A Randomized, Double-blind, Placebo-controlled, Parallel-group, Multicenter Study to Evaluate the Safety and Efficacy of Secukinumab 300 mg and 150 mg in Adult Patients With Active Psoriatic Arthritis After 16 Weeks of Treatment Compared to Placebo and to Assess the Safety, Tolerability and Efficacy up to 52 Weeks
Phase: PHASE4
Conditions: Psoriatic Arthritis
Sponsor: Novartis Pharmaceuticals

US Clinical Development & Medical Affairs - General Medicine 
AIN457/Secukinumab
Clinical Trial Protocol CAIN457FUS01 / NCT02798211
A randomized, double-blind, placebo-controlled, parallel-
group, multicenter study to evaluate the safety and efficacy 
of secukinumab 300 mg and 150 mg in adult patients with 
active psoriatic arthritis after 16 weeks of treatment 
compared to placebo and to assess the safety, tolerability 
and efficacy up to 52 weeks
Authors
Document type:
Amended Protocol Version
Version number:
v02 Clean
Clinical trial phase:
IV 
Release date:
12-Dec-2016
Property of Novartis
Confidential
May not be used, divulged, published, or otherwise disclosed
without the consent of Novartis
Clinical Trial Protocol Template Version 03 (August 2015)

Novartis
Confidential
Page 2
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Table of contents
Table of contents .................................................................................................................2
List of tables ........................................................................................................................5
List of figures ......................................................................................................................6
List of abbreviations............................................................................................................7
Glossary of terms.................................................................................................................9
Amendment 2 ....................................................................................................................10
Amendment 1 ....................................................................................................................10
Protocol summary..............................................................................................................12
1
Introduction .......................................................................................................................22
1.1
Background............................................................................................................22
1.2
Purpose ..................................................................................................................23
2
Study objectives.................................................................................................................24
2.1
Primary objective(s)...............................................................................................24
2.2
Secondary objectives .............................................................................................24
25
3
Investigational plan ...........................................................................................................25
3.1
Study design...........................................................................................................25
3.2
Rationale for study design .....................................................................................27
3.3
Rationale for dose/regimen, route of administration and duration of treatment....27
3.4
Rationale for choice of comparator .......................................................................28
3.5
Purpose and timing of interim analyses/design adaptations..................................29
3.6
Risks and benefits..................................................................................................29
4
Population..........................................................................................................................30
4.1
Inclusion criteria ....................................................................................................30
4.2
Exclusion criteria...................................................................................................31
5
Treatment...........................................................................................................................33
5.1
Protocol requested treatment .................................................................................33
5.1.1
Investigational treatment.......................................................................33
5.1.2
Additional study treatment....................................................................34
5.2
Treatment groups...................................................................................................34
5.3
Treatment assignment and randomization.............................................................35
5.4
Treatment blinding.................................................................................................35
5.5
Treating the patient................................................................................................36
5.5.1
Patient numbering .................................................................................36
5.5.2
Dispensing the investigational treatment ..............................................36

Novartis
Confidential
Page 3
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
5.5.3
Handling of study treatment..................................................................36
5.5.4
Instructions for prescribing and taking study treatment........................37
5.5.5
Permitted dose adjustments and interruptions of study treatment ........38
5.5.6
Rescue medication ................................................................................38
5.5.7
Concomitant treatment..........................................................................39
5.5.8
Prohibited treatment..............................................................................40
5.5.9
Discontinuation of study treatment .......................................................42
5.5.10
Withdrawal of consent ..........................................................................42
5.5.11
Loss to follow-up ..................................................................................43
5.5.12
Emergency breaking of assigned treatment code..................................43
5.5.13
Study completion and post-study treatment..........................................43
5.5.14
Early study termination.........................................................................44
6
Visit schedule and assessments .........................................................................................44
6.1
Information to be collected on screening failures..................................................50
6.2
Patient demographics/other baseline characteristics .............................................50
6.2.1
Demographics .......................................................................................50
6.2.2
PsA/Psoriasis history/ Prior psoriasis therapies ....................................50
6.2.3
Smoking history ....................................................................................50
6.2.4
Co-morbidities-Cardiovascular history.................................................50
6.2.5
Relevant medical history / Current medical conditions ........................50
6.2.6
Prior and concomitant medications.......................................................51
6.2.7
Chest X-ray ...........................................................................................51
6.2.8
Determination of tuberculosis status.....................................................51
6.3
Treatment exposure and compliance .....................................................................52
6.4
Efficacy..................................................................................................................52
6.4.1
American College of Rheumatology (ACR) response..........................53
6.4.2
Tender 78 joint count and swollen 76 joint count.................................54
6.4.3
Patient Reported Outcomes (PRO)/QoL Assessments .........................54
6.4.4
Physician’s global assessment of disease activity.................................57
6.4.5
High Sensitivity C-reactive protein (hsCRP)........................................57
6.4.6
Erythrocyte sedimentation rate (ESR) ..................................................57
58
6.4.8
DAS28 and EULAR response...............................................................58
6.4.9
Psoriatic Arthritis Disease Activity Score (PASDAS)..........................58
6.4.10
Minimal disease activity .......................................................................59
6.4.11
Dactylitis Assessments..........................................................................59

Novartis
Confidential
Page 4
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.4.12
Enthesitis Assessments..........................................................................59
60
6.4.14
Psoriasis Area and Severity Index (PASI) ............................................60
6.4.15
Investigator’s Global Assessment (IGA mod 2011) .............................62
62
6.4.17
Physician’s global assessment of fingernail disease severity (VAS)....64
64
6.4.19
Appropriateness of efficacy assessments..............................................64
6.5
Safety.....................................................................................................................65
6.5.1
Physical examination ............................................................................65
6.5.2
Vital signs..............................................................................................65
6.5.3
Height and weight .................................................................................66
6.5.4
Electrocardiogram (ECG) .....................................................................66
6.5.5
Laboratory evaluations..........................................................................66
6.5.6
Pregnancy and assessments of fertility .................................................67
6.5.7
Tolerability of secukinumab .................................................................67
6.5.8
Additional parameters ...........................................................................67
6.5.9
Appropriateness of safety measurements..............................................67
7
Safety monitoring ..............................................................................................................67
7.1
Adverse events.......................................................................................................67
7.2
Serious adverse events...........................................................................................69
7.2.1
Definition of SAE .................................................................................69
7.2.2
SAE reporting........................................................................................70
7.3
Liver safety monitoring .........................................................................................70
7.4
Pregnancy reporting...............................................................................................71
8
Data review and database management.............................................................................71
8.1
Site monitoring ......................................................................................................71
8.2
Data collection.......................................................................................................71
8.3
Database management and quality control............................................................72
8.4
Data Monitoring Committee..................................................................................72
8.5
Adjudication Committee........................................................................................72
9
Data analysis......................................................................................................................72
9.1
Analysis sets ..........................................................................................................73
9.2
Patient demographics and other baseline characteristics.......................................73
9.3
Treatments .............................................................................................................73
9.4
Analysis of the primary variable............................................................................73

Novartis
Confidential
Page 5
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
9.4.1
Variable.................................................................................................73
9.4.2
Statistical model, hypothesis, and method of analysis..........................74
9.4.3
Handling of missing values/censoring/discontinuations.......................74
9.4.4
Supportive analyses...............................................................................74
9.5
Analysis of secondary variables ............................................................................74
9.5.1
Efficacy variables..................................................................................74
9.5.2
Safety variables .....................................................................................76
9.6
Interim analyses .....................................................................................................77
9.7
Sample size calculation..........................................................................................77
10 Ethical considerations........................................................................................................77
10.1
Regulatory and ethical compliance........................................................................77
10.2
Informed consent procedures.................................................................................77
10.3
Responsibilities of the investigator and IRB/IEC..................................................78
10.4
Publication of study protocol and results...............................................................78
11 Protocol adherence ............................................................................................................78
11.1
Protocol Amendments ...........................................................................................79
12 References .........................................................................................................................79
12.1
Appendix 1: Clinically notable laboratory values and vital signs .........................81
12.2
Appendix 2: The classification criteria for psoriatic arthritis (CASPAR).............82
83
12.4
Appendix 4: American College of Rheumatology (ACR) Measures and 
Criteria of Response ..............................................................................................83
12.5
Appendix 5: Disease Activity Score (DAS) ..........................................................84
12.6
Appendix 6: The Psoriasis Area and Severity Index (PASI).................................87
87
12.8
Appendix 8: Health Assessment Questionnaire (HAQ) ........................................89
 
91
12.10 Appendix 10: Guidelines for administering the PRO questionnaires....................92
List of tables
Table 5-1
Prohibited medication ...........................................................................41
Table 6-1
Assessment schedule.............................................................................46
Table 6-2
The PASI scoring system ......................................................................61
Table 6-3
The IGA mod 2011 rating scale............................................................62
Table 6-4
Score for percent of nail with onycholysis or oil-drop dyschromia......63

Novartis
Confidential
Page 6
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Table 6-5
Score for number of pits........................................................................63
Table 6-6
Score for percent of nail with crumbling present..................................64
List of figures
Figure 3-1
Study design..........................................................................................27

Novartis
Confidential
Page 7
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
List of abbreviations
ACR
American College of Rheumatology
AE
Adverse event
ALT/SGPT
Alanine aminotransferase/serum glutamic pyruvic transaminase
ANCOVA
analysis of covariance
Anti-CCP
Anti-cyclic citrullinated peptide
AS
Ankylosing Spondylitis
AST/SGOT
Aspartate aminotransferase/serum glutamic oxaloacetic transaminase 
BSA
Body Surface Area
BL
Baseline
CASPAR
Classification criteria for Psoriatic Arthritis
CRF
Case Report/Record Form (paper or electronic)
CRP
C-reactive protein
CTC
Common Toxicity Criteria
DAS
Disease Activity Score
DLQI
Dermatology Life Quality Index
DMARD
Disease Modifying Anti-rheumatic Drug
DS&E
Drug Safety & Epidemiology
eCRF
Electronic Case Report/Record Form
ECG
Electrocardiogram
EDC
Electronic Data Capture
EMA/EMEA
European Medicines (Evaluation) Agency
ESR
Erythrocyte Sedimentation Rate
EULAR
European League Against Rheumatism
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HAQ-DI©
Health Assessment Questionnaire – Disability Index
HRQoL
Health-related Quality of Life
hsCRP
High sensitivity C-Reactive Protein
IEC
Independent Ethics Committee
IGA mod 2011
Investigator’s Global Assessment modified 2011
IL
Interleukin
IRB
Institutional Review Board
IRT
Interactive Response Technology
IUD
Intra Uterine Device
IUS
Intra Uterine System
i.v.
intravenous(ly)
LFT
Liver function test

Novartis
Confidential
Page 8
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
LOCF
last-observation-carried-forward
MCS
Mental Component Summary
MDA
Minimal Disease Activity
MedDRA
Medical dictionary for regulatory activities
mmHg
Millimeter mercury
MTX
Methotrexate
NSAID
Non-steroidal anti-inflammatory drug
PASDAS
Psoriatic Arthritis Disease Activity Score
PASI
Psoriasis Area and Severity Index
PBO
Placebo
PCS
Physical Component Summary
PFS
Prefilled syringe
PK/PD
Pharmacokinetic/Pharmacodynamic
PoC
Proof of Concept
PPD
Purified protein derivative
PRN
Pro re nata (as required)
PRO
Patient Reported Outcome
PsA
Psoriatic arthritis
QoL
Quality of Life
RBC
Red blood cell
RF
Rheumatoid factor
SAE
Serious adverse event
s.c.
Subcutaneous(ly)
SCR
Screening
SF-12
Medical Outcome Short Form (12) Health Survey
SJC
Swollen Joint Count
SpA
Spondyloarthritis
SUSAR
Suspected Unexpected Serious Adverse Reactions
TJC
Tender Joint Count
TNF
Tumor necrosis factor
ULN
Upper limit of normal
VAS
Visual analog scale
WBC
White blood cell
WHO
World Health Organization

Novartis
Confidential
Page 9
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Glossary of terms
Assessment
A procedure used to generate data required by the study
Cohort 
A group of newly enrolled patients treated at a specific dose and 
regimen (i.e. treatment group) at the same time
Control drug
Any drug (an active drug or an inactive drug, such as a placebo) 
which is used as a comparator to the drug being tested in the trial
Dose level
The dose of drug given to the patient (total daily or weekly etc.)
Enrollment
Point/time of patient entry into the study at which informed 
consent must be obtained (i.e. prior to starting any of the 
procedures described in the protocol)
Investigational drug
The drug whose properties are being tested in the study; this 
definition is consistent with US CFR 21 Section 312.3 and is 
synonymous with “investigational new drug” or “investigational 
medicinal product.”
Investigational treatment
All investigational drug(s) whose properties are being tested in the 
study as well as their associated treatment controls. 
This includes any placebos, any active controls, as well as 
approved drugs used outside of their indication/approved dosage 
or tested in a fixed combination. 
Investigational treatment generally does not include protocol-
specified concomitant background therapies  when these are 
standard treatments in that indication
Medication number
A unique identifier on the label of each investigational/study drug 
package in studies that dispense medication using an IRT system
Protocol
A written account of all the procedures to be followed in a trial, 
which describes all the administrative, documentation, analytical 
and clinical processes used in the trial.
Premature subject withdrawal
Point/time when the patient exits from the study prior to the 
planned completion of all study treatment administration and/or 
assessments; at this time all study treatment administration is 
discontinued and no further assessments are planned, unless the 
patient will be followed for progression and/or survival
Randomization number
A unique identifier assigned to each randomized patient, 
corresponding to a specific treatment arm assignment
Study drug/ treatment
Any single drug or combination of drugs administered to the 
patient as part of the required study procedures; includes 
investigational drug (s), active drug run-ins or background therapy 
Study/investigational 
treatment discontinuation
Point/time when patient permanently stops taking 
study/investigational treatment  for any reason; may or may not 
also be the point/time of premature patient withdrawal
Subject Number 
A number assigned to each patient who enrolls into the study 
Variable
A measured value or assessed response that is determined in 
specific assessments and used in data analysis to evaluate the 
drug being tested in the study

Novartis
Confidential
Page 10
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Amendment 2
Rationale for Amendment
The purpose for Amendment 2 is to update Table 6-1 (Assessment Schedule) to include the 
visits at which the Enthesitis Evaluation must be done.
Amendment 1 
Rationale for Amendment
The purpose for Amendment 1 is to update the following Sections and Tables.

Section 4.1: Inclusion criteria number four (4) was updated to justify the need for a 
baseline skin scoring accordingly.  Therefore, it was reworded to: a target psoriatic skin 
lesion and a PASI score of 1 or greater. 

Section 5.2: Patients will receive treatment up to Week 48 and no treatment will be 
administered at the EOT Visit/Week 52. 

Section 5.5.8 and Table 5.1: The table was rearranged to clarify that no biologics are 
allowed in the study. This is to prevent any further confusion that was observed since the 
study launched.

Section 6: Previous version required a 4 week waiting time even for those patients who 
are treatment naïve, and do not need a washout or repeat assessments. The related section 
of FUTURE 5 global protocol is adapted to prevent a 4 week waiting period for those 
patients. Screening will now be more flexible in duration up to 8 weeks prior to 
randomization based on the time required to wash out prior anti-rheumatic medications.  
Patients that do not require a washout can proceed onto the baseline visit once all 
inclusion criteria and none of the exclusion criteria are met.  

Section 6.4.2: Was updated to remove the Independent Joint Assessor requirement.  This 
is the first study evaluating various typical findings for PsA such as TJC, SJC, PASI, IGA, 
enthesitis, dactylitis 
. Therefore, it is unlikely for the site personnel to have 
independent assessors for each evaluation. In order to best reflect the current standard of 
practice, it is per the Investigator’s discretion to decide who will be performing the 
evaluations.

Novartis
Confidential
Page 11
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

Section 6.4.6: Updated to emphasize the importance that the Erythrocyte Sedimentation 
Rate test must be performed locally.

Section 6.5.6: Updated to include that a serum β-hCG test will be performed in all women 
of child bearing potential at Screening Visit 2; and a local urine pregnancy tests will be 
performed at the specified visits as indicated in Table 6-1.

Appendix 12.10: The PROs Guidelines for the SitePad have been updated.

Novartis
Confidential
Page 12
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Protocol summary
Protocol number
CAIN457FUS01
Title
A randomized, double-blind, placebo-controlled, parallel-group, 
multicenter study to evaluate the safety and efficacy of secukinumab 300 
mg and 150 mg in adult patients with active psoriatic arthritis after 16 
weeks of treatment compared to placebo and to assess the safety, 
tolerability and efficacy up to 52 weeks
Brief title
Study to evaluate the safety and efficacy of Cosentyx® (secukinumab) 
300 mg and 150 mg in adult patients with active psoriatic arthritis (PsA) 
after 16 weeks of treatment compared to placebo 
Sponsor and Clinical 
Phase
Novartis / Phase IV
Investigation type
Drug: Biological
Study type
Interventional
Purpose and rationale
The purpose of this study is to provide 16 week safety, efficacy and 
tolerability data in adult biologic naïve PsA patients with target skin 
lesions and evaluate the effect of secukinumab on PsA specific clinical 
findings such as dactylitis, enthesitis and psoriatic lesions. The study will 
also evaluate the early efficacy of the treatment at the first scheduled 
clinical visit after starting a treatment (i.e., at Week 4) and long term 
safety and efficacy up to 52 weeks
Primary Objective(s) 
To demonstrate that the efficacy of secukinumab 300 mg at Week 16 is 
superior to placebo in adult patients with active PsA based on the 
proportion of patients achieving an American College of Rheumatology 
20 (ACR20) response.
Secondary Objectives
To evaluate: 

The efficacy of secukinumab 150 mg compared to placebo at 
Week 16 in patients with active PsA based on the proportion of 
patients achieving an American College of Rheumatology 20 
(ACR20) response.

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 based on the proportion of patients with 
dactylitis in the subset of patients who have dactylitis at baseline.

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 based on the proportion of patients with 
enthesitis in the subset of patients who have enthesitis at 
baseline.

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 in subset of patients with active PsA and 
number of tender and swollen joints less than 10 at baseline 
based on the proportion of patients achieving ACR20, ACR50, 
and ACR70 responses

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 based on the proportion of patients 
achieving ACR50 and ACR70 responses.

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 based on the proportion of patients 
achieving Minimal Disease Activity (5 of the following 7 criteria: 
≤1 tender joint, ≤1 swollen joint, PASI ≤1 or IGA mod 2011 ≤1, 

Novartis
Confidential
Page 13
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
patient assessment of pain (0-100 Visual Analog Scale (VAS)) 
≤15, patient global assessment of disease (VAS) ≤20, HAQ-DI 
≤0.5, tender entheseal points ≤1).

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 based on the proportion of patients 
achieving a PASI75, PASI90, and PASI100 responses 

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 based on the change from baseline in 
DAS28-CRP. 

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 based on the change from baseline in 
Psoriatic Arthritis Disease Activity Score (PASDAS). 

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 based on the change from baseline in SF12.

The efficacy of secukinumab 300 mg and 150 mg compared to 
placebo at Week 16 based on the change from baseline in HAQ-
DI. 

The overall safety and tolerability of secukinumab 300 mg and 
150 mg  compared with placebo as assessed by vital signs, 
clinical laboratory values, and adverse events (AE) monitoring.
Study design
This study uses a multicenter, randomized, double-blind, placebo-
controlled, parallel-group design. Approximately 250 adult patients (in 
2:2:1 ratio; 100 secukinumab 300 mg, 100 secukinumab 150 mg and  50 
placebo) with active PsA and a target skin lesion and a PASI score of 1 
or greater will be randomized from approximately 65 investigative sites in 
the United States. 
Screening will be flexible in duration based on the time required to wash 
out prior anti-rheumatic medications and have a duration of up to 8 weeks 
before randomization, followed by a treatment period up to Week 52.
Patients that do not require a washout can proceed onto the 
baseline visit once all inclusion criteria and none of the exclusion 
criteria are met.
At baseline (BL), patients whose eligibility is confirmed will be 
randomized to one of three treatment groups and will enter the Placebo 
Controlled Treatment Period.
Treatment Period 1
Treatment Period 1 is defined as the period from Randomization
through Week 16 (prior to the Week 16 dose). At the start of Treatment 
Period 1, patients will be randomized via IRT in a 2:2:1 ratio to one of
three treatment groups.

Group 1- Secukinumab 300 mg: secukinumab 300 mg (two s.c.
injections of the 150 mg dose) once weekly for five weeks (at
Baseline, Weeks 1, 2, 3, and 4), followed by dosing every four
weeks.

Group 2- Secukinumab 150 mg: secukinumab 150 mg (one s.c.
injection of the 150 mg dose and one s.c. injection of placebo)
once weekly for five weeks (at Baseline, Weeks 1, 2, 3, and 

Novartis
Confidential
Page 14
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
4), followed by dosing every four weeks.

Group 3- Placebo: placebo (t w o  s.c. injection of 150 mg 
secukinumab placebo per dose) once per week for five
weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing
every four weeks.
At each study treatment visit two s.c. injections in the form of PFS will be 
administered. This is necessary to maintain the blind, as secukinumab in 
PFS is available in either 1.0 mL (150 mg) or 2 x 1.0 mL (300mg). 
Placebo to secukinumab is also available in 1.0 mL to match the active 
drug.
Rescue medication is not allowed until Week 16.
Treatment Period 2

Patients receiving secukinumab 300 mg (Group 1) will continue 
to receive the same dose up to Week 48.

At Weeks 16, 28 and 40 patients on secukinumab 150 mg 
(Group 2) will be classified as responders (≥ 20% improvement 
from BL in both tender and swollen joint counts) or non-
responders.

At Weeks 16, 28 and 40 patients on secukinumab 150 
mg (Group 2) who are responders will continue to 
receive secukinumab 150 mg (1.0 mL) plus placebo (1.0 
mL) every 4 weeks until next evaluation of responder 
status at weeks 28 or 40. 

Patients who did not meet the responder criteria at Week 
16, 28 or 40 will start receiving secukinumab 300 mg s.c. 
every 4 weeks and will continue this dose up to Week 48.

Patients on placebo (Group 3) regardless of their responder 
status will start receiving secukinumab 300 mg s.c. every 4 
weeks from Week 16 up to Week 48.
Population
The study population will be comprised of approximately 250 patients 
who have passed screening assessments, comply with eligibility criteria 
and have provided written consent.

Male and female patients aged at minimum 18 at time of consent, 
with active PsA fulfilling the CASPAR criteria. 

Patients must have symptoms for at least 6 months with 
moderate to severe PsA and must have ≥3 tender joints out of 78 
and ≥3 swollen joints out of 76 at BL (dactylitis of a digit counts 
as one joint each).

Patients must have a target skin lesion and a PASI score of 1 or 
greater.

Patients must report active disease despite current or previous 
NSAIDs and / or DMARDs. Concomitant therapy with MTX (≤25 
mg/week) will be acceptable, if dose and route of administration 
have been stable for at least four weeks prior to the 

Novartis
Confidential
Page 15
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
randomization visit.

Patients can be re-screened only once and re-screening study
related procedures should not be performed prior to written re-
consent by the subject. Mis-randomized Patients or discontinued 
patients cannot be re-screened.

Enrollment will stop as soon as the target number of randomized 
patients is reached.
Inclusion criteria
1.
Patient 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 study assessment is performed
2.
Male or non-pregnant, non-lactating female patients at least 18 
years of age
3.
Diagnosis of PsA classified by CASPAR criteria and with 
symptoms for at least 6 months with moderate to severe PsA 
who must have had at Baseline ≥3 tender joints out of 78 and 
≥3 swollen joints out of 76 (dactylitis of a digit counts as one joint 
each)
4.
A target skin psoriatic lesion and a PASI score of 1 or greater
5.
RF and/or Anti-cyclic citrullinated peptide (antiCCP) antibodies
            negative at screening
6.
Patients who are regularly taking NSAIDs as part of their PsA 
therapy are required to be on a stable dose for at least 2 weeks 
before study randomization and should remain on a stable dose 
up to Week 16
7.
Patients taking corticosteroids should be on a stable dose of ≤10 
mg/day prednisone or equivalent for at least 2 weeks before 
randomization and must remain on a stable dose up to Week 16
8.
Patients taking MTX (≤ 25 mg/week) are allowed to continue their 
medication if the dose is stable for at least 4 weeks before 
randomization and must remain on a stable dose up to study 
completion 
9.
Patients on MTX must be on folic acid supplementation at 
randomization
10. Patients who are on a DMARD other than MTX must discontinue 
the DMARD 4 weeks prior to randomization visit except for 
leflunomide, which should be discontinued for 8 weeks prior to 
randomization unless a cholestyramine washout has been 
performed 
Exclusion criteria
1.
Chest X-ray or chest MRI with evidence of ongoing infectious or 
malignant process, obtained within 3 months prior to screening 
and evaluated by a qualified physician 
2.
Previous exposure to secukinumab or other biologic drug directly 
targeting IL-17 or IL-17 receptor
3.
Use of any investigational drug and/or devices within 4 weeks 
before randomization or a period of 5 half-lives of the 
investigational drug, whichever was longer
4.
Ongoing use of prohibited psoriasis treatments / medications 
(e.g., topical corticosteroids, ultraviolet therapy) at randomization. 
The following wash out periods need to be observed:

Novartis
Confidential
Page 16
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

Oral or topical retinoids 4 weeks

Photochemotherapy (e.g. Psoralen Plus Ultraviolet Light 
Therapy (PUVA)) 4 weeks

Phototherapy (UVA or UVB) 2 weeks 

Topical skin treatments (except on face, eyes, scalp and 
genital area during screening, only corticosteroids with 
mild to moderate potency) 2 weeks
5.
History of hypersensitivity to the study drug or its excipient or to 
drugs of similar chemical classes
6.
Any intramuscular or intravenous corticosteroid treatment within 
4 weeks before randomization
7.
Any therapy by intra-articular injections (e.g. corticosteroid) within 
4 weeks before randomization
8.
Patients who ever received biologic immunomodulating agents 
including those targeting TNFα,  IL-6 and IL-12/23 investigational 
or approved
9.
Previous treatment with any cell-depleting therapies including but 
not limited to anti-CD20, investigational agents (e.g., 
alemtuzumab, anti-CD4, anti-CD5, anti-CD3, anti-CD19)
10. Pregnant or nursing (lactating) women, where pregnancy is 
defined as the state of a female after conception and until the 
termination of gestation, confirmed by a positive human chorionic 
gonadotropin (hCG) laboratory test 
11. Women of child-bearing potential, defined as all women 
physiologically capable of becoming pregnant, unless they are 
using effective methods of contraception during the entire study 
or longer if required by locally approved prescribing information. 
Effective contraception is defined in the Exclusion Criteria in 
Section 4.2. 
12. Active ongoing inflammatory diseases other than PsA that might 
confound the evaluation of the benefit of secukinumab therapy
13. Underlying metabolic, hematologic, renal, hepatic, pulmonary, 
neurologic, endocrine, cardiac, infectious or gastrointestinal 
conditions which in the opinion of the investigator 
immunocompromises the patient and/or places
the patient at unacceptable risk for participation in an 
immunomodulatory therapy
14. Significant medical problems or diseases, including but not 
limited to the following: uncontrolled hypertension (≥160/95 
mmHg), congestive heart failure [New York Heart Association 
status of class III or IV], uncontrolled diabetes
15. History of clinically significant liver disease or liver injury as 
indicated by abnormal liver function tests such as SGOT (AST), 
SGPT (ALT), alkaline phosphatase, or serum bilirubin. The 
investigator should be guided by the following criteria:
Any single parameter should not exceed 2 × upper limit of normal 
(ULN). 
a.
A single parameter elevated up to and including 2 × ULN should 
be re-checked once more as soon as possible, and in all cases, 
at least prior to enrollment/randomization, to rule out lab error
b.
If the total bilirubin concentration is increased above 2 × ULN, 

Novartis
Confidential
Page 17
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
total bilirubin should be differentiated into the direct and indirect 
reacting bilirubin. In any case, serum bilirubin should not exceed 
the value of 1.6 mg/dL (27 µmol/L)
16. History of renal trauma, glomerulonephritis, or patients with one 
kidney only, or a serum creatinine level exceeding 1.5 mg/dL 
(132.6µmol/L)
17. Screening total White Blood Cells (WBC) count <3,000/µL, or 
platelets <100,000/µL or neutrophils 1,500/µL or hemoglobin 
<8.5 g/dL (85g/L)
18. Active systemic infections during the last two weeks (exception: 
common cold) prior to randomization
19. History of ongoing, chronic or recurrent infectious disease or 
evidence of tuberculosis infection as defined by either a positive 
Purified protein derivative (PPD) skin test (the size of induration 
will be measured after 48-72 hours, and a positive result is 
defined as an induration of ≥5mm or according to local 
practice/guidelines) or a positive QuantiFERON tuberculosis 
(TB)-Gold test as indicated in the assessment schedule. Patients 
with a positive test may participate in the study if further work-up 
(according to local practice/guidelines) established conclusively 
that the subject had no evidence of active tuberculosis. If 
presence of latent tuberculosis is established then treatment 
according to local country guidelines must have been initiated
20. Known infection with human immunodeficiency virus, hepatitis B 
or hepatitis C at screening or randomization
21. History of lymphoproliferative disease or any known malignancy 
or history of malignancy of any organ system within the past 5 
years (except for basal cell carcinoma or actinic keratoses that 
have been treated with no evidence of recurrence in the past 3 
months, carcinoma in situ of the cervix or non-invasive malignant 
colon polyps that have been removed)
22. Current severe progressive or uncontrolled disease which in the 
judgment of the clinical investigator renders the patient 
unsuitable for the trial
23. Inability or unwillingness to undergo repeated venipuncture (e.g., 
because of poor tolerability or lack of access to veins) 
24. Any medical or psychiatric condition which, in the investigator’s 
opinion, precludes the participant from adhering to the protocol or 
completing the study per protocol
25. Donation or loss of 400 mL or more of blood within 8 weeks 
before randomization
26. History or evidence of ongoing alcohol or drug abuse, within the 
last six months before randomization
27. Plans for administration of live vaccines during the study period 
or within 6 weeks preceding randomization
Investigational and 
reference therapy
Treatment Period 1

Group 1- Secukinumab 300 mg: secukinumab 300 mg (two s.c.
injections of the 150 mg dose) once weekly for five weeks (at
Baseline, Weeks 1, 2, 3, and 4), followed by dosing every four
weeks. 

Novartis
Confidential
Page 18
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

Group 2- Secukinumab 150 mg: secukinumab 150 mg (one s.c.
injection of the 150 mg dose and one s.c. injection of placebo)
once weekly for five weeks (at Baseline, Weeks 1, 2, 3, and 
4), followed by dosing every four weeks. 

Group 3- Placebo: placebo (t w o  s.c. injection of 150 mg 
secukinumab placebo per dose) once per week for five
weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by dosing
every four weeks. 
Treatment Period 2

Patients receiving secukinumab 300 mg (Group 1) will continue 
to receive the same dose up to Week 48.

At Weeks 16, 28 and 40 patients on secukinumab 150 mg 
(Group 2) will be classified as responders (≥ 20% improvement 
from BL in both tender and swollen joint counts) or non-
responders.

At Weeks 16, 28 and 40 patients on secukinumab 150 
mg (Group 2) who are responders will continue to 
receive secukinumab 150 mg (1.0 mL) plus placebo (1.0 
mL) every 4 weeks until next evaluation of responder 
status at Weeks 28 or 40. 

Patients who did not meet the responder criteria at Week 
16, 28 or 40 will start receiving secukinumab 300 mg s.c. 
every 4 weeks and will continue this dose up to Week 48.

Patients on placebo (Group 3) regardless of their responder 
status will start receiving secukinumab 300 mg s.c. every 4 
weeks from Week 16 up to Week 48.
Efficacy assessments

ACR20, ACR50, ACR70 responses 

Tender 78  joint count and swollen 76 joint count

 

Patient’s Assessment of PsA pain intensity

Patient’s global assessment of disease activity (VAS)

Health Assessment Questionnaire (HAQ-DI)

SF-12 
 
 
 

Physician’s global assessment of disease activity (VAS)

High Sensitivity C-reactive protein (hsCRP)

Erythrocyte sedimentation rate (ESR) 

PASI 

DAS28 and EULAR

PASDAS

Minimal Disease Activity

Novartis
Confidential
Page 19
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
 

IGA mod 2011 

Physician’s assessment of nail disease (VAS)
Safety assessments

Evaluation of AE/SAE’s

Physical examination

Vital signs

Height and weight

QuantiFERON TB-Gold test or PPD skin test

Electrocardiogram

Local tolerability (Injection site reactions)

Laboratory evaluations (Hematology, Clinical Chemistry, Lipid 
Panel, Urinalysis)

Pregnancy and assessment of fertility

Tolerability of secukinumab
Other assessments
Quality of Life questionnaires/ Patient reported outcomes (PROs)
Data analysis
A designated Contract Research Organization will perform the statistical 
analysis.
Unless otherwise specified, all statistical tests will be conducted against a 
two-sided alternative hypothesis, employing a significance level of 0.05.
The following analysis sets will be used for the statistical reporting and 
analyses:
Randomized Set: The Randomized Set includes all randomized patients.  
Safety Set: The Safety Set includes all patients who received at least one 
dose of study medication.  Patients will be included in the analysis 
according to treatment received.
Full Analysis Set:  The Full Analysis Set comprises all patients to whom 
study medication has been assigned.  Patients inappropriately 
randomized (e.g., IRT was called in error for randomization of a screen 
failed subject) will be excluded from this analysis set. 
Data will be summarized with respect to demographic and baseline 
characteristics of all patients, the subgroup of patients with dactylitis at 
baseline, and the subgroup of patients with enthesitis at baseline, for the 
Randomized Set and the Full Analysis Set.
Efficacy, safety, and other data will be summarized.
The primary efficacy variable is ACR20 response (yes, no). The primary 
analysis time point will be at Week 16.
The primary efficacy variable will be analyzed at each time point using a 
logistic regression model with treatment (3 treatment groups), 
methotrexate usage at baseline (yes, no), and body weight as 
explanatory variables (Stokes, Davis, and Koch, 2012).  The odds ratios 
for each dose of secukinumab versus placebo, 95% confidence intervals 
for the odds ratios, and p-values based on the fitted model will be 
reported.  
  
The primary analysis of the primary efficacy variable will be based on the 

Novartis
Confidential
Page 20
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Full Analysis Set. 
Patients who discontinued prematurely for any reason will be considered 
non-responders from the time they discontinued.  Patients who do not 
have the required data to compute ACR response (i.e., tender and 
swollen joint counts and at least three of the five ACR domains) at 
baseline and at the specific time point will be classified as non-
responders.
The primary efficacy variable will also be analyzed at each time point for 
the Full Analysis Set using the Cochran-Mantel-Haenszel (CMH) test to 
compare each dose of secukinumab against placebo, adjusting for 
methotrexate usage at baseline (yes, no) (Stokes, Davis, and Koch, 
2012).  Two 95% confidence intervals for the difference between each 
dose of secukinumab versus placebo in the proportion of patients who 
are ACR20 responders will be calculated using the normal approximation 
to the binomial distribution.  
The secondary efficacy variables are the following:
1.
Dactylitis (yes, no)
2.
Enthesitis (yes, no)
3.
ACR50 response (yes, no)
4.
ACR70 response (yes, no)
5.
Minimal Disease Activity (yes, no)
6.
PASI75 response (yes, no)
7.
PASI90 response (yes, no)
8.
PASI100 (yes, no)
9.
Change from baseline in DAS28-CRP
10. Change from baseline in PASDAS
11. Change from baseline in SF12
12. Change from baseline in HAQ-DI
Two analyses of dactylitis and enthesitis (secondary efficacy variables 1 
and 2) will be performed at each time point.  For the first analysis, the 
data for the subgroup of patients who have dactylitis at baseline will be 
used (similarly for enthesitis) and the analysis of the binary response 
variable (yes, no) will be similar to the analysis of secondary efficacy 
variables 3-8 below.  In the supporting analysis, the data for all patients 
will be used and an ordinal variable will be created based on presence 
(yes) or absence (no) of dactylitis at baseline and a post-baseline visit 
(similarly for enthesitis).  The three categories for the ordinal variable will 
be no/no (category 1), no/yes and yes/no (category 2), and yes/yes 
(category 3).  This ordinal response variable will be analyzed using a 
proportional odds regression model with treatment (3 treatment groups), 
methotrexate usage at baseline (yes, no), and body weight as 
explanatory variables (Stokes, Davis, and Koch, 2012).  
Secondary efficacy variables 3-8 will be analyzed at each time point 
using a logistic regression model with treatment (3 treatment groups), 
methotrexate usage at baseline (yes, no), and body weight as 
explanatory variables (Stokes, Davis, and Koch, 2012).  
Secondary efficacy variables 9-12 will be analyzed at each time point by 

Novartis
Confidential
Page 21
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
an analysis of covariance (ANCOVA) model with treatment (3 treatment 
groups), baseline, methotrexate usage at baseline (yes, no), and body 
weight as explanatory variables.    Missing data will be imputed using the 
last-observation-carried-forward (LOCF) method.
  
Analyses of the secondary efficacy variables will be based on the Full 
Analysis Set.
The assessment of safety will be based mainly on the frequency of 
adverse events and laboratory data. Other safety data (e.g., vital signs 
and special tests) will be considered, as appropriate.
Analysis of safety data will be based on the Safety Set.
The sample size was calculated based on the primary efficacy variable 
(i.e., ACR20 response) for the primary comparison (i.e., secukinumab 
300 mg versus placebo).  ACR20 response rates of 50% for 
secukinumab 300 mg and 20% for placebo (corresponding to an odds 
ratio of 4) at Week 16 were assumed, based on results from 
AIN457F2312 (FUTURE 2) study.  Using a continuity-corrected chi-
squared test, an allocation ratio of 2:1, a two-sided significance level of 
0.05, and a power of 0.90, approximately 88 patients in secukinumab 300 
mg group and 44 patients in placebo group will be needed (nQuery 
Advisor 7.0).  Assuming a loss to follow-up rate of 10% and a 2:2:1 
allocation ratio (secukinumab 300 mg: secukinumab 150 mg: placebo), 
the total number of randomized patients will be approximately 250 (100 
on secukinumab 300 mg, 100 on secukinumab 150 mg, and 50 on 
placebo).
Key words
Active Psoriatic Arthritis, Subcutaneous secukinumab in prefilled syringes 
(PFS) , CASPAR

Novartis
Confidential
Page 22
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
1
Introduction
1.1
Background 
Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory disease belonging to 
the spectrum of conditions commonly referred to as spondyloarthritidies (SpA). While the 
various SpA may be diverse in their clinical presentations, common environmental as well as 
genetic factors associated with susceptibility to SpA are suspected (Turkiewicz and Moreland 
2007). This latter notion was corroborated by findings in a large-scale single nucleotide 
polymorphism scan study, where interleukin (IL)-23R variants that were previously linked to 
Crohn’s disease and psoriasis (diseases that may both co-exist with SpA) conferred risk to 
developing ankylosing spondylitis (AS) (Barrett et al 2008). Together, a common pathway,
including the IL-23/IL-17 axis, may play a role in seronegative SpAs, including PsA.
PsA is a frequent and chronic immune-mediated disease encompassing a spectrum of 
overlapping clinical entities (Moll and Wright 1973). Up to 40% of patients with psoriasis 
will develop PsA, which is both more common and more severe than previously believed
(Taylor et al 2006). PsA is also associated with significant morbidity and disability, and 
constitutes a major socioeconomic burden. 
Nonsteroidal anti-inflammatory drugs (NSAIDs) may improve symptoms in patients with 
mild PsA, but can worsen skin disease and be associated with an increased risk of 
cardiovascular side effects. Similarly, intra-articular injections of corticosteroids and low 
doses of systemic corticosteroids have been used with variable efficacy and significant side 
effects with chronic use.  Disease-modifying anti-rheumatic drugs (DMARDs) are more 
typically used for PsA, and include methotrexate (MTX), sulfasalazine, cyclosporine, and 
leflunomide; however, these therapies may only partially control established disease (Mease 
2008; Mease and Armstrong 2014). Biologic agents such as the tumor necrosis factor (TNF) 
inhibitors adalimumab, certolizumab pegol, etanercept, golimumab, and infliximab are 
approved in patients with PsA to reduce joint disease activity, prevent structural damage, and
improve function (Mease et al 2000, Mease et al 2005). However, TNF-inhibitor therapy may 
result in significant dose-limiting adverse effects, including the development of 
autoantibodies and the induction of a lupus-like syndrome.
Additional approved therapies for patients with PsA 
 
 Several lines of 
evidence support additional therapeutic pathways in PsA. Prominent T cell involvement 
occurs in the pathogenesis of PsA (Tassiulas et al 1999; Curran et al 2004; Mease and 
Armstrong 2014) and clinical trials have shown efficacy of T cell-targeted treatment that has 
included cyclosporine A, CTLA4-Ig, and alefacept. Despite available therapies for PsA, an 
unmet clinical need remains for agents that can be used singly or in combination with other 
therapies and provide effective short and long-term disease control especially on those PsA 
specific clinical findings such as dactylitis and enthesitis with favorable risk/benefit profiles.
IL-17 antagonism represents a novel therapeutic approach aimed at interference with the 
chronic inflammatory process by selectively targeting the predominant pro-inflammatory 
cytokine of the helper T17 cell subset. Additional effects of anti-IL-17 on bone homoeostasis 

Novartis
Confidential
Page 23
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
via receptor activator of nuclear factor kappa-B ligand (RANKL) and IL-1, upstream of 
TNFα,, can be inferred from animal studies (Koenders et al 2005). Assuming a potential role 
of IL-17 cells in the inflammatory infiltrate in PsA, it can be speculated that locally dist urbed 
homeostasis of osteoclastogenic and osteoblastogenic mechanisms characteristic of PsA might 
be affected by IL-17 blockade, thus potentially providing a therapeutic advancement to 
effectively treat dactylitis and enthesitis in PsA.
Secukinumab (AIN457) is a high-affinity fully human monoclonal anti-human antibody that 
neutralizes IL-17A activity. IL-17A is the key cytokine in the newly discovered Th17 
pathway that is believed to be an important mediator of autoimmunity. Neutralization of IL-
17A has strong preclinical and clinical target validation. 
A proof-of-concept study conducted in patients with PsA (CAIN457A2206) suggesting a
clinically meaningful response for signs and symptoms up to Week 16. The efficacy of
secukinumab in PsA patients is further supported by positive results for signs and symptoms
(i.e. ACR20/50, PASI75/90), resolution of dactylitis, enthesitis and inhibition of radiologic
damage at Week 24 obtained in a phase III study (CAIN457F2306; N=606) employing an
intravenous (i.v.) loading regimen (3x10 mg/kg) of secukinumab Q2W followed by
secukinumab s.c. 75 mg or 150 mg administered Q4W. In another phase III study
(CAIN457F2312; N=397) secukinumab also demonstrated positive efficacy results superior to
placebo in patients with PsA through most components of the arthritic and skin measures of
signs and symptoms and physical function in a population comprised of 65% naïve to TNF -α
inhibitors and 35% patients who were inadequate responders to a TNF-α inhibitor. Based on 
the results of these phase 3 trials, secukinumab received FDA approval in January 2016 for 
the treatment of active PsA and AS in adult patients. Therefore, treatment with secukinumab 
may result in improvement of symptoms and functional joint manifestations in afflicted
patients.
The completed studies of secukinumab recruited both biologic exposed or naïve PsA patients 
with or without psoriatic skin lesions at baseline. Therefore a need for predefined prospective 
data exist for these different subgroups of patients which the precise effects of targeting IL-
17A can be observed more clearly.  The present study will evaluate the safety and efficacy of 
treatment with two doses of secukinumab compared with placebo in patients with active 
psoriatic arthritis and concomitant psoriasis who are naïve to biologic medications including 
tumor necrosis factor alpha (TNFα), IL-6 and IL-12/23 inhibitors. Also in the blinded long 
term extension period of this study, the effect of increasing the dose in non-responders after 
each evaluation every 12 weeks visit will provide valuable information regarding the 
correlation between the level of disease activity and IL-17A inhibition.
1.2
Purpose 
The purpose of this study is to provide 16 week safety, efficacy and tolerability data in 
biologic naïve PsA patients with concomitant psoriatic skin lesions and evaluate the effect of 
secukinumab on PsA specific clinical findings such as dactylitis, enthesitis and psoriatic 
lesions. The study will also evaluate the early efficacy of the treatment at the first scheduled 
clinical visit after starting a treatment (i.e., at week 4) and investigate the remission status of 
all patients at each time points by evaluating the MDA, PASDAS and DAS28-CRP. This will 
be done in the blinded long term extension by increasing the dose to 300 mg in nonresponding 

Novartis
Confidential
Page 24
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
patients in 150 mg groups to confirm or support the role of higher IL-17A activity in PsA by 
evaluating the clinical response at every 12 weeks.
2
Study objectives 
2.1
Primary objective(s)
To demonstrate that the efficacy of secukinumab 300 mg at Week 16 is superior to placebo in 
patients with active PsA based on the proportion of patients achieving an American College of 
Rheumatology 20 (ACR20) response.
2.2
Secondary objectives
To evaluate:

The efficacy of secukinumab 150 mg compared to placebo at Week 16 in patients with 
active PsA based on the proportion of patients achieving an American College of 
Rheumatology 20 (ACR20) response.

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 based 
on the proportion of patients with dactylitis in the subset of patients who have dactylitis at 
baseline.

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 based 
on the proportion of patients with enthesitis in the subset of patients who have enthesitis at 
baseline.

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 in 
subset of patients with active PsA and number of tender and swollen joints less than 10 at 
baseline based on the proportion of patients achieving ACR20, ACR50, and ACR70 
responses

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 based 
on the proportion of patients achieving ACR50 and ACR70 responses.

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 based 
on the proportion of patients achieving Minimal Disease Activity (5 of the following 7 
criteria: ≤1 tender joint, ≤1 swollen joint, PASI ≤1 or IGA mod 2011 ≤1, patient 
assessment of pain (0-100 Visual Analog Scale (VAS)) ≤15, patient global assessment of 
disease (VAS) ≤20, HAQ-DI ≤0.5, tender entheseal points ≤1).

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 based 
on the proportion of patients achieving a PASI75, PASI90, and PASI100 responses 

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 based 
on the change from baseline in DAS28-CRP. 

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 based 
on the change from baseline in Psoriatic Arthritis Disease Activity Score (PASDAS). 

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 based 
on the change from baseline in SF12.

The efficacy of secukinumab 300 mg and 150 mg compared to placebo at Week 16 based 
on the change from baseline in HAQ-DI. 

Novartis
Confidential
Page 25
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

The overall safety and tolerability of secukinumab 300 mg and 150 mg  compared with 
placebo as assessed by vital signs, clinical laboratory values, and adverse events (AE) 
monitoring.
3
Investigational plan
3.1
Study design
This study uses a multicenter, randomized, double-blind, placebo-controlled, parallel-group 
design. Approximately 250 adult patients (in 2:2:1 ratio; 100 secukinumab 300 mg, 100 
secukinumab 150 mg and  50 placebo) with active PsA and a target skin lesion with PASI 
score of 1 or greater will be randomized from approximately 65 investigative sites in the 
United States. 
Screening will be flexible in duration based on the time required to wash out prior anti -
rheumatic medications and have a duration of up to 8 weeks before randomization, followed 
by a treatment period up to Week 52.
Patients that do not require a washout can proceed onto the baseline visit once all 
inclusion criteria and none of the exclusion criteria are met.
At baseline (BL), patients whose eligibility is confirmed will be randomized to one of 
three treatment groups and will enter the Placebo Controlled Treatment Period
Treatment Period 1
The Treatment Period 1 is defined as starting from Randomization through Week 16 (prior
to the Week 16 dose). At the start of the Placebo-Controlled Treatment Period, patients will
be randomized via IRT in a 2:2:1 ratio to one of three treatment groups (secukinumab 300 mg 
s.c., secukinumab 150 mg s.c. or placebo s.c.).

Group 1- Secukinumab 300 mg: secukinumab 300 mg (two s.c. injections of the 150
mg dose) once weekly for five weeks (at Baseline, Weeks 1, 2, 3, and 4), followed
by dosing every four weeks. 

Novartis
Confidential
Page 26
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

Group 2- Secukinumab 150 mg: secukinumab 150 mg (one s.c. injection of the 150
mg dose and one s.c. secukinumab injection of placebo) once weekly for five weeks
(at Baseline, Weeks 1, 2, 3, and 4), followed by dosing every four weeks.

Group 3- Placebo: placebo (two s.c. injection of 150 mg secukinumab 
placebo per dose) once per week for five weeks (at Baseline, Weeks 1, 2, 3, 
and 4), followed by dosing every four weeks. 
Treatment Period 2

Patients receiving secukinumab 300 mg (Group 1) will continue to receive the same dose 
up to Week 48.

At Weeks 16, 28 and 40 patients on secukinumab 150 mg (Group 2) will be classified as 
responders (≥ 20% improvement from BL in both tender and swollen joint counts) or non-
responders.

At Weeks 16, 28 and 40 patients on secukinumab 150 mg (Group 2) who are 
responders will continue to receive secukinumab 150 mg (1.0 mL) plus placebo (1.0 
mL) every 4 weeks until next evaluation of responder status at weeks 28 or 40. 

Patients who did not meet the responder criteria at Week 16, 28 or 40 will start 
receiving secukinumab 300 mg s.c. every 4 weeks and will continue this dose up to 
Week 48.

Patients on placebo (Group 3) regardless of their responder status will start receiving 
secukinumab 300 mg s.c. every 4 weeks from Week 16 up to Week 48.
Rescue medication will not be allowed during the day of the clinical visit and before 
completion of Week 16 assessments (Section 5.5.6). Although no subject will be restricted 
from receiving necessary rescue medications for lack of benefit or worsening of disease, 
patients will be discontinued from the study if rescued with prohibited biologics (as described 
in (Section 5.5.8) and should obtain end of study assessments at the earliest possible date, 
provided consent to do so has not been withdrawn.   

Novartis
Confidential
Page 27
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Figure 3-1
Study design 
3.2
Rationale for study design
The double-blind, randomized, parallel-group placebo controlled design used in this study is 
aligned with Phase III trials of other biologics in this disease area and is in accordance with 
existing international guidelines. The treatment duration of the placebo group is kept to a 
minimum and the placebo group will be re-assigned to active treatment after Week 16 
(primary analysis time point). The blinding is maintained beyond Week 16 so as to ensure 
reliable efficacy and safety assessments. The regular assessments of disease activity ensures 
that patients who are experiencing worsening of disease in any of the treatment groups can 
exit the study upon their own wish or based on the advice of the investigator at any time. 
Long-term treatment data up to 52 weeks are being generated to explore secukinumab’s long-
term efficacy and safety in this population.
3.3
Rationale for dose/regimen, route of administration and duration 
of treatment
The dosing regimens in this study rely upon dose-efficacy relationships observed in a proof of 
concept (PoC) trial (CAIN457A2206) and two phase 3
trials (CAIN457F2306,
CAIN457F2312) in PsA, as described below. The PoC trial in PsA (CAIN457A2206)
suggested that after two i.v. secukinumab doses of 10 mg/kg given 3 weeks apart,
secukinumab demonstrated high efficacy, achieving an ACR20 response at Week 6 in 62% of
the TNF-naïve patients on secukinumab vs. 20% on placebo, and was well-tolerated (McInnes 
et al 2013). The phase 3 trials in PsA, CAIN457F2306 assessed the efficacy of both 75 mg 
and 150 mg s.c. maintenance doses (every 4 weeks) after loading regimens consisting of 3 i.v. 
doses of 10 mg/kg given at BL, Weeks 2 and 4, and CAIN457F2312 assessed the efficacy of 
75 mg, 150 mg and 300 mg s.c. maintenance doses (every 4 weeks) after loading regimens 
consisting of s.c. doses of 75 mg, 150 mg or 300 mg given at BL, Weeks 1, 2, and 3. Given
the similarity of the ACR20 response seen at the Week 24 primary analysis time point for the

Novartis
Confidential
Page 28
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
150 mg dose in each of these studies, regardless of whether the loading dosing was i.v.
(CAIN457F2306: 50.0% for 150 mg vs 17.3% for placebo) or s.c. (CAIN457F2312: 51.0%
for 150 mg vs 15.3% for placebo), 150 mg is a sufficient dose to provide clinically an d
statistically significant efficacy, whereas higher loading doses of secukinumab do not appear
to confer a greater response on the primary efficacy variable of ACR20 at Week 24. In Study
CAIN457F2312, PASI75 and PASI90 response was assessed in the subgroup of patients who
had ≥ 3% skin involvement with psoriasis at baseline. For both PASI75 and PASI90 response
rates, the difference to placebo at Week 24 was statistically significant for the secukinumab
150 mg and 300 mg doses (PASI75: 48.3%, p = 0.0006 and 63.4%, p < 0.0001; PASI90:
32.8%, p = 0.0029 and 48.8%, p = 0.0002, respectively). The percentage of responders
increased as secukinumab dose increased, with the secukinumab 300 mg dose demonstrating a
meaningful improvement over the secukinumab 150 mg dose (treatment differences between
secukinumab 300 mg and 150 mg for PASI75 and PASI90 were 15.1% and 16.0%,
respectively). Of note, the 75 mg s.c. loading (once weekly) followed by maintenance (once 
monthly) tested in CAIN457F2312 achieved a statistically significant but clinically lower 
effect size in ACR20 response of 29.3% and did not achieve statistically significant 
improvements in any of the efficacy variables tested in a pre-defined testing hierarchy, 
including PASI75, PASI90 DAS28 CRP, SF36 PCS, HAQ-DI©, ACR50, dactylitis and 
enthesitis.
This study is evaluating secukinumab 300 mg and 150 mg s.c. doses for the treatment of 
adults with active PsA and a baseline psoriatic skin lesions of PASI 1 and higher . As the 
phase 3 program suggested that patients with concomitant skin lesions may have more 
pronounced clinical benefits with 300 mg, all the placebo patients will receive secukinumab 
300 mg after the completion of placebo controlled period (Week 16). The non-responders in 
Group 2 (150 mg patients) will receive secukinumab 300 mg after the completion of Week 16 
as well as at every clinical visit until the completion of the study (Weeks 20, 24, 28, 32, 36, 40, 
44 and 48) based on their responder status.
Also in order to minimize the patient’s exposure to placebo, this study will utilize a 2:2:1 
randomization that only 1 out 5 patients will receive placebo for a duration of 16 weeks where 
the meaningful clinical differentiation is observed in the phase 3 FUTURE studies.
In summary, the secukinumab regimen in this study is based on data suggesting optimal 
efficacy in PsA and optimal safety and efficacy in the treatment of skin disease in patients 
with psoriasis.
3.4
Rationale for choice of comparator
A placebo arm is included in this study up to the primary analysis time point at Week 16. Due 
to the nature of the disease and the outcome measures used (ACR criteria) a placebo arm is 
necessary to obtain reliable efficacy measurements. The continuation of the placebo group up 
to the primary analysis time point at Week 16 can be supported from an ethical standpoint. 
Moreover the inclusion of a placebo group is in accordance with health authority guidelines, 
including (FDA 1999/EMA 2009). The parallel-group placebo controlled design used in this 
study is aligned with Phase III trials of other biologics in this disease area and is in 
accordance with international guidelines. The treatment duration of the placebo group is kept 
to a minimum and the placebo group will be re-assigned to active treatment at the end of 

Novartis
Confidential
Page 29
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Week 16. The regular assessment of disease activity ensures that patients who are 
experiencing worsening of disease in any of the treatment groups can exit the study upon their 
own wish or based on the advice of the investigator at any time. 
3.5
Purpose and timing of interim analyses/design adaptations
The database of this study will be locked twice, first after the end of Treatment Period 1
(Week 16) and again after the end of Treatment Period 2 (Week 52).  Data analyses will 
follow each database lock. The main analysis (or test) for the primary objective will be done 
at Week 16.  As Week 16 is the primary analysis time point, no adjustment to the significance 
level of 0.05 will be made.
3.6
Risks and benefits 
Secukinumab has shown confirmed efficacy in several inflammatory diseases and approved 
by the EMA and FDA for the treatment of active PsA and AS in adult patients. The safety
profile of secukinumab is primarily based on the aggregate safety data from 10 large 
completed phase II/III psoriasis trials. The evaluation of safety data from completed PsA 
trials did not show additional safety concerns.
Secukinumab was generally safe and well-tolerated. The most frequently reported adverse 
events (AE) are infections, especially upper respiratory tract with secukinumab relative to 
placebo. 
There 
was 
an 
increase 
in 
mucosal 
or 
cutaneous 
candidiasis 
with 
secukinumab compared to placebo, but the cases were generally mild or moderate in
severity, non-serious, and responsive to standard treatment.
There was a small increase in mild neutropenia cases with secukinumab compared to placebo. 
Common Toxicity Criteria (CTC) AE grade 3 neutropenia (<1.0-0.5x109/L) was uncommonly 
observed 
with  secukinumab, 
most 
were 
transient 
and 
reversible 
without 
a 
temporal relationship to serious infections.
Hypersensitivity reactions include urticarial and rare event of anaphylactic reaction to 
secukinumab were also observed in clinical studies.
Taking into account the individual risks as outlined above, the expected risk profile of 
secukinumab from a mechanism of action perspective is anticipated to be similar or
improved compared to the 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 in the current
version of the IB. The completed FUTURE 1 and 2 trials confirmed the significant clinical 
benefits to secukinumab treatment in PsA patients observed as early as 1-3 weeks in all PsA 
related joint, skin and other symptoms such as dactylitis and enthesitis.
From the standpoint of the overall risk-benefit assessment, current trial with secukinumab is 
justified.

Novartis
Confidential
Page 30
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
4
Population
The study population will be comprised of the following patients who have passed screening 
assessments, comply with eligibility criteria and have provided written consent:
Male and female patients aged at minimum 18 at time of consent, with active PsA fulfilling 
the CASPAR criteria (described in Appendix 2). Patients must have symptoms for at least 6 
months with moderate to severe PsA and must have ≥3 tender joints out of 78 and ≥3 swollen 
joints out of 76 at baseline (dactylitis of a digit counts as one joint each).
Patients must have a target psoriatic skin lesion with a PASI score of 1 or greater at the time 
of screening.
A total of approximately 250
patients will be randomized in approximately 65 
rheumatology/dermatology centers in the United States. A screening failure rate of 
approximately 30% and post-randomization loss to follow-up rate of 10% is anticipated. 
Patients who drop out after they have been randomized will not be replaced. 
4.1
Inclusion criteria
Patients eligible for inclusion in this study have to fulfill all of the following criteria:
1. Patient must be able to understand and communicate with the investigator and comply 
with the requirements of the study and must give a written, signed and dated informed 
consent before any study assessment is performed
2. Male or non-pregnant, non-lactating female patients at least 18 years of age
3. Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months 
with moderate to severe PsA who must have had at Baseline ≥3 tender joints out of 78 
and ≥3 swollen joints out of 76 (dactylitis of a digit counts as one joint each)
4. A target psoriatic skin lesion and a PASI score of 1 or greater
5. RF and/or Anti-cyclic citrullinated peptide (anti-CCP) antibodies negative at screening.
6. Patients who are regularly taking NSAIDs as part of their PsA therapy are required to be 
on a stable dose for at least 2 weeks before study randomization and should remain on a 
stable dose up to Week 16
7. Patients taking corticosteroids should be on a stable dose of ≤10 mg/day prednisone or 
equivalent for at least 2 weeks before randomization and must remain on a stable dose up 
to Week 16
8. Patients taking MTX (≤ 25 mg/week) are allowed to continue their medication if the dose 
is stable for at least 4 weeks before randomization and must remain on a stable dose up to 
study completion
9. Patients on MTX must be on folic acid supplementation at randomization
10. Patients who are on a DMARD other than MTX must discontinue the DMARD 4 weeks 
prior to randomization visit except for leflunomide, which should be discontinued for 
8 weeks prior to randomization unless a cholestyramine washout has been performed.

Novartis
Confidential
Page 31
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
4.2
Exclusion criteria
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients.
1. Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process, 
obtained within 3 months prior to screening and evaluated by a qualified physician 
2. Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 
receptor
3. Use of any investigational drug and/or devices within 4 weeks before randomization or a 
period of 5 half-lives of the investigational drug, whichever was longer
4. Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, 
ultraviolet therapy) at randomization. The following wash out periods need to be observed:
a.
Oral or topical retinoids 4 weeks
b. Photochemotherapy (e.g. Psoralen Plus Ultraviolet Light Therapy (PUVA)) 4 weeks
c.
Phototherapy (UVA or UVB) 2 weeks 
d. Topical skin treatments (except in face, eyes, scalp and genital area during screening, 
only corticosteroids with mild to moderate potency) 2 weeks
5. History of hypersensitivity to the study drug or its excipient or to drugs of similar 
chemical classes.
6. Any intramuscular or intravenous corticosteroid treatment within 4 weeks before 
randomization
7. Any therapy by intra-articular injections (e.g. corticosteroid) within 4 weeks before 
randomization
8. Patients who ever received biologic immunomodulating agents including those targeting 
TNFα, IL-6 and IL-12/23 investigational or approved
9. Previous treatment with any cell-depleting therapies including but not limited to anti-
CD20, investigational agents (e.g., alemtuzumab, anti-CD4, anti-CD5, anti-CD3, anti-
CD19)
10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive human 
chorionic gonadotropin (hCG) laboratory test 
11. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective contraception during the entire study or 
longer if required by locally approved prescribing information. Effective contraception 
methods include:

Total abstinence (when this is in line with the preferred and usual lifestyle of the 
subject. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception

Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy) or tubal ligation at least six weeks before taking study treatment.  
In case of oophorectomy alone, only when the reproductive status of the woman 
has been confirmed by follow up hormone level assessment

Novartis
Confidential
Page 32
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

Male sterilization (at least 6 months prior to screening). For female patients on 
the study, the vasectomized male partner should be the sole partner for that 
subject

Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps) 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 women 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)

NOTE: Women are considered post-menopausal and not of child bearing potential if 
they have had 12 months of natural (spontaneous) amenorrhea with an appropriate 
clinical profile (e.g. age appropriate, history of vasomotor symptoms) or six months 
of spontaneous amenorrhea as defined by Central Lab FSH and/or estradiol levels
12. Active ongoing inflammatory diseases other than PsA that might confound the evaluation 
of the benefit of secukinumab therapy 
13. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal conditions which in the opinion of the investigator 
immunocompromises the patient and/or places the patient at unacceptable risk for 
participation in an immunomodulatory therapy
14. Significant medical problems or diseases, including but not limited to the following: 
uncontrolled hypertension (≥160/95 mmHg), congestive heart failure [New York Heart 
Association status of class III or IV], uncontrolled diabetes
15. History of clinically significant liver disease or liver injury as indicated by abnormal liver 
function tests such as SGOT (AST), SGPT (ALT), alkaline phosphatase, or serum 
bilirubin. The investigator should be guided by the following criteria:
a.
Any single parameter should not exceed 2 × upper limit of normal (ULN). A single 
parameter elevated up to and including 2 × ULN should be re-checked once more as 
soon as possible, and in all cases, at least prior to enrollment/randomization, to rule 
out lab error
b. If the total bilirubin concentration is increased above 2 × ULN, total bilirubin should 
be differentiated into the direct and indirect reacting bilirubin. In any case, serum 
bilirubin should not exceed the value of 1.6 mg/dL (27 µmol/L)
16. History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum 
creatinine level exceeding 1.5 mg/dL (132.6µmol/L)
17. Screening total White Blood Cells (WBC) count <3,000/µL, or platelets <100,000/µL or 
neutrophils 1,500/µL or hemoglobin <8.5 g/dL (85g/L)
18. Active systemic infections during the last two weeks (exception: common cold) prior to 
randomization
19. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis 
infection as defined by either a positive Purified protein derivative (PPD) skin test (the 
size of induration will be measured after 48-72 hours, and a positive result is defined as an 

Novartis
Confidential
Page 33
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
induration of ≥5mm or according to local practice/guidelines) or a positive 
QuantiFERON tuberculosis (TB)-Gold test as indicated in the assessment schedule. 
Patients with a positive test may participate in the study if further work-up (according to 
local practice/guidelines) established conclusively that the subject had no evidence of 
active tuberculosis. If presence of latent tuberculosis is established then treatment 
according to local country guidelines must have been initiated
20. Known infection with human immunodeficiency virus, hepatitis B or hepatitis C at 
screening or randomization
21. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system within the past 5 years (except for basal cell carcinoma or actinic 
keratoses that have been treated with no evidence of recurrence in the past 3 months, 
carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been 
removed)
22. Current severe progressive or uncontrolled disease which in the judgment of the clinical 
investigator renders the patient unsuitable for the trial
23. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor 
tolerability or lack of access to veins) 
24. Any medical or psychiatric condition which, in the investigator’s opinion, precludes the 
participant from adhering to the protocol or completing the study per protocol
25. Donation or loss of 400 mL or more of blood within 8 weeks before randomization
26. History or evidence of ongoing alcohol or drug abuse, within the last six months before 
randomization
27. Plans for administration of live vaccines during the study period or within 6 weeks 
preceding randomization.
5
Treatment
5.1
Protocol requested treatment
5.1.1
Investigational treatment
Novartis will supply the following study treatments:

Investigational Treatment: 
Secukinumab 150 mg provided in 1.0 mL in PFS for s.c. injection. 

Reference Therapies: 
Secukinumab placebo provided in 1.0 mL PFS for s.c. injection.
NOTE: The PFS are packed in double blinded fashion for the entire duration of the study. The 
study medication will be labeled as follows:

All double blind secukinumab and placebo PFS will be labeled as AIN457 
150mg/1.0ml/Placebo. Patients will be provided with detailed instructions and 
guidance on how to self-administer the s.c. injection using the PFS and following the 
Instructions for Use (IFU). The investigational drug will be administered by the 

Novartis
Confidential
Page 34
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
subject into the appropriate injection site of the body under the supervision of the site 
staff at each visit.
For detailed instructions for storage of the study treatments, please refer to Section 5.5.3.1 and 
the pharmacist manual.
5.1.2
Additional study treatment
No additional treatment beyond investigational treatment is requested for this trial.
5.2
Treatment groups
At the Baseline Visit, patients will be assigned via Interactive Response Technology (IRT) in
a 2:2:1 ratio to one of the three treatment groups (secukinumab 300 mg s.c., secukinumab 150 mg 
s.c. or placebo s.c.).
Treatment Period 1

Group 1- Secukinumab 300 mg: secukinumab 300 mg (two s.c. injections of the 150 mg
dose) once weekly for five weeks (at Baseline, Weeks 1, 2, 3, and 4), followed by
dosing every four weeks. 

Group 2- Secukinumab 150 mg: secukinumab 150 mg (one s.c. injection of the 150 mg
dose and one s.c. injection of placebo) once weekly for five weeks (at Baseline, Weeks
1, 2, 3, and 4), followed by dosing every four weeks. 

Group 3- Placebo: placebo (two s.c. injection of 150 mg secukinumab 
placebo per dose) once per week for five weeks (at Baseline, Weeks 1, 2, 3, and 4),
followed by dosing every four weeks. 
Treatment Period 2

Patients receiving secukinumab 300 mg (Group 1) will continue to receive the same dose 
up to Week 48.

At Weeks 16, 28 and 40 patients on secukinumab 150 mg (Group 2) will be classified as 
responders (≥ 20% improvement from BL in both tender and swollen joint counts) or non-
responders.

At Weeks 16, 28 and 40 patients on secukinumab 150 mg (Group 2) who are 
responders will continue to receive secukinumab 150 mg (1.0 mL) plus placebo (1.0 
mL) every 4 weeks until next evaluation of responder status at Weeks 28 or 40. 

Patients who did not meet the responder criteria at Week 16, 28 or 40 will start 
receiving secukinumab 300 mg s.c. every 4 weeks and will continue this dose up to 
Week 48.

Patients on placebo (Group 3) regardless of their responder status will start receiving
secukinumab 300 mg s.c. every 4 weeks from Week 16 up to Week 48.
Patients will self-administer all secukinumab and placebo doses at the study site up to Week 
48. After they have received training by the site on how to self-administer their secukinumab 
and placebo doses.

Novartis
Confidential
Page 35
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
5.3
Treatment assignment and randomization 
At Visit 2/Baseline, all eligible patients will be randomized via Interactive Response 
Technology (IRT) to one of the treatment groups in a ratio of 2:2:1 (secukinumab 300mg: 
secukinumab 150mg: placebo). The investigator or his/her delegate will contact the IRT after 
confirming that the subject fulfills all the inclusion/exclusion criteria. The IRT will assign a 
randomization number to the subject, which will be used to link the subject to a treatment 
group in the system and will specify a unique medication number for the first package of 
investigational treatment to be dispensed to the subject. The randomization number will not be 
communicated to any of the site staff.
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from patients and investigator staff. A subject 
randomization list will be produced by the IRT provider using a validated system that 
automates the random assignment of subject numbers to randomization numbers. These 
randomization numbers are linked to the different treatment, which in turn are linked to 
medication numbers. A separate medication list will be produced by or under the 
responsibility of Novartis Drug Supply Management using a validated system that automates 
the random assignment of medication numbers to packs containing the investigational drug(s).
The randomization scheme for patients will be reviewed and approved by a member of the 
Biostatistics group.
5.4
Treatment blinding
Patients, investigators/site staff, persons performing assessments, and Novartis study 
personnel will remain blinded to individual treatment assignment from the time of
randomization until the final database lock using the following methods:
1. Randomization data will be kept strictly confidential until the time of unblinding, and will 
not be accessible by anyone else involved in the study with the following exceptions:

Specific vendors whose role in trial conduct requires their unblinding (e.g., IRT)

Drug Supply Management (DSM);
2. The identity of secukinumab and placebo prefilled syringes (PFS) will be concealed by
identical packaging, labeling, schedule of administration, and appearance.
As the primary analysis time point is Week 16, there will be a database lock after all patients 
have completed the Week 16 visit and data are clean and complete. At that time, only the 
statistician and programmer(s) from the designated CRO will be unblinded in order to 
perform the analysis. Results from the analyses of all data through Week 16, will be reported. 
For publication purposes, summary results from the Week 16 primary analysis time point may 
be shared with the health care community, however individual subject-level data will remain 
blinded until the end of the trial.
Unblinding will only occur in the case of subject emergencies (see Section 5.5.12), at the time 
of the primary analysis (Week 16) for designated CRO personnel only, and at the conclusion 
of the study.

Novartis
Confidential
Page 36
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
A full analysis of all data will be performed when all patients have completed the study.
5.5
Treating the patient
5.5.1
Patient numbering
Each subject is uniquely identified in the study by a combination of his/her center number and
subject number. The center number is assigned by Novartis to the investigative site. After the
subject has signed the ICF, the investigator or his/her staff will contact the IRT and provide
the requested identifying information for the subject. At each site, the first subject is assigned
subject number 1, and subsequent patients are assigned consecutive numbers (e.g. the second
subject is assigned subject number 2; the third subject is assigned subject number 3). Once
assigned to a subject, a subject number will not be reused. If the subject fails to be
randomized for any reason, the IRT must be notified within 2 days and the reason for not
being randomized will be entered on the Screening Phase Disposition Form within the eCRF. 
The appropriate eCRF(s) pages should also be completed.
Patients can only be re-screened once and will receive a new subject number after they have
been re-consented. Patients who are mis-randomized cannot be re-screened.
5.5.2
Dispensing the investigational treatment
Each study site will be supplied by Novartis with investigational treatment (active treatment 
or placebo) in packaging of identical appearance.
The investigational treatment packaging has a 2-part label. A unique medication number is 
printed on each part of this label, which corresponds to placebo or active treatment. 
Investigator staff will identify the investigational treatment packages to dispense to the subject 
by contacting the IRT and obtaining the medication numbers. Immediately before dispensing 
the package to the subject, the 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 subject’s unique 
subject number.
5.5.3
Handling of study treatment 
5.5.3.1
Handling of Investigational treatment
Investigational treatment must be received by a designated person at the study site, handled 
and stored safely and properly, and kept in a secured location to which only the investigator 
and designees have access. Upon receipt, all investigational treatment should be stored 
according to the instructions specified on the labels. Clinical supplies are to be dispensed only 
in accordance with the protocol. 
Medication labels will be in English and comply with legal requirements in the U.S. They will 
include storage conditions for the investigational treatment but no information about the 
patient except for the medication number.
The PFS (150 mg active/placebo) sealed in their outer box must be stored in a locked 
refrigerator between 2°C and 8°C (36°F and 46°F) and protected from light. They must be 

Novartis
Confidential
Page 37
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
carefully controlled in accordance with regulations governing investigational medicinal 
products and local regulations.
The investigator must maintain an accurate record of the shipment and dispensing of 
investigational 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 investigational treatment and packaging at the end 
of the study or at the time of discontinuation of investigational treatment.
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator will return all unused investigational 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.
Destruction of the unused drug should be done according to local requirements and after 
approval by Novartis clinical team.
5.5.4
Instructions for prescribing and taking study treatment
All study treatment (150 mg secukinumab, or placebo) will be self-administered 
subcutaneously throughout the study after the study assessments for the visit have been 
completed. Site staff will administer the injection only to those patients who are not able to 
self-administer the PFS injection. Detailed instructions on the self-administration of the study 
treatment will be described in the Instructions For Use (IFU) and provided to each subject.
The first study treatment administration will occur at the randomization visit (BL) after
inclusion/exclusion criteria have been confirmed, all study scheduled assessments have been 
performed and the scheduled blood samples have been drawn. 
The subject will be instructed by the site staff, utilizing the IFU, on how to self-inject via PFS. 
Patients will be asked to raise any questions, if they have any, and then to proceed with self -
injection. Self-injection will take place under the supervision of a site staff member. At the 
Week 1 and subsequent visits, patients will be asked to refer to the IFU and to proceed with 
self-injection of the study drug.
Study treatment will be administered weekly following the BL dose (Weeks 1, 2, 3, & 4) and 
every 4 weeks thereafter (Week 8 until Week 48)
All dates and times of injections self-administered by the subject during the study must be 
recorded on the Dosage Administration Record eCRF. Immediately before dispensing the 
drug package to the subject, the 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 subject’s unique 
subject number. 
The investigator should promote compliance by instructing the subject to attend the study 
visits as scheduled and by stating that compliance is necessary for the subject’s safety and the 
validity of the study. The subject should be instructed to contact the investigator if he/she is 
unable for any reason to attend a study visit as scheduled or if he/she is unable for any reason 
to take the study treatment as prescribed.

Novartis
Confidential
Page 38
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
5.5.4.1
Administration
Secukinumab Solution for Subcutaneous Injection (active or placebo, respectively) will be 
provided in prefilled syringes (PFS). 

Secukinumab (active) 150 mg/mL solution in a single-use Sensoready® pen or placebo 
Single syringes will be packed in individual boxes. The boxes containing the safety prefilled 
syringes with study treatment solution should be kept at 2 to 8°C (36°F and 46°F) and 
protected from light. Prior to administration the boxes containing the safety prefilled syringes 
with study treatment solution should be allowed to come to room temperature unopened for 
about 20 minutes before administration. Used safety syringe should be disposed immediately 
after use in a sharps container.
Patients will be instructed at BL by the site staff on how to self-inject either secukinumab or 
placebo (blinded) via PFS following the IFU. After the BL visit, the injections will be self-
administered into the appropriate site of the body (thighs, arms, abdomen), and each injection 
should be given at a different injection site. Each new injection should be given at least one 
inch from the previously used site. If subject chooses the abdomen, 2 inches area around navel 
should be avoided. Investigational drug should not be injected into areas where the skin is 
tender, bruised, red, or hard, or where subject has scars or stretch marks. Injection sites should 
be changed to reduce the risk of reaction.
At study visits when pre-dose blood samples have to be drawn, the study medication will be 
self-injected only after the blood samples have been taken.
5.5.5
Permitted dose adjustments and interruptions of study treatment 
Study treatment dose adjustments are not permitted. Study treatment interruption is also not 
permitted with the following exceptions:
Study treatment interruption is only permitted if, in the opinion of the investigator, a subject is 
deemed to be placed at a significant safety risk unless dosing is temporarily interrupted. In 
such cases study treatment should be interrupted only during the time that this risk is present 
and ongoing. Study treatment can be restarted at the next scheduled visit after resolution of 
the safety risk. 
The effect of secukinumab on live vaccines is unknown; therefore live vaccines should not be 
administered during participation in the study. In case a live vaccine has been administered 
due to a medical urgency, study treatment should be interrupted for 12 weeks. Any study 
treatment interruption must be recorded on the corresponding Dose Administration Record 
eCRF page and all assessments should be completed as scheduled.
5.5.6
Rescue medication
Rescue medication is defined as any new therapeutic intervention or a significant change to 
ongoing therapy made because a subject is experiencing either no benefit from participation in 
the trial or worsening / exacerbation of their disease.
Rescue medication must not be used before completion of Week 16 assessments.

Novartis
Confidential
Page 39
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Changes in NSAIDs concomitant therapy is permitted after Week 16 assessments per 
investigator’s clinical judgment.  Any use of rescue medication must be recorded on the 
corresponding Concomitant Medications eCRF.
Please see Section 5.5.7 for additional details.
5.5.7
Concomitant treatment
The investigator should instruct the patient to notify the study site about any new medications 
he/she takes after the patient was enrolled into the study. All medications, procedures and 
significant non-drug therapies (including physical therapy and blood transfusions) 
administered after the patient was enrolled into the study must be recorded.
Guidelines for the use of specific medications are provided below:
Methotrexate (MTX)
Patients taking MTX (up to 25 mg/week) must be on a stable dose for at least 4 weeks before 
randomization and maintained stable throughout the duration of the study. 
Folic acid
Patients on MTX must be taking folic acid supplementation before randomization and during 
the study to minimize the likelihood of MTX associated toxicity.
Leflunomide wash-out with cholestyramine
In case of leflunomide treatment, a wash-out of 8 weeks has to be performed. 
However, another wash-out procedure might be considered. Cholestyramine could be given 
orally to wash-out the leflunomide at a dose of 8 g t.i.d. Cholestyramine reduced plasma 
levels of the active leflunomide metabolite by approximately 40 % in 24 hours and by 49% to 
65% in 48 hours in three healthy volunteers. The administration of cholestyramine is 
recommended in patients who require a drug elimination procedure. If a subject receives 8 g 
t.i.d. for 11 days, the subject could be safely randomized 4 weeks after the beginning of the 
11-day treatment period.
Systemic corticosteroids
Treatment with systemic corticosteroids is permitted up to a maximum daily dosage of 10 mg 
prednisone equivalent and the dose is stable within the 2 weeks preceding randomization. The 
subject should remain on a stable dose until Week 16. 
Corticosteroid dose reductions below 10 mg prednisone equivalent are permitted after 
Week 16, although the corticosteroid dose should not be reduced more than 1 mg prednisone 
equivalent every 4 weeks. Any change in the dose of systemic corticosteroids during the trial 
must be recorded on the corresponding eCRF page.
Intra-articular corticosteroids are not permitted within the 4 weeks preceding randomization 
and up to Week 16. After Week 16, no more than one joint per 24-week period may be 
injected. No single injection should exceed 40 mg of triamcinolone (or equivalent) and the 

Novartis
Confidential
Page 40
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
total dose of intra-articular corticosteroid may not exceed 80 mg of triamcinolone (or 
equivalent) during the study.
Non-steroidal anti-inflammatory drugs (NSAIDs) (including COX-1 or COX-2 
inhibitors), low strength opioids and acetaminophen
Patients on regular use of NSAIDs, low strength opioids, or acetaminophen PRN should be on 
stable dose for at least 2 weeks before randomization to allow inclusion. They should remain 
on a stable dose during the study up to Week 16; however, they have to refrain from any 
intake at least 1 day before a visit with disease activity assessments.
After the Week 16 assessments are completed, a change in the NSAIDs, low strength opioids, 
or acetaminophen treatment regimen is permitted
Any change of the NSAIDs, low strength opioids, or acetaminophen treatment during the trial 
should be recorded on the corresponding eCRF page.
5.5.8
Prohibited treatment
Patients who received any biologics such as etanercept, infliximab, adalimumab, golimumab, 
certolizumab, ustekinumab, cocilizumab, abatacept or rituximab before this study are not 
allowed to participate in this trial.
Use of the treatments displayed in Table 5-1 below is NOT allowed during the study for any 
indication unless otherwise specified; wash-out periods for these treatments are provided in 
Table 5-1. If the use of any of these treatments is required, then the subject must not be 
randomized into the study.

Novartis
Confidential
Page 41
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Table 5-1
Prohibited medication
Prohibited treatments
Washout period
(before randomization)
Conventional DMARDs (except MTX) 
including 
4 weeks
Leflunomide
8 weeks
Leflunomide with cholestyramine washout
4 weeks
Any investigational treatment or participation in 
any interventional trial
4 weeks or 5 half-lives
(whichever is longer)
Unstable dose of NSAIDs (including 
selective COX-2 inhibitors)
2 weeks
Analgesics other than NSAIDs, 
paracetamol/acetaminophen, and low strength 
opioids PRN
2 weeks
Systemic corticosteroids > 10 mg prednisone 
equivalent
2 weeks
Unstable dose of systemic corticosteroids ≤10 
mg prednisone equivalent 
2 weeks
Intra-articular corticosteroids injections
4 weeks
Intramuscular or intravenous corticosteroid 
treatment
4 weeks
Live vaccinations
6 weeks
Oral or topical retinoids
4 weeks
Photochemotherapy (e.g. PUVA)
4 weeks
Phototherapy (UVA or UVB)
2 weeks
Topical skin treatments (except in face, eyes, 
scalp and genital area during screening, only 
corticosteroids with mild to moderate potency)
2 weeks

Novartis
Confidential
Page 42
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
5.5.9
Discontinuation of study treatment
Study treatment must be discontinued if the investigator determines that continuation of study 
treatment would result in a significant safety risk for a subject. The following circumstances 
require study treatment discontinuation:

Withdrawal of informed consent

Emergence of the following adverse events:
a.
Any severe or serious adverse event that is not compatible with administration of 
study medication, including adverse events that require treatment with an 
unacceptable co-medication
b. Onset of lymphoproliferative disease or any malignancy except for treated basal cell 
carcinoma, treated actinic keratoses, treated in situ carcinoma of the cervix or non-
invasive malignant colon polyps which are being or have been removed
c.
Life-threatening infection

Any laboratory abnormalities that in the judgment of the investigator are clinically 
significant and are deemed to place the subject at a safety risk for continuation in the study 
(A general guidance on clinically notable laboratory values is provided in (Appendix 1).

Pregnancy

Use of any biologic immunomodulating agent except secukinumab (please refer to section 
5.5.8 for the other prohibited medications. Any protocol deviation that results in a 
significant risk to the subject’s safety
In addition to these requirements for study treatment discontinuation, the investigator should 
discontinue study treatment for a given subject if there is a lack of improvement or worsening 
of their symptoms, or if on balance, he/she thinks that continuation would be detrimental to 
the subject’s well-being.
For any subject whose treatment code has been broken inadvertently for any reason, the 
appropriate personnel from the site and Novartis will assess whether study treatment should 
be discontinued. 
The investigator must also contact the IRT to register the subject’s discontinuation from study 
treatment.
Patients may voluntarily withdraw from the study for any reason at any time. They may be 
considered withdrawn if they state an intention to withdraw, fail to return for visits, or become 
lost to follow-up for any other reason.
5.5.10
Withdrawal of consent
Patients may voluntarily withdraw consent to participate in the study for any reason at any 
time. 
Withdrawal of consent occurs only when a patient does not want to participate in the study 
anymore, and does not 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.

Novartis
Confidential
Page 43
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
If premature withdrawal occurs for any reason, the investigator must make every effort (e.g. 
telephone, e-mail, letter) to determine the primary reason for this decision and record this 
information on the appropriate study completion eCRF. 
Patients who prematurely discontinue or withdraw during a specific treatment period should 
return for a final visit (see Table 6-1). The final visit should be scheduled approximately four 
weeks after the last study treatment, and should be performed before any new treatment is 
initiated.
Patients who are prematurely withdrawn from the study will not be replaced by newly 
enrolled patients.
5.5.11
Loss to follow-up
For patients who are lost to follow-up (i.e., those patients whose status is unclear because they 
fail to appear for study visits without stating an intention to withdraw), the investigator should 
show "due diligence" by documenting in the source documents steps taken to contact the 
subject, e.g. dates of telephone calls, registered letters, etc.
5.5.12
Emergency breaking of assigned treatment code
Emergency treatment code breaks should only be undertaken when it is essential to treat the 
subject safely and efficaciously. Most often, study discontinuation and knowledge of the 
possible treatment assignments are sufficient to treat a study subject who presents with an 
emergency condition. 
Emergency treatment code breaks are performed using the IRT. When the investigator 
contacts the system to break a treatment code for a subject, he/she must provide the requested 
subject identifying information and confirm the necessity to break the treatment code for the 
subject. The investigator will then receive details of the investigational drug treatment for the 
specified subject and a fax or email confirming this information. The system will 
automatically inform the Novartis and CRO study personnel that the code has been broken.
It is the investigator’s responsibility to ensure that there is a procedure in place to allow access 
to the IRT in case of emergency. The investigator will inform the subject how to contact 
his/her backup in cases of emergency when he/she is unavailable.
5.5.13
Study completion and post-study treatment
A subject’s individual study participation is completed once Visit 19/Week 52 Treatment 
Period has been completed. Any SAEs that occur in the following 84 days (12 week s) after 
the dose of study drug must be reported. The investigator will also follow any AEs for which 
there is no outcome that can be reported at the final study visit. 
The study as a whole will be completed once all randomized patients have completed the
study as per the protocol and the clinical database has been locked. Recruitment into the study 
will be terminated by the sponsor once the targeted number of randomized patients has been 
met or is foreseen to be met with the patients already in screening. Patients who have been
screened and have a screening visit recorded in the IRT system at the time that the planned

Novartis
Confidential
Page 44
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
enrollment number is met will be allowed to enter the trial and to be randomized if they are
eligible.
Upon completion of their study participation, patients will return to individual treatment, as 
determined by their treating physician.
The investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care.
5.5.14
Early study termination
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit risk assessment of participating in the study, practical reasons, or for 
regulatory or medical reasons (including slow enrollment). Should this be necessary, the 
subject should be seen as soon as possible and treated as a prematurely withdrawn as 
described in Section 5.5.9 The investigator may be informed of additional procedures to be 
followed in order to ensure that adequate consideration is given to the protection of the 
subject’s interests. The investigator will be responsible for informing Institutional Review 
Board/Independent Ethics Committee (IRBs/ECs) of the early termination of the trial.
6
Visit schedule and assessments
Table 6-1 lists all of the assessments, indicated with an “X” at the visits they are performed 
from screening to Week 52.
Patients should be seen for all visits on the designated day, or as closely as possible to the 
original planned visit schedule (recommended visit windows are in Table 6-1). Every effort 
should be made to respect the time frame for the Week 16 visit.

For visits scheduled through Week 4, the study treatment should not be administered 
within less than 7 days after the previous administration

For visits scheduled after Week 4, the study treatment should not be administered within 
less than 14 days after the previous administration
Patient Screening
Screening will be flexible in duration based on the time required to wash out prior anti -
rheumatic medications and have a duration of up to 8 weeks before randomization. During 
which time the subject will sign the informed consent form (ICF), be evaluated for eligibility, 
and allowed sufficient time for medication washout, if required (see Table 5-1), in addition to 
other assessments indicated in Table 6-1.
If patients do not have a chest X-ray available within 3 months of screening, the X-ray should 
be performed only after it is certain the subject meets inclusion/exclusion criteria in order to 
minimize unnecessary exposure to radiation. 
Patients evaluated at visit 1 and 2 for Inclusion/Exclusion criteria should not be screen failed 
on the basis of a medication requiring washout, unless the subject will be unable to complete 
the washout in the appropriate time frame before randomization.

Novartis
Confidential
Page 45
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Premature Discontinuation
For patients who discontinue study treatment prematurely for any reason before the end of
Treatment Period 1, (Visit 10/Week 16 EOT1) must be performed approximately four
weeks after the last dose of study treatment (secukinumab 300 mg, secukinumab 150 mg or 
placebo). Patients should also be contacted via telephone, 84 days (12 weeks) after last dose 
of study drug, to inquire about any AE/SAEs that occurred during this period.
For patients who discontinue study treatment prematurely for any reason before the end of
Treatment Period 2, (Visit 19/ Last visit EOT2) must be performed approximately four
weeks after the last dose of study treatment (300 mg or 150 mg s.c. secukinumab). Patients 
should also be contacted via telephone, 84 days (12 weeks) after last dose of study drug, to 
inquire about any AE/SAEs that occurred during this period.
If patients refuse to return for these assessments or are unable to do so, every effort should be 
made to contact them or a knowledgeable informant by telephone to determine the reason.
At a minimum, patients will be contacted for safety evaluations during the 84 days (12 weeks)  
following the last study visit or following the last administration of study treatment 
(whichever is later), including a final contact at the 84-day point. Documentation of attempts 
to contact the subject should be recorded in the source documentation.
AE/SAE information obtained as a result of these calls must be recorded in the eCRF.
Unscheduled visits
Patients may be seen at any time for an unscheduled visit, e.g., if they experience 
deterioration or AEs that in the opinion of the investigator/qualified site staff need 
intervention or repeat laboratory testing. The assessment(s) performed at an unscheduled visit 
must 
include 
at 
minimum: 
an 
assessment 
of 
concomitant 
medication 
and 
procedures/significant non-drug therapies, vital signs, and an AE/SAE assessment. Any 
additional assessments performed are at the investigator/qualified site staff’s discretion. 
During an unscheduled visit, study treatment will not be administered.

Novartis
Confidential
Page 46
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Table 6-1
Assessment schedule
Period
SCR1
Treatment Period 1
Treatment Period 2
Unscheduled Visit
Week
-8 to BL
BL
1
2
3
4
8
12
16/E
OT
20
24
28
32
36
40
44
48
52/  
EOT
Day 84 
Safety 
Follow-
up4
Visit No
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
Visit Window 
(days)2
+/-2
+/-2
+/-2
+/-2
+/-2
+/-2
+/-2
+/-7
+/-7
+/-7
+/-7
+/-7
+/-7
+/-7
+/-7
+/-7
Assessments
Obtain informed 
consent
X
Inclusion/exclusio
n criteria
X
X
X
Demographics
X
Psoriasis/PsA 
medical history / 
previous therapies
X
Relevant medical 
history/current 
medical 
conditions
X
Washout 
evaluation/instruct
ion
X
PsA CASPAR 
criteria
X
Smoking and 
alcohol history
X
Cardiovascular 
medical history
X
Physical Exam4
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Height
X

Novartis
Confidential
Page 47
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Weight
X
X
X
X
Vital signs
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Chest X-ray5
X
ECG
X
Prior/Concomitant 
medication/ non-
drug therapy
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Randomization 
via IRT
X
Administration of 
sc study treatment 
via PFS at study 
site
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Adverse 
Events/SAEs3
(incl. injection site 
reaction & 
occurrence of 
infections)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
QuantiFERON 
TB-Gold test
X
Hematology, 
blood chemistry 6
X
X
X
X
X
X
X
Serum pregnancy 
test
X
Urinalysis/Urine 
pregnancy test 7
X
X
X
X
X
X
X
X
Anti-CCP
X
Rheumatoid factor 
(RF)
X
High sensitivity 
C-Reactive 
protein (hsCRP)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Erythrocyte 
Sedimentation 
Rate (ESR) 7
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Tender and 
swollen joint 
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

Novartis
Confidential
Page 48
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
counts
(TJC78, SJC76)
Enthesitis 
evaluation8
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Dactylitis 
evaluation
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Physician’s global 
assessment of 
disease activity 
(VAS)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PASI 
X
X
X
X
X
X
X
X
X
X
IGA mod 2011 
X
X
X
X
X
X
X
X
X
X
 
 
 
VAS 
physician’s 
assessment of 
nail disease
X
X
X
X
X
X
X
X
X
Health 
Assessment 
Questionnaire 
(HAQ-DI)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s 
assessment of 
PsA pain (VAS)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s global 
assessment of 
disease activity 
(VAS)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient’s global 
assessment of 
psoriasis and 
arthritis disease 
activity(VAS)
X
X
X
X
X
X
X
X
X
X
SF-12
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X

Novartis
Confidential
Page 49
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Responder Status 
Assessment9
X
X
X
X
X
X
X
X
X
X
Treatment period 
1 completion form
X
Treatment period 
2 completion form
X
1 If washout period is < 4 weeks, visit 1 & visit 2 can be performed the same day
2 Patients who discontinued prematurely or withdrawn during a specific treatment period should return for a final visit. The final visit should be scheduled approximately four (4) weeks after 
the last study treatment, and should be performed before any new treatment is initiated
3 AEs/SAEs occurring after informed consent has been obtained must be reported. Patients who discontinued prematurely should be contacted via telephone to collect AE/SAEs 
information. Any   AE/SAEs that occur in the following 84 days (12 weeks) after last dose of study drug must be reported. 
4 These assessments are source documented only and will not be entered into the eCRF
5 Not necessary if done within past 3 months. If not, should be scheduled only after patient has met inclusion/exclusion criteria
6 Fasting sample
7 Tests performed locally using kits supplied by central lab 
 
9Those patients on secukinumab 150 mg who are non-responders at Week 16,  28, or 40 will start receiving secukinumab  300 mg s.c. every 4 weeks up to Week 48.

Novartis
Confidential
Page 50
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.1
Information to be collected on screening failures 
All patients who sign informed consent but discontinue prior to randomization at Visit 3 are 
considered screening failures. The IRT must be notified about the discontinuation, and the 
primary reason for the screen failure should be entered in the Screening Phase Disposition 
eCRF. 
In addition, only the following eCRFs should be completed: Demography eCRF, Informed 
Consent eCRF, Inclusion/Exclusion eCRF, and the adverse event (AE) eCRF should be 
completed for any Serious Adverse Events (SAEs) that occurred during the screening period. 
Adverse events that are not serious will be followed by the investigator and collected only in 
the source data.
6.2
Patient demographics/other baseline characteristics
All baseline assessments should be performed prior to the first study treatment administration.
6.2.1
Demographics
Subject demographic and baseline characteristic data to be collected on all patients and 
recorded in the eCRF include: 

date of birth, subject initials, gender, race, and child-bearing potential (for females only).
6.2.2
PsA/Psoriasis history/ Prior psoriasis therapies
Disease history will be collected at the screening visit. The information to be collected and 
entered in the eCRF includes the following:

date of first diagnosis of plaque psoriasis (by a physician)

presence of psoriatic arthritis and the date of first diagnosis (by a physician)

disease duration (if different from time since diagnosis)

previous PsA/psoriasis treatments (including previous use of biologic therapies, as well as 
phototherapy and/or photo chemotherapy) and the reason for discontinuation of each 
therapy
6.2.3
Smoking history
The current and/or previous use of tobacco products will be recorded, as well as the estimated 
number of pack-years based on the approximate consumption per year. Non-smokers will be 
advised to not start smoking during the study.
6.2.4
Co-morbidities-Cardiovascular history
Any information pertaining to cardiovascular medical history assessed prior to signing 
informed consent should be reported on the Cardiovascular History eCRF.
6.2.5
Relevant medical history / Current medical conditions
Whenever possible, diagnoses and not symptoms will be recorded.

Novartis
Confidential
Page 51
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Relevant medical history/current medical conditions, not including psoriasis or psoriatic 
arthritis, will be recorded on the Medical History eCRF. 
Relevant medical history/current medical conditions will include data up to six months prior 
to signing of the informed consent. Whenever possible, diagnoses (and not symptoms) will be 
recorded. 
Significant findings that are observed after the subject has provided informed consent, and 
that meet the definition of an AE, must be recorded on the Adverse Event eCRF.
Investigators will have the discretion to record abnormal test findings on the Medical History 
eCRF when in their judgment, the test abnormality occurred prior to the informed consent 
signature.
6.2.6
Prior and concomitant medications
Concomitant medications and prior medications taken over the six months preceding study 
enrollment will be captured at the Screening visit, and updated at Visit 3 (Randomization).
6.2.7
Chest X-ray
A chest X-ray, CT scan, or MRI obtained within 3 months prior to randomization will be used 
to determine eligibility. If patients do not have a chest X-ray, CT scan, or MRI available 
within 3 months prior to randomization, a chest X-ray only must be done after it is fairly 
certain the subject meets the other inclusion/exclusion criteria in order to minimize 
unnecessary exposure to X-ray radiation for patients.
If the chest X-ray, CT scan, or MRI evaluated by a qualified physician shows evidence of 
ongoing infection or malignancy and the subject was not treated subsequent to the X-ray (CT 
scan or MRI), the subject will not be eligible to enter the study.
6.2.8
Determination of tuberculosis status
Determination of tuberculosis (TB) status will be required before administration of study 
treatment. TB status must be determined by medical history, signs, symptoms, and TB testing 
(QuantiFERON-TB Gold assay). Any significant findings will be recorded in the appropriate 
eCRF(s), as necessary.
If the QuantiFERON-TB Gold Assay test is positive or indeterminate, a TB workup 
should be performed as defined by local guidelines to determine the subject’s TB status.
QuantiFERON TB-Gold In-Tube assay
A QuantiFERON® TB-Gold In-Tube assay will be performed to assess the TB status at 
screening for all patients. This test will only be used to determine subject’s eligibility for the 
trial. The test will be used to screen the subject population for latent tuberculosis infection 
(Doherty et al 2008).
This blood-based assay is specific for Mycobacterium tuberculosis and is not influenced by 
previous Bacillus Calmette-Guérin vaccination or exposure to other Mycobacteria species.
This test, in contrast to the purified protein derivative (PPD) skin test, is also insensitive to a 
booster effect since the subject is not exposed to the vaccine. The assay measures the 

Novartis
Confidential
Page 52
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
production of interferon-gamma and presents it relative to a negative and a positive control 
sample (Manuel and Kumar 2008)
The QuantiFERON®-TB Gold assay test will be supplied by the central laboratory. Details on 
the collection, shipment of samples and reporting of results by the central laboratory are 
provided in the Laboratory Manual.
The results of a TB workup for a subject with a positive or indeterminate test must be 
recorded in the eCRF.

If the test result is negative, the subject may be randomized.

If the test result is positive, the investigator should perform a TB workup for the test result 
as per local procedures.

Patients positive for latent TB per workup may be randomized to the trial if sufficient 
treatment has been initiated according to local routine clinical practice and will be 
maintained for the prescribed duration.

Patients positive for active TB per workup are not eligible for the study.

Patients negative for TB (no signs of latent or active TB) per workup may be randomized 
to the trial.

If the test result is indeterminate, it is recommended to repeat the test once. The 
investigator may decide to skip the repetition of the test and proceed directly to the 
workup (however this is not recommended). If a TB workup was conducted prior to 
screening, results from the workup can be used to assess eligibility if the workup was 
conducted within 12 weeks prior to randomization.

If the second test is negative, the subject may be randomized.

If the second test is positive or indeterminate, the investigator should perform a TB 
workup as per local guidelines. The subject will not be eligible for randomization if: 
“active tuberculosis is present”, or if “latent tuberculosis is present” and is untreated as per 
local guidelines.
6.3
Treatment exposure and compliance
All doses of secukinumab or placebo administration will be recorded on the Dosage 
Administration Record eCRF. Compliance will be assessed by Novartis and CRO study 
personnel using the Dosage Administration Record eCRF, medication numbers, Drug Label 
Form information, and information collected by IRT.
Compliance is expected to be 100% since all doses of study treatment will be administered at 
the site in the presence of the investigator or site staff, unless temporary interruption is 
needed for safety reasons as described in Section 5.5.5.
6.4
Efficacy
The primary efficacy variable is ACR20 response (yes, no). The primary analysis time point 
will be at Week 16.
The secondary efficacy variables are the following:

Novartis
Confidential
Page 53
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
1. Dactylitis (yes, no)
2. Enthesitis (yes, no) 
3. ACR50 response (yes, no)
4. ACR70 response (yes, no)
5. Minimal Disease Activity (yes, no)
6. PASI75 response (yes, no)
7. PASI90 response (yes, no)
8. PASI100 response (yes, no)
9. Change from baseline in DAS28-CRP
10. Change from baseline in PASDAS
11. Change from baseline in SF12
12. Change from baseline in HAQ-DI
6.4.1
American College of Rheumatology (ACR) response
The ACR response (Appendix 4) will be used to determine efficacy (Felson 1995)-*A subject 
is defined as e.g. an ACR20 responder if, and only if, the following three conditions hold:

Novartis
Confidential
Page 54
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

they have a ≥ 20% improvement in the number of tender joints (based on 78 joints)

they have a ≥ 20% improvement in the number of swollen joints (based on 76 joints)

they have a ≥ 20% improvement in three of the following five domains:

Patient’s global assessment of disease activity (measured on a VAS scale, 0-100)

Physician’s global assessment of disease activity (measured on a VAS scale, 0-
100)

Patient’s assessment of PsA pain (measured on a VAS scale, 0-100)

Health Assessment Questionnaire (HAQ©) score

Acute phase reactant (hsCRP or ESR) 
ACR50 = 50 % improvement in at least 3 of the 5 domains and 50 % improvement in the swollen and 
tender joint count.
ACR70 = 70 % improvement in at least 3 of the 5 domains and 70 % improvement in the swollen and 
tender joint count.
The ACR response is to be assessed at the visits/time points shown in Table 6-1.
6.4.2
Tender 78 joint count and swollen 76 joint count
Joint counts will be performed by the assessor(s) who must be well trained and part of the site 
personnel. Whenever possible, the same evaluator should perform these assessments at all 
visits.
The 78 joints assessed for tenderness include the 2 temporomandibular, 2 sternoclavicular, 2 
acromioclavicular joints, 2 shoulders, 2 elbows, 2 wrists, 2 first carpometacarpal, 10 
metacarpophalangeal, 10 proximal interphalangeal, 8 distal interphalangeal joints of the hands, 
the 2 hip, 2 knee, 2 talo-tibial, 2 mid-tarsal, 10 metatarsophalangeal, 10 proximal 
interphalangeal, and 8 distal interphalangeal joints of the feet. All of these except for the hips 
are assessed for swelling. Joint tenderness and swelling are to be graded present (1) or absent 
(0). Synovial fluid and/or soft tissue swelling but not bony overgrowth represents a positive 
result for swollen joint count. Dactylitis of a digit in the foot or hand counts as one tender and 
swollen joint. 
Data is recorded for tender and swollen joints (right or left side), i.e. a box (no, yes or not 
applicable) needs to be ticked for all joints. The total number of tender and swollen joints 
(right and left) will be automatically calculated in the eCRF.
6.4.3
Patient Reported Outcomes (PRO)/QoL Assessments
Patients should complete all assessments prior to any investigator evaluations.

Patient’s Assessment of PsA pain intensity

Patient’s global assessment of disease activity (VAS)

Patient’s global assessment of psoriasis and arthritis disease activity (VAS)
The impact of PsA on various aspects of patients’ health-related quality of life (HRQoL) will 
be assessed using the following validated instruments:

Novartis
Confidential
Page 55
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

Health Assessment Questionnaire (HAQ-DI)

SF-12 
All questionnaires will be completed at the defined visits/ time points listed in Table 6-1, and 
prior to the subject seeing the investigator for any clinical assessment or evaluation. The 
subject should be given sufficient instruction, space, time and privacy to complete the 
questionnaires. The study coordinator should check the questionnaires for completeness and 
encourage the subject to complete any missing responses. Completed questionnaires should be 
reviewed and assessed by the investigator before the clinical examination, for responses 
which may indicate potential AEs or SAEs. This assessment should be documented in the 
source records. If AEs or SAEs are confirmed the investigator should record the events as per 
instructions given in the relevant section of the protocol (see Section 7).
Guidelines for administering the PRO questionnaires can be found in Appendix 10.
6.4.3.1
Patient’s assessment of PsA pain intensity
The patient’s assessment of pain will be performed using 100 mm visual analog scale (VAS) 
ranging from “no pain” to “unbearable pain” after the question “Please indicate with a vertical 
mark ( | ) through the horizontal line the most pain you had from your psoriatic arthritis 
today”.
6.4.3.2
Patient’s global assessment of disease activity
The patient’s global assessment of disease activity will be performed using 100 mm VAS 
ranging from ”very good” to ”very poor”, after the question "Considering all the ways 
psoriatic arthritis affects you, please indicate with a vertical mark ( | ) through the horizontal 
line how well you are doing today”. 
6.4.3.3
Health Assessment Questionnaire (HAQ-DI)
The HAQ-DI© was developed by Stanford University and is one of the most widely used 
measures to assess the long-term influence of chronic disease on a subject's level of functional 
ability and activity restriction. The disability assessment component of the HAQ, the HAQ-DI, 
assesses a subject's level of functional ability and includes questions of fine movements of the 
upper extremity, locomotor activities of the lower extremity, and activities that involve both 
upper and lower extremities. There are 20 questions in eight categories of functioning 
including dressing, rising, eating, walking, hygiene, reach, grip, and usual activities. The stem 
of each item asks over the past week "Are you able to …" perform a particular task. Each item 
is scored on a 4-point scale from 0 to 3, representing normal (normal, no difficulty [0]), some 
difficulty (1), much difficulty (2), and unable to do (3). 
The purpose of the HAQ-DI in this study is to assess the functional ability of patients with 
PsA.

Novartis
Confidential
Page 56
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.4.3.4
Medical Outcome Short Form Health Survey (SF-12) Version 12
The SF-12v2® Health Survey is a shorter version of the SF-36v2® Health Survey that uses 
just 12 questions to measure functional health and well-being from the patient’s point of view.
Taking only two to three minutes to complete, the SF-12v2® is a practical, reliable and valid 
measure of physical and mental health and is particularly useful in large population health 
surveys or for applications that combine a generic and disease-specific health survey. The SF-
12v2® covers the same eight health domains as the SF-36v2® with one or two questions per 
domain.
As the survey uses norm-based scoring, comparisons can be made among the other generic 
health surveys such as SF-36v2 and it can measure outcomes concisely at the population level, 
and it is a widely used tool for monitoring population health, comparing and analyzing disease 
burden and predicting medical expenses.
The purpose of the SF-12 in this study is to assess the HRQoL of patients. Given the acute 
nature of this disease, version 2, with a 1-week recall period, will be used in this study. 

Novartis
Confidential
Page 57
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.4.4
Physician’s global assessment of disease activity
The physician’s global assessment of disease activity will be performed using 100 mm VAS 
ranging from no disease activity to maximal disease activity, after the question "Considering 
all the ways the disease affects your patient, draw a line on the scale for how well his or her 
condition is today”. To enhance objectivity, the physician must not be aware of the specific 
patient’s global assessment of disease activity, when performing his own assessment on that 
subject.
6.4.5
High Sensitivity C-reactive protein (hsCRP)
Blood for this assessment will be obtained in order to identify the presence of inflammation, 
to determine its severity, and to monitor response to treatment.
Since the results of this test may unblind study personnel, results from the central lab will be 
provided for screening and baseline only. The hsCRP results from samples collected during 
the treatment period will be revealed following database lock only.
6.4.6
Erythrocyte sedimentation rate (ESR)
ESR tests MUST be performed locally. Blood for ESR, which is helpful in diagnosing 
inflammatory diseases and is used to monitor disease activity and response to therapy, will be 
obtained at scheduled visits as indicated in Table 6-1.

Novartis
Confidential
Page 58
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.4.8
DAS28 and EULAR response
The DAS28 is a measure of disease activity based on Swollen and Tender Joint Counts, ESR 
or CRP and the Patient Global Assessment. A DAS28 score > 5.1 implies active disease, ≤ 3.2 
low disease activity, and < 2.6 remission. EULAR response criteria are based on DAS28 
status in combination with DAS28 improvements.
6.4.9
Psoriatic Arthritis Disease Activity Score (PASDAS)
PASDAS is a new composite measure developed to access disease activity in Psoriasis 
(GRACE Project) (Helliwell 2012). It is calculated by utilizing seven measures; the seven 
components are: Patient reported measures (excluding mental component summary score 
(MCS) of the medical outcomes survey Short Form-36 (SF-36-PCS)), skin, peripheral joint 
counts (Tender and Swollen joint counts), Dactylitis (LDI), 
 acute phase 
response (CRP) and Patient & Physician global VAS scores. 
PASDAS = 
(0.18 x √Physician global VAS) 
+ (0.159 x √Patient global VAS) 
- (0.253 x √SF36-PCS) 
+ (0.101 x LN (Swollen joint count + 1)) 
+ (0.048 x LN (Tender joint count + 1)) 
+ (0.23 x LN (Leeds Enthesitis Count + 1)) 
+ (0.377 LN (Dactylitis count + 1)) 
+ (0.102 x LN (CRP + 1)) +2)*1.5.
VAS for PASDAS assessment: 
Instruct patients to place marks on the lines below to indicate answer to the following 
questions relating to the past week.
Global Disease Activity: The patient’s assessment of PSORIASIS and ARTHRITIS will be 
performed using 100 mm VAS ranging from “Excellent” to “Poor” after the question 

Novartis
Confidential
Page 59
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
"Considering all the ways PSORIASIS and ARTHRITIS affects you, please indicate with a 
vertical mark ( | ) through the horizontal line how well you are doing over the past week”.
6.4.10
Minimal disease activity
The proportion of patients achieving minimal disease activity (MDA (Coates 2010) (5 of the 7 
following: ≤ 1 tender joint count, ≤ 1 swollen joint count, PASI  ≤ 1 or IGA ≤ 1, patient pain 
VAS ≤ 15, patient global VAS ≤ 20, HAQ-DI ≤ 0.5, tender entheseal points ≤ 1).
6.4.11
Dactylitis Assessments
 
Presence of dactylitis
If dactylitis is present with any finger or toe, the subject is counted as a subject with dactylitis.
6.4.12
Enthesitis Assessments
Presence of enthesitis:
If enthesitis is present with any of the 18 sites below, the subject is counted as a subject with 
enthesitis.

Medial epicondyle humerus (left/right (L/R)

Lateral epicondyle humerus (L/R)

Supraspinatus insertion into greater tuberosity of humerus (L/R)

Greater trochanter (L/R)

Medial condyle  femur (L/R)

Quadriceps insertion into superior border of patella (L/R)

Patellar ligament insertion into inferior pole of patella or tibial tubercle (L/R)

Achilles tendon insertion into calcaneum (L/R)

Plantar fascia insertion into calcaneum (L/R)

Novartis
Confidential
Page 60
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.4.14
Psoriasis Area and Severity Index (PASI)
The PASI assessment will be conducted for patients in whom at least 3% of the body surface 
area (BSA) was affected by psoriatic skin involvement at BL. The PASI assesses the extent of 
psoriasis on four body surface areas (head, trunk and upper and lower limbs) and the degree 
of plaque erythema, scaling and thickness. A PASI score (Fredriksson and Pettersson 1978, 
Weisman 2003, Gottlieb 2005) will be derived as indicated in Table 6-2.
The head, trunk, upper limbs and lower limbs are assessed separately for erythema, thickening 
(plaque elevation, induration), and scaling (desquamation). The average degree of severity of 
each sign in each of the four body regions is assigned a score of 0-4. The area covered by 
lesions on each body region is estimated as a percentage of the total area of that particular 
body region. Further practical details help the assessment:
The neck is assessed as part of the head.
The axillae and groin are assessed as part of the trunk.
The buttocks are assessed as part of the lower limbs.
When scoring the severity of erythema, scales should not be removed.

Novartis
Confidential
Page 61
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Table 6-2
The PASI scoring system
Body 
region
Erythema (E)
Thickening
(plaque elevation,
induration)(I)
Scaling
(desquamation) (D)
Area score
(based on true 
area %)( A)*
Head  (H)**
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0 = 0%
1 = 1-9%
2 = 10-29%
3 = 30-49%
4 = 50-69%
5 = 70-89%
6 = 90-100%
Trunk,   
(T)***
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0 = 0%
1 = 1-9%
2 = 10-29%
3 = 30-49%
4 = 50-69%
5 = 70-89%
6 = 90-100%
Upper 
limbs (U)
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0 = 0%
1 = 1-9%
2 = 10-29%
3 = 30-49%
4 = 50-69%
5 = 70-89%
6 = 90-100%
Lower 
limbs 
(L)****
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0=none 
1=slight 
2=moderate 
3=severe
4=very severe
0 = 0%
1 = 1-9%
2 = 10-29%
3 = 30-49%
4 = 50-69%
5 = 70-89%
6 = 90-100%
* Percentage (not score) of body region (not whole body) affected will be entered in the eCRF
**Neck is assessed as part of the Head (H) body region.
***Axillae and groin are assessed as part of the Trunk (T) body region.
****Buttocks are assessed as part of the Lower limbs (L) body region.
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the body surface area, respectively, the PASI score is calculated 
using the formula:
PASI = 0.1 (EH+IH+DH)AH + 0.2 (EU+IU+DU)AU + 0.3(ET+IT+DT)AT + 0.4(EL+IL+DL)AL
where E = erythema, I = induration, S = scaling, and A = area, 
H = Head, U = Upper limbs, T = Trunk, and L = Lower limbs
PASI scores can range from a lower value of 0, corresponding to no signs of psoriasis, up to a 
theoretic maximum of 72.0. The investigator is only responsible for collecting the components 
or scoring signs and total regional area. More information is provided in Appendix 6. 

Novartis
Confidential
Page 62
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.4.15
Investigator’s Global Assessment (IGA mod 2011)
IGA mod 2011 will be conducted for overall psoriatic disease as indicated in Table 6-3 for 
patients in whom at least 3% of the body surface area (BSA) was affected by psoriatic skin 
involvement at BL. It is recommended that the same evaluator conducts the assessment 
throughout the study wherever possible.
The IGA mod 2011 rating scale has been developed based on a previous version of the scale 
used in secukinumab phase II psoriasis studies in collaboration with health authorities in 
particular the FDA. The explanations/descriptions of the points on the scale have been 
improved to ensure appropriate differentiation between the points (see Table 6-3).
The IGA mod 2011 used in this study is static, i.e. it refers exclusively to the subject’s disease 
state at the time of the assessments, and does not attempt a comparison with any of the 
subject’s previous disease states, whether at baseline or at a previous visit.  
The IGA mod 2011 score will be recorded in the eCRF at the given visits/time points of Table 
6-1.
Table 6-3
The IGA mod 2011 rating scale
Score
Short Description
Detailed Description
0
Clear
No signs of psoriasis. Post-inflammatory hyperpigmentation may 
be present.
1
Almost clear
Normal to pink coloration of lesions; no thickening; no to minimal 
focal scaling.
2
Mild
Pink to light red coloration; just detectable to mild thickening; 
predominantly fine scaling.
3
Moderate
Dull bright red, clearly distinguishable erythema; clearly 
distinguishable to moderate thickening; moderate scaling.
4
Severe
Bright to deep dark red coloration; severe thickening with hard 
edges; severe / coarse scaling covering almost all or all lesions.
Note: Involvement of nails is not part of the assessment.
Based on this scale, a subject will be considered as IGA 0 or 1 responder if the subject 
achieves a score of 0 or 1 and improved by at least 2 points on the IGA scale compared to 
baseline.

Novartis
Confidential
Page 63
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

Novartis
Confidential
Page 64
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.4.17
Physician’s global assessment of fingernail disease severity (VAS)
The physician’s assessment of nail disease activity will be performed using 100 mm VAS 
ranging from no disease activity to maximal disease activity, after the question “After you 
have viewed all the fingernails of a subject, consider all aspects of the subject’s fingernails 
and place a vertical line on the scale giving a global assessment of their fingernails”.
6.4.19
Appropriateness of efficacy assessments
The efficacy assessments used in this study are the standard assessments used across many 
psoriatic arthritis trials.

Novartis
Confidential
Page 65
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.5
Safety 
Evaluation of all AEs and SAEs including injection site reactions, ECGs, physical 
examination, vital signs and laboratory assessments, Assessment of anti-secukinumab 
antibody development (immunogenicity).
All blood draws and safety assessments should be done prior to study treatment 
administration. Appropriate safety assessments (e.g. evaluation of AEs and SAEs including 
injection site reactions) should be repeated after the dose is administered.

Evaluation of AE/ SAE’s

Physical examination

Vital signs

Height and weight

QuantiFERON TB-Gold test or PPD skin test

Electrocardiogram

Local tolerability (Injection site reactions)

Laboratory evaluations (Hematology, Clinical Chemistry, LFTs, Urinalysis)

Pregnancy and assessment of fertility

Tolerability of secukinumab
6.5.1
Physical examination
A complete physical examination will be performed by a professionally trained physician or 
health professional licensed to perform physical examinations and listed on FDA Form 1572, 
at the scheduled study visits as indicated in Table 6-1.
The physical examination will include the examination of general appearance, skin, neck, 
eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular and 
neurological system.
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present before signing the ICF must be included in the 
relevant medical history eCRF. Significant findings made after signing the ICF which meet 
the definition of an AE must be recorded in the Adverse Event eCRF.
6.5.2
Vital signs 
Vital signs include BP and pulse rate measurements. After the subject has been sitting for five 
minutes, with back supported and both feet placed on the floor, systolic and diastolic blood 
pressure will be measured using a validated device with an appropriately sized cuff.
If possible, vital signs assessments should be performed by the same study site staff member 
using the same validated device throughout the study.
Clinically notable vital signs are defined in Appendix 1.

Novartis
Confidential
Page 66
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.5.3
Height and weight 
Height and body weight (in indoor clothing but without shoes) will be measured at scheduled 
study visits as indicated in Table 6-1. If possible, body weight assessments should be 
performed using the same scale throughout the study. The Body Mass Index will be calculated 
programmably.
6.5.4
Electrocardiogram (ECG)
A standard 12 lead ECG will be performed as indicated in Table 6-1. 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 first, followed by vital 
signs, and blood sampling. Each ECG tracing should be labeled with study number, subject 
initials, subject number, date and time, and filed in the study site source documents.
Clinically relevant abnormalities should be recorded on the relevant medical history/Current 
medical conditions eCRF page for the baseline ECG. 
Clinically relevant abnormalities noted after the baseline ECG should be reported as AE (see 
Section 7)
6.5.5
Laboratory evaluations
A central laboratory will be used for analysis of all specimens collected listed below (except 
urinalysis). Details on the collection, 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 Appendix 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.
6.5.5.1
Hematology
Hemoglobin, platelet, red blood cell (RBC), white blood cell (WBC) and differential white 
blood cell counts will be measured at scheduled visits. 
6.5.5.2
Clinical chemistry
Serum chemistry will include glucose, urea, creatinine, total bilirubin, AST (SGOT), ALT 
(SGPT), GGT, alkaline phosphatase, sodium, potassium, bicarbonate, calcium, phosphorous, 
total protein, albumin, and uric acid.
6.5.5.3
Urinalysis
Dipsticks will be provided by the central laboratory to the sites for local urinalysis 
assessments. The urinalysis results for standard parameters such as protein, glucose, blood 
and WBCs will be recorded in the appropriate eCRF page. Follow-up of abnormal results is 
left to the discretion of the investigator.

Novartis
Confidential
Page 67
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
6.5.6
Pregnancy and assessments of fertility
Secukinumab must not be given to pregnant women; therefore effective methods of birth 
control must be used for women of child-bearing potential (see exclusion criteria definitions,
Section 4.2).
A serum β-hCG test will be performed in all women of child bearing potential at Screening 
Visit 2; and a local urine pregnancy test at the specified visits as indicated in Table 6-1. A 
positive urine pregnancy test requires immediate interruption of study treatment until serum β-
hCG is performed and found to be negative. If positive, the subject must be discontinued from 
the trial.
6.5.7
Tolerability of secukinumab
Tolerability will be assessed by adverse events, laboratory values and injection site reaction. 
6.5.8
Additional parameters
Blood will be obtained at the first screening visit (Visit 1) for anti-CCP antibodies and the 
Rheumatoid Factor (RF).
6.5.9
Appropriateness of safety measurements
The safety measures used in this study are reliable and relevant standard measures for a 
biologic in PsA. A chest X-ray at screening (or within 3 months prior to screening) is 
performed to rule out the presence of a pulmonary malignancy or infectious process, in 
particular tuberculosis. The radiation exposure that results from the chest X-ray safety 
measurements are estimated to be far below 1 mS. Effective radiation doses under 3 mS (300 
mrem), are considered to be minimal risk. Therefore, the radiation exposure in this study 
involves minimal risk and is necessary to ensure reliable safety measures before the treatment 
with a biologic.
The safety assessments selected are standard and adequate for this indication/subject 
population.
7
Safety monitoring 
7.1
Adverse events 
An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a subject or 
clinical investigation subject after providing written informed consent for participation in the 
study. Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product.
The occurrence of adverse events should be sought by non-directive questioning of the patient 
at each visit during the study. Adverse events also may be detected when they are volunteered 
by the patient during or between visits or through physical examination, laboratory test, or 
other assessments.

Novartis
Confidential
Page 68
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least
one of the following criteria:

they induce clinical signs or symptoms 

they are considered clinically significant 

they require therapy 
Clinically significant abnormal laboratory values or test results should be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in patient with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
patient and identifying adverse events. Alert ranges for labs and other test abnormalities are 
included in Appendix 1.
Adverse events should be recorded in the Adverse Events CRF under the signs, symptoms or 
diagnosis associated with them, accompanied by the following information.

the severity grade 

mild: usually transient in nature and generally not interfering with normal activities

moderate: sufficiently discomforting to interfere with normal activities

severe: prevents normal activities

relationship to the study treatment (no/yes)

duration (start and end dates) or if the event is ongoing an outcome of not recovered/not 
resolved should be reported.

whether it constitutes a serious adverse event (SAE - See Section 7.2 for definition of SAE)

action taken regarding study treatment 

All adverse events should be treated appropriately. Treatment may include one or more of 
the following: 

no action taken (i.e. further observation only) 

study treatment temporarily interrupted 

study treatment permanently discontinued due to this adverse event 

concomitant medication given 

non-drug therapy given 

patient hospitalized/patient’s hospitalization prolonged 

outcome (not recovered/not resolved; recovered/resolved; recovered/resolved with 
sequelae; fatal or unknown)
Once an adverse event is detected, it should be followed until its resolution or until it is 
judged to be permanent, and assessment should be made at each visit (or more frequently, if 
necessary) of any changes in severity, the suspected relationship to the study drug, the 
interventions required to treat it, and the outcome.
Information about common side effects already known about the investigational drug can be 
found in the Investigator Brochure (IB) or will be communicated between IB updates in the 
form of Investigator Notifications. This information will be included in the patient informed 
consent and should be discussed with the patient during the study as needed.

Novartis
Confidential
Page 69
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
The investigator should also instruct each patient to report any new adverse event (beyond the 
protocol observation period) that the patient, or the patient’s personal physician, believes 
might reasonably be related to study treatment. This information should be recorded in the 
investigator’s source documents. However, if the AE meets the criteria of an SAE, it must be 
reported to Novartis.
7.2
Serious adverse events
7.2.1
Definition of SAE
An SAE is defined as any adverse event (appearance of (or worsening of any pre-existing) 
undesirable sign(s), symptom(s) or medical conditions(s) which meets any one of the 
following criteria:

is fatal or life-threatening 

results in persistent or significant disability/incapacity

constitutes a congenital anomaly/birth defect

requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:

routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (specify what this includes)

elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent

treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 

social reasons and respite care in the absence of any deterioration in the patient’s 
general condition

is medically significant, i.e. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention.
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.
Life-threatening in the context of a SAE refers to a reaction in which the patient was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if more severe (see Annex IV, ICH-E2D Guideline).
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalization but might jeopardize the 
patient or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization or 
development of dependency or abuse (see Annex IV, ICH-E2D Guideline).
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.

Novartis
Confidential
Page 70
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
All AEs (serious and non-serious) are captured on the CRF, SAEs also require individual 
reporting to Novartis DS&E as per Section 7.2.2.
7.2.2
SAE reporting
To ensure subject safety, every SAE, regardless of causality, occurring after the subject has 
provided informed consent and until 84 days after the last dose of study medication, must be 
reported to Novartis within 24 hours of learning of its occurrence. Any SAEs experienced 
after the 84-day period should only be reported to Novartis if the investigator suspects a 
causal relationship to study treatment.
Recurrent episodes, complications, or progression of the initial SAE must be reported as 
follow-up to the original episode, regardless of when the event occurs. This report must be 
submitted within 24 hours of the investigator receiving the follow-up information. An SAE 
that is considered completely unrelated to a previously reported one should be reported 
separately as a new event.
Information about all SAEs (either initial or follow up information) is collected and recorded 
on the paper Serious Adverse Event Report Form. The investigator must assess the 
relationship of each SAE to study treatment, complete the SAE Report Form in English, and 
send the completed, signed form by fax within 24 hours after awareness of the SAE to the 
local Novartis Drug Safety and Epidemiology Department. The telephone and fax number of 
the contact persons in the local department of Drug Safety and Epidemiology, specific to the 
site, are listed in the investigator folder provided to each site. The original copy of the SAE 
Report Form and the fax confirmation sheet must be kept with the subject’s source 
documentation at the study site. Follow-up information should be provided using a new paper 
SAE Report Form stating that this is a follow-up to a previously reported SAE.
Follow-up information provided should describe whether the event has resolved or continues, 
if and how it was treated, whether the treatment code was broken or not and whether the 
subject continued or withdrew from study participation. Each re-occurrence, complication, or 
progression of the original event should be reported as a follow-up to that event regardless of 
when it occurs.
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert 
(new occurrence) and is thought to be related to the study treatment, a Drug Safety and 
Epidemiology Department associate may urgently require further information from the 
investigator for Health Authority reporting. Novartis may need to issue an Investigator 
Notification (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 relevant ethics committees in accordance with 
regulatory requirements.
7.3
Liver safety monitoring
There has been no safety signal for liver toxicity with secukinumab to date in over 6535 
patients exposed and from a mechanism of action standpoint there is no effect of blocking IL-
17A on the liver. Liver function tests will be obtained at regular intervals but special measures 
for liver safety monitoring are not planned.

Novartis
Confidential
Page 71
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
7.4
Pregnancy reporting 
To ensure patient safety, each pregnancy occurring while the patient is on study treatment 
must be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy 
should be followed up to determine outcome, including spontaneous or voluntary termination, 
details of the birth, and the presence or absence of any birth defects, congenital abnormalities, 
or maternal and/or newborn complications.
Pregnancy should be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the local Novartis Drug Safety and Epidemiology Department. Pregnancy 
follow-up should be recorded on the same form and should include an assessment of the
possible relationship to the study treatment.
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form.
8
Data review and database management
8.1
Site monitoring
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and CRFs with the investigators and their staff. During 
the study, Novartis employs several methods of ensuring protocol and GCP compliance and 
the quality/integrity of the sites’ data. The field monitor will visit the site to check the 
completeness of patient records, the accuracy of entries on the (e)CRFs, the adherence to the 
protocol and to Good Clinical Practice, the progress of enrollment, and to ensure that study 
treatment is being stored, dispensed, and accounted for according to specifications. Key study 
personnel must be available to assist the field monitor during these visits.  
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
patient's file. The investigator must also keep the original informed consent form signed by 
the patient (a signed copy is given to the patient).
The investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the CRF entries. Novartis monitoring standards require full verification 
for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the CRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
patients will be disclosed.
8.2
Data collection
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms using fully validated software that conforms to US CFR 21Part 11 

Novartis
Confidential
Page 72
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
requirements. Designated investigator site staff will not be given access to the EDC system 
until they have been trained. 
Automatic validation programs check for data discrepancies and, by generating appropriate 
error messages, allow the data to be confirmed or corrected before transfer of the data to the 
CRO working on behalf of Novartis. The Investigator must certify that the data entered into 
the Electronic Case Report Forms are complete and accurate. After database lock, the 
investigator will receive copies of the patient data for archiving at the investigational site. 
8.3
Database management and quality control 
A CRO working on behalf of Novartis will review the data entered into the eCRFs by 
investigational staff for completeness and accuracy and instruct the site personnel to make any 
required corrections or additions. Queries are sent to the investigational site using an 
electronic data query. Designated investigator site staff is required to respond to the query and 
confirm or correct the data. Randomization codes and data about all study drug(s) assigned to 
the subject 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 database will be sent 
electronically to Novartis (or a designated CRO). Each occurrence of a code break via IRT 
will be reported to the clinical team and study monitor.  The code break functionality will 
remain available until study completion or upon request of Novartis.
Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system. 
Concomitant procedures, non-drug therapies and adverse events will be coded using the 
Medical dictionary for regulatory activities (MedDRA) terminology.
Laboratory samples will be processed centrally and the results will be sent electronically to a 
designated CRO.
PRO questionnaires will be completed by the subject on an electronic tablet, and the data 
transmitted into the eCRF by investigator site staff.
The occurrence of relevant protocol deviations will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 
locked and the treatment codes will be unblinded and made available for data analysis. Any 
changes to the database after that time can only be made after written agreement by Novartis 
management.
8.4
Data Monitoring Committee
Not required.
8.5
Adjudication Committee 
Not required.
9
Data analysis 
A designated Contract Research Organization will perform the statistical analysis.

Novartis
Confidential
Page 73
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
It is planned that the data from all centers that participate in this protocol will be combined, so 
that an adequate number of patients will be available for analysis.
Unless otherwise specified, all statistical tests will be conducted against a two-sided 
alternative hypothesis, employing a significance level of 0.05.
Efficacy, safety, and other data will be summarized.  For continuous variables, summary 
statistics (mean, standard deviation, median, 25th and 75th percentiles, interquartile range, 
minimum, and maximum) at each time point and for change from baseline to each time point 
will be reported by treatment group.
9.1
Analysis sets
The following analysis sets will be used for the statistical reporting and analyses:
Randomized Set: The Randomized Set includes all randomized patients.  
Safety Set: The Safety Set includes all patients who received at least one dose of study 
medication.  Patients will be included in the analysis according to treatment received.
Full Analysis Set:  The Full Analysis Set comprises all patients to whom study medication has 
been assigned.  Patients inappropriately randomized (e.g., IRT was called in error for 
randomization of a screen failed subject) will be excluded from this analysis set.  Following 
the intent-to-treat principle, patients will be analyzed according to the treatment they were 
assigned to at randomization.
9.2
Patient demographics and other baseline characteristics
Data will be summarized with respect to demographic and baseline characteristics of all 
patients, the subgroup of patients with dactylitis at baseline, and the subgroup of patients with 
enthesitis at baseline, for the Randomized Set and the Full Analysis Set.
9.3
Treatments 
The number of patients and the length of time (in days) exposed to each treatment will be 
summarized for the Safety Set.
Concomitant medications will be summarized by treatment using frequency counts and 
percentages for the Safety Set.
Any condition entered as medical history or current medical condition at baseline will be 
coded using the MedDRA dictionary for the Safety Set. They will be summarized by system 
organ class and preferred term of the MedDRA dictionary.
9.4
Analysis of the primary variable
9.4.1
Variable
The primary efficacy variable is ACR20 response (yes, no). The primary analysis time point 
will be at Week 16.

Novartis
Confidential
Page 74
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
9.4.2
Statistical model, hypothesis, and method of analysis
Let πj denote the probability of an ACR20 response at Week 16 for treatment group j, j = 0, 1, 
2, where 0 corresponds to placebo, 1 corresponds to secukinumab 150 mg, and 2 corresponds 
to secukinumab 300 mg.  Accordingly, πj/(1 – πj) is the odds for treatment group j, j = 0, 1, 2.
The following null hypotheses (H01 and H02) will be tested against their corresponding 
alternative hypotheses (HA1 and HA2):
H01: [π1/(1 – π1)]/[π0/(1 – π0)] ≤1  versus  HA1: [π1/(1 – π1)]/[π0/(1 – π0)] > 1
H02: [π2/(1 – π2)]/[π0/(1 – π0)] ≤ 1  versus  HA2: [π2/(1 – π2)]/[π0/(1 – π0)] > 1
The primary efficacy variable will be analyzed at each time point using a logistic regression 
model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no), and body 
weight as explanatory variables (Stokes, Davis, and Koch, 2012).  The odds ratios for each 
dose of secukinumab versus placebo, 95% confidence intervals for the odds ratios, and p-
values based on the fitted model will be reported.  If the p-value for a dose of secukinumab 
versus placebo is < 0.05 and the corresponding odds ratio is greater than 1, statistical 
significance in favor of that dose of secukinumab is shown.
The primary analysis of the primary efficacy variable will be based on the Full Analysis Set.
9.4.3
Handling of missing values/censoring/discontinuations
Patients who discontinued prematurely for any reason will be considered non-responders from 
the time they discontinued.  Patients who do not have the required data to compute ACR 
response (i.e., tender and swollen joint counts and at least three of the five ACR domains) at 
baseline and at the specific time point will be classified as non-responders.
9.4.4
Supportive analyses 
The primary efficacy variable will also be analyzed at each time point for the Full Analysis 
Set using the Cochran-Mantel-Haenszel (CMH) test to compare each dose of secukinumab 
against placebo, adjusting for methotrexate usage at baseline (yes, no) (Stokes, Davis, and 
Koch, 2012).  If the treatment comparison p-value is < 0.05 and the proportion of patients 
who are ACR20 responders is higher in a secukinumab treatment group compared to the 
placebo treatment group, statistical significance in favor of that dose of secukinumab is shown.  
Two 95% confidence intervals for the difference between each dose of secukinumab versus 
placebo in the proportion of patients who are ACR20 responders will be calculated using the 
normal approximation to the binomial distribution.
9.5
Analysis of secondary variables
9.5.1
Efficacy variables
The secondary efficacy variables are the following:
1. Dactylitis (yes, no)

Novartis
Confidential
Page 75
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
2. Enthesitis (yes, no)
3. ACR50 response (yes, no)
4. ACR70 response (yes, no)
5. Minimal Disease Activity (yes, no)
6. PASI75 response (yes, no)
7. PASI90 response (yes, no)
8. PASI100 response (yes, no)
9. Change from baseline in DAS28-CRP
10. Change from baseline in PASDAS
11. Change from baseline in SF12
12. Change from baseline in HAQ-DI
Two analyses of dactylitis and enthesitis (secondary efficacy variables 1 and 2) will be 
performed at each time point.  For the first analysis, the data for the subgroup of patients who 
have dactylitis at baseline will be used (similarly for enthesitis) and the analysis of the binary 
response variable (yes, no) will be similar to the analysis of secondary efficacy variables 3-8
below.  In the supporting analysis, the data for all patients will be used and an ordinal variable 
will be created based on presence (yes) or absence (no) of dactylitis at baseline and a post-
baseline visit (similarly for enthesitis).  The three categories for the ordinal variable will be 
no/no (category 1), no/yes and yes/no (category 2), and yes/yes (category 3).  This ordinal 
response variable will be analyzed using a proportional odds regression model with treatment 
(3 treatment groups), methotrexate usage at baseline (yes, no), and body weight as 
explanatory variables (Stokes, Davis, and Koch, 2012). The odds ratios for each dose of 
secukinumab versus placebo, 95% confidence intervals for the odds ratios, and p-values based 
on the fitted model will be reported.
Secondary efficacy variables 3-8 will be analyzed at each time point using a logistic 
regression model with treatment (3 treatment groups), methotrexate usage at baseline (yes, no), 
and body weight as explanatory variables (Stokes, Davis, and Koch, 2012).  The odds ratios 
for each dose of secukinumab versus placebo, 95% confidence intervals for the odds ratios, 
and p-values based on the fitted model will be reported.  
Secondary efficacy variables 9-12 will be analyzed at each time point by an analysis of
covariance (ANCOVA) model with treatment (3 treatment groups), baseline, methotrexate 
usage at baseline (yes, no), and body weight as explanatory variables.  The least squares 
means of the three treatment groups, least squares mean differences between each dose of 
secukinumab and placebo, 95% confidence intervals for the difference between each dose of 
secukinumab and placebo, and p-values based on the fitted linear model will be reported.  
Missing data will be imputed using the last-observation-carried-forward (LOCF) method.
Analyses of the secondary efficacy variables will be based on the Full Analysis Set.

Novartis
Confidential
Page 76
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
9.5.2
Safety variables
The assessment of safety will be based mainly on the frequency of adverse events and 
laboratory data. Other safety data (e.g., vital signs and special tests) will be considered, as 
appropriate.
Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of patients having any adverse event, having an adverse event in each body system 
and having each individual adverse event. Any other information collected (e.g., severity or 
relatedness to study medication) will be listed, as appropriate.

Novartis
Confidential
Page 77
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Adverse events and serious adverse events up to and including Week 16 visit will be included 
in the database for the analysis at the primary analysis time point (Week 16). All Adverse 
events and serious adverse events will be included in the final database analysis (Week 52).
Laboratory variables will be summarized.
Analysis of safety data will be based on the Safety Set.
9.6
Interim analyses
The database of this study will be locked twice, first after the end of Treatment Period 1
(Week 16) and again after the end of Treatment Period 2 (Week 52).  Data analyses will 
follow each database lock.  The main analysis (or test) for the primary objective will be done 
at Week 16.  As Week 16 is the primary analysis time point, no adjustment to the significance 
level of 0.05 will be made.
9.7
Sample size calculation
The sample size was calculated based on the primary efficacy variable (i.e., ACR20 response)
for the primary comparison (i.e., secukinumab 300 mg versus placebo).  ACR20 response 
rates of 50% for secukinumab 300 mg and 20% for placebo (corresponding to an odds ratio of 
4) at Week 16 were assumed, based on results from AIN457F2312 (FUTURE 2) study.  Using 
a continuity-corrected chi-squared test, an allocation ratio of 2:1, a two-sided significance 
level of 0.05, and a power of 0.90, approximately 88 patients in secukinumab 300 mg group 
and 44 patients in placebo group will be needed (nQuery Advisor 7.0).  Assuming a loss to 
follow-up rate of 10% and a 2:2:1 allocation ratio (secukinumab 300 mg: secukinumab 150
mg: placebo), the total number of randomized patients will be approximately 250 (100 on 
secukinumab 300 mg, 100 on secukinumab 150 mg, and 50 on placebo)
10
Ethical considerations
10.1
Regulatory and ethical compliance
This clinical study was designed and shall be implemented and reported in accordance with 
the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable local 
regulations (including European Directive 2001/20/EC, US CFR 21, and Japanese Ministry of 
Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of 
Helsinki.
10.2
Informed consent procedures 
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if incapable of doing 
so, after such consent has been provided by a legally acceptable representative(s) of the 
patient. In cases where the patient’s representative gives consent, the patient should be 
informed about the study to the extent possible given his/her understanding. If the patient is 
capable of doing so, he/she should indicate assent by personally signing and dating the written 
informed consent document or a separate assent form. Informed consent must be obtained 

Novartis
Confidential
Page 78
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
before conducting any study-specific procedures (i.e. all of the procedures described in the 
protocol). The process of obtaining informed consent should be documented in the patient 
source documents. 
Novartis will provide to investigators in a separate document a proposed informed consent 
form that complies with the ICH GCP guideline and regulatory requirements and is 
considered appropriate for this study. Any changes to the proposed consent form suggested by 
the 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.
Women of child bearing potential should be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirement for the 
duration of the study. If there is any question that the patient will not reliably comply, they 
should not be entered in the study.
10.3
Responsibilities of the investigator and IRB/IEC
Before initiating a trial, the investigator/institution should obtain approval/favorable opinion 
from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial 
protocol, written informed consent form, consent form updates, subject recruitment 
procedures (e.g., advertisements) and any other written information to be provided to patients. 
Prior to study start, the investigator is required to sign a protocol signature page confirming 
his/her agreement to conduct the study in accordance with these documents and all of the 
instructions and procedures found in this protocol and to give access to all relevant data and 
records to Novartis monitors, auditors, Novartis Quality Assurance representatives, designated 
agents of Novartis, IRBs/IECs, and regulatory authorities as required. If an inspection of the 
clinical site is requested by a regulatory authority, the investigator must inform Novartis 
immediately that this request has been made.
10.4
Publication of study protocol and results
Novartis assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and 
finalization of the study report the results of this trial will be either submitted for publication 
and/or posted in a publicly accessible database of clinical trial results.
11
Protocol adherence
This protocol defines the study objectives, the study procedures and the data to be collected 
on study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances should an 
investigator collect additional data or conduct any additional procedures for any research 
related purpose involving any investigational drugs.
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 

Novartis
Confidential
Page 79
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
and approved by the IRB/IEC and health authorities, where required, it cannot be 
implemented. All significant protocol deviations will be recorded and reported in the CSR. 
11.1
Protocol Amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, Health Authorities where required, and the IRB/IEC prior to 
implementation. Only amendments that are intended to eliminate an apparent immediate 
hazard to patients may be implemented immediately provided the Health Authorities are 
subsequently notified by protocol amendment and the reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 7 Safety Monitoring should be followed.
12
References
References are available upon request.
Barrett JC, Hansoul S, Nicolae DL, et al (2008) Genome-wide association defines more than 
30 distinct susceptibility loci for Crohn's disease. Nat Genet. 40(8):955-62.
 
 
 
 
 
 
 
Coates LC, Fransen J, Helliwell PS (2010) Defining minimal disease activity in psoriatic 
arthritis: a proposed objective target for treatment. Ann Rheum Dis.69(1):48-53.
Curran SA, FitzGerald OM, Costello PJ, et al (2004) Nucleotide sequencing of psoriatic 
arthritis tissue before and during methotrexate administration reveals a complex inflammatory 
T cell infiltrate with very few clones exhibiting features that suggest they drive the 
inflammatory process by recognizing antigens. J Immunol 172:1935-44.
Doherty SD, Van Voohes A, Lebwohl MG (2008) National Psoriasis Foundation consensus
statement on screening for latent tuberculosis infection in patients with psoriasis treated with 
systemic and biologic agents. J Am Acad Dermatol; 59(2):209-17.
EMA guidance document: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC5
00003439.pdf

Novartis
Confidential
Page 80
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
FDA guidance document: 
www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/UC
M071579.pdf
Feldman SR and Krueger GG (2005) Psoriasis assessment tools in clinical trials. Ann Rheum 
Dis; 64 Suppl 2:ii65-8; discussion ii69-73.
Felson DT, Anderson JJ, Boers M, et al. (1995) American College of Rheumatology. 
Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum; 38(6):727-35.
Finlay AY and Khan GK (1994) Dermatology Life Quality Index (DLQI): A simple practical 
measure for routine clinical use. Clin Exp Dermatol; 19:210-216. 
Fredriksson T and Pettersson U (1978) Severe psoriasis-oral therapy with a new retinoid. 
Dermatologica; 157:238-44.
Fries JF, Spitz P, Kraines G, Holman H. (1980) Measurement of Patient Outcome in Arthritis. 
Arthritis Rheum; 23:137-145.
Gottlieb A, Griffiths CEM, Ho VC, et al (2005) Efficacy and tolerability of oral pimecrolimus 
in the treatment of moderate to severe chronic plaque type psoriasis: a double-blind, 
multicentre, randomized dose-finding trial. Br J Dermatol; 152:1219-27.
Helliwell PS, Firth J, Ibrahim GH, et al (2005). Development of an assessment tool for 
dactylitis in patients with psoriatic arthritis. J Rheumatol 32:1745-50.
Helliwell PS, Fitzgerald O, Fransen J et al (2012). The development of candidate composite 
disease activity and responder indices for psoriatic arthritis (GRACE project). Ann Rheum 
Dis 0:1–6. 
Koenders MI, Lubberts E, Oppers_Walgreen B, et al. (2005) Blocking of interleukin-17 
during reactivation of experimental arthritis prevents joint inflammation and bone erosion by 
decreasing RANKL and interleukin-1. Am J Pathol; 167:141-9.
Kushner I. (1991) C-reactive protein in rheumatology. Arthritis Rheum; 34(8):1065-68. 
 
 
Mallya RK, De Beer FC, Berry H, et al (1982) Correlation of clinical parameters of disease 
activity in rheumatoid arthritis with serum concentration of C-reactive protein and 
erythrocytesedimentation rate. J Rheumatol; 9(2):224-8.
Manuel O, Kumar D (2008) QuantiFERON-TB Gold assay for the diagnosis of latent 
tuberculosis infection. Expert Rev Diagn; 8(3):247-56.
McInnes IB, Kavanaugh A, Gottlieb AB, et al, on behalf of the PSUMMIT 1 Study Group 
(2013)  Efficacy and safety of ustekinumab in patients with active psoriatic arthritis: 1 year 
results of the phase 3, multicentre, double-blind, placebo-controlled PSUMMIT 1 trial. Lancet 
2013; published online June 13. http://dx.doi.org/10.1016/ S0140-6736(13)60594-2.
Mease PJ (2008) Psoriatic Arthritis. In: Klippel JH, Stone JH, Crofford LJ et al, eds. Primer 
on Rheumatic Diseases. 13th ed. New York: Springer Science, p. 170-192.
Moll JM, Wright V (1973) Psoriatic arthritis. Semin Arthritis Rheum 3:55-78.

Novartis
Confidential
Page 81
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Philip J Mease, Bernard S Goffe, James Metz, Ann VanderStoep, Barbara Finck, Daniel J 
Burge (2000) Etanercept in the treatment of psoriatic arthritis and psoriasis: a randomised trial. 
THE LANCET Vol 356: 385-90 
Philip J. Mease,1 Dafna D. Gladman,2 Christopher T. Ritchlin,3 Eric M. Ruderman,4 Serge D. 
Steinfeld,5 Ernest H. S. Choy,6 John T. Sharp,7 Peter A. Ory,8 Renee J. Perdok,9 and Mark A. 
Weinberg,9 for the Adalimumab Effectiveness in Psoriatic Arthritis Trial Study Group (2005) 
Adalimumab for the Treatment of Patients With Moderately to Severely Active Psoriatic 
Arthritis ARTHRITIS & RHEUMATISM Vol. 52, No. 10, pp 3279–3289
Philip J. Mease·April W.Armstrong (2014) Managing Patients with Psoriatic Disease: The
Diagnosis and Pharmacologic Treatment of Psoriatic Arthritis in Patients with
Psoriasis Drugs74:423-441
 
 
Stokes ME, Davis CS, Koch GG (2012) Categorical data analysis using the SAS system. 3rd 
ed; Cary, NC: SAS Institute, Inc.
Taylor W, Gladman D, Helliwell, et al (2006) Classification criteria for psoriatic arthritis. 
Arthritis Rheum 54:2665-73.
Tassiulas I, Duncan SR, Centola M, et al (1999) Clonal characteristics of T cell infiltrates in 
skin and synovium of patients with psoriatic arthritis. Hum Immunol 60:479-491.
Turkiewicz AM, Moreland LW (2007) Psoriatic arthritis: current concepts on pathogenesis-
oriented therapeutic options. Arthritis Rheum 56(4):1051-66.
Van Leeuwen MA, Van Rijswijk MH, Van der Heijde DMFM, et al (1993) The acute phase 
response in relation to radiographic progression in early rheumatoid arthritis: a prospective 
study during the first three years of the disease. Br J Rheumatol; 32(suppl 3):9-13.
Ware J, Kosinki M, Gandeck B. (1993) SF-36 Health Survey manual and interpretation guide. 
Boston: The Health Institute, New England Medical Center.
Ware J, Kosinki M, Gandeck BS (1994) F-36 Health Survey manual and interpretation guide. 
Update. Boston: The Health Institute, New England Medical Center.
Weisman S, Pollack CR, Gottschalk RW (2003) Psoriasis disease severity measures: 
comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat; 14:158-165.
Wolfe F. (1997) Comparative usefulness of C-reactive protein and erythrocyte sedimentation 
rate in patients with rheumatoid arthritis. J Rheumatol; 24:1477-85.
 
 
12.1
Appendix 1: Clinically notable laboratory values and vital signs
The following criteria will be used to define expanded limits and notable abnormalities of key
laboratory tests. Whether or not any action needs to be taken to address notable laboratory or 
vital signs values will be determined by the investigator/qualified site staff, taking into 

Novartis
Confidential
Page 82
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
account the overall status of the subject. No specific action is pre-defined within this study 
protocol.
Liver function and related variables 
ALT (SGPT) 
> 3 x Upper Limit of Normal (ULN)
AST (SGOT) 
> 3 x ULN
Total bilirubin 
> 1.5 x ULN
Alkaline phosphatase > 2 x ULN
Renal function and electrolyte variables
Creatinine (serum) 
> 1.5 x ULN
Hematology values
Hemoglobin
≥ 2.0 g/dL decrease from baseline
Platelet count 
< Lower Limit of Normal (LLN)
White blood cell            < 0.8 x LLN
Neutrophils 
< 0.9 x LLN
Eosinophils 
> 1.1 x ULN
Lymphocytes
> 1.1 x ULN
12.2
Appendix 2: The classification criteria for psoriatic arthritis 
(CASPAR)
To meet the Classification of Psoriatic Arthritis (CASPAR) criteria for diagnosis of psoriatic 
arthritis according to (Taylor 2006), a subject must have inflammatory articular disease (joint, 
spine or entheseal) and at least 3 points from the following 5 categories:
1. Evidence of current psoriasis, a personal history of psoriasis, or a family history of 
psoriasis (2 points) 

Current psoriasis is defined as psoriatic skin or scalp disease present today as judged 
by a rheumatologist or dermatologist.† 

A personal history of psoriasis is defined as a history of psoriasis that may be 
obtained from a patient, family physician, dermatologist, rheumatologist, or other 
qualified health care provider. 

A family history of psoriasis is defined as a history of psoriasis in a first- or second-
degree relative according to patient report.
2. Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis 
observed on current physical examination (1 point) 
3. A negative test result for the presence of rheumatoid factor by any method except latex        
(1 point) 

Novartis
Confidential
Page 83
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
4. Either current dactylitis, defined as swelling of an entire digit, or a history of dactylitis 
recorded by a rheumatologist (1 point) 
5. Radiographic evidence of juxta-articular new bone formation appearing as ill-defined 
ossification near joint margins (but excluding osteophyte formation) on plain radiographs 
of the hand or foot (1 point)
Total score: _______  
(The CASPAR criteria eCRF will autopopulate the total number of points of the CASPAR 
criteria met by the subject.  If the total score ≥ 3, the subject meets CASPAR criteria for PsA 
diagnosis.)
† Current psoriasis is assigned a score of 2; all other features are assigned a score of 1
12.4
Appendix 4: American College of Rheumatology (ACR) Measures 
and Criteria of Response
Number of tender joints:
Joint counts will be performed by the assessor(s) who must be well trained and part of the site 
personnel. Whenever possible, the same evaluator should perform these assessments at all 
visits.
The 78 joints assessed for tenderness include the 2 temporomandibular, 2 sternoclavicular, 2 
acromioclavicular joints, 2 shoulders, 2 elbows, 2 wrists, 2 first carpometacarpal, 10 
metacarpophalangeal, 10 proximal interphalangeal, 8 distal interphalangeal joints of the hands, 
the 2 hip, 2 knee, 2 talo-tibial, 2 mid-tarsal, 10 metatarsophalangeal, 10 proximal 
interphalangeal, and 8 distal interphalangeal joints of the feet. 
Joint tenderness and swelling are to be graded present (1) or absent (0). 

Novartis
Confidential
Page 84
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Number of swollen joints:
Joints are to be scored as either swollen (1) or not swollen (0). The 76 joints to be examined 
for swelling are the same as those examined for tenderness, however excluding both hip joints.
Patient's assessment of PsA pain
On a 100 mm non- anchored visual analog scale, from no pain to unbearable pain.
Patient's global assessment of disease activity
On a 100 mm non-anchored visual analog scale, from no arthritis activity to maximal arthritis 
activity, after the question "Considering all the ways your arthritis affects you, draw a line on 
the scale for how well you are doing".
Physician's global assessment of disease activity
On a 100 mm non-anchored visual analog scale, from no arthritis activity to maximal arthritis 
activity.
Patient's assessment of physical function
Health Assessment Questionnaire – HAQ-DI©
ACR20/50/70*
A patient will be considered as improved according the ACR20 criteria* if she/he has at least 
20 % improvement in the two following measures:

Tender joint count,

Swollen joint count.

and at least 3 of the following 5 measures:
a. Patient's assessment of pain,
b. Patient's global assessment of disease activity,
c. Physician's global assessment of disease activity,
d. Health Assessment Questionnaire (HAQ©) score,
e. C-reactive protein (CRP)/Erythrocyte Sedimentation Rate (ESR).
ACR50 = 50 % improvement in at least 3 of the 5 measures and 50 % improvement in the 
swollen and tender joint count.
ACR70 = 70 % improvement in at least 3 of the 5 measures and 70 % improvement in the 
swollen and tender joint count.
Reference: (Felson 1995)
12.5
Appendix 5: Disease Activity Score (DAS)
The Disease Activity Score (DAS) is a combined index to measure the disease activity in 
patients with RA. It has been extensively validated for its use in clinical trials in combination 
with the EULAR response criteria.

Novartis
Confidential
Page 85
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
Evaluation of response to a treatment can be made much easier and more objective using the 
DAS. Just assess the number of swollen and tender joints and measure the ESR. The DAS will 
provide you with a number between 0 and 10, indicating how active the disease is at this 
moment. Recently the DAS-CRP has been developed. The C-reactive protein (CRP) may be 
used as an alternative to ESR in the calculation of the DAS or the DAS28.
Using the DAS, several thresholds have been developed for high disease activity, low disease 
activity or remission. Also response criteria have been developed based on the DAS, so when 
the DAS of a patient is measured at two time-points (e.g. before the start of a treatment and 
after 3 months), the patients clinical response can be assessed.
The DAS in the clinical trials
Comparing the DAS28 from one patient on two different time-points, it is possible to define 
improvement or response. The EULAR response criteria are defined as follows:
Present DAS28
DAS28 improvement
>1.2
0.6 - 1.2
<0.6
<3.2
good response
moderate 
response
no response
3.2 - 5.1
moderate 
response
moderate 
response
no response
>5.1
moderate 
response
no response
no response
Both the thresholds for high and low disease activity and remission and the abovementioned 
improvement criteria should give you a feel how to interpret your DAS28 scores.
In order to calculate the DAS28, information about the following disease variables is needed:

The number of swollen joints and tender joints should be assessed using 28-joint count 
(tender28 and swollen28).

The erythrocyte sedimentation rate (ESR) should be measured in mm/hour.

The patient’s general health (GH) or global disease activity measured on a Visual 
Analogue Scale (VAS) of 100 mm (both are useable for this purpose) must be obtained.
Using this data, the DAS28 can be calculated using the following formula:
DAS28 = 0.56 * sqrt(tender28) + 0.28 * sqrt(swollen28) + 0.70 * ln(ESR) + 0.014 * GH
The DAS28 provides you with a number on a scale from 0 to 10 indicating the current activity 
of the rheumatoid arthritis of your patient. A DAS28 above 5.1 means high disease activity 
whereas a DAS28 below 3.2 indicates low disease activity. Remission is achieved by a 
DAS28 lower than 2.6 (comparable to the PsA remission criteria).
Disease Activity Scores using C-reactive protein
C-reactive protein (CRP) may be used as an alternative to ESR in the calculation of the DAS 
or DAS28, using the formulas below. CRP is a more direct measure of inflammation than 
ESR, and it is more sensitive to short-term changes (Kushner 1991). CRP production is 

Novartis
Confidential
Page 86
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
associated with radiological progression in RA (Van Leeuwen 1993), and is considered at 
least as valid as ESR to measure RA disease activity (Mallya 1982, Wolfe 1997). Another 
advantage of determination of CRP is that waiting time for the laboratory result is shorter and 
that in case of multicenter studies a central laboratory can be used.
The following formulas to calculate the DAS28 using CRP (mg/L) give good estimations of 
the original DAS28 values on a group level. DAS28-4(crp) = 0.56*sqrt(TJC28) + 
0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*GH + 0.96
TJC28: 28 Tender joint count; SJC28: 28 Swollen joint count; CRP: C-reactive protein; GH: 
General Health on a 100mm. Visual Analogue Scale.
It is strongly advised to adhere either to ESR or to CRP determinations.

Novartis
Confidential
Page 87
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
12.6
Appendix 6: The Psoriasis Area and Severity Index (PASI)

Novartis
Confidential
Page 88
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

Novartis
Confidential
Page 89
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
12.8
Appendix 8: Health Assessment Questionnaire (HAQ)
The HAQ(Fries JF et al. 1980) is a validated measure of physical disability and functional 
status. It has four dimensions: disability, pain, drug side effects and dollar costs, although, the 
latter three are rarely used in clinical trials. In this trial only the disability dimension will be 
used. The disability dimension consists of 20 multiple choice items concerning difficulty in 
performing eight common activities of daily living; dressing and grooming, arising, eating, 
walking, reaching, personal hygiene, gripping and activities. Patients choose from four 
response categories, ranging from ‘without any difficulty' to 'unable to do'. The ACR 
Rheumatology Committee on Outcome Measures in RA recommends the use of this 
questionnaire in clinical trials.
Scoring of the HAQ©
The HAQ© will be scored in accordance with the recommendation from the developers 
outlined in the “HAQ PACK” from Stanford University, California.
The following coding is to be used for the 8 categories of the disability outcome dimension:
Without ANY Difficulty
0
With SOME Difficulty
1
With MUCH Difficulty
2
UNABLE to do
3
Within each of the 8 categories only the item indicating the most severe impairment 
contributes to the category score. If the patient requires the use of aids, devices, or help from 
another to accomplish any of the activities in an associated category, then the score for that 
category will be assigned the value 2, unless the score is already 3 (i.e. scores of 0 or 1 are 
increased to 2). Associated categories are defined in the “HAQ PACK”. From the scores for 
each category a Standard Disability Index (SDI) is computed by summing the computed 
scores for each category and dividing by the number of categories answered. The SDI is not 

Novartis
Confidential
Page 90
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
computed if the patient does not have scores for at least 6 categories. This SDI is the HAQ©
score, which will be used in the statistical analyses of this instrument. The range for this score 
is (0, 3).
HAQ© Data Collection
The HAQ© is to be completed by the patients in their local languages, using an electronic 
device. The questionnaires should be completed by the patients in a quiet area free from 
disturbance, and before any visit assessments. Patients should receive no help from family 
members; if questions cannot be answered alone (due to problems with reading or 
understanding), then the doctor or nurse should read the questions and record the patient’s 
responses without influencing their answers. The information provided is strictly confidential 
and will be treated as such. If a patient has missed a question or given more than one response 
per question, then this should be brought to patient. Incomplete questions should not be 
accepted without first encouraging the patient to complete unanswered questions.
The investigator must complete the patient/visit information on the electronic device and 
ensure that the center number, patient’s number and initials are identical to the Case Record 
Form. As there are no source data for this questionnaire, the data queries will be restricted to 
patient/visit information.

Novartis
Confidential
Page 91
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01

Novartis
Confidential
Page 92
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
12.10
Appendix 10: Guidelines for administering the PRO
questionnaires
Before trial start
PROs will be administered to patients using an electronic tablet called a SitePad
Study coordinators should familiarize themselves with the PRO questionnaire(s) in the trial 
and identify any items where a patient’s response might highlight issues of potential concern. 
For example, one question in the SF-12 ‘How much of the time in the past 4 weeks- have you 
felt downhearted and blue?’ If a patient responds ‘most or all of the time’, then the study 
coordinator should inform the study investigator.
Before completion
1. The SitePad will have the correct Questionnaires for the patients, at the appropriate visits, 
and in the appropriate language.  

2. Patients should have adequate space and time to complete their questionnaires on the 
SitePad
3. Questionnaires should be administered and completed before the clinical examination
During completion
1. Administrator may clarify the questions but should not influence the response
2. The SitePad will only allow one response for each question 
3. Also see ‘Addressing Problems and Concerns’
After completion
1. The Patient’s data/reports MUST be transmitted so it can be reviewed in StudyWorks.
*If any response is received which may directly impact or reflect the patient’s medical 
condition (e.g. noting of depression), that information should be communicated by the study 
coordinator to the investigator).
Addressing Problems and Concerns
Occasionally a patient may have concerns or questions about the questionnaires administered. 
Guidance related to some of the most common concerns and questions are given below.
The patient does not want to complete the questionnaire(s)
Tell the patient that completion of the questionnaire(s) is voluntary but is an important part of 
their participation in the study. The goal of these questionnaires is to better understand the 
physical, mental, and social health problems of patients. Emphasize that this information is as 
important as any of the other medical information, and that the questionnaire(s) is simple to 
complete. Suggest that the questionnaire(s) may be different from anything the respondent has 
filled in the past. If the patient still declines, please ask them to complete the end of visit 

Novartis
Confidential
Page 93
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
questionnaire which confirms they have declined to complete the questionnaires. Thank the 
patient. The patient is too ill or weak to complete the questionnaire(s)
In these instances, the coordinator may obtain patient responses by reading out loud each 
question, followed by the corresponding response categories, and entering the patient’s 
response. No help should be provided to the patient by any person other than the designated 
study coordinator. The coordinator should not influence patient responses. The study 
coordinator cannot translate the question into simpler language and has to be read verbatim.
The patient wants someone else to complete the questionnaire(s)
In no case should the coordinator or anyone other than the patient provide responses to the 
questions. Unless specified in the study protocol proxy data are not an acceptable substitute 
for patient self-reported. Patients should be discouraged from asking a family member or 
friend for help in completing a questionnaire.
The patient does not want to finish completing the questionnaire(s)
If non-completion is a result of the patient having trouble understanding particular items, ask 
the patient to explain the difficulty. Re-read the question for them verbatim, but do not 
rephrase the question. If the respondent is still unable to complete the questionnaire, that 
questionnaire will be forfeited since partial response will not be saved. Thank the patient.
The patient is concerned that someone will look at his/her responses
Emphasize that all responses are to be kept confidential. Point out that their names do not 
appear anywhere on the questionnaire, so that their results will be linked with an ID number 
and not their name. Tell the patient that his/her answers will be pooled with other patients’ 
answers and that they will be analyzed as a group rather than as individuals. Tell the patient 
that completed questionnaires are not routinely shared with treating staff, and that their 
responses will only be seen by you and possibly the investigator. Any response which may 
directly impact on or reflect their medical condition (e.g. noting of severe depression) will be 
communicated by the coordinator to the physician.
The patient asks the meaning of a question/item
While completing the questionnaire, some patients might ask the meaning of specific items so 
that they can better understand and respond. If this happens, assist the patient by rereading the 
question for them verbatim. If the patient asks to interpret the meaning of an item, do not try 
to explain it, but suggest that he/she use his/her own interpretation of the question. Patients 
should answer the questions based on what they think the questions mean. 
General Information about all questionnaire(s): 
All questionnaires are to be completed by the patients on the SitePad. The questionnaires 
should be completed by the patients in a quiet area free from disturbance, and before any visit 
assessments. Patients should receive no help from family members; if questions cannot be 
answered alone (due to problems with reading or understanding), then the doctor or nurse 
should read the questions verbatim without influencing their answers. The information 
provided is strictly confidential and will be treated as such.

Novartis
Confidential
Page 94
Amended Protocol Version 02 (Clean)
Protocol No. CAIN457FUS01
The investigator must complete the patient/visit information on the SitePad and ensure that 
the center number, patient’s number and initials are identical to the electronic Case Record 
Form. As there are no source data for the questionnaires, the data queries will be restricted to 
patient/visit information