
Study treatment 
Any drug administered to the study participants as part of the required study 
procedures; includes investigational drug (s), control(s) or non-investigational 
medicinal product(s) 
Study treatment 
discontinuation 
When the patient permanently stops taking study treatment prior to the defined study 
treatment completion date 
Patient number 
A unique number assigned to each patient upon signing the informed consent. This 
number is the definitive, unique identifier for the patient and should be used to 
identify the patient throughout the study for all data collected, sample labels, etc. 
Variable 
A measured value or assessed response that is determined in specific assessments 
and used in data analysis to evaluate the drug being tested in the study 
Withdrawal of 
consent (WoC) 
Withdrawal of consent from the study is defined as when a patient does not want to 
participate in the study any longer, and does not want any further visits or 
assessments, and does not want any further study related contact, and does not 
allow analysis of already obtained biologic material 
 


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Protocol summary 
Protocol number 
CAIN457F2304E1 
Full Title 
An extension study of subcutaneous secukinumab to evaluate the long-term 
efficacy, safety and tolerability up to 4 years in patients with Juvenile 
Idiopathic Arthritis subtypes of Juvenile Psoriatic Arthritis and Enthesitis 
Related Arthritis 
Brief title 
Secukinumab long-term safety, tolerability and efficacy in JPsA and ERA up 
to 4 years 
Sponsor and Clinical Phase 
Novartis Pharma AG 
Investigation type 
Drug 
Study type 
Interventional 
Purpose and rationale 
CAIN457F2304 is a 2-year Phase III study which enrolled children ≥2 to <18 
years of age with active ERA or JPsA categories of JIA.  
The study CAIN457F2304E1 is designed as an up to 4-year extension to the 
core study CAIN457F2304. The aim of this 4-years extension study is to 
provide continuous treatment with secukinumab (AIN457) in pre-filled syringes 
(PFS) for patients who complete the core study CAIN457F2304 Week 104 
and opt to enter the extension trial and to obtain further long-term efficacy, 
safety and tolerability information. 
Patients from core study CAIN457F2304 can participate in this optional, 
open label extension study for a minimum of one year or until one of the 
following conditions are met, whichever is earlier; the drug is locally 
approved, marketed, and reimbursed, OR– secukinumab can be provided 
free of charge to patients in compliance with local guidelines, OR– a 
maximum of 4 years study duration. 
Primary Objective(s)  
To evaluate the long-term efficacy of subcutaneously administered 
secukinumab (provided as pre-filled syringes) with respect to JIA ACR30 
response over time up to Week 308 visit  in patients with active JPsA and 
ERA subtypes of JIA and who completed the Phase III study 
CAIN457F2304. 
Secondary Objectives 
1. To evaluate the long-term safety, tolerability and immunogenicity of 
secukinumab as assessed by vital signs, clinical laboratory variables 
and adverse events monitoring over time up to Week 308. 
2. To evaluate the long-term effect of secukinumab treatment for all 
patients and each JIA category with respect to:- 
- JIA ACR/50/70/90/100 and inactive disease status 
- Each JIA ACR core component 
- Change from baseline of core study CAIN457F2304  
- Juvenile Arthritis Disease Activity Score (JADAS) 
- Total Enthesitis count 
- Total Dactylitis count 
3. To evaluate Pharmacokinetics (PK) of secukinumab 
Study design 
This is a multicenter, optional, open-label, pediatric extension study of 
subcutaneous (s.c.) secukinumab in pre-filled syringes to evaluate the long-
term efficacy, safety and tolerability up to 4-years in patients with JIA 
subtypes of JPsA and ERA. 


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Population 
Male and female patients aged from ≥2 years to <18 years at SCREENING 
in the core study CAIN457F2304, who are diagnosed with either Enthesitis 
Related Arthritis (ERA) based on fulfilling the ILAR JIA classification criteria 
or Juvenile Psoriatic Arthritis (JPsA) based on fulfilling a modified ILAR JIA 
classification criteria who have completed the entire treatment period up to 
and including Week 104 of the core study. 
Key Inclusion criteria 
1. Patients must have participated in core study CAIN457F2304, and must 
have completed the entire treatment period up to and including Week 
104. 
2. Patients must be deemed by the investigator to benefit from continued 
secukinumab therapy. 
3. For patients who did not reach the age of consent (as per local law): 
Parents or legal guardian’s signed written informed consent and child’s 
assent, if appropriate, must be obtained prior to participation in the study 
and before any study related procedure is performed. Of note, if the 
patient reaches age of consent (age as per local law) during the study, 
they will also need to sign the corresponding study ICF (Informed 
Consent Form). 
4. For patients who reached the age of consent (age as per local law), 
signed written informed consent must be obtained prior to participation in 
the study and before any study related procedure are performed. 
Key Exclusion criteria 
1. Plans for administration of live vaccines during the extension study 
period. 
2. Any patient taking other concomitant biologic immunomodulating 
agent(s) except secukinumab. 
3. Any patient who is deemed not to be benefiting from the study treatment 
based upon lack of improvement or worsening of their symptoms. 
4. Pregnant or nursing (lactating) women, where pregnancy is defined as 
the state of a female after conception and until the termination of 
gestation, confirmed by a positive hCG laboratory test. 
5. Females of child-bearing 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 an effective contraception. 
Study treatment 
All subjects will receive the same dose of secukinumab at Week 104E1 as 
they were receiving at Week 100 in core study. No re-randomization is 
planned. The two treatment groups are:  
 
 
• 
Group1: Secukinumab (AIN457) 75mg/0.5mL, liquid formulation 
provided in 0.5 mL PFS (Pre-filled syringe) 
• 
Group 2:Secukinumab (AIN457) 150mg/1.0mL, liquid formulation 
provided in 1.0 mL PFS (Pre-filled syringe) 
 
Starting Week 108  
The dose may be escalated from 75 mg to 150 mg sc for patients whose 
signs and symptoms are not fully controlled, as judged by the investigator, 
with the current 75 mg.  
Further the dose may also be escalated to 300 mg s.c. every 4 weeks for 
patients 50kg and over and currently on 150 mg dose, and whose signs and 
symptoms are not controlled well, as judged by investigator.  


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The dose escalation from secukinumab 75 mg sc to 300 mg sc should 
be implemented in two steps (first 150 mg sc and then 300 mg sc based 
on investigator’s judgement).  
Efficacy assessments 
• 
JIA ACR 30, 50, 70, 90 and 100 response criteria, 
• 
Physician’s Global Assessment of disease activity (VAS) (Visual 
Analogue Score), 
• 
Parent’s/patient’s Global Assessment of patients overall well-being (VAS 
included within CHAQ©), 
• 
Childhood Health Assessment Questionnaire (CHAQ©), 
• 
Active joint count, 
• 
Joint count with limited range of motion, 
• 
CRP (C-Reactive Protein) (local), 
• 
Inactive disease status,  
 
, 
• 
Swollen Joint Count (SJC), 
• 
Tender Joint Count (TJC), 
• 
JADAS score, 
• 
Total Enthesitis count  
• 
Total Dactylitis count, 
Safety Assessments  
• 
Adverse events/serious adverse events (AE/SAE) 
• 
Electrocardiogram (ECG), (local), 
• 
Laboratory evaluations, 
• 
Immunogenicity, 
• 
Injection site reactions,  
• 
Physical examination,  
• 
Vital signs,  
• 
Height and weight,  
• 
Pregnancy and assessment of fertility,  
• 
Tolerability of secukinumab 
Pharmacokinetic 
assessments  
• 
Secukinumab levels 
Data analysis 
All data will be summarized descriptively for all patients by a dose group 
and/or possibly by JPsA and ERA subtypes. 
Summary statistics for continuous variables will generally include the number 
of patients (N), minimum, lower quartile, mean, median, upper quartile, and 
maximum. For categorical or binary variables, the number and percent of 
patients in each category will be presented. The 95% confidence intervals 
will be provided as appropriate to evaluate the efficacy of the treatment 
regimens. 
Key words 
JIA, JPsA, ERA, secukinumab (AIN457) 


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1 
Introduction 
1.1 
Background  
Juvenile Idiopathic Arthritis (JIA) represents a heterogeneous group of chronic idiopathic arthritides 
of at least 6 weeks duration, which presents in children less than 16-years of age. These conditions 
have variable clinical presentations and prognoses, variable age of onset, and are a major cause of 
morbidity. The reported prevalence and incidence of JIA varies widely. The prevalence in Europe 
ranges from 0.2 to 2.0 per 1000 children, and in the US (United States), the prevalence has been 
reported to be approximately 0.45 per 1000 children. 
The International League of Associations for Rheumatology (ILAR) classification criteria (Petty et 
al 2004) identify the following 7 JIA categories characterized by different clinical presentations: 
• Polyarthritis (Rheumatoid Factor (RF) positive); 
• Polyarthritis (Rheumatoid Factor (RF) negative); 
• Oligoarthritis; 
• Juvenile psoriatic Arthritis (JPsA); 
• Enthesitis Related Arthritis (ERA); 
• Systemic Arthritis and;  
• Undifferentiated Arthritis 
Of the 7 JIA categories, Juvenile Psoriatic Arthritis (JPsA) and Enthesitis Related Arthritis (ERA) 
represent a spondyloarthropathy (SpA) similar to the adult spondyloarthropathies of Psoriatic 
Arthritis (PsA) and Ankylosing Spondylitis (AS). 
Juvenile Psoriatic Arthritis (JPsA) is an inflammatory arthritis, which can present with or without 
psoriasis skin involvement and accounts for approximately 5% to 10% of the total JIA population. 
The current ILAR classification criteria for JPsA include two distinct groups of patients; one 
clinically similar to JIA oligoarthritis and the other clinically similar to the adult spondyloarthritis 
condition of PsA (Martini 2003, Horneff 2009, Martini 2012). Those with an oligoarthritis like 
condition usually present at a young age (2 to 4 years old) with asymmetric oligoarthritis, are at risk 
for the development of iridocyclitis, and are frequently ANA (Antinuclear antibodies) positive. 
Those with a more adult PsA-like condition usually present at a later age (> 6 to 9 years old) with a 
lower extremity arthritis, enthesitis and, in a minority of patients, axial involvement, and are often 
Human Leukocyte Antigen HLA-B27 positive. 
Enthesitis Related Arthritis (ERA) is a clinically heterogeneous group including some who have 
predominantly enthesitis, enthesitis and arthritis, juvenile ankylosing spondylitis, or inflammatory 
bowel disease-associated (IBD) arthropathy. ERA accounts for approximately 3% to 11% of JIA. 
ERA has a strong genetic predisposition as evidenced by a positive family history and the high 
frequency of the presence of HLA-B27 in affected patients. The hallmarks of the disease are pain, 
stiffness, and eventual loss of mobility of the back, similar to adult ankylosing spondylitis. ERA 
should be suspected in any child with chronic arthritis of the axial and peripheral skeleton, enthesitis 
(inflammation at points where tendons insert to bone), and Rheumatoid Factor (RF) and Anti-nuclear 
antibody (ANA) seronegativity. Peripheral arthritis, also similar to adult AS, usually affecting few 
joints of the lower extremity, precedes axial involvement, and arthritis of the sacroiliac joints may 
take years to develop. Unlike adults with AS, the arthritis in children with ERA can be very 


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aggressive and lead to hip replacement more often than in adult AS patients. Radiographic changes 
of the sacroiliac joint include joint space narrowing, erosions, sclerosis, osteoporosis of the pelvis, 
and fusion (a late finding). 
In 2011, the American College of Rheumatology (ACR) established JIA treatment guidelines which 
are applicable to all JIA categories, including the spondyloarthropathies JPsA and ERA. The 
guidelines aim to quickly control active inflammation and patient symptoms and to 
prevent/minimize disease and/or treatment related morbidities (e.g. growth disturbances, joint 
damage, and functional limitations). In general, the treatment goal is to target controlling the 
inflammation with NSAIDs (Non-steroidal anti-inflammatory drugs), corticosteroids as intra-
articular injections, DMARDs (Disease modifying anti-rheumatic drugs) and biologic agents either 
as monotherapy or in combination with other therapies (DMARD and/or NSAID). Successful 
management requires careful long-term monitoring of disease activity and willingness to adjust 
treatments as necessary to achieve and maintain the lowest level of disease activity. 
Secukinumab (AIN457) is a high-affinity fully human monoclonal anti-human antibody that targets 
(Interleukin) IL-17A and neutralizes it’s activity. Secukinumab treatment has demonstrated 
significant and clinically meaningful efficacy in treating adults with ankylosing spondylitis (AS) and 
psoriatic arthritis (PsA), both are approved indications. 
Patients from core trial CAIN457F2304 study can participate in this optional open label extension 
study for a minimum of one year or until one of the following conditions are met, whichever is 
earlier: the drug is locally approved, marketed, and reimbursed, OR– secukinumab can be provided 
free of charge to patients in compliance with local guidelines, OR– a maximum of 4 years study 
duration. 
1.2 
Purpose 
Study CAIN457F2304 is a 2-year Phase III study which enrolled children ≥2 to <18 years of age 
with active ERA or JPsA categories of JIA. The study CAIN457F2304E1 is designed as an up to 4-
year extension to the core study CAIN457F2304. The aim of this 4-year extension study is to provide 
continuous treatment with secukinumab in pre-filled syringes (PFS) for patients who complete the 
core study CAIN457F2304 Week 104 and opt to enter the extension trial and to obtain further long-
term efficacy, safety and tolerability information. 
2 
Objectives and endpoints 
Table 2-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary 
objective(s) 
• 
To evaluate the long-term efficacy of secukinumab (provided as 
pre-filled syringes) with respect to JIA ACR30 response over 
time up to Week 308 in patients with active JPsA and ERA 
subtypes of JIA and who completed the Phase III study 
CAIN457F2304. 
• 
JIA ACR Response 
Secondary objective(s) 
Endpoint(s) for secondary 
objective(s) 


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Objective(s) 
Endpoint(s) 
• 
To evaluate the long-term safety, tolerability and 
immunogenicity of secukinumab as assessed by vital signs, 
clinical laboratory variables and adverse events monitoring 
over time up to Week 308 
• 
AEs 
• 
Lab values 
• 
Vital signs 
• 
Anti-Drug Antibodies (ADAs) 
• 
To evaluate the long-term effect of secukinumab treatment for 
all patients and each JIA category with respect to: 
 JIA ACR/50/70/90/100 and inactive disease status; 
 Each JIA ACR core component; 
 Change from baseline of core study CAIN457F2304  
 Juvenile Arthritis Disease Activity Score (JADAS); 
 Total Enthesitis count; 
 Total Dactylitis count 
 
 
• 
JIA ACR /50/70/90/100  
• 
JIA ACR Core Components 
• 
Inactive Disease Status 
• 
JADAS Score 
• 
Total Enthesitis count 
• 
Total Dactylitis count 
• 
To evaluate pharmacokinetics (PK) of secukinumab 
• 
Secukinumab serum 
concentrations and derived PK 
parameters 
3 
Study design 
A multicenter, optional, open-label, pediatric extension study of subcutaneous secukinumab in pre-
filled syringes to evaluate the long-term efficacy, safety and tolerability up to 4-years in patients 
with Juvenile Idiopathic Arthritis subtypes of Juvenile Psoriatic and Enthesitis Related Arthritis. 
The aim of this 4-year extension study is to provide continuous treatment with secukinumab in pre-
filled syringes (PFS) for patients who complete the core study CAIN457F2304 and opt to enter the 
extension trial and to obtain further long-term efficacy, safety and tolerability information.  
 


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4 
Rationale  
4.1 
Rationale for study design 
This up to 4-year open label extension study will offer continuous secukinumab therapy to patients 
who opt to continue in to the extension study from the core study CAIN457F2304 and will provide 
long-term efficacy and safety data. Patients can exit the study upon their own wish or based on the 
advice of the investigator at any time. 
Although the cause for arthritis in children and adults is not known, children are expected to respond 
similarly to adults with similar conditions. Data from multiple secukinumab studies evaluating a 
range of doses (75 mg to 300 mg) are available for two adult spondyloarthritides (AS (Ankylosing 
Spondylitis) and PsA (Psoriatic Arthritis)) and RA (Rheumatoid Arthritis). A favorable benefit risk 
was established in adult ankylosing spondylitis and psoriatic arthritis patients. These indications are 
approved in multiple countries including the European Union (EU) and the US. 
Based on the totality of the adult arthritis clinical data where secukinumab treatment resulted in 
robust efficacy in adults with a spondyloarthropathy (PsA or AS), the appropriate pediatric arthritic 
population to study secukinumab treatment is children aged ≥ 2 to < 18 years diagnosed with 
enthesitis related arthritis or juvenile psoriatic arthritis JIA which are the two JIA categories which 
represent pediatric correlates of the approved adult SpA indications. The core study is adequately 
powered to demonstrate effectiveness of secukinumab treatment in a placebo-controlled study design 
following EMA (European Medicine Agency) JIA treatment guidelines evaluating a pediatric dose 
regimen equivalent to the 150 mg adult AS and PsA dose regimen. No additional safety risks or 
vulnerabilities are expected from exposure to secukinumab at this dose in the proposed pediatric 
population. 




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Adverse Event (CTCAE) Grade 3 neutropenia (<1.0-0.5 x 109/L) was uncommonly observed with 
secukinumab, most were mild to moderate, transient and reversible, and without a temporal 
relationship to serious infections. Hypersensitivity reactions include urticaria. Rare events of 
anaphylactic reaction to secukinumab have also been observed in clinical studies.  
The immunogenicity potential, e.g. eliciting the production of anti-drug antibodies (ADAs) is low. 
In psoriasis, psoriatic arthritis and ankylosing spondylitis clinical studies, less than 1% of patients 
treated with secukinumab (n>9600) developed antibodies over up to 52 weeks of treatment. 
Taking into account the individual risks as outlined above, the expected risk profile of secukinumab 
from its mechanism of action is anticipated to be similar or improved compared to the other approved 
inflammatory cytokine-targeting therapies. The risk to patients in this trial will be minimized by 
compliance with the eligibility criteria, close clinical monitoring, and extensive guidance to the 
investigators provided by Novartis and in the current version of the Investigator’s brochure (IB) for 
secukinumab. Based on overall risk-benefit assessment, the current trial with secukinumab is 
justified.  
It should be noted that patients must be deemed by the investigator to benefit from continued 
secukinumab therapy. 
5 
Population 
The study population will consist of male and female patients aged from ≥2 years to <18 years at 
SCREENING in the core study CAIN457F2304, who are diagnosed with either Enthesitis Related 
Arthritis (ERA) based on fulfilling the ILAR JIA classification criteria or Juvenile Psoriatic Arthritis 
(JPsA) based on fulfilling a modified ILAR JIA classification criteria who have completed the entire 
treatment period up to and including Week 104 of the core study. 
5.1 
Inclusion criteria 
Patients eligible for inclusion in this study must meet all of the following criteria: 
1. Patient must have participated in core study CAIN457F2304, and must have completed the 
entire treatment period up to and including Week 104. 
2. Patients must be deemed by the investigator to benefit from continued secukinumab therapy. 
3. For patients who did not reach the age of consent (as per local law): Parent’s or legal 
guardian’s signed written informed consent and child’s assent, if appropriate, must be obtained 
prior to participation in the study and before any study related procedure is performed. Of note, 
if the patient reaches age of consent (as per local law) during the study, they will also need to 
sign the corresponding study ICF (Informed Consent Form). 
4. For patients who reached the age of consent (age as per local law), signed written informed 
consent must be obtained prior to participation in the study and before any study related 
procedure are performed. 
5.2 
Exclusion criteria 
Patients meeting any of the following criteria are not eligible for inclusion in this study. 
1. Plans for administration of live vaccines during the extension study period. 


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2. Any patient taking other concomitant biologic immunomodulating agent(s) except 
secukinumab.  
3. Any patient who is deemed not to be benefiting from the study treatment based upon lack of 
improvement or worsening of their symptoms. 
4. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive hCG laboratory 
test.  
5. Females of child-bearing 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 an effective 
contraception as defined in Section 8.4.6. 
No additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients. 
6 
Treatment 
6.1 
Study treatment 
6.1.1 
Investigational and control drugs 
Novartis will supply the following study drugs: 
Table 6-1 
Investigational drug 
Investigational Drug 
(Name and Strength) 
Pharmaceutical 
Dosage Form 
Route of 
Administration 
Packaging of 
Drug 
Sponsor (global 
or local) 
Secukinumab (AIN457) 
75 mg/0.5mL 
liquid formulation 
provided in 0.5 mL 
pre-filled syringe 
Subcutaneous 
Labelled 
Investigational 
Drug 
Sponsor global 
Secukinumab (AIN457) 
150 mg/1.0mL 
liquid formulation 
provided in 1 mL 
pre-filled syringe 
Subcutaneous 
Labelled 
Investigational 
Drug 
Sponsor global 
All study drugs will be labeled accordingly: 
• AIN457 150 mg/1.0mL 
•  AIN457 75 mg/0.5mL 
For detailed instructions on handling of the study drug, please refer to Section 6.7.1.2. 
Before enrolment in this extension study, all patients electing to continue will sign an Informed 
Consent form. Detailed instructions for self-administration of the “s.c” injection using the PFS 
formulation will be provided to each patient or parent/guardian. Each injection will be administered 
into an appropriate injection site of the body. For the first visit at Week 104E1, injections will be 
performed at site.  
Starting from Week 108 patients will have the choice of self-administration or injection by 
parent/guardian (once trained) at home or continuing with administration at site, based on personal 
preference and the investigator’s clinical judgment. Site staff or parent/guardian (once trained) will 
administer the injection to patients who are not able or feel insecure to self-administer the PFS 
injection. 


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6.1.2 
Additional study treatments  
No additional treatment beyond investigational drug are included in this trial. 
6.1.3 
Treatment group  
All subjects (in Treatment Period (TP3) of core study) will continue to receive the same dose of 
secukinumab at Week 104E1 as they were receiving at the last visit Week 100 of the core study. 
Patients who would be blinded at Week 100 still in Treatment Period (TP2) and choose to enter the 
extension study, will also receive secukinumab 75mg or 150 mg at Week 104E1 according to their 
weight as they were receiving at the last visit Week 100 of the core study. No re-randomization is 
planned.  
At Week 104 of core study, all eligible patients from core study can opt to be enrolled in extension 
study via Interactive Response Technology (IRT) and will receive secukinumab dosing. The Week 
104E1 will be performed on the same day once the Week 104 is completed by patient. The 
investigator or his/her delegate will contact the IRT after confirming that the patient fulfills all the 
extension study inclusion/exclusion criteria. The IRT will then specify a unique medication 
number for the first package of investigational treatment to be dispensed to the patient for Week 
104E1. 
 
From Core Week104/Extension Week 104E1 until Week 308  
 
Group 1: secukinumab 75mg/0.5ml once every four weeks until (and including) Week 308 
Group 2: secukinumab 150mg/1.0ml once every four weeks until (and including) Week 308 
 
At each study treatment time point starting at Week 108, one or two s.c. injections in the form 
of PFS will be administered. This will be open label treatment.  
• The dose may be escalated from 75 mg to 150 mg sc for patients whose signs and 
symptoms are not fully controlled, as judged by the investigator, with the current 75 mg 
dose.  
• Further the dose may also be escalated to 300 mg s.c. every 4 weeks for patients 50kg and 
over and currently on 150 mg dose, and whose signs and symptoms are not controlled well, 
as judged by investigator.  
• The dose escalation from secukinumab 75 mg sc to 300 mg sc should be implemented in 
two steps (first 150 mg sc and then 300 mg sc based on investigator’s judgement).  
As this long-term study extends the pivotal registration study CAIN457F2304 by up to an additional 
4-years it may be affected by agency review or potential product approval considerations. If the 
product is approved during study conduct, dose groups in this extension study may be amended (via 
a future protocol amendment) based on eventual agency recommendations for product usage in this 
indication. 
6.1.4 
Treatment duration 
Patients who completed the core CAIN457F2304 study and who are deemed by the investigator to 
benefit from continuous secukinumab therapy can participate in this optional open label extension 
study. Patients can participate for a minimum of one year or until one of the following conditions 


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are met, whichever is earlier: the drug is locally approved, marketed, and reimbursed, OR– 
secukinumab can be provided free of charge to patients in compliance with local guidelines, OR– a 
maximum of 4 years study duration. 
6.2 
Other treatment(s)  
6.2.1 
Concomitant therapy 
The investigator must instruct the patient/guardian to notify the study site about any new medications 
the patient takes after he/she was enrolled into the study. All medications, procedures and significant 
non-drug therapies (including physical therapy and blood transfusions) administered at least once 
between the start of the first dose in this extension trial and the date of the last study visit in the 
extension study must be recorded in the concomitant medications/significant non-drug therapies 
eCRF page, including those which were started before Week 104E1 and continued into the extension 
study where study treatment is administered. 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt the Investigator should contact the Novartis medical monitor before enrolling 
a patient or allowing a new medication to be started. Medications /treatments not explicitly 
mentioned in the protocol can be evaluated by Novartis for suitability with the study on a case-by-
case basis. 
Guidelines for the use of specific medications are provided below. 
Non-biologic DMARDs (limited to MTX or SSZ) 
For patients on Methotrexate (MTX) (maximum of 20 mg/m2/ Body Surface Area (BSA)/ week) and 
folic/folinic acid supplementation (according to standard medical practice of the center), or 
sulfasalazine (SSZ) (only for ERA patients, stable dose of <50 mg/kg/day and up to max 3000 
mg/day), dose may be adjusted as deemed appropriate and necessary by the investigator. 
Systemic corticosteroids 
Treatment with oral corticosteroids ≤ 0.2 mg/kg/day (or maximum 10 mg/day whichever is lower) 
of oral prednisone (or equivalent) is permitted, dose may be adjusted as deemed appropriate and 
necessary by the investigator.  
Any change in the dose of oral corticosteroids during the trial should be recorded on the 
corresponding eCRF page. 
Intra-articular corticosteroid injections will be permitted. No more than 4 joints per 24-week period 
may be injected and no single injection should exceed 40 mg of triamcinolone (or equivalent) during 
any 52-week period. Intra-articular corticosteroid injections will be recorded appropriately and the 
injected joints will be considered active for the following 3 months for the purposes of analysis. 
Non-steroidal anti-inflammatory drugs (NSAIDs) (including selective cyclooxygenase-2 (COX-
2) inhibitors), low strength opioids and acetaminophen/paracetamol 
Patients are permitted to enter the trial using regular dose of a single non-steroidal anti-inflammatory 
drugs (NSAID) for their arthritis. Dose may be adjusted as deemed appropriate and necessary by the 
investigator. Other NSAIDs, low strength opioids, and paracetamol/acetaminophen are permitted 
during the trial only if used on an as required (PRN) basis for non-arthritis treatment. In such cases, 


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the patient must refrain from intake of the PRN medication during at least 24 hours before a visit 
with a disease activity assessment. 
6.2.2 
Prohibited medication 
Use of the treatments displayed in Table 6-2 is NOT allowed after enrollment due to their 
confounding effect and/or safety interactions. 
Note: Live vaccination is NOT allowed until the last study dose. Killed or inactivated vaccines may 
be permitted according to the investigator’s discretion. 
It is recommended not to initiate biologic treatment until 3 months after the last dose of study drug. 
Therefore, biologic treatment should not be used any time during study participation. 
Table 6-2 
Prohibited Medication 
Medication 
Action taken 
Any biologic drugs, including but not limited to 
TNFα inhibitors, other biologic drug directly 
targeting IL-17 or IL-17 receptor, any biological 
DMARD (bDMARDs) 
Discontinue investigational treatment, complete 
Week 312/EOT visit 
Any cell-depleting therapies including but not 
limited to anti-CD20 or investigational agents [e.g. 
alemtuzumab (Campath), anti-CD4, anti-CD5, anti-
CD3, and anti-CD19]. 
Discontinue investigational treatment, complete 
Week 312/EOT visit 
Leflunomide 
Discontinue investigational treatment, complete 
Week 312/EOT visit 
Any investigational treatment or participation in any 
interventional trial 
Discontinue investigational treatment, complete 
Week312/EOT visit 
Analgesics other than NSAIDs, 
paracetamol/acetaminophen, and low strength 
opioids PRN 
 Discontinue investigational treatment, complete 
Week 312/EOT visit 
Intramuscular or intravenous corticosteroid 
treatment are not permitted 
To be reviewed on a case by case basis 
Live vaccinations 
Discontinue investigational treatment, complete 
Week 312/EOT visit 
6.2.3 
Rescue medication 
Rescue medication is defined as medication used to control symptoms that are not adequately 
controlled on investigational study treatment. 
Use of rescue medication is prohibited. Please see Section 6.2.1 and Section 6.2.2 for details on 
concomitant therapy and prohibited medications, respectively. Although no patient will be restricted 
from receiving necessary rescue medications for lack of benefit or worsening of disease, patients 
will be discontinued from the study and complete Week 312/EOT visit if treated with prohibited 
medications (as described in Section 6.2.2) and should complete an Early termination visit at the 
earliest possible time point and enter the Post-treatment follow-up period. Efficacy and safety will 
be assessed in detail at every study visit and, patients who are deemed by the Investigator not to be 
benefiting from study treatment, or for any reason on the patient’s own accord, will be free to 
discontinue study participation at any time. 


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Use of rescue medication must be recorded on the corresponding eCRF page. 
6.2.3.1 
Recommendation 
Table 6-3 
Recommendation 
Medication 
Action taken 
Conventional DMARDs (except SSZ (for ERA only) 
or MTX) including apremilast 
To be reviewed on a case by case basis. 
Leflunomide with cholestyramine 
To be reviewed on a case by case basis. 
6.3 
Patient numbering, treatment assignment, randomization  
6.3.1 
Patient numbering 
This being an extension study, the patient numbers will remain same as that of core study 
CAIN457F2304; new patient numbers will NOT be assigned. 
Each patient is identified in the extension study by a patient number (patient No.), that is assigned 
when the patient is first enrolled in core study (CAIN457F2304) and is retained as the primary 
identifier for the patient throughout his/her entire participation in the extension trial. The patient No. 
consists of the Center Number (Center No.) (as assigned by Novartis to the investigative site) with 
a sequential patient number suffixed to it, so that each patient is numbered uniquely across the entire 
database.  
6.3.2 
Treatment assignment, randomization 
All patients will continue to receive secukinumab dosing based on their weight at each drug 
dispensing visit. 
There is no re-randomization in this extension study, see Section 6.1.3 for more details. 
6.4 
Treatment blinding  
Treatment will be open to patients, investigator staff, persons performing the assessments, and the 
Clinical Trial Team (CTT). 
6.5 
Dose escalation and dose modification  
 
Starting from Week 108, the secukinumab dose can be escalated from 75 mg to 150 mg for 
patients whose signs and symptoms are not fully controlled with the current dose of 75 mg, and 
may improve with higher dose as judged by the investigator. 
 
Further, the dose can also be escalated to 300 mg for patients currently on 150 mg, and whose 
signs and symptoms are not fully controlled and may improve further with an increase in dose as 
judged by the investigator. 
The dose escalation from secukinumab 75 mg sc to 300 mg sc should be implemented in two steps 
(first 150 mg sc and then 300 mg sc based on investigator’s judgement) .  
 


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All escalation are allowed only at mandated site visits. For patients escalated to 150 mg or 300 mg, 
no dose reduction can be performed at a later stage. 
6.5.1 
Dose escalation guidelines 
6.5.1.1 
Starting dose 
The starting dose of study treatment during extension study, administered at Week 104E1 visit, will 
be 75 mg/0.5mL or 150 mg/1.0mL. 
6.5.2 
Dose modifications 
Investigators are permitted to increase the dose from 75 mg to 150 mg or from 150 mg to 300 mg 
for patients, per their discretion at each drug dispensing visit starting from Week 108. 
No dose adjustments or interruptions are permitted for patients, in any other case unless there is a 
medical/safety reason documented by the investigator that indicates the rationale for the dose 
adjustment or interruption. 
 
The reason for any study treatment interruption must be recorded on the corresponding eCRF page. 
6.5.3 
Follow-up for toxicities 
Not applicable 
6.6 
Additional treatment guidance 
6.6.1 
Treatment compliance 
All dates and times of study treatment administration will be recorded on the appropriate Dosage 
Administration Record eCRF page. 
Drugs administered at Week 104E1 and other drugs/procedures continuing or started during the 
extension roll over visit will be entered in the concomitant medications or significant non-drug 
therapies eCRF page. 
For visits where treatment is administered at site: compliance is expected to be 100%, unless 
temporary interruption is needed for safety reasons as described in Section 6.5.2. Compliance will 
also be assessed by a Novartis monitor using information provided by the authorized site personnel. 
For visits where treatment is administered at home: The investigator must promote compliance by 
instructing the patient to take the study treatment exactly as prescribed and by stating that compliance 
is necessary for the patient’s safety and the validity of the study. The patient must also be instructed 
to contact the investigator if he/she is unable for any reason to take the study treatment as prescribed. 
Compliance will be assessed by the investigator and/or study personnel at each visit using 
information provided by the patient. This information should be captured in the source document at 
each visit. All study treatment dispensed and returned must be recorded in the Drug Accountability 
Log. Pharmacokinetic parameters (measures of treatment exposure) will be determined in all patients 
treated with secukinumab (AIN457) as detailed in pharmacokinetics section. 


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6.6.2 
Emergency breaking of assigned treatment code  
Not applicable 
6.7 
Preparation and dispensation 
Each study site will be supplied with study drug in packaging as described under investigational and 
control drugs Section 6.1.1. 
A unique medication number is printed on the study medication label. 
Investigator staff will identify the study medication kits to dispense to the patient by contacting the 
IRT and obtaining the medication number(s). The study medication has a 2-part label (base plus tear-
off label), immediately before dispensing the medication kit to the patient, site personnel will detach 
the outer part of the label from the packaging and affix it to the source document. 
6.8 
Administration 
Secukinumab solution for s.c. injection will be provided in PFS. One s.c. injection should be self-
administered at each visit / time-point (secukinumab 75mg in 0.5mL or secukinumab 150mg in 1mL) 
until (and including Week 308). Starting at Week 108 only one or two s.c. injections would be 
dispensed for each dosing time point, depending on the secukinumab dose the patient is assigned to 
by the investigator. 
Subjects will be instructed at Week 104E1 by site staff on how to self-inject secukinumab via PFS, 
in accordance with the Instructions for use (IFU). The study treatment solution should be injected 
subcutaneously into an appropriate injection site, and each injection should be given at a different 
site. 
Each new injection should be given at least one inch from the previously used site. If the subject 
chooses the abdomen, 2 inches area around navel should be avoided. Investigational treatment 
should not be injected into areas where the skin is tender, bruised, red, or hard, or where the subject 
has scars or stretch marks. Injection sites should be rotated to reduce the risk of reaction. 
Single syringes will be packed in individual boxes. The boxes containing the PFS with study 
treatment solution should be kept at 2 to 8°C (36°F to 46°F, do not freeze) and protected from light. 
Prior to administration, the unopened boxes containing the PFS should be allowed to come to room 
temperature in a place protected from light for approximately 20 minutes. Used syringes should be 
disposed immediately after use in a sharps container OR according to the regulatory requirements in 
the respective country. 
The caregiver or site staff will administer the injection only to those subjects who are not able to 
self-administer the PFS injection. 
6.8.1.1 
Handling of study treatment and additional treatment  
6.8.2 
Handling of study treatment  
Study treatment must be received by a designated person at the study site, handled and stored safely 
and properly and kept in a secured location to which only the investigator and designated site 
personnel have access. Upon receipt, all study treatment must be stored according to the instructions 
specified on the labels and in the Investigator’s brochure. Clinical supplies are to be dispensed only 


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in accordance with the protocol. Technical complaints are to be reported to the respective Novartis 
Country Pharma Organization (CPO) Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the study treatment but no information about the 
patient except for the medication number. 
The investigator must maintain an accurate record of the shipment and dispensing of study treatment 
in a drug accountability log. Monitoring of drug accountability will be performed by monitors during 
site visits or remotely and at the completion of the trial. Patients will be asked to return all unused 
study treatment and packaging at the end of the study or at the time of discontinuation of study 
treatment. 
At the conclusion of the study, and as appropriate during the course of the study, the investigator 
will return all unused study treatment, packaging, drug labels, and a copy of the completed drug 
accountability log to the Novartis monitor or to the Novartis address provided in the investigator 
folder at each site. 
6.8.3 
Handling of additional treatment  
Not applicable 
6.9 
Instruction for prescribing and taking study treatment 
The first study treatment administration will occur at the Week104E1 visit after inclusion/exclusion 
criteria have been confirmed, all study scheduled assessments have been performed and the 
scheduled blood samples have been drawn.  
Starting at Week 108 of extension study the patients will be allowed to self-administer or 
parent/guardian can inject the patient with the PFS at home or continuing with administration at 
site, based on personal preference and the investigator’s clinical judgment, only if they have 
exhibited correct use for self-administering the PFS at the site. 
At such time points, a patient or parent/guardian would be allowed to administer study medication 
after having received proper training by site staff and having exhibited ability to perform the 
injection procedure to the patient at the site. 
 
It should be recorded on the corresponding eCRF(s) whether the patient self-administered the PFS 
and whether it was administered at home or at the site. 
 
Study treatment may be self-administered by patient or can be administered by parent/guardian 
subcutaneously every four weeks throughout the study at all site/optional home visits. The 
parent/guardian or site staff will administer the injection only to those patients who are not able or 
feel insecure to self-administer the PFS injection. 
All study medication packages assigned to the patient during the study will be in the IRT database. 
It shall be recorded on the corresponding eCRF(s) whether the patient self-administered the PFS, or 
whether site staff or the caregiver administered the PFS and whether it was administered at home or 
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For those who wish to self-inject, initially self-injection by patient or by parent/guardian will take 
place under the supervision of a site staff member. At Week 104E1 visit the patients, parent/guardian 
will be instructed by the site staff, using the Instructions for use (IFU), on how to self-inject or inject 
the patient via PFS.  
The copy of the PFS will be provided by site staff to the patient, parent/guardian. Detailed 
instructions for self-administration of study treatment will be described in the Instructions for use 
(IFU). Patients, parent/guardian will be asked to raise questions (if any), and then to proceed with 
self-injection or injection to the patient.  
At subsequent site visits, patients, parent/guardian will be asked to refer to the Instructions for use 
(IFU) and to proceed with self-injection or injecting the patient. 
At each subsequent study visit at site, all study assessments, including the completion of Patient 
Reported Outcomes (PROs) and pre-dose blood sample collection (wherever required), should be 
completed prior to the self-administration of the study treatment. 
All dosages dispensed to the patient and all dose changes during the study must be recorded on the 
Dosage Administration Record eCRF. Immediately before dispensing the package to the patient, 
investigator staff will detach the outer part of the label from the packaging and affix it to the source 
document (Drug Label Form) for that patient’s unique patient number. For those patients who opt 
for domiciliary / home administrations (at protocol specified time points) site staff will dispense 
(via IRT), at the prior site visit, an appropriate number of investigational treatment packages for 
the applicable upcoming domiciliary administrations. 
 
If the subject is not able / not confident to self-administer the PFS, and the caregiver is 
unable/unwilling to perform the injection, he/she should visit the site every 4 weeks during 
the treatment period and site staff will administer the PFS. 
 
Administration of study treatment must occur only after the study assessments for the visit have 
been completed (when these visits occur at site), and with the timing indicated in Table 8 -1 
(Assessment Schedule). 
For extension study the first study treatment administration will occur at the Week 104E1. At each 
subsequent site visit, all study assessments (as applicable per Table 8-1) should be completed prior 
to the injection of study treatment. Administration of study treatment should occur after sample 
collection for PK assessments (at visits specified in Table 8-1). 
All investigational treatment kits assigned by the IRT will be recorded in the IRT. The Investigator 
must promote compliance by instructing the patient/guardian to attend the study visits as scheduled 
and by stating that compliance is necessary for the patient’s safety and the validity of the study. The 
patient/guardian should be instructed to contact the Investigator if he/she is unable for any reason to 
attend a study visit as scheduled. 
Should a visit be delayed, every attempt should be made to bring the patient back on schedule for 
the next visit (referring to Baseline visit of core trial). 


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7 
Informed consent procedures  
Patients from core CAIN457F2304 study can participate in this optional, open label extension study 
after providing personally signed and dated written informed consent form, (witnessed, where 
required by law or regulation and IRB/IEC approved. 
If applicable, in cases where the patient's representative(s) gives consent (if allowed according to 
local requirements), the patient must be informed about the study to the extent possible given his/her 
understanding. If the patient is capable of doing so, he/she must indicate agreement by personally 
signing and dating the written informed consent document. 
Informed consent must be obtained before conducting any extension study-specific procedures (e.g. 
all of the procedures described in the protocol). The process of obtaining informed consent must be 
documented in the patient source documents. 
Novartis will provide to investigators in a separate document a proposed informed consent form that 
complies with the ICH GCP guidelines and regulatory requirements and is considered appropriate 
for this study. Any changes to the proposed consent form suggested by the investigator must be 
agreed by Novartis before submission to the IRB/IEC. 
Information about common side effects already known about the investigational drug can be found 
in the Investigator's brochure (IB). This information will be included in the patient informed consent 
and should be discussed with the patient during the study as needed. Any new information regarding 
the safety profile of the investigational drug that is identified between IB updates will be 
communicated as appropriate, for example, via an investigator notification or an aggregate safety 
finding. New information might require an update to the informed consent and then must be 
discussed with the patient. 
Females of child-bearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy was to occur during the study and agree that in order to 
participate in the study they must adhere to the contraception requirements. 
A copy of the approved version of all consent forms must be provided to Novartis after IRB/IEC 
approval. 
8 
Visit schedule and assessments 
Assessment schedule lists all of the assessments and indicates with an “X” or “S”, the visits when 
they are performed. All data obtained from these assessments must be supported in the patient’s 
source documentation. 
Patients should be seen for all visits/assessments as outlined in the assessment schedule or as close 
to the designated day/time as possible. Missed or rescheduled visits should not lead to automatic 
discontinuation. Patients who prematurely discontinue the study for any reason should be scheduled 
4 weeks after last study drug administration for the Week 312/EOT visit. At this visit, all dispensed 
investigational product should be reconciled, and the adverse event and concomitant medications 
recorded on the eCRF. The patient should then return for the final follow up visit 12 weeks after last 
drug administration. Week 320/PWD (Premature Withdrawal of Subject) at which time all of the 
assessments listed for the final visit will be performed. 
 




























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X = Assessment to be recorded in the clinical database or received electronically from a vendor 
S = Assessment to be recorded in the source documentation only 
1 = ECG to be collected locally at the end of every year 
2 = CRP will be measured at the local lab, including during unscheduled visit, and the actual sample 
collection date, time and result will be collected.  
3 = PK – Pharmacokinetic samples should be obtained prior to study drug administration. 2 aliquots to be 
collected at each scheduled visit  
4 = IG - Immunogenicity samples should be obtained prior to study drug administration. 2 aliquots to be 
collected at each scheduled visit  
5 = Only if positive pregnancy urine dipstick test, samples to be collected and shipped to central lab  
6 = IRT to be contacted based on type of visit  
a. For Site administration:- Contact IRT every week  
b. For Home administration:- Contact IRT at the previous site visit and collect drug for 
subsequent home visits. 
 
7 = Study drug administration is to be done after all assessments are completed. All dose escalations are 
allowed only at mandated site visits. For patients escalated to 150 mg or 300 mg, no dose reduction can 
be performed at a later stage.  
8 = Starting Week 108 patients will have the choice of self-administration or injection by parent /guardian 
(once trained) at home visits in which there are no scheduled site assessments or they can come to the 
site if they are not able or feel insecure to self-administer. 
9= In order to prevent bias, the physician's global assessment of disease activity (VAS) should be 
completed prior to the investigator reviewing the parent’s /patients Global Assessment of disease activity 
(which is completed as part of the CHAQ©). 
10 = If patients decides to discontinue study at any point of time, the patients would need to complete the 
follow-up visit 12 weeks after the last dose.  
11 = Weight to be taken and IRT to be contacted if the patient comes for site administration 
12 = If the dipstick result is positive for protein, glucose and/or blood, a urine sample will be sent to central 
laboratory for microscopic analysis. 
13 = The site will need to submit the joint count assessment worksheet to central vendor for ACR pediatric 
response at each scheduled visit, the results will be communicated to the investigator.  
14= Assessment required only at first visit, not listed for the subsequent year. 
 


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8.1 
Screening 
There is no screening and re-randomization in this extension study. At Week 104, all eligible patients 
from the core study can opt to be enrolled in the extension study via Interactive Response Technology 
(IRT). They will continue to receive secukinumab dosing, which is assigned based on their weight. 
The Week 104E1 will be performed on the same day once the Week 104 is completed by patient. 
Patients must be able to understand and communicate with the investigator and comply with the 
requirements of the study and must give a written, signed and dated informed consent before any 
extension study assessments are performed. 
The investigator or his/her delegate will contact the IRT after confirming that the patient fulfills all 
the inclusion/exclusion criteria. The IRT will then specify a unique medication number for the first 
package of investigational treatment to be dispensed to the patient for Week 104E1. 
8.2 
Patient demographics/other baseline characteristics 
Patient demographic and baseline characteristics will NOT be separately captured in the extension 
database, patient No. from core CAIN457F2304 study will be the only information captured.  
Investigators will have the discretion to record ongoing medical history in the extension database 
whenever in their judgment. 
Investigator does have to capture all ongoing AE and concomitant medication at Week 104 of core 
trial to the extension study database. 
8.3 
Efficacy 
The efficacy outcome measures used in this study are standard measures used across JIA trials. 
• JIA ACR 30, 50, 70, 90 and 100 response criteria 
• Physician’s Global Assessment of disease activity (VAS) 
• Parent’s/patient’s Global Assessment of patient’s overall well-being (VAS included within 
CHAQ©) 
• Childhood Health Assessment Questionnaire (CHAQ©) 
• Active joint count 
• Swollen Joint Count (SJC) 
• Tender Joint Count (TJC) 
• Joint count with limited range of motion 
• CRP (local) 
• Inactive disease status 
• JADAS score 
• Total dactylitis count 
• Total enthesitis count 
 
 


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All efficacy assessments should be performed prior to administration of study treatment. 
Table 8-2 
Efficacy outcome measures and related assessments  
 
Outcome 
measure 
Relevant 
section 
Efficacy assessment 
CHAQ© * 
including 
parent’s/pa
tient’s 
Global 
Assessme
nt (VAS) 
Physician 
global 
assessmen
t (VAS) 
Active 
Joint 
count 
Tender and 
Swollen 
Joint Count 
Joint 
count with 
limited 
range of 
motion 
C-
reactive 
protein 
Assessment 
of morning 
stiffness due 
to ERA/JPsA 
Uveitis 
Tol. 
Enthesitis 
count 
Tol. 
Dactylitis 
count 
PK blood 
collection 
Section 
16.6 
Section 
8.3.1.2 & 3 
Section 
16.5 
Section 
8.3.1.1 
Section 
8.3.1.4 
Section 
8.3.1.7 
Section 
8.3.1.5 
Section 
8.3.1.6 
Section 8.3.4 
Section 
8.3.5 
Section 
8.3.6 
Section 
8.3.7 
Section 
8.5.2 
JIA ACR 
Response 
Section 
16.8 
Section 
8.3.1 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
JIA ACR 
50/70/90/100 
JIA ACR Core 
Components 
Section 
16.8 
Section 
8.3.1 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Inactive 
Disease 
Status 
Section 
8.3.2 
 
 
 
 
 
 
X 
X 
 
 
 
JADAS Score 
Section 
8.3.3 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
Total 
Enthesitis 
count   
Section 
8.3.6 
 
 
 
 
 
 
 
 
X 
 
 
Total 
Dactylitis 
count 
Section 
8.3.7 
 
 
 
 
 
 
 
 
 
X 
 
Secukinumab 
serum 
concentration
s and derived 
PK 
parameters 
Section 
8.5.2 
 
 
 
 
 
 
 
 
 
 
X 


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8.3.1 
JIA ACR response criteria 
Standard ACR pediatric Criteria (JIA ACR criteria) consists of 6 core components which will 
be assessed as scheduled in Table 8-1. JIA ACR 30/50/70/90/100 are defined as 30%, 50%, 
70%, 90% and 100% improvement from baseline of core study CAIN457F2304 respectively in 
a minimum of three variables in the core set with no more than one variable worsening more 
than 30% as defined in the ACR criteria. 
The 6 core set variables are summarized below: 
• Physician global assessment of disease activity on a 0 - 100 mm VAS from 0 mm = no 
disease activity to 100 mm = very severe disease activity 
• Parent or patient’s (if appropriate in age) Global Assessment of patient’s overall well-
being on a 0-100 mm VAS from 0 mm = very well to 100 mm = very poor. 
• Functional ability: Childhood Health Assessment Questionnaire (CHAQ©)  
• Number of active joints using the ACR definition (any joint with swelling or in the 
absence of swelling, limitation of motion accompanied by either pain on motion or 
tenderness not due to deformity) 
• Number of joints with limited range of motion 
• Laboratory measure of inflammation: CRP (local) (mg/L) 
The respective response variables listed above will be used by a central vendor to determine 
ACR Pediatric response. These results will be communicated to the investigator. Additionally, 
these components will be used to determine JADAS and inactive disease status (Wallace et al 
2011) as part of secondary 
analyses.  
8.3.1.1 
Physician’s Global Assessment of disease activity (VAS) 
The physician will rate the patient’s current condition on a 0-100 mm VAS Section 16.5, 
ranging from no disease activity (0 mm) to very severe disease activity (100 mm), at each 
scheduled visit for all patients throughout the study. 
Scores on the 100 mm linear scale will be measured to the nearest millimeter from the left. To 
enhance objectivity, the physician must not be aware of the specific parent’s or patient’s global 
assessment of patient’s overall well-being, when performing his own assessment on that patient. 
8.3.1.2 
Parent’s/patients Global Assessment of patients overall well-being 
(VAS) 
The parent’s or patients global assessment of the 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. 
8.3.1.3 
Childhood Health Assessment Questionnaire (CHAQ©) 
The Childhood Health Assessment Questionnaire (CHAQ©), Section 16.6, will be used to assess 
physical ability and functional status of patients as well as quality of life. The disability 
dimension consists of multiple choice and VAS items concerning difficulty in performing eight 


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common activities of daily living; dressing and grooming, arising, eating, walking, reaching, 
personal hygiene, gripping and activities. Patients choose from four response categories, 
ranging from ‘without any difficulty’ to ‘unable to do’.  
This questionnaire should be completed by the parent (or, for patients 18 years and older, the 
questionnaire will be completed together by both the patient and parent) according to schedule 
in Table 8-1.The (CHAQ©) will be completed only in a validated version of the instrument in 
the language understandable to the parent and/or patient. 
Completed questionnaires will be reviewed and examined by the investigator, before the clinical 
examination, for responses which may indicate potential AEs or SAEs. If AEs or SAEs are 
confirmed, then the physician must record the events as per instructions given in Section 10.1.1 
and Section 10.1.2 of the protocol. Investigators should not encourage the patients and/or 
parents to change the responses reported in the PRO questionnaires. 
8.3.1.4 
Active joint count  
The number of joints with active arthritis at each visit will be determined by applying the ACR 
definition to the number of joints with swelling, tenderness and limited range of motion at each 
scheduled visit for all patients throughout the study (see Section 8.3.1.5 and Section 8.3.1.7 for 
more details). 
Joint counts will be performed by an assessor who must be well trained and part of the site 
personnel. For there to be consistency between the joint assessments, it is strongly 
recommended that the same evaluator perform these assessments at all visits. 
The ACR definition of active arthritis is any joint with swelling or, in the absence of swelling, 
limitation of motion accompanied by either pain on motion or tenderness not due to deformity. 
The active joint count will therefore range from 0 to 73. 
The site will need to submit the joint count assessment worksheet to central vendor for ACR 
Pediatric response at each scheduled visit per Table 8-1, the results will be communicated to 
the investigator.  
8.3.1.5 
Joint counts with limitation of motion 
A total of 69 joints will be assessed for limitation of motion at each scheduled visit for all 
patients throughout the study. The same 75 joints assessed for tenderness (Section 8.3.1.7) will 
also be assessed for limitation of motion excluding the 2 sternoclavicular, 2 acromioclavicular 
joints as well as the 2 sacroiliac joints.  
For there to be consistency between the joint assessments, it is strongly recommended that the 
same evaluator perform these assessments at all visits. 
8.3.1.6 
C-reactive Protein (CRP) 
C-reactive Protein CRP (local) is used as an inflammation marker, to determine its severity, and 
to monitor response to treatment. 
CRP (local) will be measured at the local lab, at each scheduled visit for all patients throughout 
the study including during unscheduled visit, and the actual sample collection date, time and 
result will be collected.  


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8.3.1.7 
Tender and Swollen Joint Count 
Tender 75 joint counts (TJC) 
The following 75 joints will be scored as either tender or not tender:  
• Temporomandibular joints: 2  
• Sternoclavicular joints: 2  
• Acromioclavicular joints: 2  
• Shoulders: 2  
• Elbows: 2  
• Wrists: 2 
• Hands:  
• 8 Distal interphalangeal  
• 10 proximal interphalangeal  
• 10 metacarpophalangeal  
• Hips: 2  
• Knees: 2 
• Ankles: 2 
• Subtalar joints: 2 
• Intertarsal joints: 2 
• Feet:  
• 10 metatarsophalangeal joints  
• 10 toes  
• Cervical spine is assessed as a single joint 
• Thoracic spine is assessed as a single joint 
• Lumbar spine is assessed as a single joint 
• Sacroiliac joints: 2 
Joint tenderness is to be scored as present or absent. For there to be consistency between the 
joint assessments, it is strongly recommended that the same evaluator perform these 
assessments at all visits. 
Swollen joint count (SJC) 
A total of 68 joints are to be scored as either swollen or not swollen. The same 75 joints assessed 
for tenderness will also be assessed for swelling excluding the cervical spine, thoracic spine, 
lumbar spine, 2 hips and 2 sacroiliac joints. 
For there to be consistency between the joint assessments, it is strongly recommended that the 
same evaluator perform these assessments at all visits. 
8.3.2 
Inactive Disease Status 
Clinical inactive disease definition is adapted from the ACR criteria of (Wallace et al 2011). 
All must be met: 


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• No joints with active arthritis  
• No uveitis 
• CRP (local) value within normal limits for the laboratory where tested or, if elevated, not 
attributable to ERS/JPsA Physician’s global assessment of disease activity score of best 
possible on the scale used (i.e. best possible score is defined as ≤ 10mm) 
• The absence of patient-reported morning stiffness attributable to JPsA or ERA lasting ≥15 
minutes. 
8.3.3 
Juvenile Arthritis Disease Activity Score (JADAS) 
Juvenile Arthritis Disease Activity Score (JADAS) (Consolaro et al 2009) will be derived from 
the following assessments performed at all scheduled visits: 
• physician global assessment of disease activity;  
• parent/patient global assessment of overall well-being;  
• active joint count;  
• Tender and Swollen Joint Count; 
• CRP (local) 
8.3.4 
Assessment of duration of morning stiffness 
The presence or absence of patient/parent-reported morning stiffness that day attributable to 
JPsA or ERA lasting at least 15 minutes will be assessed as part of evaluation of inactive disease 
status. 
8.3.5 
Assessment of Uveitis due to JIA 
The presence or absence of uveitis that day will be assessed as part of evaluation of inactive 
disease status. Clinically suspected uveitis should be confirmed as per the Standardization of 
Uveitis Nomenclature (SUN) Working Group definition. No uveitis is defined as “grade zero 
cells,” indicating < 1 cell in field sizes of 1 mm by a 1 mm slit beam (Zierhut 2007). 
8.3.6 
Total enthesitis count 
The following 16 entheseal sites will be assessed for the presence or absence of tenderness 
(enthesitis) on each side of the body: 
• Anterior Entheses: Greater trochanter of the Femur; Medial condyle of the femur; Lateral 
condyle of the femur 
• Posterior Entheses: Greater tuberosity of humerus; medial epicondyle of humerus; lateral 
epicondyle of humerus, Achilles tendon; and calcaneal insertion of the plantar fascia. 
8.3.7 
Total dactylitis count 
The dactylitis count is the number of fingers and toes presenting with dactylitis, with a range of 
0-20.  




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8.4.3 
Height and weight 
Height in centimeters (cm) will be assessed with the patient wearing indoor clothing, but 
without shoes, socks, hats or hair accessories interfering with assessment, 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.  
Body weight (to the nearest 0.1 kilogram (kg) will be assessed with the patient wearing similar 
clothing (indoor clothing but without shoes) at each visit and where possible, by the same study 
site staff member using the same scale throughout the study. 
8.4.4 
Laboratory evaluations 
A central laboratory will be used for analysis of all specimens listed below (except dipstick 
urinalysis and CRP which are done locally). Details on the collection, processing and shipment 
of samples and reporting of results by the central laboratory are provided in the laboratory 
manual. For the identification of clinically notable values, see Section 16.1. All patients with 
laboratory tests containing clinically significant abnormal values are to be followed until the 
values return to normal ranges or until a valid reason, other than treatment related AE, is 
defined. 
8.4.4.1 
Hematology 
Hematology will include hemoglobin, hematocrit, platelets, red blood cell (RBC), white blood 
cell (WBC), neutrophils, lymphocytes, monocytes, eosinophils, basophils, absolute neutrophils, 
absolute lymphocytes, absolute monocytes, absolute eosinophils, absolute basophil, at 
scheduled visits as per assessment schedule in Table 8-1. 
8.4.4.2 
Clinical chemistry 
Serum chemistries will include sodium, potassium, bicarbonate, BUN/urea, creatinine, glucose, 
calcium, phosphorus, total protein, albumin, total bilirubin (TBL), ALT (SGPT), AST (SGOT), 
GGT (Gamma-glutamyl transferase), alkaline phosphatase (ALP) and uric acid will be 
measured at scheduled visits as per assessment schedule in Table 8-1. 
8.4.4.3 
Urinalysis 
Dipsticks will be provided by the central laboratory to the sites for local urinalysis assessments 
at scheduled visits as per Table 8-1. The urinalysis results for standard parameters such as 
glucose, protein, blood and WBC will be recorded in the appropriate eCRF page. 
If the dipstick result is positive for protein, glucose and/or blood a urine sample will be sent to 
central laboratory for microscopic analysis as indicated in the renal safety Section 10.2.2.  
8.4.4.4 
Lipid panel 
A lipid profile including total cholesterol, High Density Lipoprotein (HDL), Low Density 
Lipoprotein (LDL), and triglycerides will be measured from a fasting blood sample that will be 
collected at scheduled visits as per assessment schedule in Table 8-1. 


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8.4.5 
Electrocardiogram (ECG) 
A standard 12-lead ECG (local) will be performed as indicated in Table 8-1. ECGs must be 
recorded after 10 minutes rest in the supine position to ensure a stable baseline. The preferred 
sequence of cardiovascular data collection during study visits is ECG collection followed by 
vital signs and blood sampling. The Frederica’s QT correction formula (QTcF) should be used 
for clinical decisions. 
All ECGs will be collected locally at site .The investigator must maintain source ECG 
documents for each patient in the study. Information for all ECGs examinations must be 
included in the source documentation at the study site system. Significant findings made after 
signing the ICF which meet the definition of an AE must be recorded in the Adverse Event 
section of the eCRF. 
 
8.4.6 
Pregnancy and assessments of fertility 
Females of child-bearing potential are defined as all females physiologically capable of 
becoming pregnant. This includes female adolescents who are menarchal or who become 
menarchal during the study.  
A serum β-hCG test will be performed only if there is positive urine dipstick test.   
Urine pregnancy tests are performed at visits indicated in Table 8-1 in all female patients of 
child-bearing potential. Additional pregnancy tests may be performed at the investigator’s 
discretion during the study. A positive urine pregnancy test requires immediate interruption of 
study treatment until serum β-hCG is performed and found to be negative. If positive, the patient 
must be discontinued from study drug.  
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 adolescent 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 adolescent should be considered in accordance with the local law and ethics. 
Female patients of child-bearing potential, who are or might become sexually active, must be 
informed of the need to prevent pregnancy during the study and for 20 weeks after study 
completion. At a minimum, the acceptable effective contraception is: 
• Total abstinence (when this is in line with the preferred and usual lifestyle of the patient. 
Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and 
withdrawal are not acceptable methods of contraception) 


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• Barrier method of contraception: Condom or Occlusive cap (diaphragm or cervical/vault 
caps). For UK (United Kingdom): with spermicidal foam/gel/film/cream/vaginal 
suppository 
• Use of oral, injected or implanted hormonal methods of contraception or other forms of 
hormonal contraception that have comparable efficacy (failure rate <1%), for example 
hormone vaginal ring or transdermal hormone contraception. In case of use of oral 
contraception Female should have been stable on the same pill for a minimum of 3 months 
before taking study treatment 
• Placement of an intrauterine device (IUD) or intrauterine system (IUS) 
• Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy), total hysterectomy or tubal ligation at least six weeks before taking study 
treatment. In case of oophorectomy alone, the sterile reproductive status of the woman 
must have been tested by follow up hormone level assessment 
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 and the need for additional 
pregnancy testing. 
8.4.7 
Tolerability of secukinumab 
Tolerability will be assessed by adverse events, laboratory values, injection site reactions and 
immunogenicity. 
8.4.8 
Immunogenicity 
Blood samples for immunogenicity (anti-AIN457 antibodies) will be taken pre-dose at the 
scheduled time points as indicated in Table 8-1. 
In addition, if a patient discontinues from the study at any time, he/she will need to provide a 
sample at the last visit. The actual sample collection date and exact time will be entered on the 
Immunogenicity Blood collection eCRF page. Sampling problems will be noted in the 
Comment section of the eCRF page. 
All blood samples will be taken by either direct venipuncture or an indwelling cannula inserted 
in a forearm vein. 
A laboratory manual will be provided to investigators with detailed information on sample 
collection, handling and shipment. 
Tubes and preprinted labels will be provided by the central lab to the sites. 
Analytical Method 
An electrochemiluminescence method will be used for the detection of potential anti-
secukinumab antibody formation. The detailed method description to assess immunogenicity 
will be described in the bioanalytical raw data of the study and in the respective Bioanalytical 
Data Report. 


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Table 8-3 
IG sample log 
Week 
IG Sample number 
W128 
306 
W156 
307 
W180 
308 
W208 
309 
W232 
310 
W260 
311 
W284 
312 
W308 
313 
W312 
314 
Unscheduled1 
4001.... 
1= If an IG sample is collected at an unscheduled visit, the sample numbers will follow the 
pattern: 4001, 4002, etc. 
8.4.9 
Other safety evaluations 
Not applicable. 
8.4.10 
Appropriateness of safety measurements 
The safety measures used in this study are standard for a use of a biologic in patients with JPsA 
/ ERA and are standard and adequate for this indication/patient population. The frequency of 
the visits and the close medical monitoring will ensure possible safety concerns are properly 
addressed. 
8.5 
Additional assessments  
8.5.1 
Pharmacokinetics  
PK samples will be obtained for all patients and the secukinumab concentrations will be 
assessed in serum. The PK samples will be collected pre-dose at scheduled visits/time points as 
indicated in Table 8-1. 
All blood samples will be drawn by direct venipuncture in a forearm vein. 
The actual sample collection date and exact time will be entered on the PK blood collection 
summary eCRF page. Sampling problems will be noted in the Comments section of the eCRF 
page. 
The bioanalyst will receive a copy of the randomization schedule to facilitate analysis of the 
PK samples. The bioanalyst will provide the samples’ concentration data to the team under 
blinded conditions. Bioanalyst will keep this information confidential until clinical database 
lock. 
PK sample handling, labeling and shipment instructions 
Laboratory manuals will be provided by the central laboratory with detailed information on 
sample collection, sample handling and shipment. 


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Tubes and labels will be provided by the central laboratory with study/sample type information 
pre-printed on the label. 
Analytical methods 
An ELISA (enzyme-linked immunosorbent assay) method will be used for bioanalytical 
analysis of secukinumab in serum, with an anticipated lower limit of quantification (LLOQ) of 
80 ng/mL. The detailed method description to assess secukinumab concentration will be 
described in the bioanalytical raw data of the study and in the respective Bioanalytical Data 
Report (BDR). 
Table 8-4 
PK sample log 
Week 
Time 
Sample number 
Dose reference ID 
W128 1 
pre-dose 
91 
1 
W156 1 
pre-dose 
92 
1 
W180 1 
pre-dose 
93 
1 
W208 1 
pre-dose 
94 
1 
W232 1 
pre-dose 
95 
1 
W260 1 
pre-dose 
96 
1 
W284 1 
pre-dose 
97 
1 
W308 1 
pre-dose 
98 
1 
W312 1 
(Any time at visit) 
99 
1 
Unscheduled 
Pre-dose 
2001... 
 
1=Required samples in every patient.  
 
If a PK sample is collected at an unscheduled visit, the sample numbers will follow the pattern: 2001, 
2002, etc.  
9 
Study discontinuation and completion 
9.1 
Discontinuation 
9.1.1 
Discontinuation of study treatment  
Discontinuation of study treatment for a patient occurs when study treatment is stopped earlier 
than the protocol planned duration i.e. Week 308, and can be initiated by either the patient or 
the investigator. 
The investigator must discontinue study treatment for a given patient if, he/she believes that 
continuation would negatively impact the patient's well-being. 
Study treatment must be discontinued under the following circumstances: 
• Patient/parent/guardian decision 
• Physician decision 
• Adverse Event 
• Lack of efficacy 


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• Loss to follow up  
• Pregnancy 
• Use of prohibited treatment as per recommendations in the prohibited treatment section 
• Any situation in which study participation might result in a safety risk to the patient 
If discontinuation of study treatment occurs, the investigator should make a reasonable effort 
to understand the primary reason for the patient’s premature discontinuation of study treatment 
and record this information. 
Patients who discontinue study treatment or who decide they do not wish to participate in the 
study further should NOT be considered withdrawn from the study UNLESS they withdraw 
their consent (see withdraw of informed consent Section 9.1.2). Where possible, they should 
return for the assessments indicated in the assessment schedule. If they fail to return for these 
assessments for unknown reasons, every effort (e.g. telephone, e-mail, letter) should be made 
to contact the patient/pre-designated contact as specified in the lost to follow-up Section 9.1.3 
This contact should preferably be done according to the study visit schedule. 
If the patient cannot or is unwilling to attend any visit(s), the site staff should maintain regular 
telephone contact with the patient, or with a person pre-designated by the patient. This telephone 
contact should preferably be done according to the study visit schedule. 
After study treatment discontinuation, at a minimum, in abbreviated visits, the following data 
should be collected at clinic visits or via telephone/email contact: 
• new / concomitant treatments 
• adverse events/Serious Adverse Events 
The investigator must also contact the IRT to register the patient’s discontinuation from study 
treatment. 
9.1.2 
Withdrawal of informed consent  
Patients in consultation with the guardian or the guardian may voluntarily withdraw patient’s 
consent to participate in the study for any reasons at any time, without being obliged to give 
any explanation. Withdrawal of consent from the study is defined as when a patient/guardian: 
• Does not want to participate in the study anymore, and 
• Discontinues all elements outlined in the protocol, and 
• Does not want any further visits or assessments, and 
• Does not want any further study related contacts, and 
• Does not allow analysis of already obtained biologic material 
In this situation, the Investigator must make every effort (e.g. telephone, e-mail, letter) to 
determine the primary reason for the patient/guardian’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. All biological 
material that has not been analyzed at the time of withdrawal must not be used. 


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Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the patient’s study withdrawal should be made as detailed in Table 8-1. 
This up to 4 year extension study will offer continuous secukinumab therapy to eligible patients 
from the core study CAIN457F2304. Patients from core study CAIN457F2304 can participate 
in this optional, open label extension study for a minimum of one year or until one of the 
following conditions are met, whichever is earlier:  the drug is locally approved, marketed, and 
reimbursed, OR– secukinumab can be provided free of charge to patients in compliance with 
local guidelines, OR– a maximum of 4 years study duration. 
9.1.3 
Lost to follow-up  
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the Investigator should show "due diligence" by 
documenting in the source documents steps taken to contact the patient/guardian, e.g. dates of 
telephone calls, registered letters, etc. A patient can not be considered as lost to follow-up until 
the time point of his/her scheduled end of study visit has passed. 
9.1.4 
Early study termination by the sponsor  
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit risk assessment of participating in the study, practical reasons, or for 
regulatory or medical reasons. In taking the decision to terminate, Novartis will always consider 
patient welfare and safety. Should early termination be necessary, the patient must be seen as 
soon as possible and treated as a premature patient/subject withdrawal (PSW) provide 
instruction to  the patient, when the patient should stop taking drug, when the patient should 
come for a final visit (see Table 8-1). 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/Novartis depending on local regulation will be responsible 
for informing the Institutional Review Board/Independent Ethics Committee (IRBs/IECs) of 
the early termination of the trial. 
9.2 
Study completion and post-study treatment  
A patient will be considered “Treatment Completed” ONLY when the patient has received all 
doses at each visit as per Table 8-1.  
If patient discontinues the study treatment due to any of the criteria as described in Section 
9.1.1, the patient would be captured at premature discontinuation of the treatment and still needs 
to come for the follow up visit at Week 320. 
A patient will considered “Study Completed” ONLY when the patient has completed all of the 
scheduled study assessment and procedures at Week 320 visit. 
Information on the patient’s completion or premature discontinuation of the study and the 
reason for discontinuation of the study will be recorded on the appropriate eCRF page. 
Additionally, the investigator or site staff must contact the IRT as soon as possible to record the 
patient’s study completion and/or discontinuation. 


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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. This care may 
include initiating another treatment outside of the study as deemed appropriate by the 
investigator. In case of a biologic treatment, a waiting period of 3 months before initiating the 
treatment is recommended. 
10 
Safety monitoring and reporting  
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events  
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and 
unintended sign, including abnormal laboratory findings, symptom or disease) in a patient or 
clinical investigation patient after providing written informed consent for participation in the 
study. Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. 
The investigator has the responsibility for managing the safety of individual patient and 
identifying adverse events. 
The occurrence of adverse events must be sought by non-directive questioning of the patient at 
each visit during the study. Adverse events also may be detected when they are volunteered by 
the patient during or between visits or through physical examination findings, laboratory test 
findings, or other assessments. 
Information about adverse drug reactions for the investigational drug can be found in the 
Investigator’s brochure (IB). 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria: 
• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline of core study CAIN457F2304 or the previous visit, or values which are considered to 
be non-typical in patient with underlying disease. Investigators have the responsibility for 
managing the safety of individual patient and identifying adverse events. Alert ranges for 
laboratory and other test abnormalities are included in Section 16. 1. 
Adverse events must be recorded in the Adverse Events CRF page 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 
• severe: prevents normal activities 


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• its relationship to the study treatment (no/yes), or other treatment (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 must be reported. 
• whether it constitutes a serious adverse event (see Section 10.1.2 for definition of SAE) 
• action taken regarding investigational treatment  
All adverse events must be treated appropriately. Treatment may include one or more of the 
following:  
• no action taken (e.g. further observation only)  
• investigational treatment dosage adjusted/temporarily interrupted  
• investigational treatment permanently discontinued due to this adverse event  
• concomitant medication given  
• non-drug therapy given  
• patient hospitalized/patient’s hospitalization prolonged (see Section 10.1.2 for definition 
of SAE) 
• its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown) 
Once an adverse event is detected, it must be followed until its resolution or until it is judged to 
be permanent, and assessment must be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the study drug, the interventions required 
to treat it, and the outcome. 
Information about common side effects already known about the investigational drug can be 
found in the Investigator’s brochure (IB). This information will be included in the patient 
informed consent and should be discussed with the patient/guardian during the study as needed. 
Any new information regarding the safety profile of the medicinal product that is identified 
between IB updates will be communicated as appropriate, for example, via an Investigator 
Notification or an Aggregate Safety Finding. New information might require an update to the 
informed consent and has then to be discussed with the patient/guardian. 
The Investigator must also instruct each patient/guardian to report any new adverse event 
(beyond the protocol observation period) that the patient/guardian, or the patient’s personal 
physician, believes might reasonably be related to study treatment. This information must be 
recorded in the investigator’s source documents; however, if the AE meets the criteria of an 
SAE, it must be reported to Novartis. 
10.1.2 
Serious adverse events  
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: 
• fatal 
• life-threatening 


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Life-threatening in the context of a SAE refers to a reaction in which the patient was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to the ICH-E2D Guidelines). 
• results in persistent or significant disability/incapacity 
• constitutes a congenital anomaly/birth defect 
• requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:  
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition   
• elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
• social reasons and respite care in the absence of any deterioration in the patient’s 
general condition 
• treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
• is medically significant, e.g. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life-threatening or result in death or hospitalization but might jeopardize the patient or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant”. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do 
not result in hospitalization or development of dependency or abuse. 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All reports of intentional misuse and abuse of the product are also considered serious adverse 
event irrespective if a clinical event has occurred. 
10.1.3 
SAE reporting  
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 12 weeks after last administered dose of study treatment 
or 30 days after the patient has stopped study participation (whichever is later) must be reported 
to Novartis within 24 hours of learning of its occurrence. Any SAEs experienced after this 
period should only be reported to Novartis if the Investigator suspects a causal relationship to 
study treatment.  
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the Investigator receiving the follow-up information. An SAE occurring at a 


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different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event. 
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form; all applicable sections of the form must be completed in order to provide a clinically 
thorough report. The Investigator must assess the relationship of each SAE to the study 
treatment, complete the SAE Report Form in English, and submit the completed form within 
24 hours to Novartis. Detailed instructions regarding the submission process and requirements 
for signature are to be found in the Investigator folder provided to each site.  
Follow-up information is submitted as instructed in the Investigator folder. Each re-occurrence, 
complication, or progression of the original event must be reported as a follow-up to that event 
regardless of when it occurs. The follow-up information should describe whether the event has 
resolved or continues, if and how it was treated, whether the blind was broken or not, and 
whether the patient continued or withdrew from study participation. 
If the SAE is not previously documented in the Investigator’s brochure or Package Insert (new 
occurrence) and is thought to be related to the study treatment a Novartis Chief Medical Office 
& Patient Safety (CMO&PS) Department associate may urgently require further information 
from the Investigator for health authority reporting. Novartis may need to issue an Investigator 
Notification (IN) to inform all investigators involved in any study with the same study treatment 
that this SAE has been reported. Suspected Unexpected Serious Adverse Reactions (SUSARs) 
will be collected and reported to the competent authorities and relevant Ethics committees (EC) 
in accordance with EU Guidance 2011/C 172/01 or as per national regulatory requirements in 
participating countries. 
10.1.4 
Pregnancy reporting  
To ensure patient safety, each pregnancy occurring after signing the informed consent must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications. 
Pregnancy should be recorded and reported by the investigator to the Novartis Chief Medical 
Office and Patient Safety (CMO&PS). Pregnancy follow-up should be recorded on the same 
form and should include an assessment of the possible relationship to the study treatment, any 
pregnancy outcome. Any SAE experienced during pregnancy must be reported. 
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form. 
10.1.5 
Reporting of study treatment errors including misuse/abuse  
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, patient or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. 


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Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be collected in 
the DAR (dose administration record) eCRF irrespective of whether or not associated with an 
AE/SAE and reported to Safety only if associated with an SAE. Misuse or abuse will be 
collected and reported in the safety database irrespective of it being associated with an AE/SAE 
within 24 hours of Investigator’s awareness. 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error type 
Document in Dose 
Administration (DAR) 
eCRF (Yes/No) 
Document in AE 
eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated with 
an AE 
Only if associated with 
an SAE 
Misuse/Abuse 
Yes 
Yes 
Yes, even if not 
associated with a SAE 
For more information on AE and SAE definition and reporting requirements, please see the 
respective sections. 
10.2 
Additional Safety Monitoring 
10.2.1 
Liver safety monitoring  
To ensure patient safety and enhance reliability in determining the hepatotoxic potential of an 
investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed. 
The following two categories of abnormalities / adverse events have to be considered during 
the course of the study (irrespective of whether classified/reported as AE/SAE): 
• 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 16-3 in  Section 16.2  for complete definitions of liver laboratory triggers 
and liver events. 
Every liver event defined in Table 16-3 in Section 16.2 should be followed up by the 
investigator or designated personnel at the trial site, as summarized below. Additional details 
on actions required in case of liver events are outlined in Table 16-4. 
For the liver laboratory trigger: 
• Repeating the liver function test (LFT) within the next week to confirm elevation. 
These LFT repeats must be performed using the central laboratory if possible. If this is not 
possible, then the repeats can be performed at a local laboratory to monitor the safety of the 
patient. Repeats laboratory must then be performed at central laboratory as soon as possible. If 


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a liver event is subsequently reported, any local LFTs previously conducted that are associated 
with this event must be reported on the Liver CRF pages. 
• If the elevation is confirmed, close observation of the patient will be initiated, including 
consideration of treatment interruption if deemed appropriate. 
For the liver events: 
• Repeating the LFT to confirm elevation as appropriate 
• Discontinuation of the investigational drug if appropriate 
• Hospitalization of the patient if appropriate 
• A causality assessment of the liver event via exclusion of alternative causes (e.g. disease, 
co-medications) 
• An investigation of the liver event which needs to be followed until resolution. 
These investigations can include serology tests, imaging and pathology assessments, 
hepatologist’s consultancy; based on investigator's discretion. 
All follow-up information, and the procedures performed must be recorded as appropriate in 
the CRF pages. 
10.2.2 
Renal safety monitoring  
The following two categories of abnormal renal laboratory values have to be considered during 
the course of the study: 
• Serum event:  
• confirmed (after ≥24hours) increase in serum creatinine of ≥25% compared to 
baseline of core study CAIN457F2304 which exceeds the normal limits for the 
patient’s gender and age during normal hydration status and continues for ≥3 
consecutive months. 
• Urine event  
• new onset (≥1+) proteinuria; confirmed by doubling in the urinary albumin-creatinine 
ratio (ACR) or urinary protein-creatinine ratio (PCR) (if applicable) 
• new onset (≥1+), hematuria or glycosuria  
Every renal laboratory trigger or renal event as defined in Table 16-5 should be followed up by 
the investigator or designated personnel at the trial site as summarized in Section 16.3. 
11 
Data Collection and Database management  
11.1 
Data collection  
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRF). The eCRFs have been built using fully validated secure web-
enabled software that conforms to 21 CFR Part 11 requirements, Investigator site staff will not 
be given access to the EDC system until they have been trained. 
Automatic validation 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 


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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. 
Adapted ACR Pediatric response will be determined centrally from data (ACR components) 
provided by the investigator. These will be derived and communicated to the investigator the 
same day. 
The investigator/designee is responsible for assuring that the data recorded on CRFs (entered 
into eCRF) is complete, accurate, and that entry and updates are performed in a timely manner. 
The Investigator must certify that the data entered are complete and accurate. 
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification. 
After final database lock, the investigator will receive copies of the patient data for archiving at 
the investigational site. 
11.2 
Database management and quality control  
Novartis personnel will review the data entered by investigational staff for completeness and 
accuracy. Electronic data queries stating the nature of the problem and requesting clarification 
will be created for discrepancies and missing values and sent to the investigational site via the 
EDC system. Designated investigator site staff are required to respond promptly to queries and 
confirm or make any necessary changes to the data.  
Concomitant treatments and medications entered into the database will be coded using the 
World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions and 
adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology. 
Data about all study treatment(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 IRT database. The data will be sent electronically to Novartis. 
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked. Any changes to the database after that time can only 
be made after written agreement by Novartis development management. 
11.3 
Site monitoring  
During the study, Novartis employs several methods of ensuring protocol and GCP compliance 
and the quality/integrity of the sites’ data. The field monitor will visit the site to check the 
completeness of patient records, the accuracy of data capture / data entry, the adherence to the 
protocol and to Good Clinical Practice, the progress of enrollment, and to ensure that study 
treatment is being stored, dispensed, and accounted for according to specifications. Key study 
personnel must be available to assist the field monitor during these visits. Continuous remote 
monitoring of each site’s data may be performed by a centralized Novartis/Clinical Research 
Associate (CRA) organization. Additionally, a central analytics organization may analyze data 


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and identify risks and trends for site operational parameters, and provide reports to Novartis 
clinical teams to assist with trial oversight. 
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
patients file. The investigator must also keep the original informed consent form signed by the 
patient (a signed copy is given to the patient). 
The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. Novartis monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the CRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
patients will be disclosed. 
12 
Data analysis and statistical methods  
A general description of the statistical methods to be used to analyze the efficacy and safety 
data is outlined below. Specific details will be provided in the Statistical Analysis Plan. 
All data will be summarized descriptively for all patients, by dose groups and/or possibly by 
JPsA and ERA subtypes.  
Summary statistics for continuous variables will generally include the number of patients (N), 
minimum, lower quartile, mean, median, upper quartile, and maximum. For categorical or 
binary variables, the number and percent of patient in each category will be presented. The 95% 
confidence intervals will be provided as appropriate to evaluate the efficacy of the treatment 
regimens. 
12.1 
Analysis sets 
The following analysis sets will be used in this trial: 
The Full Analysis Set (FAS) will consist of all patients who came from core trial and received 
at least one dose of study drug in the extension trial.  
The Safety Set will consist of all patients that received at least one dose of study drug in the 
extension trial.  
12.2 
Patient demographics and other baseline characteristics  
Summary statistics will be presented for continuous demographic and baseline characteristic 
variables for all patients, dose groups and/or possibly by JPsA and ERA subtypes and for all 
patients in the FAS population of the study. The number and percentage of patients in each 
category will be presented for categorical variables similarly.  


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12.3 
Treatments  
Study treatment  
The analysis of study treatment data will be based on the safety set. The number of active 
injections received will be presented for all patients by dose groups and/or possibly by JPsA 
and ERA subtypes. In addition, the number and percentage of patients with cumulative exposure 
levels will be presented. 
Concomitant medication 
Concomitant medications will be summarized for all patients and by dose groups and/or 
possibly by JPsA and ERA subtypes. Any medication given at least once between the start of 
the first dose in this extension trial and the date of the last study visit in the extension study will 
be a concomitant medication, including those which were started before Week 104E1 and 
continued into the extension study where study treatment is administered. 
Medications will be presented in alphabetical order, by Anatomical Therapeutic Classification 
(ATC) codes and grouped by anatomical main group. Tables will show the overall number and 
percentage of patients receiving at least one treatment of a particular ATC code and at least one 
treatment in a particular anatomical main group. 
Significant concomitant non-drug therapies and procedures will be summarized by primary 
system organ class and MedDRA preferred term. 
The number and percentage of patients receiving concomitant psoriatic arthritis therapy will be 
presented for all patients by dose groups , as well as the reasons for stopping their therapies 
(primary lack of efficacy, secondary lack of efficacy, lack of tolerability, other) and the total 
duration of exposure to psoriatic arthritis therapies previously. 
12.4 
Analysis of the primary endpoint(s) 
12.4.1 
Definition of primary endpoint(s) 
Primary objective evaluates the long-term efficacy of secukinumab with respect to JIA ACR30. 
12.4.2 
Variable(s) 
The primary efficacy variable(s) is the clinical response to treatment according to ACR30 
improvement in disease activity over time up to Week 312 in patients with active JPsA and 
ERA subtypes of JIA and who completed the Phase III study CAIN457F2304. ACR response 
criteria denote the response (i.e. improvement) in signs and symptoms of the disease of a patient 
compared to baseline of the core study CAIN457F2304 . The analysis of the primary variables 
will be based on the FAS.  
12.4.3 
Statistical model, hypothesis, and method of analysis 
No formal hypotheses are planned for this study.  
The proportion of patients meeting the ACR30 criteria will be descriptively summarized for all 
patients by dose groups and/or possibly by JPsA and ERA subtypes.. Treatment efficacy will 
be evaluated by the 95% confidence interval of the proportion of patients responding to 
treatment according to the ACR criteria.  




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AEs will be summarized for all patients by dose groups and/or possibly by JPsA and ERA 
subtypes, the number and percentage of patients having any AE, having an AE in each primary 
system organ class and having each individual AE (preferred term). Summaries will also be 
presented for AEs by severity and for study treatment related AEs. If a patient reported more 
than one adverse event with the same preferred term, the adverse event with the greatest severity 
will be presented. If a patient reported more than one adverse event within the same primary 
system organ class, the patient will be counted only once with the greatest severity at the system 
organ class level, where applicable. Serious adverse events will also be summarized.  
  
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 and relative risks, as 
appropriate, will be presented. 
When adjudication is required of major cardiovascular events, a summary of those types of 
events as reported by the investigator and confirmed by adjudication will be provided. 
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 and laboratory test. Change from baseline will only be summarized for 
patients with both baseline (of core study) and post-baseline values.  
For each parameter, the maximum change from baseline within each study period will be 
evaluated analogously.  
In addition, shift tables will be provided for all parameters to compare a patient’s baseline 
laboratory evaluation relative to the visit’s observed value. For the shift tables, the normal 
laboratory ranges will be used to evaluate whether a particular laboratory test value was normal, 
low, or high for each visit value relative to whether or not the baseline value was normal, low, 
or high. These summaries will be presented by laboratory test for all patients by dose groups 
and/or possibly by JPsA and ERA subtypes. Shifts will be presented by visit as well as for most 
extreme values post-baseline. 
Immunogenicity 
A listing of patient’s positive for anti-secukinumab antibodies, both binding and neutralizing, 
will be provided. 
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 
for all patients by dose group and/or possibly by JPsA and ERA subtypes.. Change from 
baseline will only be summarized for patients with both baseline and post-baseline values. 
ECG 


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Summary statistics will be presented for ECG variables by visit for all patients’ dose groups 
and/or possibly by JPsA and ERA subtypes. Qualitative changes will be summarized. 
12.5.3 
Pharmacokinetics 
All patients with concentration data will be included in the pharmacokinetic data analysis. 
Pharmacokinetic variables 
The following pharmacokinetic parameter will be determined: Cmin,ss. Cmin,ss will be 
determined using Phoenix software. Individual serum concentrations in g/mL will be listed. All 
concentrations below the limit of quantification or missing data will be labeled as such in the 
concentration data listings. Concentrations below the Limit of Quantification will be treated as 
zero in summary statistics for concentration data only. 
During modeling of the pharmacokinetics of secukinumab, the broad principles outlined in the 
FDA Guidance for Industry: Population Pharmacokinetics will be followed. 
Statistical methods for pharmacokinetic analyses 
Summary statistics by visit/time will be provided for the above mentioned parameter and will 
include arithmetic and geometric means, standard deviation (SD), median, minimum and 
maximum. Individual concentrations will be listed by patient. 
12.6 
Interim analyses  
Interim analyses may be performed for purposes of publication and/or to support heath authority 
interactions, as necessary. 
12.7 
Sample size calculation 
This is an extension study, all patients complete the core study CAIN457F2304 Week 104 and 
opt to enter the extension trial will be included in final analysis, so no sample size justification 
is needed. 
13 
Ethical considerations and administrative procedures  
13.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations (including European Directive 2001/20/EC, US CFR 21), and with the ethical 
principles laid down in the Declaration of Helsinki. 
13.2 
Informed consent procedures 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), Institutional Review Board (IRB)/ Independent Ethics 
Committee (IEC)-approved informed consent, or, if incapable of doing so, after such consent 
has been provided by a legally acceptable representative(s) of the patient. In cases where the 
patient’s representative gives consent, the patient must be informed about the study to the extent 


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possible given his/her understanding. If the patient is capable of doing so, he/she must indicate 
assent by personally signing and dating the written informed consent document or a separate 
assent form. Informed consent must be obtained before conducting any study-specific 
procedures (e.g. all of the procedures described in the protocol). The process of obtaining 
informed consent must be documented in the patient source documents.  
Novartis will provide to investigators in a separate document a proposed informed consent form 
that complies with the ICH GCP guideline and regulatory requirements and is considered 
appropriate for this study. Any changes to the proposed consent form suggested by the 
Investigator must be agreed to by Novartis before submission to the IRB/IEC, and a copy of the 
approved version must be provided to the Novartis monitor after IRB/IEC approval. 
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/approval. 
Female of child-bearing potential/guardian must be informed that taking the study treatment 
may involve unknown risks to the fetus if pregnancy were to occur during the study and agree 
that in order to participate in the study they must adhere to the contraception requirement for 
the duration of the study. If there is any question that the patient will not reliably comply, they 
must not be entered in the study. 
13.3 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, 
written informed consent form, consent form updates, patient recruitment procedures (e.g. 
advertisements) and any other written information to be provided to patients. Prior to study 
start, the investigator is required to sign a protocol signature page confirming his/her agreement 
to conduct the study in accordance with these documents and all of the instructions and 
procedures found in this protocol and to give access to all relevant data and records to Novartis 
monitors, auditors, Novartis Quality Assurance representatives, designated agents of Novartis, 
IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site is 
requested by a regulatory authority, the investigator must inform Novartis immediately that this 
request has been made. 
13.4 
Publication of study protocol and results 
The key design elements of this protocol will be posted in a publicly accessible database such 
as clinicaltrials.gov. In addition, upon study completion and finalization of the study report the 
results of this trial will be either submitted for publication and/or posted in a publicly accessible 
database of clinical trial results. 


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13.5 
Quality Control and Quality Assurance 
Novartis maintains a robust Quality Management System (QMS) that includes all activities 
involved in quality assurance and quality control, to ensure compliance with written Standard 
Operating Procedures as well as applicable global/local GCP regulations and ICH Guidelines. 
Audits of investigator sites, vendors, and Novartis systems are performed by auditors, 
independent from those involved in conducting, monitoring or performing quality control of the 
clinical trial. The clinical audit process uses a knowledge/risk based approach. 
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal standard operating procedures (SOPs), and are performed according to 
written Novartis processes. 
14 
Protocol adherence  
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances including 
incidental collection is an investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the investigator shall immediately disclose it to 
Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be implemented. 
14.1 
Protocol Amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. 
Only amendments that are required for patient safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 10 Safety Monitoring must be followed. Novartis should be 
notified of this action and the IRB/IEC at the study site should be informed according to local 
regulations. 




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16 
Appendices 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs  
The following defined notable laboratory or vital sign abnormalities, except creatinine 
clearance, will be communicated at the same time as they are sent to investigators to Novartis. 
Novartis will determine if further consultations with Investigator(s) are appropriate. 
Laboratory Criteria 
Newly occurring selected notable laboratory abnormalities in pediatric patients at the time of 
the assessment: 
Biochemistry 
• Alanine aminotransferase (ALT)(SGPT):  
• > Upper Limit of Normal (ULN), 
• ≥3 x ULN, 
• ≥5 x ULN, 
• ≥8 x ULN, 
• ≥10 x ULN, 
• Aspartate aminotransferase (AST) (SGOT):  
• >ULN, 
• ≥3 x ULN, 
• ≥5 x ULN, 
• ≥8 x ULN, 
• ≥10 x ULN, 
• Total Bilirubin (TBL)  
• >ULN, 
• ≥1.5 x ULN, 
• ≥ 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 
• Gamma-Glutamyl transferase (GGT):  
• >ULN, 
• ≥3 x ULN, 


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• ≥5 x ULN, 
• Creatinine (serum): ≥1.5 x ULN 
• Creatinine clearance (Schwartz formula): ≥ 25% decrease from baseline, ≥3 months in 
duration 
• Protein urine dipstick:  
• New protein ≥1+, ≥3 months in duration 
• Creatinine clearance (Schwartz formula): ≥ 25% decrease from baseline, ≥3 months in 
duration in combination with protein urine dipstick resulting in new protein ≥1+, ≥3 
months in duration 
• Total Cholesterol: ≥1.5xULN 
• Triglycerides: ≥5.7 mmol/L. 
Schwartz formula- Creatinine clearance (mL/min/1.73m2) was derived using the following 
formula 0.413 x length (cm) /(serum creatinine (mg/dL)  
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:  
• Grade 1:<LLN – 3.0 x10E9/L 
• Grade 2:<3.0 – 2.0 x10E9/L 
• Grade 3:<2.0 – 1.0 x10E9/L 
• Grade 4: <1.0 x10E9/L 
• Absolute Lymphocytes: < LLN 
• Absolute Eosinophils: ≥ 1.1 x ULN 
• Absolute Eosinophils: ≥0.45 x 109/L 
Vital Signs 
The following criteria will be used. 
Note: The age is the age at the time of the visit. 


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Systolic blood pressure (mmHg): 
• High: >ULN and Increased >20 in change from baseline 
Diastolic blood pressure (mmHg): 
• High: >ULN and Increased >20 in change from baseline 
Pulse (bpm):  
• High: >ULN and Increased >20 in change from baseline 
• Low: <LLN and Decreased >20 in change from baseline 
Note: Only post-baseline values will be flagged as notable abnormalities 
Table 16-1 
Reference ranges for systolic and diastolic blood pressures and pulse 
Age 
Systolic Blood 
Pressure lower and 
upper limits 
(mmHg) 
Diastolic Blood 
pressure lower and 
upper limits 
(mmHg) 
Pulse lower and 
upper limits 
(Beats per minute) 
2 yrs 
84-117 
39-72 
90-150 
3 yrs 
86-120 
44-76 
90-150 
4 yrs 
88-122 
47-79 
90-150 
5 yrs 
89-123 
50-82 
65-135 
6 yrs 
91-125 
53-84 
65-135 
7 yrs 
92-126 
55-86 
60-130 
8 yrs 
94-127 
56-88 
60-130 
9 yrs 
95-129 
57-89 
60-130 
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 
60-110 
18 yrs 
108-147 
64-97 
60-100 
Table 16-2 
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 LG and Corey H (2007): Hypertension in childhood, Pediatric in Review 28: 283-98 


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16.2 
Appendix 2: Liver event and Laboratory trigger Definitions and 
Follow-up Requirements  
Table 16-3 
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* 
*  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 
TBL: total bilirubin; ULN: upper limit of normal 
Table 16-4 
Follow Up Requirements for Liver Events and Laboratory Triggers 
Criteria 
Actions required 
Follow-up monitoring 
 
 
Potential Hy’s Law casea 
• 
Discontinue the study 
treatment immediately 
• 
Hospitalize, if clinically 
appropriate 
• 
Establish causality 
• 
Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in 
the appropriate CRF  
ALT, AST, TBL, Alb, PT/INR, 
ALP and γGT until resolutionc 
(frequency at investigator 
discretion) 
ALT or AST 


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Criteria 
Actions required 
Follow-up monitoring 
 
 
> 8 × ULN 
• 
Discontinue the study 
treatment immediately 
• 
Hospitalize if clinically 
appropriate 
• 
Establish causality 
• 
Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in 
the appropriate 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 
treatment immediately 
• 
Hospitalize, if clinically 
appropriate 
• 
Establish causality 
• 
Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in 
the appropriate 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 
• 
Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in 
the appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and γGT until resolutionc 
(frequency at investigator 
discretion) 
> 3 × ULN accompanied by 
symptomsb 
• 
Discontinue the study 
treatment immediately 
• 
Hospitalize if clinically 
appropriate 
• 
Establish causality 
• 
Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in 
the appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and γGT until resolutionc 
(frequency at investigator 
discretion) 
> 3 to ≤ 5 × ULN (patient is 
asymptomatic) 
• 
Repeat LFT within the next 
week 
• 
If elevation is confirmed, 
initiate close observation of 
the patient 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks 


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Criteria 
Actions required 
Follow-up monitoring 
 
 
ALP (isolated) 
  
  
> 2 × ULN (in the absence of 
known bone pathology) 
• 
Repeat LFT within 48 
hours 
• 
If elevation persists, 
establish causality 
• 
Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in 
the appropriate 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 
• 
Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in 
the appropriate 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 (patient is 
asymptomatic) 
 
 
 
 
 
• 
Repeat LFT within the next 
week 
• 
If elevation is confirmed, 
initiate close observation of 
the patient 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
Jaundice 
• 
Discontinue the study 
treatment immediately 
• 
Hospitalize the patient 
• 
Establish causality 
• 
Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in 
the appropriate 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 treatment 
interruption or 
discontinuation 
• 
Hospitalization if clinically 
appropriate 
• 
Establish causality 
• 
Record the AE and 
contributing factors (e.g., 
Investigator discretion 


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Criteria 
Actions required 
Follow-up monitoring 
 
 
conmeds, med hx, lab) in 
the appropriate CRF 
*  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 
a Elevated 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 
c Resolution 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. 


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16.3 
Appendix 3: Specific Renal Alert Criteria and Actions and Event 
Follow-up  
Table 16-5 
Specific Renal Alert Criteria and Actions 
Serum Event 
Serum creatinine increase 
25% to 49% compared to baseline 
Confirm 25% increase after 24h to 48h 
Follow up within 2 to 5 days 
Acute Kidney Injury: Serum creatinine increase  
≥ 50% compared to baseline 
Follow up within 24h to 48h if possible 
Consider study treatment interruption 
Consider patient hospitalization /specialized 
treatment 
Urine Event 
New dipstick proteinuria ≥1+ 
Albumin- or Protein-creatinine ratio increase ≥2-
fold 
Albumin-creatinine ratio (ACR) ≥30 mg/g or ≥3 
mg/mmol; 
Protein-creatinine ratio (PCR )≥150 mg/g or >15 
mg/mmol 
Confirm value after 24h to 48h 
Perform urine microscopy 
Consider study treatment interruption / or 
discontinuation 
New dipstick glycosuria ≥1+ not due to diabetes 
Blood glucose (fasting) 
Perform serum creatinine, ACR 
New dipstick hematuria ≥1+ not due to trauma 
Urine sediment microscopy 
Perform serum creatinine, ACR 
For all renal events: 
Document contributing factors in the CRF: co-medication, other co-morbid conditions, and additional 
diagnostic procedures performed 
Monitor patient regularly (frequency at investigator’s discretion) until either: 
Event resolution: sCr within 10% of baseline or protein-creatinine ratio within 50% of baseline, or 
Event stabilization: sCr level with ±10% variability over last 6 months or protein-creatinine ratio 
stabilization at a new level with ±50% variability over last 6 months. 
 
 


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16.4 
Appendix 4: Weight ranges: recommended maximum sample 
blood volume per blood draw 
Recommended maximum blood collections are in accordance with the 2008 EU Commission 
Guideline on Ethical Considerations for Clinical Trials on Medicinal Products Conducted with 
the Pediatric Population. As per the guideline, collections specified in the protocol do not 
exceed 3% of patients total blood volume during a 4-week period and/or 1% at any single visit. 
Patients total blood volume is estimated at 80 to 90 mL/kg body weight; 3% is 2.4 mL blood 
per kg body weight, 1% is 0.8 mL blood per kg body weight. The table below outlines the 
maximum allowable blood volume by weight category. In order to stay within these limits, 
detailed instructions are provided by the Central Laboratory for all weight categories less than 
38 kg.  Weight range: Recommended maximum blood volume drawn per visit, and per 4 week 
period 
Weight Range Category (kg) 
Maximum Allowable Blood 
Volume Drawn / visit 
(mL) 
Maximum Allowable Blood 
Volume Drawn / 4 week 
period (mL) 
7-10 
5.6 
16.8 
>10-12 
8.0 
24.0 
>12-14 
9.6 
28.8 
>14-26 
11.2 
33.6 
>26-38 
20.8 
62.4 
>38 
30.4 
91.2 
16.5 
Appendix 5: Physician’s global assessment of disease activity 
(VAS) 
The question text below will be shown to and will be answered by the physician. The 
physician’s assessment should be made and recorded without viewing ANY of the patient’s 
assessments. The result of the physician’s assessment of the patient’s disease activity should be 
withheld from the patient / parents/guardian so as not to influence his/her own assessment. 
The following is the text of the question, but does not represent the final formatting used in the 
study. 
“Considering all the ways ERA/JPsA affects your patient, how would you rate his or her 
condition today?” 
 
 
 
 
No disease activity  
0 
Very severe disease activity  
100 


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16.6 
Appendix 6: Childhood Health Assessment Questionnaire 
(CHAQ©) 
The following does not represent the final formatting of the CHAQ© used in the study. 
 


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16.7 
Appendix 7: ILAR classification criteria 
  
Criteria 
Exclusions 
JPsA (MODIFIED) 
Arthritis and psoriasis, or  
arthritis with two or more of: 
a. Dactylitis 
b. Nail pitting or onycholysis 
c. Psoriasis in a first degree 
relative 
• 
Presence of IgM RF on at 
least 2 occasions at least 
3 months apart 
• 
Presence of systemic JIA 
ERA 
Arthritis and enthesitis, or  
Arthritis or enthesitis with two 
or more of: 
a. Presence of or history of 
sacroiliac joint tenderness 
and/or inflammatory 
lumbosacral pain  
b. HLA-B27 positivity 
c. Acute (symptomatic) 
anterior uveitis 
d. History of ankylosing 
spondylitis, enthesitis 
related arthritis, sacroiliitis 
with inflammatory bowel 
disease, Reiter’s 
syndrome, or acute 
anterior uveitis in a first-
degree relative 
e. Onset of arthritis in a boy 
over the age of 6 years 
• 
Psoriasis or in first-degree 
relative 
• 
Presence of IgM RF on at 
least 2 occasions more 
than 3 months apart 
• 
Presence of systemic JIA  
JPsA criteria (Petty et al 2004) have been modified by removal of the following 2 exclusions:  
1) Arthritis in a HLA-B27 positive male beginning after the sixth birthday and  
2) Diagnosis of ankylosing spondylitis, ERA, sacroiliitis with Inflammatory Bowel Disease (IBD), 
reactive arthritis (Reiter’s syndrome), or acute anterior uveitis, or a history of one of these 
disorders in a first-degree relative. 
16.8 
Appendix 8: ACR response criteria 
The adapted ACR Pediatric 30/50/70/90/100 criteria will be used to determine efficacy defined 
as improvement from baseline of at least 30/50/70/90/100% respectively in at least 3 of 6 
variables  with no more than one variable  worsening more than 30% as defined in the ACR 
criteria. 
The components are: 
• Physician’s Global Assessment of disease activity on a 0-100 mm VAS from 0 mm = no 
disease activity to 100 mm = very severe disease activity. 
• Parent’s or patient’s (if appropriate in age) Global Assessment of patient’s overall well-
being on a 0-100 mm VAS from 0 mm= very well to 100 mm= very poor. 
• Functional ability: Childhood Health Assessment Questionnaire (CHAQ©) 


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• Number of joints with active arthritis using the ACR definition (The ACR definition of 
active arthritis is any joint with swelling, or in the absence of swelling, limitation of 
motion accompanied by either pain on motion or tenderness not due to deformity) 
• Number of joints with limitation of motion 
• Laboratory measure of inflammation: CRP (local) (mg/L) 
16.9 
Appendix 9: Criteria for deﬁning clinical inactive disease 
All must be met: Inactive disease: 
• No joints with active arthritis 
• No Uveitis 
• CRP (local) level within normal limits in the laboratory where tested or, if elevated, not 
attributable to ERA/JPsA 
• Physician’s global assessment of disease activity score of best possible on the scale 
used  (i.e. best possible score is defined as  ≤10 mm) 
• The absence of patient-reported morning stiffness attributable to JPsA or ERA lasting 
≥15 minutes 
Adapted from (Wallace  et al 2011). 

SAP_001.pdf: 
Clinical Development 
CAIN457/Secukinumab/Cosentyx® 
Clinical Trial Protocol [CAIN457F2304E1 / NCT03769168] 
An extension study of subcutaneous secukinumab to evaluate the 
long-term efficacy, safety and tolerability up to 4 years in patients with 
Juvenile Idiopathic Arthritis subtypes of Juvenile Psoriatic Arthritis and 
Enthesitis Related Arthritis 
Statistical Analysis Plan (SAP) 
Authors: 
Statistician 
 Statistician 
Document type: 
SAP Documentation 
Document status: 
Amendment 2.0 
Release date: 
05-NOV-2024
Number of pages: 
34 
Property of Novartis 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 


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Document History – Changes compared to previous final version of SAP 
Date 
Timepoint 
Outcome for update 
Section and title 
impacted (Current) 
 
 
 
 
01-Apr-
2024 
Prior to Final DBL 
Added Entire treatment and entire 
study definition 
Added Efficacy end point related 
table 
Added study related clarification 
 
Updated Treatment group table 
Updated, corrected and added 
necessary study related details 
 
 
Added Imputation details and 
updated derivation details 
Section 1 
 
Section 1.2 
 
Section 2.1.1, 2.1.2, 
2.13.2.1.4 
Section 2.2.2 
Section 2.3.2, 2.5, 2.7, 
2.8, 2.10.1, 2.10.2, 
2.10.3, 2.10.6 
 
 
Section 6.1, 6.1.2, 6.1.3, 
6.2.3 
20-Jun-
2024 
Prior to Final DBL 
Updated the FAS definition  
Section 2.2.1 Analysis 
Sets and section 4 
Change to protocol 
specified analyses 
29-Oct-
2024 
Prior to Final DBL 
Added pooled AIN457 related 
information for efficacy related 
outputs as appropriate 
 
Corrected study design diagram 
 
Updated or added clarification as 
per team discussion 
Section 2.2.2, Section 
2.8 
 
 
Section 1 
 
 
Section 2.2.2, Section 4 
and Section 5 
 
 
 


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Table of contents 
Table of contents ................................................................................................................. 3 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 5 
List of abbreviations ............................................................................................................ 6 
1 
Introduction ......................................................................................................................... 8 
1.1 
Study Design ............................................................................................................ 8 
1.2 
Study objectives and Endpoints ............................................................................... 8 
2 
Statistical Methods ............................................................................................................ 10 
2.1 
Data analysis general information ......................................................................... 10 
2.1.1 
Study Day 1 and other study days ......................................................... 10 
2.1.2 
Baseline, and post-baseline definitions ................................................. 10 
2.1.3 
Day of last dose of study treatment ....................................................... 10 
2.1.4 
Visit windows........................................................................................ 11 
2.2 
Analysis sets and treatments .................................................................................. 11 
2.2.1 
Analysis Sets ......................................................................................... 11 
2.2.2 
Treatment groups .................................................................................. 11 
2.3 
Subject disposition, background and demographic characteristics ....................... 13 
2.3.1 
Subject disposition ................................................................................ 13 
2.3.2 
Demographic and baseline characteristics ............................................ 13 
2.4 
Medical history ...................................................................................................... 14 
2.5 
Study medication ................................................................................................... 14 
2.6 
Concomitant medication ........................................................................................ 14 
2.6.1 
Concomitant medication in extension ................................................... 14 
2.7 
Analysis of Primary Variable(s) ............................................................................ 15 
2.7.1 
Handling of missing data ...................................................................... 15 
2.7.2 
Statistical model, hypothesis, and method of analysis .......................... 15 
2.8 
Analysis of secondary 
 variables .................................................. 15 
2.9 
Efficacy evaluation ................................................................................................ 16 
2.9.1 
Description of efficacy variables .......................................................... 16 
2.10 
Safety evaluation ................................................................................................... 22 
2.10.1 
Adverse events ...................................................................................... 22 
2.10.2 
Laboratory data ..................................................................................... 24 
2.10.3 
Vital signs.............................................................................................. 26 
2.10.4 
Electrocardiogram (ECG) ..................................................................... 27 
2.10.5 
Immunogenicity .................................................................................... 27 


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2.10.6 
Compound specific safety evaluation ................................................... 28 
2.11 
Pharmacokinetics ................................................................................................... 28 
3 
Sample size calculation ..................................................................................................... 28 
4 
Change to protocol specified analyses .............................................................................. 28 
 
 29 
6 
Appendix ........................................................................................................................... 30 
6.1 
Imputation rules ..................................................................................................... 30 
6.1.1 
Study drug ............................................................................................. 30 
6.1.2 
AE date imputation ............................................................................... 30 
6.1.3 
Concomitant medication date imputation ............................................. 31 
6.2 
Statistical methodology and assumptions .............................................................. 32 
6.2.1 
Analysis of continuous data .................................................................. 32 
6.2.2 
Analysis of binary (and categorical) data .............................................. 32 
6.2.3 
Crude incidence and related risk estimates ........................................... 32 
 
 33 
7 
References ......................................................................................................................... 34 


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List of tables 
Table 1-1 
Primary, secondary 
 efficacy variables .......................................... 9 
Table 2-1 
Joints Identification for Disease Activity Scores and Indexes .............................. 20 
Table 2-2 
Overview of analyses on some safety endpoints .................................................. 23 
Table 2-3 
CTCAE grades for laboratory parameters to be analyzed .................................... 25 
Table 2-4 
Liver-related events .............................................................................................. 26 
Table 2-5 
Criteria for notable vital sign abnormalities ......................................................... 27 
 
 
List of figures 
Figure 1-1 Study design .............................................................................................................. 8 
 


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List of abbreviations 
ACR 
American College of Rheumatology 
AE 
Adverse event 
ALT/SGPT 
Alanine aminotransferase/serum glutamic pyruvic transaminase 
AST/SGOT 
Aspartate aminotransferase/serum glutamic oxaloacetic transaminase 
ATC 
Anatomical Therapeutic Classification 
bid 
bis in diem/twice a day 
BMI 
Body Mass Index 
BP 
Blood Pressure 
CHAQ© 
Childhood Health Assessment Questionnaire 
CK 
creatinine kinase 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CRA 
Clinical Research Associate 
CRP 
C-Reactive Protein 
CTC 
Common Toxicity Criteria 
CTCAE 
Common Terminology Criteria for Adverse Event 
CV 
coefficient of variation 
JADAS 
Juvenile Arthritis Disease Activity Score 
JIA 
Juvenile Idiopathic Arthritis 
JPsA 
Juvenile Psoriatic Arthritis 
LLN  
Lower Limit Normal 
LOCF 
Last Observation Carried Forward 
LLOQ 
Lower Limit of Quantification 
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
mmHg 
Millimeter mercury 
PK/PD 
Pharmacokinetics/Pharmacodynamic 
PRO 
Patient-reported Outcomes 
PsA 
Psoriatic Arthritis 
QoL 
Quality of Life 
RA 
Rheumatoid Arthritis 
RAP 
Report and Analysis Process 
RBC 
Red Blood Cells 
SAE  
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
s.c. 
Subcutaneous(ly) 
SCE 
Summary of Clinical Efficacy 
SCS 
Summary of Clinical Safety 
SD 
Standard Deviation 
SJC 
Swollen Joint Count 
SpA 
Spondyloarthritis 


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SOC 
System Organ Class 
TFLs 
Tables, Figures, Listings 
TJC 
Tender Joint Count 
ULN 
Upper Limit of Normal 
VAS 
Visual Analog Scale 
WBC 
White Blood Cells 
WHO 
World Health Organization 
 


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1 
Introduction 
Data will be analyzed by 
according to the data analysis section 12 of the study protocol 
CAIN457F2304E1 version 00. That statistical methodology is described below and any 
deviations from the protocol are documented. Additional detailed information regarding the 
analysis methodology is contained in the Appendix section. 
This document contains the detailed statistical and analytical plans for full analysis of 
CAIN457F2304E1 study. 
1.1 
Study Design 
A multicenter, optional, open-label, pediatric extension study of subcutaneous secukinumab in 
prefilled syringes to evaluate the long-term efficacy, safety and tolerability up to 4-years in 
patients with Juvenile Idiopathic Arthritis subtypes of Juvenile Psoriatic Arthritis and Enthesitis 
Related Arthritis. 
The aim of this 4-year extension study is to provide continuous treatment with secukinumab in 
prefilled syringes (PFS) for patients who complete the core study CAIN457F2304 and opt to 
enter the extension trial and to obtain further long-term efficacy, safety and tolerability 
information. 
Figure 1-1 Study design 
 
The following study periods will be considered for analysis: 
• Entire treatment period: W104E1 (Extension trial start) to Week 312 (EOT), for 
safety analysis, exposure including follow-up period up to last dose + 84 days. 
• Entire study period: W104E1(Extension trial start) to Week 320 (EOS), including 
follow-up period visits. 
1.2 
Study objectives and Endpoints 
The primary objective of study is to evaluate the long-term efficacy of secukinumab (provided 
as pre-filled syringes) with respect to JIA ACR30 response over time up to Week 312 in patients 


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with active JPsA and ERA subtypes of JIA and who completed the Phase III study 
CAIN457F2304. 
Following are the secondary objectives 
• To evaluate the long-term safety, tolerability and immunogenicity of secukinumab as 
assessed by vital signs, clinical laboratory variables and adverse events monitoring over 
time up to Week 312 and follow-up period 
• To evaluate the long-term effect of secukinumab treatment for all patients and each JIA 
category with respect to: 
o JIA ACR 50/70/90/100 
o Each JIA ACR core component 
o Inactive disease status  
o Juvenile Arthritis Disease Activity Score (JADAS) 
o Total Enthesitis count 
o Total Dactylitis count 
• To evaluate pharmacokinetics (PK) of secukinumab 
 
• 
 
 
• 
 
 
A summary of primary, secondary 
endpoints are included in Table 1-
1 below. 
Table 1-1 
Primary, secondary 
efficacy variables 
Variable 
Type 
JIA ACR30 Response over time up to week 312 
Primary 
JIA ACR 50/70/90/100 over time up to week 312  
Secondary 
Each JIA ACR Core Components over time up to week 312  
Secondary 
Inactive Disease Status 
Secondary 
Change from baseline of JADAS Score 
Secondary 
Total Enthesitis count 
Secondary 
Total Dactylitis count 
Secondary 
Secukinumab serum concentrations and derived PK parameters 
Secondary 


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2 
Statistical Methods 
2.1 
Data analysis general information 
Data will be analyzed by the 
, using SAS version 9.4 or above. 
All data will be summarized descriptively for all patients, by dose groups and possibly by JPsA 
and ERA subtypes, as appropriate.  
Summary statistics for continuous variables will include the number of patients (N), mean, 
standard deviation, minimum, lower quartile, median, upper quartile, maximum.  
For categorical or binary variables, the number and percent of patient in each category will be 
presented. The 95% confidence intervals will be provided as appropriate to evaluate the efficacy 
of the treatment regimens. 
Baseline from core study (CAIN457F2304) and Week 104E1 visit data will be presented, as 
appropriate. 
All listings will be presented by treatment sequence. 
2.1.1 
Study Day 1 and other study days 
The first day of administration of study treatment (first dose) in extension study is defined as 
Study Day 1 or Day 1 (i.e. Week 104E1). 
All other study days will be labelled relative to Day 1. For event dates on or after Day 1, study 
day for a particular event date is calculated as [Date of event] – [Date of first dose] +1, i.e., Day 
2, Day 3, etc., will be one day, two days, etc., after Day 1, respectively. For the dates before 
Day 1, study day for an event date is calculated as [Date of event] – [Date of first dose], i.e., 
Day -1, Day -2, etc., will be one day, two days, etc., before Day 1, respectively. Duration of an 
event will be calculated as (Event end date – Event start date + 1). 
The descriptor “Day 0” will not be used. 
2.1.2 
Baseline, and post-baseline definitions 
In general, a baseline value refers to the core study and is the last measurement made prior to 
administration of the first dose of study treatment in core. Baseline information will be 
presented appropriately in the “by visit” summaries in both safety and efficacy tables. 
A post-baseline value refers to a measurement taken after the first dose of study treatment in 
core study.  
For early discontinuation visit mapping in different assessments, the early discontinuation week 
will be the next visit of corresponding assessment based on the patients’ last scheduled visit. 
2.1.3 
Day of last dose of study treatment 
The date of last dose will be collected via the CRF. The subject’s exposure will be calculated 
considering the end of treatment period visit. The end of treatment period will be defined as the 
last dose plus 84 days or last visit whichever occurs earlier. i.e., for subjects who discontinued 


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or have their last visit earlier than last dose plus 84 days, the end of study treatment exposure 
will be the date of the last study visit in the corresponding treatment period.  
On-treatment event is defined as assessments within last dose plus 84 days, for safety analysis 
(i.e., Lab, Vitals, and ECG). 
2.1.4 
Visit windows 
During extension trial, only nominal planned CRF visits will be considered for analysis of 
efficacy and safety by visit summary tables. Unplanned visits will not be included in summaries.  
2.2 
Analysis sets and treatments 
2.2.1 
Analysis Sets  
The following analysis sets will be used for the data analysis:  
Full Analysis Set (FAS): The Full Analysis Set (FAS) will consist of all patients who enrolled 
in the extension trial.  
Safety Set: The Safety Set will consist of all patients who received at least one dose of study 
drug in the extension trial. 
 
2.2.2 
Treatment groups 
Treatment groups for efficacy and safety will be used as follows:  
 
Endpoint 
Table/Figu
re/Listing 
Assigned 
Treatment 
group 
Actual 
Treatment 
group 
sequence 
Additional 
comment  
Disposition, Protocol 
deviations, Demographic 
and Baseline 
Characteristics 
Table 
AIN457 75 mg  
AIN457 75 mg  
Treatment group 
along with 
sequence will be 
used for 
summaries  
 
 
 
AIN457 150 mg  
 
 
 
AIN457 300 mg  
 
 
 
Total 
 
 
AIN457 150 mg  
AIN457 150 mg  
 
 
 
AIN457 300 mg  
 
 
 
Total 
 
Any AIN457 
AIN457 75 mg  
This includes 
number of subjects 
treated with 75 mg 
or 150 mg or 300 
mg dose group at 
least once 
AIN457 150 mg  
AIN457 300 mg  
Total 


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Endpoint 
Table/Figu
re/Listing 
Assigned 
Treatment 
group 
Actual 
Treatment 
group 
sequence 
Additional 
comment  
Efficacy 
Tables  
AIN457 75 mg  
 
 
For efficacy tables, 
we will report 
assigned and 
actual treatment 
groups  
 
 
AIN457 150 mg 
 
 
 
AIN457  
 
As pooled 
treatment group 
[total of assigned 
treatment group at 
start of extension 
trial (AIN457 75 mg 
+ AIN457 150 
mg)]. 
 
Figures 
AIN457 75 mg 
(Total) 
75 mg to 75 mg 
Treatment group 
along with 
sequence will be 
used for figures 
 
 
  
 
 
 
75 mg to 150 mg  
 
 
 
75 mg to 150 mg 
to 300 mg  
 
 
AIN457 150 mg 
(Total) 
150 mg  
 
 
 
150 mg to 300 
mg  
 
Listing  
AIN457 75 mg  
 
Original treatment 
group 
 
 
AIN457 150 mg 
 
AEs, SAEs, and 
Concomitant medication 
Tables  
Any AIN457 75 
mg  
 
This includes 
number of subjects 
treated with 75 mg 
dose group at least 
once 
 
 
Any AIN457 150 
mg 
 
This includes 
number of subjects 
treated with 150 
mg dose group at 
least once 
 
 
Any AIN457 300 
mg 
 
This includes 
number of subjects 
treated with 300 
mg dose group at 
least once 
 
 
Any AIN457 
 
This includes 
number of subjects 
treated with 75 mg 
or 150 mg or 300 
mg dose group at 
least once 


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Endpoint 
Table/Figu
re/Listing 
Assigned 
Treatment 
group 
Actual 
Treatment 
group 
sequence 
Additional 
comment  
Lab and Vital signs by 
visit 
Tables 
AIN457 75 mg  
AIN457 75 mg  
Treatment received 
at that visit.  
 
 
 
AIN457 150 mg  
 
 
 
AIN457 300 mg  
 
 
 
Total 
 
 
AIN457 150 mg 
AIN457 150 mg  
 
 
 
AIN457 300 mg  
 
 
 
Total 
 
 
 
 
 
Listings 
AIN457 75 mg  
 
Assigned treatment 
group at start.  
 
 
AIN457 150 mg 
2.3 
Subject disposition, background and demographic 
characteristics 
2.3.1 
Subject disposition 
The number of subjects enrolled in the extension will be presented. The number and percentage 
of subjects in the FAS who completed the period up to week 312 and/or the follow up visit and 
who discontinued the treatment or study prematurely (including the reason for discontinuation) 
will be presented for each treatment group. Also, separate disposition summary report will be 
created 
.  
For each protocol deviation (PD), the number and percentage of subjects for whom the PD 
applies will be tabulated. 
2.3.2 
Demographic and baseline characteristics 
Demographics and baseline characteristics will be presented for FAS.  
The following common background and demographic variables will be analyzed according to 
the treatment group or sequence (when dose escalation occurs). 
Continuous variables: 
• Age  
• Height 
• Weight 
• Body mass index (BMI) = (body weight in kilograms) / (height in meters)2 
Categorical variables: 
• Age categories (2 - < 6 years, 6 - < 12 years and 12 - < 18 years) 
• Gender 
• Race 


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• Ethnicity 
• Weight categories (< 50 kg or >= 50 kg) 
• Smoking status at baseline 
Patient demographic and baseline characteristics will be derived from the core study data and 
demographics captured in the extension database will not be summarized.  
2.4 
Medical history 
Any condition entered on the Relevant medical history / current medical conditions CRF will 
be coded using the MedDRA dictionary. Data collected for core study will be used for the 
extension as well. Data will be summarized by system organ class (SOC) and preferred term 
(PT) of the MedDRA dictionary. Disease history and baseline characteristics will be presented 
by treatment group. 
Unless otherwise specified, analyses will be based on the extension FAS. 
2.5 
Study medication 
The analysis of study treatment data will be based on the safety set. The number of active 
injections will be summarized by dose received. The duration of exposure to study treatment 
will also be summarized by dose groups. In addition, the number and percentage of subjects 
with cumulative exposure levels (e.g. any exposure, ≥ 1 week, ≥ 2 weeks, ≥ 3 weeks, ≥ 4 weeks, 
≥ 8 weeks, etc.) will be presented. 
Duration of exposure will be calculated as time from first dose of secukinumab in extension 
study to the minimum of (last dose of the treatment + 84 days) and (last visit date).  
Duration of exposure (days) = min (last visit date, last dose date +84) – first dose date +1 
Duration of exposure (years) = duration of exposure (days) / 365.25 
Duration of exposure (100 subject years) = duration of exposure (years) / 100 
The analyses of duration of exposure described above will be done for each AIN457 dose level 
and also for the entire study treatment period. 
2.6 
Concomitant medication  
2.6.1 
Concomitant medication in extension 
Concomitant medications in extension will be summarized by dose groups based on Safety Set. 
Any medication given at least once between the start of the first dose in this extension trial and 
the date of the last study visit + 84 days in the extension study, will be a concomitant medication, 
including those which were started before Week 104E1 visit and continued into the extension 
study where study treatment is administered. 
Medications will be presented in alphabetical order, by Anatomical Therapeutic Classification 
(ATC) codes and preferred term according to the Novartis Drug and Therapy Dictionary 
(NovDTD). Tables will 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 preferred term. 


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Significant concomitant non-drug therapies and procedures will be summarized by primary 
system organ class and MedDRA preferred term. 
Prior surgeries and procedures are defined as surgeries and procedures executed prior to the 
first study dose. Any surgeries and procedures started between the day of the first dose of study 
treatment in this extension trial and within 84 days after the last dose will be concomitant 
surgeries and procedures, including those which were started pre-baseline and continued into 
the period where study treatment is administered. 
2.7 
Analysis of Primary Variable(s) 
The primary efficacy variable is the clinical response to treatment according to JIA ACR30 
improvement in disease activity over time up to Week 312 in patients with active JPsA and 
ERA subtypes of JIA and who completed the Phase III study CAIN457F2304. JIA ACR 
response criteria denote the response (i.e., improvement) in signs and symptoms of the disease 
of a patient compared to baseline of the core study CAIN457F2304. The analysis of the primary 
variable will be based on the FAS. 
2.7.1 
Handling of missing data 
For the calculation of JIA ACR, partially missing data for JIA ACR components will be imputed 
by Last Observation Carried Forward (LOCF).  
Missing data for JIA ACR30 variables will not be imputed and observed data except JIA ACR 
components will be used in all analysis. 
2.7.2 
Statistical model, hypothesis, and method of analysis 
No formal hypotheses are planned for this study. 
The proportion of patients meeting the JIA ACR30 criteria will be descriptively summarized 
and presented graphically for all patients by treatment groups, and by JPsA and ERA subtypes, 
as appropriately. Treatment efficacy will be evaluated by the 95% confidence interval of the 
proportion of patients responding to treatment according to the JIA ACR criteria. 
Results will be presented for the FAS.  
2.8 
Analysis of secondary 
 variables  
Secondary variables include: 
• JIA ACR 50/70/90/100 and inactive disease status 
• Each JIA ACR core component 
• Change from baseline of core study CAIN457F2304  
o Juvenile Arthritis Disease Activity Score (JADAS) 
o Total enthesitis count 
o Total dactylitis count 
 
• 
 


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• 
 
• 
 
• 
 
All these above efficacy variables will be analyzed on the FAS (unless otherwise specified) for 
all applicable analysis visits based on the observed data. The summary table will display in 
assigned treatment and actual treatment in JPsA, ERA, and total categories. Additionally, data 
from the assigned AIN457 treatment groups will be pooled (AIN457 75 mg + AIN457 150 mg) 
and reported as “AIN457” for each visit, for efficacy outputs.   
For binary variables, the proportion of responders along with the 95% CI will be presented by 
dose groups over analysis visits.  
For continuous variables, the change from baseline (baseline of core) when available, will be 
summarized.  
Additionally, observed data tables will summarize the JIA ACR30, ACR50, ACR70, ACR90 
and ACR100 response following dose escalation when assessed. Results will be illustrated in 
line plots. 
Also, individual subject listings of the JIA ACR components as well as for the JIA 
ACR30/50/70/90/100 response will be given. 
  
Graphical presentation using line plot or bar charts of secondary 
will 
also be included as appropriate.  
 
 
2.9 
Efficacy evaluation 
2.9.1 
Description of efficacy variables 
2.9.1.1 
JIA ACR response criteria 
Standard ACR pediatric Criteria (JIA ACR criteria) consist of 6 core components which will 
be assessed as scheduled in [Table 8-1 of the protocol].  JIA ACR 30/50/70/90/100 are defined 
as 30%, 50%, 70%, 90% and 100% improvement from baseline respectively in a minimum of 
three variables in the core set with no more than one variable worsening more than 30% as 
defined in the ACR criteria. 
The 6 core set variables are summarized below: 
• Physician global assessment of disease activity on a 0 - 100 mm VAS from 0 mm = no 
disease activity to 100 mm = very severe disease activity 


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• Parent or patient’s (if appropriate in age) Global Assessment of patient’s overall 
wellbeing on a 0-100 mm VAS from 0 mm = very well to 100 mm = very poor. 
• Functional ability: Childhood Health Assessment Questionnaire (CHAQ©) 
• Number of active joints using the ACR definition (any joint with swelling or in the 
absence of swelling, limitation of motion accompanied by either pain on motion or 
tenderness not due to deformity) 
• Number of joints with limited range of motion 
• Laboratory measure of inflammation: CRP (local) (mg/L) 
The respective response variables listed above will be used by a central vendor to determine 
ACR Pediatric response. These results will be communicated to the investigator. Additionally, 
these components will be used to determine JADAS and inactive disease status as part of 
secondary 
 analyses.  
2.9.1.2 
Physician’s Global Assessment of disease activity (VAS) 
The physician will rate the patient’s current condition on a 0-100 mm VAS [Protocol Section 
16.5], ranging from no disease activity (0 mm) to very severe disease activity (100 mm), at each 
scheduled visit for all patients throughout the study. 
Scores on the 100 mm linear scale will be measured to the nearest millimeter from the left. To 
enhance objectivity, the physician must not be aware of the specific parent’s or patient’s global 
assessment of patient’s overall well-being, when performing his own assessment on that patient. 
2.9.1.3 
Parent’s/patient’s Global Assessment of patients overall well-being 
(VAS) 
The parent’s or patient’s global assessment of the 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. 
2.9.1.4 
Childhood Health Assessment Questionnaire (CHAQ©) 
The Childhood Health Assessment Questionnaire (CHAQ©), [Protocol Section 16.6], will be 
used to assess physical ability and functional status of patients as well as quality of life. The 
disability dimension consists of multiple choice and VAS items concerning difficulty in 
performing eight common activities of daily living; dressing and grooming, arising, eating, 
walking, reaching, personal hygiene, gripping and activities. Patients choose from four response 
categories, ranging from ‘without any difficulty’ to ‘unable to do’. 
This questionnaire should be completed by the parent (or, for patients 18 years and older, the 
questionnaire will be completed together by both the patient and parent) according to schedule 
in [Protocol Table 8-1]. The (CHAQ©) will be completed only in a validated version of the 
instrument in the language understandable to the parent and/or patient. 
Completed questionnaires will be reviewed and examined by the investigator, before the clinical 
examination, for responses which may indicate potential AEs or SAEs. If AEs or SAEs are 


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confirmed, then the physician must record the events as per instructions given in [Section 
10.1.1] and [Section 10.1.2 of the protocol]. Investigators should not encourage the patients 
and/or parents to change the responses reported in the PRO questionnaires. 
2.9.1.5 
Active joint count 
The number of joints with active arthritis at each visit will be determined by applying the ACR 
definition to the number of joints with swelling, tenderness and limited range of motion at each 
scheduled visit for all patients throughout the study (see [Protocol Section 8.3.1.5] and [Section 
8.3.1.7] for more details). 
The ACR definition of active arthritis is any joint with swelling or, in the absence of swelling, 
limitation of motion accompanied by either pain on motion or tenderness not due to deformity. 
The active joint count will therefore range from 0 to 73. 
The site will need to submit the joint count assessment worksheet to central vendor for ACR 
Pediatric response at each scheduled visit per [Protocol Table 8-1], the results will be 
communicated to the investigator. 
2.9.1.6 
Joint counts with limitation of motion 
A total of 69 joints will be assessed for limitation of motion at each scheduled visit for all 
patients throughout the study. The same 75 joints assessed for tenderness [Protocol Section 
8.3.1.7] will also be assessed for limitation of motion excluding the 2 sternoclavicular, 
2 acromioclavicular joints as well as the 2 sacroiliac joints. 
For there to be consistency between the joint assessments, it is strongly recommended that the 
same evaluator perform these assessments at all visits. 
2.9.1.7 
C-reactive Protein (CRP) 
C-reactive Protein CRP (local) is used as an inflammation marker, to determine its severity, and 
to monitor response to treatment. 
CRP (local) will be measured at the local lab, at each scheduled visit for all patients throughout 
the study including during unscheduled visit, and the actual sample collection date, time and 
result will be collected. 
2.9.1.8 
 Tender and Swollen Joint Count 
Tender 75 joint counts (TJC) 
The following 75 joints will be scored as either tender or not tender: 
• Temporomandibular joints: 2 
• Sternoclavicular joints: 2 
• Acromioclavicular joints: 2 
• Shoulders: 2 
• Elbows: 2 
• Wrists: 2 
• Hands: 


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• 8 Distal interphalangeal 
• 10 proximal interphalangeal 
• 10 metacarpophalangeal 
• Hips: 2 
• Knees: 2 
• Ankles: 2 
• Subtalar joints: 2 
• Intertarsal joints: 2 
• Feet: 
• 10 metatarsophalangeal joints 
• 10 toes 
• Cervical spine is assessed as a single joint 
• Thoracic spine is assessed as a single joint 
• Lumbar spine is assessed as a single joint 
• Sacroiliac joints: 2 
Joint tenderness is to be scored as present or absent. For there to be consistency between the 
joint assessments, it is strongly recommended that the same evaluator perform these 
assessments at all visits. 
2.9.1.9 
Swollen joint count (SJC) 
A total of 68 joints are to be scored as either swollen or not swollen. The same 75 joints assessed 
for tenderness will also be assessed for swelling excluding the cervical spine, thoracic spine, 
lumbar spine, 2 hips and 2 sacroiliac joints. 
For there to be consistency between the joint assessments, it is strongly recommended that the 
same evaluator perform these assessments at all visits. 
2.9.1.10 Inactive Disease Status 
Clinical inactive disease definition is adapted from the ACR criteria of Wallace et al 2011. All 
must be met: 
• No joints with active arthritis 
• No uveitis 
• CRP (local) value within normal limits for the laboratory where tested or, if elevated, 
not attributable to ERA/JPsA  
• Physician’s global assessment of disease activity score of best possible on the scale 
used (i.e. best possible score is defined as ≤ 10mm) 
The absence of patient-reported morning stiffness attributable to JPsA or ERA lasting ≥15 
minutes. 






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2.9.1.12 Assessment of duration of morning stiffness 
The presence or absence of patient/parent-reported morning stiffness that day attributable to 
JPsA or ERA lasting at least 15 minutes will be assessed as part of evaluation of inactive disease 
status. 
2.9.1.13 Assessment of Uveitis due to JIA 
The presence or absence of uveitis that day will be assessed as part of evaluation of inactive 
disease status. Clinically suspected uveitis should be confirmed as per the Standardization of 
Uveitis Nomenclature (SUN) Working Group definition. No uveitis is defined as “grade zero 
cells,” indicating < 1 cell in field sizes of 1 mm by a 1 mm slit beam (Zierhut 2007). 
2.9.1.14 Total enthesitis count 
The following 16 entheseal sites will be assessed for the presence or absence of tenderness 
(enthesitis) on each side of the body: 
• Anterior Entheses: Greater trochanter of the Femur; Medial condyle of the femur; 
Lateral condyle of the femur 
• Posterior Entheses: Greater tuberosity of humerus; medial epicondyle of humerus; 
lateral epicondyle of humerus, Achilles tendon; and calcaneal insertion of the plantar 
fascia 
2.9.1.15 Total dactylitis count 
The dactylitis count is the number of fingers and toes presenting with dactylitis, with a range of 
0-20. 
2.10 
Safety evaluation 
Safety analyses will be summarized descriptively on the safety set. 
Subjects who switch treatment during the study (e.g. dose escalation) will be counted to both 
groups using the appropriate start and stop exposure date. 
Patient status of COVID-19 will be included in AE and Protocol deviation summary and 
listings. 
2.10.1 
Adverse events 
Treatment emergent adverse events (i.e. events started after the first dose of secukinumab in 
extension study, or events present prior to the first dose of secukinumab but increased in severity 
based on preferred term and within 84 days after last dose of secukinumab) will be summarized. 
All AEs will be included in the listing, with flags for treatment emergent. 


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A separate treatment emergent adverse events summary report will be created 
 
. 
AEs will be summarized for all patients by dose groups and/or possibly by JPsA and ERA 
subtypes, the number and percentage of patients having any AE, having an AE in each primary 
system organ class and having each individual AE (preferred term). Summaries will also be 
presented for AEs by severity and for study treatment related AEs. If a patient reported more 
than one adverse event within same dose level, with the same preferred term, the adverse event 
with the greatest severity will be presented. If a patient reported more than one adverse event 
within the same primary system organ class, the patient will be counted only once with the 
greatest severity at the system organ class level within the same dose level and will be counted 
separately for different dose level. Serious adverse events will also be summarized. 
 
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 and relative risks, as 
appropriate, will be presented. 
The safety analyses that will be performed for treatment emergent AEs, LABS and Vital signs 
for each analysis period is described in the table below. 
An overview of the safety analyses and which will be performed for each analysis period is 
described in Table 2-2 
Table 2-2 
Overview of analyses on some safety endpoints 
Analysis 
period 
AEs & SAEs 
AEs by 
severity 
Study drug 
related AEs 
AEs-SMQ 
Risk 
Notables 
for 
(vitals/lab 
criteria 
Entire 
treatment 
period  
crude 
incidence 
 
crude 
incidence 
 
crude 
incidence 
 
crude 
incidence 
 
crude 
incidence 
 
crude 
incidence 
 
 
 
 
 
  
 
 
 
The tables will include data from the extension part of the trial. 
For the legal requirements of ClinicalTrials.gov and EudraCT, two required tables on treatment 
emergent adverse events which are not serious adverse events with an incidence greater than 
X% and on treatment emergent serious adverse events and SAE suspected to be related to study 
treatment will be provided by system organ class and preferred term on the safety set population. 


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Here, the threshold value X is set to 2-5 (%) but it may be updated following review of the dry 
run outputs. 
If for a same patient, several consecutive AEs (irrespective of study treatment causality, 
seriousness, and severity) occurred with the same SOC and PT: 
• a single occurrence will be counted if there is ≤ 1 day gap between the end date of the 
preceding AE and the start date of the consecutive AE 
• more than one occurrence will be counted if there is > 1 day gap between the end date 
of the preceding AE and the start date of the consecutive AE 
For occurrence, the presence of at least one SAE / SAE suspected to be related to study 
treatment / non-SAE to be checked in a block e.g., among AE's in a ≤ 1 day gap block, if at 
least one SAE is occurring, then one occurrence is calculated for that SAE. 
2.10.2 
Laboratory data 
The summary of lab data will only include on-treatment data, which are defined as those lab 
assessments after the first dose of secukinumab in extension study and on or before last dose + 
84 days.  
The summary of laboratory evaluations will be presented for three groups of laboratory tests 
(hematology, chemistry, and urinalysis). In addition to the individual laboratory parameters the 
ratio “total cholesterol / HDL” will be derived and summarized. 
For urinalysis, frequency tables across visits will be presented. 
Descriptive summary statistics for the absolute value at study visits as well as the change from 
baseline to extension study visits will be presented in tabular fashion. These descriptive 
summaries will be presented by laboratory test and treatment dose, dose sequence. Change from 
baseline will only be summarized for subjects with both baseline (from core study) and post 
baseline values and will be calculated as: 
change from baseline = post baseline value – baseline value 
The maximum change (maximum decrease and maximum increase) from baseline for each lab 
parameter, will also be analyzed. These summaries will be presented by laboratory test and 
treatment dose, dose sequence. 
In addition, shift tables will be provided for all parameters to compare a patient’s baseline 
laboratory evaluation relative to the visit’s observed value. For the shift tables, the normal 
laboratory ranges will be used to evaluate whether a particular laboratory test value was normal, 
low, or high for each visit value relative to whether the baseline value was normal, low, or high 
These summaries will be presented by laboratory test for all patients by dose groups and/or 
possibly by JPsA and ERA subtypes. Shifts will be presented by visit as well as for most 
extreme values post-baseline. 
Reported laboratory assessments with either a less than or greater than sign (“<” or “>”) will be 
used for analysis after removal of the sign and conversion to standard unit. These laboratory 
data will be displayed in listings using the standard unit with the reported sign (“<” or “>”). 
The following laboratory parameters will be analyzed with respect to numerical Common 
Terminology Criteria for Adverse Events (CTCAE) grades, given in Table 2-3: hemoglobin, 


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platelets, white blood cell count, neutrophils, lymphocytes, creatinine, total bilirubin (TBL), 
gamma-glutamyl 
transferase 
(GGT), 
alanine 
aminotransferase 
(ALT), 
aspartate 
aminotransferase (AST), alkaline phosphatase (ALP), glucose, cholesterol, triglycerides (TG). 
These summaries will be split into hematology and chemistry for study level reports and the 
pooled summary of clinical safety. 
Shift tables will be presented comparing baseline laboratory result (CTCAE grade) with the 
worst results (expressed in CTCAE grade) during the treatment phase (either initial or entire) 
analyzed. Of note, baseline will be defined as last assessment prior to first dosing in the initial 
treatment phase of the core study. Subjects with abnormal laboratory values will be listed and 
values outside the normal ranges will be flagged. 
Table 2-3 
CTCAE grades for laboratory parameters to be analyzed 
CTCAE v4.0 
Term 
Grade 1    
Grade 2    
Grade 3    
Grade 4    
HGB decreased 
(Anemia) 
<LLN – 100 g/L 
<100 – 80 g/L 
<80 g/L 
Life-threatening 
consequences: 
urgent 
intervention 
indicated 
Platelet count 
decreased 
<LLN – 75.0 
x10e9 /L 
<75.0 - 50.0 
x10e9 /L 
<50.0 – 25.0 
x10e9 /L 
<25.0 x 10e9 /L 
White blood cell 
decreased 
<LLN - 3.0 x 10e9 
/L 
<3.0 - 2.0 x 10e9 
/L 
<2.0 - 1.0 x 10e9 
/L 
<1.0 x 10e9 /L 
Neutrophil count 
decreased 
<LLN - 1.5 x 10e9 
/L 
<1.5 - 1.0 x 10e9 
/L 
<1.0 - 0.5 x 10e9 
/L 
<0.5 x 10e9 /L 
Lymphocyte count 
decreased 
<LLN - 0.8 x 
10e9/L 
<0.8 - 0.5 x 10e9 
/L 
 
<0.5 - 0.2 x 10e9 
/L 
<0.2 x 10e9 /L 
Creatinine 
increased 
 
>ULN - 1.5 x ULN 
>1.5 - 3.0 x ULN 
>3.0 - 6.0 x ULN 
>6.0 x ULN 
TBL increased 
>ULN - 1.5 x ULN 
>1.5 - 3.0 x ULN 
>3.0 - 10.0 x ULN 
>10.0 x ULN 
GGT increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALT increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
AST increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALP increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
Glucose 
increased 
(Hyperglycemia)  
  
>ULN - 8.9 
mmol/L 
>8.9 - 13.9 
mmol/L 
>13.9 - 27.8 
mmol/L 
>27.8 mmol/L 
Glucose 
decreased 
(Hypoglycemia) 
<LLN - 3.0 
mmol/L 
<3.0 - 2.2 mmol/L 
<2.2 - 1.7 mmol/L 
<1.7 mmol/L 
Cholesterol high 
>ULN - 7.75 
mmol/L 
>7.75 - 10.34 
mmol/L 
>10.34 - 12.92 
mmol/L 
>12.92 mmol/L 
Hypertriglyceride
mia 
1.71 - 3.42 
mmol/L 
>3.42 - 5.7mmol/L 
>5.7 - 11.4 
mmol/L 
>11.4 mmol/L 


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Summaries for newly occurring or worsening clinically notable lipid abnormalities will also be 
provided cumulatively for each of the following parameters and categories: 
• HDL: 
• <=LLN 
• <0.8 x LLN 
• LDL, cholesterol, triglycerides: 
• >=ULN  
• >1.5 x ULN  
• >2.5 x ULN 
Newly occurring or worsening liver enzyme abnormalities will also be summarized based on 
the event criteria given in Table 2-4: 
Table 2-4 
Liver-related events 
Parameter 
Criterion 
ALT 
>3xULN; >5xULN; >8xULN;>10xULN, >20xULN 
AST 
>3xULN; >5xULN; >8xULN >10xULN; >20xULN 
ALT or AST 
>3xULN; >5xULN; >8xULN >10xULN; >20xULN 
TBL 
>1.5xULN, >2xULN, >3xULN, 
ALP 
>2xULN, >3xULN. >5xULN 
ALT or AST & 
TBL 
ALT or AST>3xULN & TBL >2xULN; 
ALT or AST >5xULN & TBL >2xULN; 
ALT or AST >8xULN & TBL >2xULN; 
ALT or AST >10xULN & TBL >2xULN 
ALP & TBL 
ALP >3xULN & TBL >2xULN 
ALP >5xULN & TBL >2xULN 
ALT or AST & 
TBL & ALP 
ALT or AST>3xULN & TBL >2xULN & ALP <2xULN (Hy’s Law) 
Note: elevated ALP may suggest obstruction as a consequence of gall bladder or 
bile duct disease; ALP may also be increased in malignancy. FDA therefore terms 
Hy’s Law cases as indicators of pure hepatocellular injury. This does not mean 
that cases of ALT or AST >3xULN & TBL >2xULN & ALP ≥2xULN may not result 
in severe DILI. 
Notes:1) In studies which enroll subjects with pre-existing liver disease, baseline LFT may 
be increased above ULN; in such a case it is meaningful to add the condition “and worse than 
baseline” to the abnormality criteria 
For a combined criterion to be fulfilled, all conditions have to be fulfilled on the same visit. The 
criteria are not mutually exclusive, e.g. a subject with ALT = 6.42xULN is counted for 
ALT >3xULN and ALT>5x ULN. 
2.10.3 
Vital signs 
The summary of vital signs will only include on-treatment data, which are defined as those vital 
sign measurements after the first dose of extension study treatment and on or before last dose + 
84 days.  


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Analysis in vital sign measurement, using descriptive summary statistics for the change from 
baseline for each post-baseline visit in extension, will only be presented for subjects with both 
a baseline (of core study) and post baseline values. These descriptive summaries will be 
presented by vital sign and treatment dose, dose sequence. Change from baseline will be 
calculated as: 
change from baseline = post-baseline value – baseline value 
Systolic blood pressure (mmHg): 
• High: >ULN and Increased >20 in change from baseline 
Diastolic blood pressure (mmHg): 
• High: >ULN and Increased >20 in change from baseline 
Pulse (bpm):  
• High: >ULN and Increased >20 in change from baseline 
• Low: <LLN and Decreased >20 in change from baseline 
The number and percentage of subjects with newly occurring notable vital signs will be 
presented. Criteria for notable vital sign abnormalities are provided in Table 2-5 below. 
Table 2-5 
Criteria for notable vital sign abnormalities 
Age group 
Systolic BP(mmHg) 
Diastolic BP(mmHg) 
Pulse (bpm) 
2-5 yrs 
76-120 
45-80 
55-120 
6 -11 yrs 
 90-130 
 50-80 
 50-105 
12-17 yrs 
 90-145 
 55-90 
 45-95 
18 yrs and over 
 90-140 
 60-90 
 60-100 
Note: The age is the age at the time of the visit. It will be derived as follows: 
Integer part of ((assessment date – birth date) / 365.25) 
Individual subject listing of vital signs and a listing for the newly occurring notably 
abnormalities will be provided. 
Additionally, age and body weight over visit related analysis will be performed 
.  
2.10.4 
Electrocardiogram (ECG) 
ECG information was collected locally at the site and not collected in the database for extension 
study and will not be analyzed for the study. 
2.10.5 
 
Immunogenicity 
Summary statistics will be provided for the percent of subjects with blood samples for 
immunogenicity (anti-AIN457 antibodies). The summary statistics will include extension study 
immunogenicity summary. 


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2.10.6 
Compound specific safety evaluation 
Safety topics of interest, such as risks defined in the Safety Profiling Plan (SPP), Risk 
Management Plan or Safety topics of interest regarding signal detection or routine analysis are 
defined in the most recent version of Program Case Retrieval Sheet and can be retrieved via the 
“SP” flag.  
The crude incidence 
 for potential compound and class-
related risks and routine risks will be summarized. In addition, listings will be provided 
presenting which subjects experienced which risk. 
2.11 
Pharmacokinetics 
All subjects with quantifiable pharmacokinetic (PK) measurements of secukinumab will be 
included in the pharmacokinetic data analysis. Serum concentrations will be expressed in mass 
per volume units. All concentrations below the limit of quantification as well as missing data 
will be labeled as such in the concentration data listings. PK concentrations will be summarized 
by visit and treatment group. In addition to mean, standard deviation (SD), coefficient of 
variation (CV), median and quartiles, the geometric mean and geometric coefficient of variation 
(CV) and n(log) will be presented. n(log) is the number of patients with non-zero 
concentrations. The formula for deriving the geometric mean and CV (%) is as following:  
• CV (%) = (SD/mean) *100, 
• geometric mean=exp ((sum of log transformed data) / number of non-missing data points 
after log transformation), 
• geometric CV = sqrt (exp (variance of log-transformed data)-1) *100. 
In addition, sample number, concentration, sample date, sample time at pre-dose and minutes 
pre-dose will be listed by treatment sequence. 
Values below lower limit of quantification/below detection limit will be imputed by 0. 
 
3 
Sample size calculation 
This is an extension study, all patients who complete the core study CAIN457F2304 Week 104 
and opt to enter the extension trial will be included in final analysis, so no sample size 
justification is needed. 
4 
Change to protocol specified analyses 
Prior and concomitant therapies will be reported based on the Safety Set (instead of FAS 
specified in the protocol), since Safety Set is the standard analysis set for reporting prior and 
concomitant therapies. 
ECG information was collected locally and not collected in the database. So, no analysis will 
be performed for ECG parameters. 


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Updated the Full Analysis Set (FAS) definition as per the study requirement. 
Corrected the typo in “Figure 1-1 Study design” diagram, Week 168 appears two times, so 
corrected visit information as Week 168 and Week 180. 
 
 
 
 
 
 


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6 
Appendix 
6.1 
Imputation rules 
6.1.1 
Study drug 
Any partial dates will be imputed as follows: 
The earlier day will be taken from below 
• The last day in the month and  
• The end day of the corresponding Treatment Period 
6.1.2 
AE date imputation 
Impute AE end date: 
1. If the AE end date ‘month’ is missing, the imputed end date should be set to the 
earliest of the (min (last visit date, last dose date + 84 days), 31DECYYYY, date of 
death).  
2. If the AE end date ‘day’ is missing, the imputed end date should be set to the earliest 
of the (min (last visit date, last dose date + 84 days), last day of the month, date of 
death).  
3. If AE ‘year’ is missing or AE is ongoing, the end date will not be imputed.  
Impute AE start date:  
Before imputing AE start date, find the AE start reference date.  
1. If the (imputed) AE end date is complete and the (imputed) AE end date < treatment 
start date then AE start reference date = min (informed consent date, earliest visit 
date).  
2. Else AE start reference date = treatment start date  
1. If the AE start date ‘year’ value is missing, the date uncertainty is too high to impute a 
rational date. Therefore, if the AE year value is missing, the imputed AE start date is 
set to NULL.  
2. If the AE start date ‘year’ value is less than the treatment start date year value, the AE 
started before treatment. Therefore:  
If AE ‘month’ is missing, the imputed AE start date is set to the mid-year point 
(01JULYYYY).  
Else if AE ‘month’ is not missing, the imputed AE start date is set to the mid-month 
point (15MONYYYY).  
3. If the AE start date year value is greater than the treatment start date year value, the 
AE started after treatment. Therefore:  
a. If the AE month is missing, the imputed AE start date is set to the year start point 
(01JANYYYY).  
b. Else if the AE month is not missing, the imputed AE start date is set to the later of 
(month start point (01MONYYYY), AE start reference date + 1 day).  


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4. If the AE start date year value is equal to the treatment start date year value:  
a. And the AE month is missing the imputed AE start date is set to the AE reference 
start date + 1 day.  
b. Else if the AE month is less than the treatment start month, the imputed AE start 
date is set to the mid-month point (15MONYYYY).  
c. Else if the AE month is equal to the treatment start date month or greater than the 
treatment start date month, the imputed AE start date is set to the later of (month 
start point (01MONYYYY), AE start reference date + 1 day).  
If complete (imputed) AE end date is available and the imputed AE start date is greater than the 
(imputed) AE end date, then imputed AE start date should be set to the (imputed) AE end date. 
6.1.3 
Concomitant medication date imputation 
Impute CM end date:  
1. If CM end day is missing and CM month/year are non-missing then impute CM day as 
the minimum of treatment end date and the last day of the month.  
2. If CM end day/month are missing and CM year is non-missing then impute CM day as 
the minimum of treatment end date and the end of the year (31DECYYYY).  
3. If imputed CM end date is less than the CM start date, use the CM start date as the 
imputed CM end date.  
Impute CM start date:  
1. If the CM start date year value is missing, the imputed CM start date is set to one day 
prior to treatment start date.  
2. If the CM start date year value is less than the treatment start date year value, the CM 
started before treatment. Therefore:  
a. If the CM month is missing, the imputed CM start date is set to the mid-year point 
(01JULYYYY).  
b. Else if the CM month is not missing, the imputed CM start date is set to the mid-
month point (15MONYYYY).  
3. If the CM start date year value is greater than the treatment start date year value, the 
CM started after treatment. Therefore:  
a. If the CM month is missing, the imputed CM start date is set to the year start point 
(01JANYYYY).  
b. Else if the CM month is not missing, the imputed CM start date is set to the month 
start point (01MONYYYY).  
4. If the CM start date year value is equal to the treatment start date year value:  
a. And the CM month is missing or the CM month is equal to the treatment start date 
month, then the imputed CM start date is set to one day prior treatment start date.  
b. Else if the CM month is less than the treatment start date month, the imputed CM 
start date is set to the mid-month point (15MONYYYY).  
c. Else if the CM month is greater than the treatment start date month, the imputed 
CM start date is set to the month start point (01MONYYYY).  


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If complete (imputed) CM end date is available and the imputed CM start date is greater than 
the (imputed) CM end date, then imputed CM start date should be set to the (imputed) CM end 
date.  
6.2 
Statistical methodology and assumptions 
6.2.1 
Analysis of continuous data 
6.2.1.1 
Summary statistics for continuous data 
Summary statistics (including N, mean, standard deviation, minimum, lower quartile, median, 
upper quartile, maximum) will be provided for continuous data by visit and treatment group.  
6.2.2 
Analysis of binary (and categorical) data 
6.2.2.1 
Summary statistics for binary and categorical data 
Summary statistics for discrete variables will be presented in contingency tables and will 
include count and frequency in each category. If applicable, confidence intervals will be derived 
as well based on the score method including continuity correction Newcombe (1998): 
With z as (1-alpha/2)-quantile of the standard normal distribution (SAS: z=PROBIT(1-
alpha/2), n  as total number of subjects (i.e. number of subjects in the denominator), and p as 
estimated crude incidence (number of subjects with event / n ) it is 
p
q
−
=1
 
Then the lower limit is 
(
)
(
)










+
+
+
−
−
−
−
+
=
2
2
2
2
1
4
1
2
1
2
,0
max
z
n
nq
p
n
z
z
z
np
L
 
and the upper limit is 
(
)
(
)










+
−
+
−
+
+
+
+
=
2
2
2
2
1
4
1
2
1
2
,1
min
z
n
nq
p
n
z
z
z
np
U
. 
Note: if 𝐿> 𝑝 then 𝐿= 𝑝 and if 𝑈< 𝑝 then 𝑈= 𝑝. For percentages multiply p, L and U by 
100. 
6.2.3 
Crude incidence and related risk estimates  
6.2.3.1 
Crude incidence and 100*(1-α) % confidence interval 
For n subjects, each at risk to experience a certain event with probability π, the crude incidence 
is estimated as p=x/n, where x is the number of subjects with the event. 


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Study No. CAIN457F2304E1 
 
Absolute and relative frequencies will be displayed as well as 95% confidence interval for the 
relative frequency based on the score method including continuity correction (Newcombe 
1998).  
With z  as (1-α/2)-quantile of the standard normal distribution (SAS: z=PROBIT(1-alpha/2), 
n  as total number of subjects (i.e. number of subjects in the denominator), and p as estimated 
crude incidence (number of subjects with event / n ) it is 
p
q
−
=1
. 
Then the lower limit is: 
(
)
(
)










+
+
+
−
−
−
−
+
=
2
2
2
2
1
4
1
2
1
2
,0
max
z
n
nq
p
n
z
z
z
np
L
 
and the upper limit is 
(
)
(
)










+
−
+
−
+
+
+
+
=
2
2
2
2
1
4
1
2
1
2
,1
min
z
n
nq
p
n
z
z
z
np
U
. 
Note: if L > p then L = p and if U < p then U = p. 


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SAP Amendment 2.0 
 
Study No. CAIN457F2304E1 
 
7 
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