Conditions: Psoriatic Arthritis
Keywords: PsA immune-mediated chronic inflammatory disease spondylarthritis SpA inflammatory musculoskeletal disease China bridging study AIN457 secukinumab
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 41
Healthy volunteers: no

Brief summary:
The purpose of this study was to assess the efficacy and safety of secukinumab in Chinese participants with active Psoriatic arthritis (PsA ) compared to placebo.

Detailed description:
This study used a randomized, double-blind, placebo-controlled, parallel-group design.

A screening period running up to 10 weeks before randomization was used to assess participant eligibility followed by 52 weeks of treatment.

A follow-up visit was done 12 weeks after last study treatment administration for all participants, regardless of whether they completed the entire study as planned or discontinued prematurely.

At Baseline, the patients fulfilling the inclusion criteria were randomized to one of the following two groups.

Group 1 : Secukinumab Dose level 1 s.c. at BSL, Week 1, 2, 3, 4, 8, and 12 Group 2 : Secukinumab Placebo s.c. at BSL, Week 1, 2, 3, 4, 8, and 12.

At Week 16, participants in Group 1 and Group 2 were to be re-randomized separately in a 1:1 ratio to receive secukinumab 150 mg or secukinumab 300 mg.

The duration of the entire treatment period was 52 weeks.

The primary objective was to demonstrate the treatment effect of secukinumab in Chinese subjects with active PsA by assessing American College of Rheumatology rresponse 20 (ACR20 response) rates at Week 16.

Arms:
arm 1: Participants received 150 mg dose (dose level 1) of Secukinumab arm 2: Participants received Placebo of the study drug. arm 3: Participants who received Placebo and switched to dose level 1 (150 mg) of secukinumab. arm 4: Participants who received Placebo and switched to dose level 2 (300 mg) of secukinumab.

Interventions: intervention 1: AIN457 intervention 2: Secukinumab Placebo
Intervention descriptions: intervention 1: Secukinumab 150 mg was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection intervention 2: Secukinumab placebo was supplied in 1.0 mL prefilled syringe, administered via subcutaneous injection

Protocol document:
Prot_000.pdf: 
Novartis Research and Development 
AIN457 
Clinical Trial Protocol CAIN457F2367 / NCT04711902
A phase III randomized, double-blind, placebo controlled, 
multicenter, bridging study of subcutaneous secukinumab, 
to demonstrate efficacy after sixteen weeks of treatment 
and to assess safety, tolerability and long-term efficacy 
follow-up to one year in Chinese subjects with active 
psoriatic arthritis 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
Not Applicable 
Version number: 
00 (Original Protocol) 
Clinical Trial Phase: 
III 
Release date: 
16-Nov-2020 (content final)
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 3.0 dated 31-Jan-2020 


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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 6 
List of abbreviations ............................................................................................................ 7 
Glossary of terms ............................................................................................................... 11 
Protocol summary .............................................................................................................. 13 
1 
Introduction ....................................................................................................................... 17 
1.1 
Background ............................................................................................................ 17 
1.2 
Purpose .................................................................................................................. 19 
2 
Objectives and endpoints ................................................................................................... 20 
2.1 
Primary estimands ................................................................................................. 21 
2.2 
Secondary estimands ............................................................................................. 22 
3 
Study design ...................................................................................................................... 23 
4 
Rationale ............................................................................................................................ 24 
4.1 
Rationale for study design ..................................................................................... 24 
4.2 
Rationale for dose/regimen and duration of treatment .......................................... 25 
4.3 
Rationale for choice of control drugs (comparator/placebo) ................................. 26 
4.4 
Purpose and timing of primary endpoint analysis/design adaptations ................... 26 
4.5 
Risks and benefits .................................................................................................. 26 
5 
Study Population ............................................................................................................... 28 
5.1 
Inclusion criteria .................................................................................................... 28 
5.2 
Exclusion criteria ................................................................................................... 29 
6 
Treatment ........................................................................................................................... 32 
6.1 
Study treatment ...................................................................................................... 32 
6.1.1 
Investigational and control drugs .......................................................... 32 
6.1.2 
Additional study treatments .................................................................. 32 
6.1.3 
Treatment arms/group ........................................................................... 32 
6.1.4 
Treatment duration ................................................................................ 33 
6.2 
Other treatment(s) .................................................................................................. 33 
6.2.1 
Concomitant therapy ............................................................................. 33 
6.2.2 
Prohibited medication ........................................................................... 35 
6.2.3 
Rescue medication ................................................................................ 37 
6.3 
Participant numbering, treatment assignment, randomization .............................. 38 
6.3.1 
Participant numbering ........................................................................... 38 
6.3.2 
Treatment assignment, randomization .................................................. 38 
6.4 
Treatment blinding ................................................................................................. 39 


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6.5 
Dose escalation and dose modification .................................................................. 39 
6.5.1 
Dose modifications ................................................................................ 40 
6.5.2 
Dose interruptions ................................................................................. 40 
6.6 
Additional treatment guidance ............................................................................... 40 
6.6.1 
Treatment compliance ........................................................................... 40 
6.6.2 
Emergency breaking of assigned treatment code .................................. 40 
6.7 
Preparation and dispensation ................................................................................. 41 
6.7.1 
Handling of study treatment and additional treatment .......................... 41 
6.7.2 
Instruction for prescribing and taking study treatment ......................... 42 
7 
Informed consent procedures ............................................................................................ 44 
8 
Visit schedule and assessments ......................................................................................... 45 
8.1 
Screening ............................................................................................................... 53 
8.1.1 
Information to be collected on screening failures ................................. 54 
8.2 
Participant demographics/other baseline characteristics ....................................... 54 
8.3 
Efficacy .................................................................................................................. 54 
8.3.1 
American College of Rheumatology (ACR) response .......................... 55 
8.3.2 
DAS28 and EULAR response ............................................................... 57 
8.3.3 
Psoriatic Arthritis Disease Activity Score (PASDAS) .......................... 57 
 
 58 
 
 58 
 
 58 
 
 60 
8.3.8 
Appropriateness of efficacy assessments .............................................. 60 
8.4 
Safety ..................................................................................................................... 60 
8.4.1 
Laboratory evaluations .......................................................................... 62 
8.4.2 
Electrocardiogram (ECG) ..................................................................... 63 
8.4.3 
Pregnancy and assessments of fertility ................................................. 63 
8.4.4 
Other safety evaluations ........................................................................ 64 
8.4.5 
Appropriateness of safety measurements .............................................. 64 
8.5 
Additional assessments .......................................................................................... 65 
8.5.1 
Clinical Outcome Assessments (COAs) ............................................... 65 
9 
Study discontinuation and completion .............................................................................. 67 
9.1 
Discontinuation and completion ............................................................................ 67 
9.1.1 
Study treatment discontinuation and study discontinuation.................. 67 
9.1.2 
Withdrawal of informed consent ........................................................... 69 
9.1.3 
Lost to follow-up ................................................................................... 69 
9.1.4 
Early study termination by the sponsor ................................................. 69 
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9.2 
Study completion and post-study treatment .......................................................... 70 
10 Safety monitoring and reporting ........................................................................................ 70 
10.1 
Definition of adverse events and reporting requirements ...................................... 70 
10.1.1 
Adverse events ...................................................................................... 70 
10.1.2 
Serious adverse events .......................................................................... 72 
10.1.3 
SAE reporting........................................................................................ 73 
10.1.4 
Pregnancy reporting .............................................................................. 73 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 74 
10.2 
Additional Safety Monitoring ................................................................................ 75 
10.2.1 
Liver safety monitoring ......................................................................... 75 
10.2.2 
Renal safety monitoring ........................................................................ 76 
11 Data Collection and Database management ...................................................................... 76 
11.1 
Data collection ....................................................................................................... 76 
11.2 
Database management and quality control ............................................................ 76 
11.3 
Site monitoring ...................................................................................................... 77 
12 Data analysis and statistical methods ................................................................................ 78 
12.1 
Analysis sets .......................................................................................................... 78 
12.2 
Participant demographics and other baseline characteristics ................................. 79 
12.3 
Treatments ............................................................................................................. 80 
12.4 
Analysis of the primary endpoint(s)/estimand(s) .................................................. 80 
12.4.1 
Definition of primary endpoint(s)/estimand(s) ..................................... 81 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 81 
12.4.3 
Handling of missing values/censoring/discontinuations ....................... 81 
12.4.4 
Sensitivity analyses for primary endpoint/estimand ............................. 81 
12.4.5 
Supplementary analysis ......................................................................... 82 
12.5 
Analysis of secondary endpoints/estimands .......................................................... 82 
12.5.1 
Efficacy and/or Pharmacodynamic endpoint(s) .................................... 82 
12.5.2 
Safety endpoints .................................................................................... 83 
12.5.3 
Patient reported outcomes ..................................................................... 84 
 
 85 
12.7 
Interim analyses ..................................................................................................... 85 
12.8 
Sample size calculation .......................................................................................... 86 
12.8.1 
Primary endpoint(s) ............................................................................... 86 
13 Ethical considerations and administrative procedures ...................................................... 86 
13.1 
Regulatory and ethical compliance ........................................................................ 86 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 87 
13.3 
Publication of study protocol and results............................................................... 87 


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13.4 
Quality Control and Quality Assurance ................................................................. 87 
14 Protocol adherence ............................................................................................................ 87 
14.1 
Protocol amendments ............................................................................................. 88 
15 References ......................................................................................................................... 89 
16 Appendices ........................................................................................................................ 93 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs ......................... 93 
16.2 
Appendix 2: Liver event and laboratory trigger definitions & follow-up 
requirements .......................................................................................................... 95 
16.3 
Appendix 3: Specific Renal Alert Criteria and Actions and Event Follow-up ...... 98 
16.4 
Appendix 4: The classification criteria for psoriatic arthritis (CASPAR) ............. 98 
16.5 
Appendix 5: American College of Rheumatology (ACR) Measures and 
Criteria of Response .............................................................................................. 99 
16.6 
Appendix 6 Disease Activity Score (DAS) ......................................................... 100 
 
 101 
16.8 
Appendix 8: Guidelines for administering the questionnaires for patient 
reported outcomes ................................................................................................ 102 
16.9 
Appendix 9: Study management during potential future pandemic/epidemic 
(e.g. COVID-19) .................................................................................................. 104 
List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 20 
Table 4-1 
Rationale for study design ..................................................................... 24 
Table 6-1 
Investigational and control drug ............................................................ 32 
Table 6-2 
Prohibited medication ........................................................................... 35 
Table 6-3 
Dose and treatment schedule ( BSL to Week 12) ................................. 43 
Table 6-4 
Dose and treatment schedule (Group 1 & Group 2 participants- 
Week 16 to Week 48) ............................................................................ 43 
Table 8-1 
Assessment Schedule ............................................................................ 46 
 
 59 
 
 60 
Table 8-4 
General safety assessments ................................................................... 61 
Table 8-5 
Laboratory evaluations .......................................................................... 62 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 75 
Table 12-1 
Probability of Success with Different Observed Response Rates ......... 86 
Table 16-1 
Clinically notable laboratory values and vital signs ............................. 93 
Table 16-2 
Liver event and laboratory trigger definitions ...................................... 95 
Table 16-3 
Follow up requirements for liver events and laboratory triggers .......... 95 
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Table 16-4 
Specific Renal Alert Criteria and Actions and Event Follow -up ......... 98 
Table 16-5 
EULAR response criteria .................................................................... 100 
 
 101 
 
 102 
List of figures 
Figure 3-1 
Study design .......................................................................................... 24 
 


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List of abbreviations 
ACR 
American College of Rheumatology 
AE 
Adverse Event 
Alb 
Albumin 
ALP 
Alkaline Phosphatase 
ALT 
Alanine Aminotransferase 
ANA 
antinuclear antibody 
anti-CCP 
Anti-cyclic citrullinated peptide 
anti-dsDNA 
anti-double stranded DNA antibodies 
AS 
ankylosing spondylitis  
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Classification 
β-hCG 
Beta human chorionic gonadotropin 
BMI 
Body Mass Index 
BP 
Blood Pressure 
BSA 
Body Surface Area  
BSL 
Baseline 
BUN 
Blood Urea Nitrogen 
°C  
degree Celsius 
CASPAR 
Classification of Psoriatic Arthritis 
CD4 
Cluster of differentiation 4 
CD8 
Cluster of differentiation 8 
CFDA 
China Food and Drug Administration  
CFR 
Code of Federal Regulation 
CI 
confidence interval 
ClinRO 
Clinician Reported Outcomes 
CMO&PS  
Chief Medical Office and Patient Safety 
CO 
Country Organization 
COA 
Clinical Outcome Assessment 
COVID-19 
Coronavirus disease 2019 
COX-1 
cyclooxygenase-1 
COX-2 
cyclooxygenase-2 
CRA 
Clinical Research Associate 
CRF 
Case Report/Record Form (paper or electronic) 
CRP 
C-Reactive Protein 
csDMARDs 
Conventional Synthetic Disease-Modifying Antirheumatic Drugs 
CTLA4 Ig 
Cytotoxic T lymphocyte associated antigen-4 immunoglobulin fusion proteins  
DAS 
Disease Activity Score 
DAS28-CRP 
Disease Activity Score for 28 joints - C reactive protein 
DLT 
Dose Limiting Toxicity 
DMARDs 
Disease modifying antirheumatic drug(s) 
DNA 
Deoxyribonucleic Acid 
EC 
Ethics committee  
ECG 
Electrocardiogram 
eCOA 
Electronic Clinical Outcome Assessment 
eCRF 
electronic case report form 
EDC 
Electronic Data Capture 


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EDD 
Estimated date of delivery 
EMA 
European Medicines Agency 
EMEA 
European Medicines Evaluation Agency 
EOS 
End of study 
ESR 
erythrocyte sedimentation rate  
EU 
European Union 
EULAR 
European League Against Rheumatism 
°F 
degree Fahrenheit  
 
 
FAS 
Full analysis set 
FDA 
Food and Drug Administration 
FSH 
Follicle Stimulating Hormone 
GCP 
Good Clinical Practice 
GCS 
Global Clinical Supply 
GGT 
Gamma-glutamyl transferase 
h 
Hour 
HAQ-DI 
Health Assessment Questionnaire – Disability Index  
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B Virus 
HCV 
Hepatitis C Virus 
HDL 
high-density lipoprotein 
HIV 
Human immunodeficiency virus 
HRQoL 
Health-Related Quality of Life 
hs-CRP 
high-sensitivity C-reactive protein  
i.v. 
intravenous 
IB 
Investigator’s Brochure 
IBD 
Inflammatory bowel disease 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use 
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
 
  
IL-17 
Interleukin-17  
IN 
Investigator Notification 
INR 
International Normalized Ratio 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IUD 
 Intrauterine Device 
IUS 
intrauterine system 
LDH 
lactate dehydrogenase 
 
  
LDL 
low-density lipoprotein 
 
  
LFT 
Liver function test  
LN 
natural logarithm 
LOCF 
Last observation carried forward 
MAP 
Meta-Analytic-Predictive 


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MAR 
missing at random  
MCS 
mental component score 
MedDRA 
Medical dictionary for regulatory activities  
mg 
milligram(s) 
mL 
milliliter(s) 
MMRM 
mixed-effects model repeated measures  
MRI 
Magnetic resonance imaging 
MTX 
methotrexate  
NSAIDs 
Non-steroidal anti-inflammatory drugs  
PaGA 
Patient's Global Assessment of disease activity 
PASDAS 
Psoriatic Arthritis Disease Activity Score 
PASI 
Psoriasis Area and Severity Index  
PCS 
Physical component score 
PFS 
prefilled syringe 
PhGA 
Physician's global assessment of disease activity 
PK 
Pharmacokinetic(s) 
PMDA 
Pharmaceuticals and Medical Devices Agency 
PoC 
Proof of concept 
PPD 
purified protein derivative 
PRN 
pro re nata 
PRO 
Patient Reported Outcomes 
PsA 
Psoriatic arthritis 
PsO 
Psoriasis 
PSW 
Premature Study Withdrawal  
PT 
prothrombin time 
PUVA 
psoralen and ultraviolet A 
q1w 
every week 
q4w 
every 4 weeks  
QMS  
Quality Management System 
RA 
Rheumatoid arthritis 
RANKL 
Receptor activator of NF-kappaB ligand 
RBC 
red blood cell(s) 
RF 
Rheumatoid factor 
s.c. 
subcutaneous 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
sCR 
serum creatinine 
SD 
standard deviation 
SF36-PCS 
Short form health survey -physical component summary 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamic Pyruvic Transaminase 
SJC 
Swollen Joint Count 
SNP 
Single nucleotide polymorphism 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
t.i.d 
3 times a day 
TB 
Tuberculosis 
TBL 
total bilirubin 


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TCM 
Traditional Chinese medicine 
TD 
Study Treatment Discontinuation 
TFQ 
Trial feedback questionnaire 
TJC 
Tender Joint Count  
TNF-IR 
Tumor Necrosis Factor - Inadequate Response 
TNFα 
Tumor necrosis factor alpha  
TP1 
Treatment period 1 
ULN 
upper limit of normal 
US 
United States 
UV 
Ultraviolet 
UVA 
ultraviolet A  
UVB 
ultraviolet B 
VAS 
Visual Analog Scale 
WBC 
white blood cell(s) 
WHO 
World Health Organization  
WoC 
Withdrawal of Consent 
WoCBP 
Women of Childbearing Potential 


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Glossary of terms 
Additional 
treatment 
Medicinal products that may be used during the clinical trial as described in the protocol, 
but not as an investigational medicinal product (e.g. any background therapy) 
Assessment 
A procedure used to generate data required by the study 
Biologic Samples 
A biological specimen including, for example, blood (plasma, serum), saliva, tissue, urine, 
stool, etc. taken from a study participant  
Cohort 
A specific group of participants fulfilling certain criteria and generally treated at the same 
time 
Control drug 
A study drug (active or placebo) used as a comparator to reduce assessment bias, 
preserve blinding of investigational drug, assess internal study validity, and/or evaluate 
comparative effects of the investigational drug 
Dosage 
Dose of the study treatment given to the participant in a time unit (e.g. 100 mg once a 
day, 75 mg twice a day) 
Electronic Data 
Capture (EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical study data using 
data collection systems, such as Web-based applications, interactive voice response 
systems and clinical laboratory interfaces. EDC includes the use of Electronic Case 
Report Forms (eCRFs) which are used to capture data transcribed from paper source 
forms used at the point of care 
End of the clinical 
trial 
The end of the clinical trial is defined as the last visit of the last participant or at a later 
point in time as defined by the protocol  
Enrollment 
Point/time of participant entry into the study at which informed consent must be obtained  
EOS 
End of Study 
eSource (DDE) 
eSource Direct Data Entry (DDE) refers to the capture of clinical study data electronically, 
at the point of care. eSource Platform/Applications combines source documents and case 
report forms (eCRFs) into one application, allowing for the real time collection of clinical 
trial information to sponsors and other oversight authorities, as appropriate 
Estimand  
A precise description of the treatment effect reflecting the clinical question posed by the 
trial objective. It summarizes at a population-level what the outcomes would be in the 
same patients under different treatment conditions being compared. Attributes of an 
estimand include the population, variable (or endpoint) and treatment of interest, as well 
as the specification of how the remaining intercurrent events are addressed and a 
population-level summary for the variable. 
Intercurrent events 
Events occurring after treatment initiation that affect either the interpretation or the 
existence of the measurements associated with the clinical question of interest. 
Investigational 
drug/ treatment 
The drug whose properties are being tested in the study 
Medication 
number 
A unique identifier on the label of medication kits 
Mis-randomized 
participants 
Mis-randomized participants are those who were not qualified for randomization and who 
did not take study treatment, but have been inadvertently randomized into the study  
Other treatment 
Treatment that may be needed/allowed during the conduct of the study (i.e. concomitant 
or rescue therapy) 
Part  
A sub-division of a study used to evaluate specific objectives or contain different 
populations. For example, one study could contain a single dose part and a multiple dose 
part, or a part in participants with established disease and in those with newly-diagnosed 
disease 
Participant 
A trial participant (can be a healthy volunteer or a patient) 
Participant 
number 
A unique number assigned to each participant upon signing the informed consent. This 
number is the definitive, unique identifier for the participant and should be used to identify 
the participant throughout the study for all data collected, sample labels, etc. 
Period 
The subdivisions of the trial design (e.g. Screening, Treatment, Follow-up) which are 
described in the Protocol. Periods define the study phases and will be used in clinical trial 
database setup and eventually in analysis 
Perpetrator drug 
A drug which affects the pharmacokinetics of the other drug 


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Personal data 
Participant information collected by the Investigator that is coded and transferred to 
Novartis for the purpose of the clinical trial. This data includes participant identifier 
information, study information and biological samples. 
Premature 
participant 
withdrawal 
Point/time when the participant exits from the study prior to the planned completion of all 
study drug administration and/or assessments; at this time all study drug administration is 
discontinued and no further assessments are planned 
Randomization 
number 
A unique identifier assigned to each randomized participant 
Screen Failure 
A participant who did not meet one or more criteria that were required for participation in 
the study 
Source 
Data/Document 
Source data refers to the initial record, document, or primary location from where data 
comes. The data source can be a database, a dataset, a spreadsheet or even hard-
coded data, such as paper or eSource 
Start of the clinical 
trial 
The start of the clinical trial is defined as the signature of the informed consent by the first 
participant 
Study treatment 
Any drug or combination of drugs   or intervention administered to the study participants 
as part of the required study procedures; includes investigational drug(s), control(s) or 
background therapy 
Study treatment 
discontinuation 
When the participant permanently stops taking any of the study drug(s) prior to the 
defined study treatment completion date (if any) for any reason; may or may not also be 
the point/time of study discontinuation  
Treatment 
arm/group  
A treatment arm/group defines the dose and regimen or the combination, and may 
consist of 1 or more cohorts. 
Variable (or 
endpoint) 
The variable (or endpoint) to be obtained for each participant that is required to address 
the clinical question. The specification of the variable might include whether the 
participant experiences an intercurrent event. 
Withdrawal of 
consent (WoC) 
Withdrawal of consent from the study occurs only when a participant does not want to 
participate in the study any longer and does not allow any further collection of personal 
data   


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Protocol summary 
Protocol 
number 
CAIN457F2367 
Full Title 
A phase III randomized, double-blind, placebo controlled, multicenter, bridging study of 
subcutaneous secukinumab, to demonstrate efficacy after sixteen weeks of treatment and to 
assess safety, tolerability and long-term efficacy follow-up to one year in Chinese subjects 
with active psoriatic arthritis 
Brief title 
Study of efficacy and safety of secukinumab in Chinese subjects with active PsA compared 
to placebo  
Sponsor and 
Clinical Phase 
Novartis 
Phase III 
Investigation 
type 
Biological 
Study type 
Interventional 
Purpose and 
rationale 
The purpose of this bridging study is to assess the efficacy and safety of secukinumab 150 
mg subcutaneous (s.c.) in Chinese participants with active PsA compared to placebo to 
support registration in China. 
 
Primary 
Objective(s)  
To demonstrate the treatment effect of secukinumab 150 mg s.c. [every week (q1w) ×4, 
followed by dosing every 4 weeks (q4w)] in Chinese subjects with active PsA is consistent 
with global population by assessing American College of Rheumatology 20 (ACR20) 
response rates in participants treated with secukinumab 150 mg s.c. compared to placebo 
s.c. at Week 16. 
The clinical question of interest is: What is the effect of secukinumab 150 mg s.c. versus 
placebo on the composite endpoint ACR20 response at Week 16 and the completion of 16 
week-treatment in Chinese patients with active PsA?  
The justification for targeting this treatment effect is to estimate the effect of the study drug 
for the full duration when administered without dose changes. 
Secondary 
Objectives 
● To evaluate the efficacy of secukinumab 150 mg s.c. (q1w×4, followed by dosing q4w) at 
Week 16 compared with placebo by assessing the proportion of subjects achieving an 
ACR50 response. 
● To evaluate the efficacy of secukinumab 150 mg s.c. (q1w×4, followed by dosing q4w) at 
Week 16 compared with placebo by assessing the changes from BSL in Disease Activity 
Score for 28 joints (DAS28-CRP) . 
● To evaluate the efficacy of secukinumab 150 mg s.c. (q1w×4, followed by dosing q4w) at 
Week 16 compared with placebo by assessing change from BSL in Psoriatic Arthritis 
Disease Activity Score (PASDAS). 
● To evaluate the efficacy of secukinumab 150 mg s.c. (q1w×4, followed by dosing q4w) at 
Week 16 compared with placebo by assessing the changes from BSL in medical outcome 
short form health survey (SF36-PCS) . 
● To evaluate the efficacy of secukinumab 150 mg s.c. (q1w×4, followed by dosing q4w) at 
Week 16 compared with placebo by assessing the changes from BSL in Health Assessment 
Questionnaire - Disability Index (HAQ-DI©) . 
● To evaluate the overall safety and tolerability of secukinumab 150 mg s.c. (q1w×4, 
followed by dosing q4w). 
The clinical questions of interest are: What is the effect of secukinumab 150 mg s.c. relative 
to placebo on ACR50 response after 16 week-treatment in Chinese participants with active 
PsA? What is the effect of secukinumab 150 mg s.c. relative to placebo on change from BSL 
in DAS28-CRP, PASDAS, SF36 PCS and HAQ-DI after 16 week-treatment in Chinese 
participants with active PsA? 
Study design 
Study CAIN457F2367 is a randomized, double-blind, placebo-controlled, parallel-group 
design. A screening period running up to 10 weeks before randomization will be used to 
assess participant eligibility followed by 52 weeks of treatment. 


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Key Inclusion 
criteria 
● Chinese male or non-pregnant, non-lactating Chinese female participants at least 18 years 
of age 
● Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months 
with moderate to severe PsA who must have at BSL ≥3 tender joints out of 78 and ≥3 
swollen joints out of 76 (dactylitis of a digit counts as one joint each) 
● Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies negative 
at screening 
● Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or a 
documented history of plaque psoriasis 
● Participants with PsA should have taken NSAIDs for at least 4 weeks prior to 
randomization with inadequate control of symptoms or at least one dose if stopped due to 
intolerance to Non-steroidal anti-inflammatory drugs (NSAIDs) 
● Participants taking methotrexate (MTX) (≤ 25 mg/week) are allowed to continue their 
medication if the dose is stable for at least 4 weeks before randomization and should remain 
on a stable dose up to Week 16 
● Participants who have been on a Tumor necrosis factor alpha (TNFα) inhibitor must have 
experienced an inadequate response to previous or current treatment with a TNFα inhibitor 
given at a dose in clinical use for at least 3 months or have stopped treatment due to 
safety/tolerability problems after at least one administration of a TNFα inhibitor. 
Key Exclusion 
criteria 
● Chest X-ray or chest (magnetic resonance imaging) MRI with evidence of ongoing 
infectious or malignant process, obtained within 3 months prior to screening and evaluated 
by a qualified physician 
● Participants taking high potency opioid analgesics (e.g., methadone, hydromorphone, 
morphine) 
● Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 
receptor 
● 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 is longer 
● Any intramuscular or intravenous corticosteroid treatment within 4 weeks before 
randomization 
● Any therapy by intra-articular injections (e.g., corticosteroid) within 4 weeks before 
randomization 
● Participants who have previously been treated with more than 3 different TNF-α inhibitors 
(investigational or approved). 
Study treatment 
Participants fulfilling the inclusion criteria will be randomized to one of the following two 
groups in a 1:1 ratio, with 20 participants in each of the two groups as depicted below: 
● Group 1 : Secukinumab 150 mg s.c. at BSL, Week 1, 2, 3, 4, 8, and 12 
● Group 2 : Secukinumab Placebo s.c. at BSL, Week 1, 2, 3, 4, 8, and 12 
At Week 16, the participants in Group 1 and Group 2 will be re-randomized in 1:1 ratio 
separately: 
● Group 1 will be re-randomized in 1:1 ratio to: 
Secukinumab 150 mg s.c. regimen (1.0 mL prefilled syringe (PFS) of 150 mg dose + 1.0 mL 
PFS of placebo) OR secukinumab 
 s.c. regimen (
 
dose) every 4 weeks from Week 16 to Week 48. 
● Group 2 will be re-randomized in 1:1 ratio to: 
Secukinumab 150 mg s.c. regimen (1.0 mL PFS of 150 mg dose + 1.0 mL PFS of placebo) 
OR secukinumab 
 s.c. regimen (
) every 4 weeks 
from Week 16 to Week 48. 


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Efficacy 
assessments 
1. American College of Rheumatology (ACR) 20, 50 
 responses 
 
ƔSwollen Joint Count (SJC)/Tender Joint Count (TJC) 
 
ƔPatient's global assessment of disease activity [(Visual Analog Scale(VAS)] 
 
ƔPhysician's global assessment of disease activity (VAS) 
 
ƔPatient's assessment of PsA pain intensity (VAS) 
 
ƔHealth Assessment Questionnaire – Disability Index (HAQ-DI©) 
 
ƔHigh sensitivity C-Reactive Protein (hs-CRP) and Erythrocyte Sedimentation Rate 
(ESR) 
2. Disease Activity Score (DAS28) and European League Against Rheumatism (EULAR) 
response criteria 
3. PASDAS 
Key safety 
assessments 
Adverse event monitoring, Physical examination, Vital signs, Height and weight, 
QuantiFERON TB-Gold test or purified protein derivative (PPD) skin test, Electrocardiogram 
(ECG), Local tolerability (Injection site reactions), Laboratory evaluations (Hematology, 
Clinical Chemistry, Lipid Panel, Urinalysis), Pregnancy and assessment of fertility, 
Tolerability of secukinumab 
Other 
assessments  
Clinician Reported Outcomes (ClinRO) 
ƔSwollen Joint Count (SJC)/Tender Joint Count (TJC) 
ƔPhysician's global assessment of disease activity (PhGA, VAS) 
Patient reported 
outcomes (PRO) 
ƔMedical Outcome Short Form Health Survey (SF-36 v2) version 2 (Acute form) 
ƔHAQ-DI©  
ƔPatient's Global Assessment of Disease Activity 
ƔPatient’s assessment of PsA Pain 
PPD
PPD
PPD


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Data analysis 
The primary analysis of ACR20 at Week 16 in the Full analysis set (FAS) will be evaluated 
using a logistic regression with treatment as a factor and weight as a covariate. Difference in 
response proportions between secukinumab regimen and placebo regimen and the 
corresponding 95% confidence interval (CI) will be computed utilizing the logistic regression 
model fitted. 
The primary efficacy variable will be ACR20 response at Week 16. The analysis of the 
primary efficacy variable will be based on the FAS . Primarily, CRP will be used instead of 
ESR to calculate ACR response; ESR will only be used in the event CRP is missing. 
Sensitivity analysis will be conducted in order to provide evidence that the results seen from 
the primary analysis are robust. These analyses will center on the deviations in model 
assumptions and the treatment of missing data. 
In order to determine the robustness of the logistic regression model used for the primary 
analysis, ACR20 response in active PsA participants at Week 16 will also be evaluated 
using a non-parametric regression model with the same independent variables as the 
logistic regression model. 
 
 
 
The impact of missing data on the analysis results of ACR20 in active PsA participants will 
be assessed as well by repeating the logistic regression model using different ways to 
handle missing data. This may include, but are not limited to: 
● Multiple imputation 
● Observed data analysis 
The secondary efficacy variables are described below. Secondary efficacy variables will be 
analyzed using the FAS population. Handling of missing data for secondary variables will be 
the same as for the primary variable. 
Safety analysis will include summaries of Adverse Events (AEs), laboratory measurement, 
ECG , and vital signs 
Full details of data analysis will be specified in statistical analysis plan 
Key words 
Psoriatic Arthritis, PsA, subcutaneous, secukinumab in prefilled syringe, Secukinumab, 
AIN457 


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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 spondylarthritis (SpA). While the various SpA 
may be diverse in their clinical presentations, common environmental, immunologic as well as 
genetic factors associated with susceptibility to SpA are suspected Turkiewicz et al (2007). This 
latter notion was corroborated by findings in a large-scale single nucleotide polymorphism 
(SNP) scan study, where IL-23R variants that were previously linked to Crohn`s disease and 
psoriasis (diseases that may both co-exist with spondylarthritides) 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. The prevalence of PsA 
varies from 1 to 420 per 100,000 across the world, with estimates of 20-420 per 100,000 in 
Europe and North America, 1 per 100,000 in Japan and 20 per 100,000 in China Li R et al 2012. 
However, the low prevalence of PsA in China may be due to underdiagnosis as suggested in a 
study Yang Q et al 2011. 
Psoriatic arthritis is a chronic inflammatory musculoskeletal disease that has 5 disease domains: 
peripheral arthritis, axial disease, dactylitis, enthesitis, and skin and nail disease 
Ritchlin et al 2009. About 6-48% of patients with psoriasis suffer from PsA. It is not only more 
common but also more severe than previously thought Gladman 2004, Taylor et al 2006. 
Median follow up of 2 years of diagnosis, radiological erosions were developed in 47% of the 
participants Kane D et al 2003. Without proper monitoring and treatment, it will lead to 
significant structural damage and loss of physical function, and even arthritis mutilans, which 
is the most severe destructive form of PsA Acosta et al 2015. PsA is associated with significant 
morbidity and disability, and thus constitutes a major socioeconomic burden. Typically 
conventional synthetic diseases modifying antirheumatic drugs (DMARDs) are used for PsA 
including methotrexate (MTX), sulfasalazine, cyclosporine, and leflunomide, however, these 
are often inadequate because they only partially control established disease Mease et al 2008. 
Several lines of evidence support the notion of prominent T cell involvement in the pathogenesis 
of PsA. Memory cluster of differentiation 4 (CD4+) and cluster of differentiation 8 (CD8+) 
cells are present in skin lesions as well as the inflamed synovium that express activation markers 
and have characteristics of oligoclonal expansion. Curran et al 2004; Tassiulas et al 1999 
Clinical trials demonstrated efficacy of T cell targeted therapy in PsA (cyclosporine A, CTLA4 
Ig, alefacept). TNF blocking therapy was successfully introduced to the treatment of 
participants with PsA Mease et al 2000. Despite these efforts, an unmet clinical need exists for 
participants with PsA for better disease control and long term prevention of structural damage 
beyond mere abrogation of inflammatory processes. 
IL-17 antagonism represents a novel therapeutic approach aimed at interference with the 
chronic inflammatory process by selectively targeting the predominant proinflammatory 
cytokine of the helper Th17 cell subset. Additional effects of anti-IL-17 on bone homoeostasis 
via 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 disturbed homeostasis of osteoclastogenic and 


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osteoblastogenic mechanisms characteristic of PsA might be affected by IL-17 blockade, thus, 
potentially providing a therapeutic advancement to prevent structural damage 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 
which is thought to be an important mediator of autoimmunity. Neutralization of IL-17A has 
strong pre-clinical and clinical target validation and documentation of efficacy in a proof-of-
concept study conducted in participants with PsA (CAIN457A2206) suggesting a clinically 
meaningful response for signs and symptoms up to Week 16. The safety and efficacy of 
secukinumab were further assessed in three randomized, double-blind, placebo-controlled 
phase III studies in participants with active psoriatic arthritis (≥3 swollen and ≥3 tender joints) 
despite non-steroidal anti-inflammatory drug (NSAID), corticosteroids or disease-modifying 
anti-rheumatic drug (DMARD) therapy 
The phase III studies CAIN457F2306 and CAIN457F2312 in PsA (McInnes 2013, 
Baeten 2013, Kavanaugh 2017, Strand 2017), CAIN457F2305 and CAIN457F2310 in AS 
(Baeten 2015, Deodhar 2016, Baraliakos 2017, Braun 2017, Marzo-Ortega 2017) and 
CAIN457H2315 in nr-axSpA (manuscript in review) demonstrated significant improvement 
with inhibition of IL-17A through secukinumab in measures of disease signs and symptoms, 
physical function, quality of life and objective markers of inflammation, thus confirming the 
pivotal role of IL-17A in both PsA and axSpA. 
In a Phase III study (CAIN457F2306; N=606) employing an intravenous (i.v.) loading regimen 
with 10mg/kg i.v at Wk 0, 2, and 4, then 75 mg s.c. q4wk or 10 mg/kg i.v. at Wk 0, 2, and 4, 
then 150 mg s.c. q4wk, the efficacy of secukinumab in PsA participants is supported by positive 
results for signs and symptoms (i.e. ACR20/50, PASI75/90), resolution of dactilytis, enthesitis 
and inhibition of radiologic damage at Week 24  
Another Phase III study (CAIN457F2312; N=397) employing a prefilled syringe (PFS) with 75 
mg s.c./wk x 4 (75 mg loading regimen) then dosing q4wk, 150 mg s.c./ wk x 4 (150 mg loading 
regimen) then dosing q4wk, or 300 mg s.c./wk x 4 (300 mg loading regimen) then dosing q4wk. 
Secukinumab demonstrated positive efficacy results superior to placebo in participants 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% 
participants who were inadequate responders to a TNF-α inhibitor.  
In the third Phase III study (CAIN457F2342; N=996), employing a PFS with  150 mg s.c./q4w 
(150 mg no loading regimen), 150 mg s.c./wk x 4 (150 mg loading regimen) then dosing q4wk 
and 300 mg s.c./wk x 4 (300 mg loading regimen) then dosing q4wk. The secukinumab 
demonstrated a rapid onset of efficacy and were superior to placebo in the treatment of 
participants with PsA through all components of the disease including the arthritic and skin 
measure of signs and symptoms, radiographic endpoint and physical function in the overall 
population as well as in TNF-naïve participants and TNF-IR participants. Therefore, treatment 
with secukinumab can also reduce erosion of bone in PsA and can result in improvement of 
symptoms and functional joint manifestations in afflicted participants. 
A total of 200 Asian patients from global pivotal studies (CAIN457F2306, CAIN457F2312, 
CAIN457F2318, CAIN457F2336, and CAIN457F2342) were included in a combined analysis. 


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Consistency of efficacy results was seen between Asian population and the overall PsA 
population. Both the 300 mg and 150 mg were efficacious in the Asian population. 
As of 25 Jun 2020, over 26,000 participants have been enrolled in studies with secukinumab 
with over 22,000 having received active drug at doses ranging from single and/or multiple doses 
of 0.1 mg/kg to 30 mg/kg i.v. and 25 mg to 300 mg s.c. Full safety results from all PsA, AS and 
psoriasis completed studies show that secukinumab generally is safe and well tolerated. Please 
refer to the Investigator Brochure (IB) for a more detailed review of the pre-clinical and clinical 
information on secukinumab. From the above combined analysis, the overall pattern of adverse 
events in the Asian patient was generally consistent with the overall PsA population , with no 
distinguishable trends or dose dependence for any particular types of AEs. Besides, a psoriasis 
phase 3 study (CAIN457A2318) and an AS phase 3 study (CAIN457F2308) have confirmed 
that use of secukinumab up to 1 year was safe and well-tolerated in Chinese patients with 
psoriasis with potential PsA comorbidities (n=441) or AS (n=327). Secukinumab is approved 
for the treatment of psoriasis and AS in China. All these favorable risk and benefit profile of 
secukinumab supports the clinical development for the treatment of PsA patients with 
secukinumab in China. 
Secukinumab has been approved by Food and Drug Administration (FDA), European 
Medicines Agency (EMA) and Pharmaceuticals and Medical Devices Agency (PMDA) for the 
treatment of active PsA in adults. Secukinumab is one of the best options to control all domains 
of PsA and prevent radiographic progression. Unfortunately, the main treatment of PsA in 
China largely relies on NSAIDs and csDMARDs (conventional synthetic DMARDs) that have 
unsatisfied efficacy and safety concerns, with no biologics approved up to now. Thus there 
remains huge unmet medical needs in PsA for targeting of new mechanisms that can provide 
the clinical benefit on all clinical domains of PsA and good safety profile in Chinese 
population . 
1.2 
Purpose 
The purpose of this bridging study is to assess the efficacy and safety of secukinumab 150 mg 
s.c. in Chinese participants with active PsA compared to placebo to support registration in 
China. The clinical data in this study will be used for the extrapolation between Chinese 
population and global population by demonstrating that the treatment difference in ACR20 
response rates between Secukinumab 150mg s.c. and placebo in Chinese participants at Week 
16 is consistent with that observed in global studies. 


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2 
Objectives and endpoints 
Table 2-1 
Objectives and related endpoints 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
● To demonstrate the treatment effect of 
secukinumab 150 mg s.c. (q1w×4, followed 
by dosing q4w) in Chinese subjects with 
active PsA is consistent with global 
population by assessing American College of 
Rheumatology 20 (ACR20) response  rates in 
participants treated with secukinumab 150 
mg s.c. compared to placebo s.c. at Week 16. 
● ACR20 response at Week 16. 
A patient will be considered as improved according to the 
ACR20 criteria if he/she has at least 20% improvement in the 
three following measures: 
 
● Tender joint count; 
 
● Swollen joint count; 
 
● and at least 3 of the following 5 domains: 
 
 
a. Patient's assessment of PsA pain 
 
 
b. Patient's global assessment of disease activity 
 
 
c. Physician's global assessment of disease activity 
 
 
d. Health Assessment Questionnaire – Disability 
Index (HAQ-DI©) score 
 
 
e.  Acute phase reactant (hsCRP or ESR) 
Secondary objective(s) 
Endpoint(s) for secondary objective(s) 
● To evaluate the efficacy of secukinumab 
150 mg s.c. (q1w×4, followed by dosing q4w) 
at Week 16 compared with placebo by 
assessing the proportion of subjects 
achieving an ACR50 response. 
● ACR50 response rate at Week 16. 
● To evaluate the efficacy of secukinumab 
150 mg s.c. (q1w×4, followed by dosing q4w) 
at Week 16 compared with placebo by 
assessing the changes from BSL in Disease 
Activity Score for 28 joints - C reactive protein 
(DAS28-CRP) . 
● Change from BSL in DAS28-CRP at Week 16. 
● To evaluate the efficacy of secukinumab 
150 mg s.c. (q1w×4, followed by dosing q4w) 
at Week 16 compared with placebo by 
assessing change from BSL in PASDAS 
● Change from BSL in PASDAS at Week 16. 
● To evaluate the efficacy of secukinumab 
150 mg s.c. (q1w×4, followed by dosing q4w) 
at Week 16 compared with placebo by 
assessing the changes from BSL in medical 
outcome short form health survey - physical 
component summary(SF36-PCS). 
● Change from BSL in SF36-PCS at Week 16. 
● To evaluate the efficacy of secukinumab 
150 mg s.c. (q1w×4, followed by dosing q4w) 
at Week 16 compared with placebo by 
assessing the changes from BSL in Health 
Assessment Questionnaire - Disability Index 
(HAQ-DI©) . 
● Change from BSL in HAQ-DI© at Week 16. 
● To evaluate the overall safety and 
tolerability of secukinumab 150 mg s.c. 
(q1w×4, followed by dosing q4w). 
● Physical examination, vital signs, laboratory values, 
AEs/SAEs. 


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2.1 
Primary estimands 
The clinical question of interest is: What is the effect of secukinumab 150 mg s.c. versus placebo 
on the composite endpoint ACR20 response at Week 16 and the completion of 16 week-
treatment in Chinese patients with active PsA?  


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The justification for targeting this treatment effect is that we wish to estimate the effect of the 
study drug for the full duration when administered without dose changes. 
The primary estimand is described by the following attributes: 
a. Population: defined through appropriate inclusion/exclusion criteria to reflect the targeted 
PsA population 
b. Variable: composite of remaining on the study and on randomized treatment through 16 
weeks and achieving ACR20 response at 16 weeks 
c. Intercurrent event: the intercurrent event of discontinuation from treatment or study prior 
to Week 16 has been addressed via the composite variable definition 
d. Population-level summary: difference in proportions of responders between secukinumab 
and placebo groups 
2.2 
Secondary estimands 
The clinical questions of interest are: 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the composite endpoint 
ACR50 response at week 16 and the completion of 16 week-treatment in Chinese patients 
with active PsA? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on change from BSL in 
DAS28-CRP at week 16 in Chinese patients with active PsA had patients completed 16 
week-treatment? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on change from BSL in 
PASDAS at week 16 in Chinese patients with active PsA had patients completed 16 week-
treatment 
• What is the effect of secukinumab 150 mg s.c. versus placebo on change from BSL in SF-
36 PCS at week 16 in Chinese patients with active PsA had patients completed 16 week-
treatment? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on change from BSL in 
HAQ-DI at week 16 in Chinese patients with active PsA had patients completed 16 week-
treatment? 
The justification for targeting the treatment effect is that we wish to estimate the effect of the 
study drug for the full duration when administered without dose changes. 
The estimand definition of all secondary objectives related to response (e.g., ACR50, etc.) will 
have the same attributes as that for the primary estimand, except for the variable of interest. 
Estimand definition for the secondary continuous variables (e.g., HAQ-DI©, etc.) is the 
following: 
a. Population: defined through appropriate inclusion/exclusion criteria to reflect the targeted 
PsA population 
b. Variable: change from BSL in the variable of interest 
c. Intercurrent event: discontinuation from treatment or study prior to Week 16 
d. Population-level summary: difference in variable means between secukinumab and 
placebo groups 


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3 
Study design 
This bridging study uses a randomized, double-blind, placebo-controlled, parallel-group design. 
A screening period running up to 10 weeks before randomization will be used to assess 
participant eligibility followed by 52 weeks of treatment. 
At BSL, approximately 40 Chinese participants whose eligibility is confirmed will be 
randomized to one of two treatment groups in 1:1 ratio: 
• Group 1 - secukinumab 150mg s.c. : 
Secukinumab 150 mg (1.0 mL PFS of 150 mg dose) administered at BSL, Weeks 1, 2, and 3 
followed by dosing every four weeks starting at Week 4. 
• Group 2 - placebo s.c. 
Placebo (1.0 mL PFS) administered at BSL, Weeks 1, 2 and 3, followed by dosing every four 
weeks starting at Week 4. 
At Week 16, the participants in Group 1 and Group 2 will be re-randomized in a blinded manner 
in 1:1 ratio separately: 
• The participants in Group 1 will be re-randomized in 1:1 ratio to secukinumab 150 mg s.c. 
q4w regimen (1.0 mL PFS of 150 mg dose + 1.0 mL PFS of placebo) 
 
 
• The participants in Group 2 will be re-randomized in 1:1 ratio to secukinumab 150 mg s.c. 
q4w regimen (1.0 mL PFS of 150mg dose + 1.0 mL PFS of placebo) or
 
 
A primary endpoint analysis will be conducted after all participants complete Week 16 visit. 
Rescue medication will not be allowed before the completion of Week 16 assessments 
(Section 6.2.3). Although no participant will be restricted from receiving necessary rescue 
medications for lack of benefit or worsening of disease, if rescue with prohibited biologics (as 
described in Section 6.2.2) occurs prior to completion of Week 16 assessments, participants 
will be discontinued from the study treatment and will enter into the follow-up period after an 
End of Study visit. Safety and efficacy will be assessed in detail at every study visit, and 
participants who are deemed not to be benefiting from the study treatment based upon safety 
and efficacy assessments by the investigator, or for any reason of their own accord, are free to 
discontinue participation in the study at any time. 
A follow-up visit will be done 12 weeks after last study treatment administration for all 
participants, regardless of whether they complete the entire study as planned or discontinue 
prematurely. 
The total combined duration of treatment for this Phase III study is 52 weeks.  


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Figure 3-1 
Study design 
 
4 
Rationale 
4.1 
Rationale for study design 
Table 4-1 
Rationale for study design 
Study Design Aspect 
Rationale 
Overall (double-blind, randomized, 
parallel-group, placebo-controlled) 
The double-blind, randomized, parallel-group, placebo-controlled design 
used in this study up to Week 16 is in alignment with Phase III trials of 
other biologics in this disease area and in compliance with the European 
Medicines (Evaluation) Agency (EMA/EMEA) guidelines (EMA 2006) 
and China Food and Drug Administration (CFDA) requirement in use of 
biologics drug.  
The design in this study up to Week 16 is similar with global PsA Phase 
III trials, to enable the evaluation of treatment effect of secukinumab 150 
mg s.c. regimen compared to placebo in Chinese population.  
Randomization (strata, allocation 
ratio) 
At BSL, all eligible participants will be randomized via Interacive 
Response Technology (IRT) in a 1:1 ratio to one of the treatment arms. 
At Week 16,all participants will be re-randomized in a 1:1 ratio to 
secukinumab 150 mg s.c. 
 to enable to assess long-
term efficacy and safety of secukinumab 150 mg s.c. regimen
 
  
Blinding 
Double-blinding is used in this study to minimize bias in the evaluation of 
safety and efficacy assessment. Blinding is maintained beyond the 
primary endpoint, to ensure reliable efficacy and safety measures over 
time.  
Duration of study periods 
Primary endpoint of the trial is assessed at Week 16, allowing for 
comparisons of efficacy at a point in time which is same as global PsA 
Phase III trials. 
The treatment duration in the placebo group is kept a minimum. The 
participants in placebo arm will start receiving active treatment at Week 
16. 
The total study duration, including 52 weeks of treatment plus the follow-
up period, will allow for the assessment of long term safety and efficacy. 


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4.2 
Rationale for dose/regimen 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 III trials (CAIN457F2312, 
CAIN457F2342) 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 ACR 20 response at Week 6 in 62% of the TNF-naïve 
subjects on secukinumab vs. 20% on placebo, and was well-tolerated . 
A phase III study CAIN457F2312 assessed the efficacy of 75 mg, 150 mg and 300 mg s.c. at 
BSL, Weeks 1, 2, 3, then q4w starting at Week 4 , and CAIN457F2342 assessed the efficacy of 
150 mg q4w s.c. starting at BSL, and 150 mg, 300 mg s.c. at BSL, Week 1, 2, 3 , then q4w 
starting at Week 4. The primary endpoint ACR 20 was assessed at Week 24 (study 
CAIN457F2312) or Week 16 (study CAIN457F2342). Given the similarity of the ACR 20 
response seen at the Week 24/Week 16 primary endpoint for the 150 mg dose in each of these 
studies, 150 mg dose is a sufficient dose to provide clinically and statistically significant 
efficacy.  
Refer current Secukinumab (AIN457) Investigator's Brochure (IB) for details. 
The loading regimen is supported by model-based analyses using data from psoriasis studies, 
predicting significantly improved PASI75 response rate after 12 weeks of treatment, compared 
to the response rates with initial monthly dosing. A loading regimen with four weekly doses of 
either 150 mg s.c. is expected to sustain rapid onset and greater magnitude of the effect of 
secukinumab on PASI75 and PASI90 in participants with PsA and psoriasis.  
Selecting secukinumab 150 mg dose in this study (CAIN457F2367) enables to evaluate the 
efficacy and safety of 150 mg in Chinese population and allow the extrapolation of clinical data 
between Chinese population and global overall population. 
In Study CAIN457F2312 and CAIN457F2342, PASI75 and PASI90 response was assessed in 
the subgroup of participants who had ≥ 3% skin involvement with psoriasis at BSL. For both 
PASI75 and PASI90 response rates, the difference to placebo was statistically significant for 
the secukinumab 150 mg and 300 mg doses. The percentage of PASI 75/90 responders 
increased as secukinumab dose increased, with the secukinumab 300 mg dose demonstrating a 
meaningful improvement over the secukinumab 150 mg dose. 
 
 
 
  
Refer current Secukinumab (AIN457) Investigator's Brochure (IB) for details. 
Of note, the 75 mg s.c. loading/s.c. maintenance regimen tested in CAIN457F2312 achieved a 
statistically significant but clinically lower effect size in ACR 20 response of 29.3% and did 
not achieve statistically significant improvements in any of the efficacy endpoints tested in a 
pre-defined testing hierarchy, including PASI75, PASI90 DAS28 CRP, SF36 PCS, HAQ-DI©, 
ACR 50, dactylitis and enthesitis. 
The maintenance regimens with secukinumab 150 mg in this study aims at ensuringsustainable 
improvement for PsA signs and symptoms and enabling evaluation of long-term efficacy and 
safety. . 


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The selected doses are expected to be safe and well tolerated as the positive safety profile has 
been demonstrated across all approved indications (including safety data from PsO Phase III 
study and AS Phase III study in China).  
Formulation to be used 
This study (CAIN457F2367) will use secukinumab liquid in PFSs. Secukinumab at 150 mg 
s.c. administered in PFSs has been substantiated in China-central study CAIN457A2308 in the 
indication of PsO and in global PsA study CAIN457F2312, CAIN457F2336, and 
CAIN457F2342 in the indication of PsA. 
4.3 
Rationale for choice of control drugs (comparator/placebo) 
A placebo group is included in this study up to the Week 16. Due to the nature of the disease 
and the primary outcome measure used (ACR20 response), a placebo group is necessary to 
obtain reliable efficacy measurements for comparison between the active treatment groups and 
placebo in a controlled fashion. It is necessary to maintain placebo up to Week 16 to evaluate 
secukinumab treatment effect at Week 16. The continuation of the placebo group up to Week 
16 can be supported from an ethical standpoint. Firstly, treatment duration of the placebo group 
is kept to a minimum and the participants in placebo group will start receiving active treatment 
at the end of Week 16. Secondly, the regular assessments of disease activity ensures that 
participants experiencing worsening of their 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. In addition, 
the inclusion of a placebo group is in accordance with health authority guidelines, including 
FDA 1999/EMA 2006, and the parallel-group, placebo controlled design is in alignment with 
phase III trials of other biologics in this therapeutic domain as outlined in EMA guidelines 
EMA 2006. 
4.4 
Purpose and timing of primary endpoint analysis/design 
adaptations 
The primary endpoint analysis will be performed after all participants have completed Week16 
visit (or discontinued earlier) to support health authority review on the new indication of PsA 
registration in China. The final analysis will be conducted after all participants have completed 
Week F60 visit. Additional analyses may be performed to support interactions with health 
authorities, as necessary. 
Novartis Clinical Team will be unblinded after week 16 database lock to placebo versus 
secukinumab (Treatment Period 1), but will remain blinded on re-randomization (Treatment 
Period 2) until final database lock. 
All investigators, site personnel, participants, and monitors will remain blinded to all treatments 
during the whole duration of study, until the Week F60 database lock has occurred. 
4.5 
Risks and benefits 
The risks and benefits of secukinumab in psoriatic arthritis are based from the following 
completed studies: 
Data from analyses of 2 pivotal phase III trials (CAIN457F2306 and CAIN457F2312) 
demonstrated s.c. secukinumab 150 mg s.c. weekly dose regimen for the first month, followed 


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by 150 mg monthly dose regimen significantly improved participant clinical signs and 
symptoms of arthritis and psoriasis, their quality of life including physical function and 
demonstrated radiographic evidence of delayed progression of joint damage. The participants 
with a history of an inadequate response for their arthritis to a TNFα-inhibitor and/or with 
moderate to severe PsO achieved the highest levels of clinical response with the 300 mg s.c. 
dose regimen. Secukinumab 150 mg and 300 mg demonstrated sustained efficacy in the 
treatment of participants with PsA throughout the 5-year treatment period for the disease 
domains including the arthritic, skin measures signs and symptoms, physical function, and 
quality of life measures. The safety profile of secukinumab 150 mg, and 300 mg showed no 
new or unexpected safety signals in PsA participants over a treatment period of up to 5 years. 
Data from the CAIN457F2318 phase III trial with both secukinumab 150 mg and 300 mg s.c. 
doses demonstrated efficacy. For both secukinumab treatment groups, the responses achieved 
at Week 24 for the primary and secondary endpoints at the end of the placebo-controlled phase 
were generally maintained through Week 104. Study CAIN457F2336, a phase III trial, 
demonstrated that secukinumab s.c. 150 mg administered as a load or no load regimen had a 
rapid onset of efficacy and was superior to placebo in the treatment of participants with PsA 
through all components of the disease including the arthritic, skin signs and symptoms, and 
physical function measures. The safety profile of secukinumab 150 mg load and no load dose 
regimens up to Week 104 showed no new or unexpected safety signals. 
CAIN457F2342, a phase III trial of s.c. secukinumab (150 mg with and without load and 300 
mg) demonstrated that clinical responses reported at Week 16 were sustained through Week 
104. Radiographic progression that was significantly inhibited at Week 24 in the overall 
population with all three secukinumab regimens vs. placebo was sustained up to Week 104. . 
There are no new or unexpected safety findings up to Week 104. 
CAIN457F2366, a randomized, double-blind, active comparator phase IIIb trial in participants 
with active PsA naïve to biologic therapy for PsA or PsO, demonstrated that s.c. secukinumab 
300 mg was associated with a higher treatment retention rate than s.c. adalimumab 40 mg and 
provided numerically higher clinical responses across musculoskeletal, skin endpoints, and 
composite indices at Week 52, despite narrowly missing statistical significance for superiority 
versus adalimumab in the primary endpoint of ACR20 response at Week 52. The safety profile 
of secukinumab showed no new or unexpected safety signals. 
A combined analysis including a total of 200 Asian from global PsA Phase 3 studies, 
demonstrated higher ACR response rates at week 16 for both doses 150 mg and 300 mg 
compared to placebo. This was observed for all ACR response levels with p-values <0.05. And 
the safety results in Asian were consistent with gobal PsA pool and no dose dependence were 
noted for any particular type of SAEs in Asian subgroup.  
CAIN457A2318, a randomized, double-blind, placebo controlled, multicenter study of 
subcutaneous secukinumab, to demonstrate efficacy after twelve weeks of treatment and to 
assess safety, tolerability and long-term efficacy up to one year in subjects with moderate to 
severe chronic plaque-type psoriasis with or without psoriatic arthritis comorbidity, was 
conducted in mostly (441/543) Chinese patients, with 24 of these patients having active PsA at 
BSL. Similar trends of efficacy in Chinese patients with PsA treated by secukinumab 150mg 
and 300mg were observed as compared to the overall PsA patients studied in the global 
development program. The safety results observed in the 441 Chinese subjects was consistent 


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with the known safety profile of secukinumab in other pupulations and showed no new or 
unexpected safety signals. 
Based on the currently available data, secukinumab 150 mg and 300 mg offers a favorable 
benefit risk profile for participants for the treatment of PsA. Refer current Secukinumab 
(AIN457) Investigator's Brochure (IB) for details. 
5 
Study Population 
The study population will be comprised of the participants who have passed screening 
assessments and comply with eligibility criteria. 
Participants can be re-screened only once and no re-screening study related procedures should 
be performed prior to written re-consent by the participant. Mis-randomized participants will 
not be re-screened. 
This is a China stand-alone study and it is expected that approximately 40 Chinese participants 
will be randomized. 
Enrollment will stop as soon as the target number of randomized participants is reached. 
5.1 
Inclusion criteria 
Participants eligible for inclusion in this study must meet all of the following criteria: 
1. Signed informed consent must be obtained prior to participation in the study. 
2. Participant 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. 
3. Chinese male or non-pregnant, non-lactating Chinese female participants at least 18 years 
of age. 
4. Diagnosis of PsA classified by CASPAR criteria and with symptoms for at least 6 months 
with moderate to severe PsA who must have at BSL ≥3 tender joints out of 78 and ≥3 
swollen joints out of 76 (dactylitis of a digit counts as one joint each). 
5. Rheumatoid factor (RF) and anti-CCP antibodies negative at screening. 
6. Diagnosis of active plaque psoriasis or nail changes consistent with psoriasis or a 
documented history of plaque psoriasis. 
7. Participants with PsA should have taken NSAIDs for at least 4 weeks prior to 
randomization with inadequate control of symptoms or at least one dose if stopped due to 
intolerance to NSAIDs. 
8. Participants 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 
9. Participants taking corticosteroids must be on a stable dose of ≤10 mg/day prednisone or 
equivalent for at least 2 weeks before randomization and should remain on a stable dose 
up to Week 16. 


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10. Participants taking MTX (≤ 25 mg/week) are allowed to continue their medication if the 
dose is stable for at least 4 weeks before randomization and should remain on a stable 
dose up to Week 16. 
11. Participants on MTX must be on folic acid supplementation at randomization. 
12. Participants who are on a DMARD other than MTX must discontinue the DMARD 4 
weeks prior to randomization visit except for leflunomide, which has to be discontinued 
for 8 weeks prior to randomization unless a cholestyramine washout has been performed. 
13. Participants who have been on a TNFα inhibitor must have experienced an inadequate 
response to previous or current treatment with a TNFα inhibitor given at a dose in clinical 
use for at least 3 months or have stopped treatment due to safety/tolerability problems 
after at least one administration of a TNFα inhibitor. 
14. Participants who have previously been treated with TNFα inhibitors (investigational or 
approved) will be allowed entry into study after appropriate wash-out period prior to 
randomization: 
• 4 weeks for Enbrel® (etanercept) or “Yi Sai Pu” (entanercept) – with a terminal half-
life of 102 ± 30 hours (s.c. route). 
• 8 weeks or longer for Remicade® (infliximab) – with a terminal half-life of 8.0-9.5 
days (i.v. infusion). 
• 10 weeks or longer for Humira® (adalimumab) – with a terminal half-life of 10-20 
days (average 2 weeks) (s.c. route). 
• 10 weeks or longer for Simponi® (golimumab) – with a terminal half-life of 11-14 
days. 
• 10 weeks or longer for Cimzia® (certolizumab) – with a terminal half-life of approx. 
14 days . 
5.2 
Exclusion criteria 
Participants meeting any of the following criteria are not eligible for inclusion in this study. 
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. Participants taking high potency opioid analgesics (e.g., methadone, hydromorphone, 
morphine). 
3. Previous exposure to secukinumab or other biologic drug directly targeting interleukin-
17 (IL-17) or IL-17 receptor. 
4. 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 is longer. 
5. Ongoing use of prohibited psoriasis treatments / medications (e.g., topical corticosteroids, 
UV therapy) at randomization. The following wash out periods need to be observed prior 
to the randomization: 
a. Oral or topical retinoids 4 weeks 
b. Photochemotherapy (e.g. 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 


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6. History of hypersensitivity to drug of similar chemical classes as that of the study drug or 
its excipient. 
7. Any intramuscular or intravenous corticosteroid treatment within 4 weeks before 
randomization. 
8. Any therapy by intra-articular injections (e.g., corticosteroid) within 4 weeks before 
randomization. 
9. Participants who have previously been treated with more than 3 different TNF-α inhibitors 
(investigational or approved). 
10. Participants who have ever received biologic immunomodulating agents except for those 
targeting TNFα. 
11. Previous treatment with any cell-depleting therapies including but not limited to anti-
CD20, investigational agents (e.g., Campath, anti-CD4, anti-CD5, anti-CD3, anti-CD19). 
12. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive hCG 
laboratory test. 
13. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective contraception during the entire study 
(during the entire study). 
Effective contraception is defined as either: 
• Barrier method: Condom or Occlusive cap (diaphragm or cervical/vault caps) with 
spermicide (where available). Spermicides alone are not a barrier method of 
contraception and should not be used alone. 
• Other more effective than the barrier method and are also acceptable: 
a. 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]. 
b. Female sterilization: have had a 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. 
c. Use of established oral, injected or implanted hormonal methods of 
contraception, intrauterine device (IUD) or intrauterine system (IUS). In case of 
use of oral contraception women should have been stabile on the same pill for a 
minimum of 12 weeks before taking study treatment. 
If local regulations deviate from the contraception methods listed above to prevent 
pregnancy, local regulations apply and will be described in the Informed Consent Form 
(ICF). 
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 have had surgical bilateral 
oophorectomy (with or without hysterectomy), total hysterectomy or bilateral tubal 
ligation at least six weeks ago. In the case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by follow up hormone level 
assessment is she considered not of child bearing potential. 


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14. Active ongoing inflammatory diseases other than PsA that might confound the evaluation 
of the benefit of secukinumab therapy, including active IBD and active uveitis. 
15. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal conditions which in the opinion of the investigator 
immunocompromises the subject and/or places the subject at unacceptable risk for 
participation in an immunomodulatory therapy. 
16. 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. 
17. History of renal trauma, glomerulonephritis, or subjects with one kidney only, or a serum 
creatinine (Scr) level exceeding 1.5 mg/dL (132.6µmol/L). 
18. Screening total white blood cell(s) (WBC) count <3,000/µL, or platelets <100,000/µL or 
neutrophils <1,500/µL or hemoglobin <8.5 g/dL (85g/L). 
19. Active systemic infections during the last two weeks (exception: common cold) prior to 
randomization. 
20. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis 
infection as defined by either a positive 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 TB-Gold test as 
indicated in the assessment schedule. Subjects with a positive test may participate in the 
study if further work up (according to local practice/guidelines) establishes conclusively 
that the subject has no evidence of active tuberculosis. If presence of latent tuberculosis is 
established then treatment according to local country guidelines must have been initiated. 
21. History or current infection with HIV, hepatitis B or hepatitis C. 
22. 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). 
23. Current severe progressive or uncontrolled disease which in the judgment of the clinical 
investigator renders the subject unsuitable for the trial. 
24. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor 
tolerability or lack of access to veins). 
25. Any medical or psychiatric condition which, in the investigator's opinion, would preclude 
the participant from adhering to the protocol or completing the study per protocol. 
26. Donation or loss of 400 mL or more of blood within 8 weeks before randomization. 
27. History or evidence of ongoing alcohol or drug abuse, within the last six months before 
randomization. 
28. Plans for administration of live vaccines during the study period or within 6 weeks 
preceding randomization. 


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6 
Treatment 
6.1 
Study treatment 
6.1.1 
Investigational and control drugs 
The following drugs will be used in this study and will be administered in accordance with this 
protocol. Secukinumab 150 mg syringes for subcutaneous injection will be provided in 1.0 mL 
pre-filled syringe. Secukinumab placebo for subcutaneous injection will be provided as a 1.0 
mL pre-filled syringe matching the appearance of 150 mg secukinumab syringe; each placebo 
pre-filled syringe contains a mixture of inactive excipients, matching the composition of the 
secukinumab 150 mg dose. 
Participants will be instructed by site staff on how to self-administer the subcutaneous injection 
using the PFS, based on the Instructions for Use (IFU). The investigational drug will be 
administered by the participant into the appropriate injection site of the body under the 
supervision of the site staff. All injections through Week 48 will be performed at the study site. 
Site staff will administer the injection to those participants who are not able or unwilling to self-
administer the PFS injection. 
Home administration will be allowed under the situation as described in Section 16.9 . 
NOTE: The PFS do not need to be prepared at the site. PFS will be packaged both as double-
blind supplies. 
The study medication will be labeled as follows: 
• Double blind Secukinumab PFS will be labeled as AIN457 150mg/1.0 ml/Placebo 
Novartis GCS will supply the following investigational products: 
Table 6-1 
Investigational and control drug 
Investigational/ 
Control Drug  
(Name and 
Strength) 
Pharmaceutical 
Dosage Form 
Route of 
Administration 
Supply Type 
Sponsor (global or 
local) 
Secukinumab 150 
mg  
PFS solution for 
injection 
Subcutaneous 
Injection 
Double Blind 
Novartis Pharma 
AG (global) 
Secukinumab 
Placebo  
PFS solution for 
injection 
Subcutaneous 
Injection 
Double Blind 
Novartis Pharma 
AG (global) 
6.1.2 
Additional study treatments 
No additional treatment beyond investigational treatment described in Section 6.1.1 is used in 
this trial. 
6.1.3 
Treatment arms/group 
Participants fulfilling the inclusion criteria will be randomized to one of the following two 
groups in a 1:1 ratio, with 20 participants in each of the two groups as depicted below: 
• Group 1 : Secukinumab 150 mg s.c. at BSL, Week 1, 2, 3, 4, 8, and 12 
• Group 2 : Secukinumab Placebo s.c. at BSL, Week 1, 2, 3, 4, 8, and 12 


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At Week 16, the participants in Group 1 and Group 2 will be re-randomized in 1:1 ratio 
separately: 
• Group 1 will be re-randomized in 1:1 ratio to: 
Secukinumab 150 mg s.c. regimen (1.0 mL PFS of 150 mg dose + 1.0 mL PFS of placebo) 
 
 
• Group 2 will be re-randomized in 1:1 ratio to: 
Secukinumab 150 mg s.c. regimen (1.0 mL PFS of 150 mg dose + 1.0 mL PFS of placebo) 
 
 
6.1.4 
Treatment duration 
The overall planned duration of study treatment is 52 weeks, split between Treatment Period 1 
(16 weeks) and Treatment Period 2 (36 weeks). Participants may voluntarily discontinue from 
the study treatment for any reason at any time. (see Section 9.1.1) 
6.2 
Other treatment(s) 
Not applicable. 
6.2.1 
Concomitant therapy 
The investigator should instruct the participant to notify the study site about any new 
medications (including over-the-counter drugs, calcium, vitamins, herbal medicines and 
tranditional Chinese medicines) administered after the participant is enrolled into the study. All 
medications (other than study treatment), procedures and significant non-drug therapies 
(including physical therapy and blood transfusions) must be recorded on the Prior and 
Concomitant medications or Procedures and Significant Non Drug Therapy eCRF. The reason, 
name of the drug, procedure or non-drug therapy should be listed. 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt, the Investigator should contact the Novartis medical monitor before 
reassigning treatment for a participant or allowing a new medication to be started. If the 
participant is already enrolled, contact Novartis to determine if the participant should continue 
participation in the study. 
6.2.1.1 
Permitted concomitant therapy requiring caution and/or action 
Participants are permitted to use the medications as described below. 
Methotrexate (MTX) 
Participants taking MTX (up to 25 mg/week) must be on a stable dose for at least 4 weeks 
before randomization and maintained stable until Week 16.  
Folic acid 


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Participants on MTX must be taking folic acid supplementation (at the dose permitted by local 
practice guideline) before randomization and during the trial to minimize the likelihood of MTX 
associated toxicity. 
Cholestyramine for leflunomide wash out 
In case of leflunomide treatment, a drug wash out of 8 weeks has to be performed. However, 
prior to randomization another wash out procedure might be considered. Cholestyramine could 
be given orally to wash out the drug at a dose of 8 g 3 times a day (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 participants who require a drug elimination procedure. If a participant receives 
8 g t.i.d. for 11 days, the wash out period could be 4 weeks (counting from the beginning of the 
11 days treatment). 
Systemic corticosteroids 
Treatment with systemic corticosteroids is permitted up to a maximum daily dosage of 10 mg 
prednisone equivalent and if the dose was stable within the 2 weeks preceding randomization. 
The participant should remain on a stable dose until Week 16. 
Corticosteroid dose reductions below 10 mg prednisone equivalent are permitted after Week 
16 assessment, 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 assessment, no more than 1 joint per 24-week period may 
be injected. No single injection should exceed 40 mg of triamcinolone (or equivalent) and the 
total dose of intra-articular corticosteroid may not exceed 80 mg of triamcinolone (or 
equivalent) . 
Non-steroidal anti-inflammatory drugs (NSAIDs) [including cyclooxygenase-1 (COX-1) 
or 
cyclooxygenase-2 
(COX-2) 
inhibitors], 
low 
strength 
opioids 
and 
acetaminophen/paracetamol 
Participants on regular use of NSAIDs, low strength opioids, or paracetamol/acetaminophen as 
required (PRN) should be on stable dose for at least 2 weeks before randomization to allow 
inclusion. They should remain on a stable dose in the study up to Week 16, however, they have 
to refrain from any intake during at least 24 hours before a visit with disease activity assessment. 
After Week 16 assessments are completed, a change in the NSAIDs, low strength opioids, or 
paracetamol/acetaminophen treatment regimen is permitted. 
Any change of the NSAIDs, low strength opioids, or paracetamol/acetaminophen treatment 
during the trial should be recorded on the corresponding eCRF page. 
Note: Background and concomitant medications will not be provided by Novartis and must be 
supplied by the the study center. 


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6.2.2 
Prohibited medication 
Use of the treatments displayed in the below table are not allowed after Screening (Visit 1). The 
minimum required period without prohibited treatment before Screening (Visit 1) is also listed 
in Table 6-2. Each concomitant drug must be individually assessed against all exclusion criteria 
and the table below to see if it is allowed. If in doubt, the investigator should contact Novartis 
or delegate before randomizing a participant or allowing a new medication to be started. 
Live vaccines should not be given until 12 weeks after last study treatment administration. 
Table 6-2 
Prohibited medication 
Medication 
Prohibition period 
Action taken 
Biological immunomodulating 
agents > 3 different TNFα 
No prior use allowed 
Discontinue from study 
Other biological 
immunomodulating agents except 
for those targeting TNFα (such as 
Ustekinumab) 
No prior use allowed 
Discontinue from study 
Etanercept 1 
a) 4 weeks prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
4-week wash out or discontinue 
from study 
b) Discontinue study treatment 
c) Stop prohibited treatment 
Infliximab 1  
a) 8 weeks prior to randomization 
b) Treatment period  
c) Follow up period  
a) Delay randomization to achieve 
8-week wash out or discontinue 
from study 
b) Discontinue study treatment 
c) Stop prohibited treatment 
Adalimumab, golimumab, 
certolizumab 1  
a) 10 weeks prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
10-week wash out or discontinue 
from study 
b) Discontinue study treatment 
c) Stop prohibited treatment 
Unstable dose of MTX 2 
a) 4 weeks prior to randomization 
b) Treatment period up to Week 16 
a) Delay randomization to achieve 
4-week stable dose or discontinue 
from study 
b) Keep MTX at a stable permitted 
dose from at least 4 weeks before 
randomization up to Week 16, 
otherwise, discontinue study 
treatment 
DMARDs (except MTX) 
a) 4 weeks prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
4-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment 
c) Stop prohibited treatment 
Leflunomide 
a) 8 weeks prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
8-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment  
c) Stop prohibited treatment 


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Medication 
Prohibition period 
Action taken 
Leflunomide with Cholestyramine 
washout 
a) 4 weeks prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
4-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment  
c) Stop prohibited treatment 
Apremilast 
a) 4 weeks prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
4-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment  
c) Stop prohibited treatment 
Unstable dose of NSAIDs 
(including COX-1 or COX-2 
inhibitors), low strength opioids 
and paracetamol/acetaminophen2 
a) 2 weeks prior to randomization 
b) Treatment period up to Week 16 
a) Delay randomization to achieve 
2-week stable dose or discontinue 
from study 
b) Keep NSAIDs, low strength 
opioid and 
paracetamol/acetaminophen at a 
stable dose from at least 2 weeks 
before randomization up to Week 
16, otherwise, discontinue study 
treatment  
Unstable dose of systemic 
corticosteroids <= 10 mg 
prednisone equivalent 2  
a) 2 weeks prior to randomization 
b) Treatment period up to Week 16 
a) Delay randomization to achieve 
2-week stable dose or discontinue 
from study 
b) Keep systemic corticosteroids 
(<= 10 mg prednisone equivalent) 
from at least 2 weeks before 
randomization up to Week 16, 
otherwise, discontinue 
study treatment 
Systemic corticosteroids > 10 mg 
prednisone equivalent 2 
a) 2 weeks prior to randomization  
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
2-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment 
c) Stop prohibited treatment 
Intra-articular injections 2 
a) 4 weeks prior to randomization 
b) Treatment period up to Week 16 
c) Treatment period after Week 16 
assessment to Week F60 
a) Delay randomization to achieve 
4-week wash out or discontinue 
from study 
b) Discontinue study treatment  
c) No more than 1 joint per 24-
week period is permitted after 
Week 16 assessment to Week F60 
Intramuscular or intravenous 
corticosteroid treatment 
a) 4 weeks prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
4-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment  
c) Stop prohibited treatment 
Any investigational treatment or 
participation in any interventional 
trial 
a) 4 weeks or 5 half-lives (which is 
longer) prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
wash out or discontinue from study 
b) Discontinue study treatment 
c) Stop prohibited treatment 


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Medication 
Prohibition period 
Action taken 
Live vaccinations 
a) within 6 weeks preceding 
randomization randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
wash out or discontinue from study 
b) Interrupt study treatment for 12 
weeks, or discontinue 
study treatment (see details in 
Section 6.5) 
c) Stop prohibited treatment 
Oral or topical retinoids 
a) 4 weeks prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
4-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment  
c) Stop prohibited treatment 
Photochemotherapy (e.g. PUVA) 
a) 4 weeks prior to randomization 
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
4-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment  
c) Stop prohibited treatment 
Phototherapy [ ultraviolet A (UVA) 
or ultraviolet B (UVB)] 
a) 2 weeks prior to randomization  
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
2-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment 
c) Stop prohibited treatment 
Topical skin treatments (except in 
face, eyes, scalp and genital area 
during screening, only 
corticosteroids with mild to 
moderate potency) 
a) 2 weeks prior to randomization  
b) Treatment period 
c) Follow up period 
a) Delay randomization to achieve 
2-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment 
c) Stop prohibited treatment 
Traditional Chinese medicine 
treatments of psoriasis and/or 
psoriatic arthritis 3 
a) 4 weeks prior to randomization  
b) Treatment period up to Week 16 
c) Treatment period after Week 16 
assessment to Week F60 
a) Delay randomization to achieve 
4-week wash out or discontinue 
from study 
b) Stop prohibited treatment or 
discontinue study treatment 
c) Stop prohibited treatment 
1. These agents fall under the category of biologic immunomodulators and are prohibited medications. 
Administration of these agents requires study discontinuation (see Section 9.1.1). 
2. See details in Section 6.2.1 
3. Traditional Chinese medicine (TCM) is defined as a compendium of methods popular in Chinese tradition for 
the treatment of a wide range of conditions. TCM practitioners use herbal remedies, acupuncture, massage, 
mind-body and dietary therapies, and other methods. 
6.2.3 
Rescue medication 
Rescue medication is defined as any new therapeutic intervention or a significant change to 
ongoing therapy made because a participant 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 (see Section 3). 
Each concomitant drug must be individually assessed against all exclusion criteria and 
prohibited medication (Table 6-2). 
When in doubt the Investigator should contact the Novartis medical monitor before treatment 
reassignment or allowing a new medication to be started. If any of the medications listed in 


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Table 6-2 is deemed a necessary rescue therapy, the Investigator must follow the actions to be 
taken outlined in this section. Rescue treatment is to be provided by the study center or personal 
physician. 
Please see Section 6.2.1 and Section 6.2.2 for details. Although no participant will be restricted 
from receiving necessary rescue medications for lack of benefit or worsening of disease, if 
rescue with prohibited treatments (as described in Table 6-2) occurs , participants will be 
discontinued from study treatment and continue to the follow-up visit . Efficacy will be assessed 
in detail at every study visit, and participants who are deemed not to be benefiting from the 
study treatment based upon safety and efficacy assessments by the investigator or for any reason 
on their own accord are free to discontinue participation from the treatment at any time. 
6.3 
Participant numbering, treatment assignment, randomization 
6.3.1 
Participant numbering 
Each participant is identified in the study by a participant Number (participant No.), that is 
assigned when the participant is first enrolled for screening and is retained as the primary 
identifier for the participant throughout his/her entire participation in the trial. The participant 
No. consists of the Center Number (Center No.) as assigned by Novartis to the investigative site 
with a sequential participant number suffixed to it, so that each participant is numbered uniquely 
across the entire database. 
Upon signing the informed consent form, the participant is assigned to the next sequential 
participant No. available. Once assigned to a participant the participant number will not re-used. 
The re-screened participant will receive a new participant Number. 
Participants numbers are assigned when the site creates the first entry for the participant in the 
Case Report/Record Form (CRF), therefore CRF must be created prior to contacting the IRT 
system. 
A new ICF will need to be signed if the investigator chooses to re-screen the participant after a 
participant has screen failed, and the participant will be assigned a new Participant No. 
6.3.2 
Treatment assignment, randomization 
At BSL, all eligible Chinese participants will be randomized via IRT to one of the two treatment 
arms. The investigator or his/her delegate will contact the IRT after confirming that the 
participant fulfills all the inclusion/exclusion criteria. The IRT will assign a randomization 
number to the participant, which will be used to link the participant to a treatment arm and will 
specify a unique medication number for the first package of study treatment to be dispensed to 
the participant. The randomization number will not be communicated to any of the site staff. 
Based on enrollment target, the participants who are anti-TNFα inhibitor inadequate responder 
(TNF-IR) should not be more than 10% of Chinese randomized participants to ensure a 
representative  population for the assessment of efficacy and safety. 
Participants who complete the Treatment period 1 (BSL to Week16) will enter Treatment period 
2 (Week 16 to Week 52). For this effect, after all Week 16 assessments would have been 
completed, the investigator or his/her delegate must contact the IRT in order to re-
randomize the participants. The IRT will assign the medication number of PFS to be 


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administered. IRT will only communicate to the caller the medication numbers, not the 
randomization number. 
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from participants and investigator staff. A 
participant randomization list will be produced by the IRT provider using a validated system 
that automates the random assignment of participant numbers to randomization numbers. These 
randomization numbers are linked to the different treatment arms, which in turn are linked to 
medication numbers. A separate medication list will be produced by or under the responsibility 
of Novartis GCS using a validated system that automates the random assignment of medication 
numbers to packs containing the study treatment. 
Stratification is not applicable in the study 
The randomization scheme for participants will be reviewed and approved by a member of the 
Randomization Office. 
6.4 
Treatment blinding 
This is a double-blind randomized treatment trial. Participants, investigator staff, persons 
performing the assessments will remain blinded to the identity of the treatment from the time 
of randomization until database lock, using the following methods: (1) Randomization data are 
kept strictly confidential until the time of unblinding and will not be accessible by anyone else 
involved in the study with the following exceptions of bioanalyst (2) the identity of the 
treatments will be concealed by the use of study treatment that are all identical in packaging, 
labeling, schedule of administration, appearance, taste, and odor.  
Unblinding of treatment dose or original randomized treatment assignment before the Week 
F60 database lock and analyses are completed will only occur in the case of participant 
emergencies Section 6.6.2. 
The hsCRP lab results from samples collected during the treatment period will be revealed only 
after the Week F60 database lock and analyses are completed to maintain blinding. 
The primary endpoint analysis  will be performed when the database is locked (after all 
participants have completed Week 16 assessments). Summary results may be shared internally 
and externally; however, individual unblinded participant data will not be disclosed. A final 
database lock will occur when all participants have completed the study. 
Unblinding will occur in the case of participant emergencies and at the conclusion of the study. 
Novartis Clinical Team will be unblinded after week 16 database lock to placebo versus 
secukinumab (Treatment Period 1), but will remain blinded after re-randomization (Treatment 
Period 2) until final database lock. 
All investigators, site personnel, participants, and monitors will remain blinded to all treatments 
during the whole duration of study, until the Week F60 database lock has occurred. 
6.5 
Dose escalation and dose modification 
Investigational or other study treatment dose adjustments and/or interruptions are not permitted.  


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6.5.1 
Dose modifications 
Investigational treatment dose modifications are not permitted. 
6.5.2 
Dose interruptions 
Study treatment interruption should be avoided with the following exceptions: 
Study treatment interruption is only permitted if, in the opinion of the investigator, a participant 
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 eCRF page. 
In all cases the original visit schedule should be maintained (no recalculation from the last 
visit). 
6.6 
Additional treatment guidance 
6.6.1 
Treatment compliance 
The site staff will provide the study treatment assigned by IRT to the participants. Kit numbers 
are collected in the IRT and the site staff will record study drug administration in the eCRF. 
The compliance will also be assessed by means of site and participant specific drug 
accountability by Novartis monitors during site monitoring visits using medication pack 
numbers, drug label information and information from IRT. 
In this study, the compliance to the planned administration schedule is expected to be high since 
the study treatment will be administered onsite by self-administration by the participants or by 
the trained site staff. 
All dates and times of study treatment administration will be recorded in the Drug 
Accountability Log. 
Compliance will also be assessed by a Novartis monitor using information provided by the 
authorized site personnel. 
6.6.2 
Emergency breaking of assigned treatment code 
Emergency code breaks must only be undertaken when it is required to in order to treat the 
participant safely. Blinding codes may also be broken after a participant discontinues treatment 
due to disease progression if deemed essential to allow the Investigator to select the participant’s 
next treatment regimen, and after discussion and agreement with the sponsor. Most often, study 
treatment discontinuation and knowledge of the possible treatment assignments are sufficient 
to treat a study participant 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 participant, he/she must provide the requested participant identifying 


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information and confirm the necessity to break the treatment code for the participant. The 
Investigator will then receive details of the investigational drug treatment for the specified 
participant and a fax or email confirming this information. The system will automatically inform 
the Novartis monitor for the site and the study team that the code has been broken. Participants 
unblinded following an intentional emergency code breaking should be discontinued from the 
study. 
It is the Investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT/code break cards at any time in case of emergency. The Investigator 
will provide: 
• protocol number 
• participant number 
In addition, oral and written information to the participant must be provided on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable, to ensure that un-blinding 
can be performed at any time. 
6.7 
Preparation and dispensation 
Each study site will be supplied with study drug in packaging as described under investigational 
and control drugs section. 
A unique medication number is printed on the study medication label. All study treament kits 
assigned to the participant during the study will be recorded in the IRT. 
Investigator staff will identify the study medication kits to dispense to the participant by 
contacting the IRT and obtaining the medication number(s). The study medication has a 2-part 
label (base plus tear-off label). Immediately before dispensing the medication kit to the 
participant, site personnel will detach the outer part of the label from the packaging and affix it 
to the source document. 
6.7.1 
Handling of study treatment and additional treatment 
6.7.1.1 
Handling of study treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only the investigator and designated 
site personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified on the labels. 
Clinical supplies are to be dispensed only in accordance with the protocol. Technical complaints 
are to be reported to the respective Novartis CO Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of China. 
They will include storage conditions for the study treatment but no information about the 
participant except for the medication number. 
The PFS (150 mg active/placebo) sealed in their outer box must be stored in a access 
controlled/locked refrigerator between 2 degree Celsius (°C) and 8°C [36 degree Fahrenheit 
(°F) and 46°F)] (Do Not Freeze) and protected from light. They must be carefully controlled in 
accordance with regulations governing investigational medicinal products and local regulations. 


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The investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
monitors during site visits or remotely and at the completion of the trial. Participants will be 
asked to return all unused study treatment and packaging at the end of the study or at the time 
of discontinuation of study treatment. 
At the conclusion of the study, and as appropriate (according to local requirements) during the 
course of the study, the investigator will return all unused study treatment, packaging, drug 
labels, and a copy of the completed drug accountability log to the Novartis monitor or to the 
Novartis address provided in the investigator folder at each site. 
6.7.1.2 
Handling of additional treatment 
Not applicable. 
6.7.2 
Instruction for prescribing and taking study treatment 
All kits of study treatment assigned by the IRT will be recorded in the IRT system. 
Secukinumab solution for subcutaneous injection (150 mg in 1.0 mL active/placebo) will be 
provided in PFSs. 
The study treatment solution must be injected into non-affected areas of the skin. 
Although all doses of study treatment (secukinumab and placebo) will be administratered at the 
study site, it is preferred that participants self-administer. However, if the participant is not able 
or not willing to self-administer, administration will be performed by study site staff. The 
injections will be self-administered by the participant at the study site under the supervision of 
a site staff member after the study assessments for the visit have been completed. Participants 
will be instructed by the site staff on how to self-inject study treatment using a PFS, following 
the IFU. 
At study visits requiring pre-dose blood samples, the study treatment will be injected only after 
the blood samples have been collected. 
For each study visit at the site, all study assessments including completion of PROs should be 
completed prior to the administration/self-administration of the study treatment. 
All dosages prescribed and dispensed to the participants and all dose changes during the study 
must be recorded on the Dosage Administration Record CRF. Immediately before dispensing 
the package to the participant, site staff will detach the outer part of the label from the packaging 
and affix it to the source document (Drug Label Form) for that participant's unique participant 
number. 
The investigator should promote compliance by instructing the participant to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the participant's 
safety and the validity of the study. 
Any PFS for which a defect or malfunction is noticed prior to or during the injection at any of 
the study visits, must be kept at the site until guidance is received from Novartis on whether it 
should be returned to Novartis for investigation or discarded. Devices identified as defective 
should be stored according to local guidelines, until specific instruction is discussed with 


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Novartis personnel. Additionally, from BSL onwards, any noticed defect, malfunction, problem 
during the injections or product complaints with the PFS should be recorded in the source 
document and the Use of Device eCRF. Sites should detail the issue, the date, the kit number 
and the visit number. Site will be asked to record based on their judgment whether the observed 
issue was primarily related to the device or to the user. Device malfunctions should also be 
immediately reported to Novartis personnel as a necessary replacement kit may need to be 
provided. 
Administration 
Single syringes will be packaged in individual boxes. The boxes containing the PFSs with study 
treatment solution should be kept at 2 to 8°C (36°F and 46°F) (Do Not Freeze) and protected 
from light. Prior to administration the boxes containing the PFSs with study treatment solution 
should be allowed to come to room temperature unopened for 15-30 minutes prior to injection. 
The injections will be administered into the appropriate site of the body (thighs, arms, 
abdomen), and each injection should be given at a different injection site to reduce the risk of 
reaction. Each new injection should be given at least one inch from the previously used site. If 
participant chooses the abdomen, a 2 inch area around the navel should be avoided. 
Investigational drug should not be injected into areas where the skin is tender, bruised, red, or 
hard, or where participant has scars or stretch marks. 
Used safety syringes should be disposed immediately after use in a sharps container or 
according to the local regulatory requirements. 
Table 6-3 
Dose and treatment schedule ( BSL to Week 12) 
Investigational / Control Drug 
(Name and Strength) 
Dose 
Frequency and/or Regimen 
Secukinumab 150 mg s.c (Group 1) 
150 mg (1.0mL PFS) 
BSL, Week 1,2,3, 4, 8 and 12 
Secukinumab Placebo s.c (Group 2) 
0 mg (1.0mL PFS) 
BSL, Week 1, 2, 3, 4, 8 and 12 
At BSL/randomization visit, the participants will be randomized to one of the above two groups in a 1:1 
ratio 
Table 6-4 
Dose and treatment schedule (Group 1 & Group 2 participants- Week 
16 to Week 48) 
Investigational / Control Drug 
(Name and Strength) 
Dose 
Frequency and/or Regimen 
Secukinumab 150 mg s.c and 
Placebo s.c.  
150 mg (1.0mL PFS) 
0 mg (1.0mL PFS) 
Q4W (Week 16, 20, 24, 28,32, 36, 
40, 44 and 48) 
 
 
 
At Week 16, the participants in Group 1 and Group 2 will be re-randomized in 1:1 ratio to either 
Secukinumab 150 mg s.c. regimen (1.0 mL PFS of 150mg dose + 1.0mL PFS of placebo) 
 
 


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7 
Informed consent procedures 
The following informed consents are included in this study: 
1. Main study consent 
2. As applicable, Pregnancy Outcomes Reporting Consent for female participants who took 
study treatment 
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation), Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC)-approved informed consent. 
If applicable, in cases where the participants's representative(s) gives consent (if allowed 
according to local requirements), the participant must be informed about the study to the extent 
possible given his/her understanding. If the participant is capable of doing so, he/she must 
indicate agreement by personally signing and dating the written informed consent document. 
Informed consent must be obtained before conducting any study-specific procedures (e.g. all of 
the procedures described in the protocol). The process of obtaining informed consent must be 
documented in the participant source documents.  
It is permissible to re-screen a participant if she/he fails the initial screening. Participants can 
be rescreened only once, and no study-related re-screening procedure should be performed prior 
to written re-consent by the participant. 
If a participant re-screens for the study, then the participant must sign a new ICF and be issued 
a new participant number prior to any screening assessment being conducted for the participant 
under the new screening participant number. For all participants, the investigator/qualified site 
staff will record if the participant was rescreened on the rescreening CRF and any applicable 
screening numbers the participant was issued prior to the current screening number. 
Novartis will provide to investigators in a separate document a proposed informed consent form 
that complies with the International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use (ICH) GCP guidelines and regulatory requirements and is 
considered appropriate for this study. Any changes to the proposed consent form suggested by 
the investigator must be agreed by Novartis before submission to the IRB/IEC. 
Information about common side effects already known about the investigational drug can be 
found in the Investigator's Brochure (IB) . This information will be included in the 
participant informed consent and should be discussed with the participant during the study as 
needed. Any new information regarding the safety profile of the investigational drug that is 
identified between IB updates will be communicated as appropriate, for example, via an 
investigator notification or an aggregate safety finding. New information might require an 
update to the informed consent and then must be discussed with the participant. 
Women of child bearing potential must be informed that taking the study treatment may involve 
unknown risks to the fetus if pregnancy were to occur during the study, and agree that in order 
to participate in the study they must adhere to the contraception requirements (see Section 5.2). 
A copy of the approved version of all consent forms must be provided to Novartis after IRB/IEC 
approval. 


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Participants might be asked to complete an optional questionnaire to provide feedback on their 
clinical trial experience. 
8 
Visit schedule and assessments 
The Assessment Schedule (Table 8-1) lists all of the assessments when they are performed. All 
data obtained from these assessments must be supported in the participant's source 
documentation. 
Participants should be seen for all visits/assessments as outlined in the assessment schedule 
(Table 8-1) or as close to the designated day/time as possible. 
• For visits scheduled through Week 4, the study treatment should not be administered less 
than 7 days from the previous administration. 
• For visits scheduled after Week 4, the study treatment should not be administered less than 
14 days from the previous administration 
Note: All efforts need to be made to maintain the actual duration of 52-week study treatment 
period. Therefore, a study visit subsequent to a visit, which has been delayed or brought forward 
needs to be planned as per original visit schedule. The original visit schedule should be 
maintained (no recalculation from the last visit). 
Missed or rescheduled visits should not lead to automatic discontinuation of study treatment. 
Participants who prematurely discontinue from treatment during a specific treatment period 
should return for the final visit within that treatment period (4 weeks after the last study 
treatment), as well as return for the follow-up visit (Week F60), 12 weeks after the last study 
treatment. At this final visit, all dispensed investigational product should be reconciled, and the 
adverse event and concomitant medications recorded on the eCRF. 
If participants 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. 
Documentation of attempts to contact the participant should be recorded in the source 
documentation. 


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Table 8-1 
Assessment Schedule 
Period 
Screening1 
Treatment Period 1 (TP1) 
Treatment Period 2 (TP2) 
Post-Treatment 
Follow-Up 
Visit Name -10 to 
-4 
≤-4 to 
BSL 
Base 
line 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
8 
Wk 
12 
Wk16/ 
End of 
TP1/TD 2 
Wk 
20 
Wk 
24 
Wk 
28 
Wk 
32 
Wk 
36 
Wk 
40 
Wk 
44 
Wk 
48 
Wk52/ 
End of 
TP2/TD2 
F60 (End of 
study/PSW)2 
Weeks -10 to 
-4 
-4 to 0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
60 
Days -70 to 
-28 
-28 to 0 
1 
7 
14 
21 
28 
56 
84 
112 
140 
168 
196 224 
252 
280 308 336 
364 
420 
Informed 
consent 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Inclusion / 
Exclusion 
criteria 
X 
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Medical 
history/current 
medical 
conditions 
  
X 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Washout 
evaluation/ins
truction3,4 
S 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Smoking 
history 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Demography 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Psoriasis/psor
iatic arthritis 
medical 
history and 
previous 
therapies 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
PsA CASPAR 
Criteria 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  


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Period 
Screening1 
Treatment Period 1 (TP1) 
Treatment Period 2 (TP2) 
Post-Treatment 
Follow-Up 
Visit Name -10 to 
-4 
≤-4 to 
BSL 
Base 
line 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
8 
Wk 
12 
Wk16/ 
End of 
TP1/TD 2 
Wk 
20 
Wk 
24 
Wk 
28 
Wk 
32 
Wk 
36 
Wk 
40 
Wk 
44 
Wk 
48 
Wk52/ 
End of 
TP2/TD2 
F60 (End of 
study/PSW)2 
Weeks -10 to 
-4 
-4 to 0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
60 
Days -70 to 
-28 
-28 to 0 
1 
7 
14 
21 
28 
56 
84 
112 
140 
168 
196 224 
252 
280 308 336 
364 
420 
Physical 
Examination4 
  
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Body Height 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Body Weight 
  
X 
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 
PPD skin test 
or 
QuantiFERO
N TB-Gold 
test 5 
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
HBV, HCV 
and HIV 
screen4,6 
  
S 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Chest X-
ray/MRI7 
  
S 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Electrocardio
gram (ECG) 
  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
X 
X 
Contact IRT 
  
  
X 
X 
X 
X 
X 
X 
X 
X8 
X 
X 
X 
X 
X 
X 
X 
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 
  
  


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Period 
Screening1 
Treatment Period 1 (TP1) 
Treatment Period 2 (TP2) 
Post-Treatment 
Follow-Up 
Visit Name -10 to 
-4 
≤-4 to 
BSL 
Base 
line 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
8 
Wk 
12 
Wk16/ 
End of 
TP1/TD 2 
Wk 
20 
Wk 
24 
Wk 
28 
Wk 
32 
Wk 
36 
Wk 
40 
Wk 
44 
Wk 
48 
Wk52/ 
End of 
TP2/TD2 
F60 (End of 
study/PSW)2 
Weeks -10 to 
-4 
-4 to 0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
60 
Days -70 to 
-28 
-28 to 0 
1 
7 
14 
21 
28 
56 
84 
112 
140 
168 
196 224 
252 
280 308 336 
364 
420 
Prior/Concomi
tant 
medication/ 
Non-drug 
therapy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy 
(Serum)4,6 
  
S 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
S 
Pregnancy 
Test 4,6,9 
  
  
S 
  
  
  
S 
  
S 
S 
  
S 
  
S 
  
S 
  
  
S 
S 
Adverse 
Events/SAE 
(incl. injection 
site reaction & 
occurrence of 
injections)10 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ANA 
  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
X 
  
anti-double 
stranded DNA 
antibodies 
( anti-dsDNA) 
  
  
X 
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
X 
  
Anti-CCP 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Rheumatoid 
factor (RF) 
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
Hematology 
  
X 
X 
  
  
  
  
  
X 
X 
  
  
X 
  
  
X 
  
  
X 
X 
Blood 
chemistry 
  
X 
X 
  
  
  
  
  
X 
X 
  
  
X 
  
  
X 
  
  
X 
X 


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Protocol No. CAIN457F2367 
 
Period 
Screening1 
Treatment Period 1 (TP1) 
Treatment Period 2 (TP2) 
Post-Treatment 
Follow-Up 
Visit Name -10 to 
-4 
≤-4 to 
BSL 
Base 
line 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
8 
Wk 
12 
Wk16/ 
End of 
TP1/TD 2 
Wk 
20 
Wk 
24 
Wk 
28 
Wk 
32 
Wk 
36 
Wk 
40 
Wk 
44 
Wk 
48 
Wk52/ 
End of 
TP2/TD2 
F60 (End of 
study/PSW)2 
Weeks -10 to 
-4 
-4 to 0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
60 
Days -70 to 
-28 
-28 to 0 
1 
7 
14 
21 
28 
56 
84 
112 
140 
168 
196 224 
252 
280 308 336 
364 
420 
Urinalysis 
  
X 
X 
  
  
  
  
  
X 
X 
  
  
X 
  
  
X 
  
  
X 
X 
High 
sensitivity C-
Reactive 
protein 
(hsCRP)11 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
Erythrocyte 
Sedimentatio
n Rate (ESR) 
  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
  
Tender and 
swollen joint 
counts 
(TJC78, 
SJC76) 
  
X 
X 
X 
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 
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 
X 
X 
  


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Clinical Trial Protocol (Version No. 00) 
 
Protocol No. CAIN457F2367 
 
Period 
Screening1 
Treatment Period 1 (TP1) 
Treatment Period 2 (TP2) 
Post-Treatment 
Follow-Up 
Visit Name -10 to 
-4 
≤-4 to 
BSL 
Base 
line 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
8 
Wk 
12 
Wk16/ 
End of 
TP1/TD 2 
Wk 
20 
Wk 
24 
Wk 
28 
Wk 
32 
Wk 
36 
Wk 
40 
Wk 
44 
Wk 
48 
Wk52/ 
End of 
TP2/TD2 
F60 (End of 
study/PSW)2 
Weeks -10 to 
-4 
-4 to 0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
60 
Days -70 to 
-28 
-28 to 0 
1 
7 
14 
21 
28 
56 
84 
112 
140 
168 
196 224 
252 
280 308 336 
364 
420 
Physician’s 
global 
assessment 
of disease 
activity (VAS) 
  
  
X 
X 
X 
X 
X 
X 
X 
X 
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 
X 
X 
  
Patient’s 
global 
assessment 
of psoriasis 
and arthritis 
disease 
activity (VAS) 
  
  
X 
  
  
  
X 
X 
X 
X 
  
X 
  
X 
  
X 
  
  
X 
  
Body Surface 
Area (BSA) 
evaluation12 
  
  
X 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  


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Clinical Trial Protocol (Version No. 00) 
 
Protocol No. CAIN457F2367 
 
Period 
Screening1 
Treatment Period 1 (TP1) 
Treatment Period 2 (TP2) 
Post-Treatment 
Follow-Up 
Visit Name -10 to 
-4 
≤-4 to 
BSL 
Base 
line 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
8 
Wk 
12 
Wk16/ 
End of 
TP1/TD 2 
Wk 
20 
Wk 
24 
Wk 
28 
Wk 
32 
Wk 
36 
Wk 
40 
Wk 
44 
Wk 
48 
Wk52/ 
End of 
TP2/TD2 
F60 (End of 
study/PSW)2 
Weeks -10 to 
-4 
-4 to 0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
60 
Days -70 to 
-28 
-28 to 0 
1 
7 
14 
21 
28 
56 
84 
112 
140 
168 
196 224 
252 
280 308 336 
364 
420 
SF-36 v2 
  
  
X 
  
  
  
X 
X 
X 
X 
  
X 
  
  
  
  
  
  
X 
  
Lipids13 
  
  
X 
  
  
  
  
X 
  
X 
  
X 
  
  
  
  
  
  
X 
X 
Treatment 
period 1 
completion 
form 
  
  
  
  
  
  
  
  
  
X 
  
  
  
  
  
  
  
  
  
  
Treatment 
period 2 
completion 
form 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X 
  
Trial feedback 
questionnaire 
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
  
X14 


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Clinical Trial Protocol (Version No. 00) 
 
Protocol No. CAIN457F2367 
 
Period 
Screening1 
Treatment Period 1 (TP1) 
Treatment Period 2 (TP2) 
Post-Treatment 
Follow-Up 
Visit Name -10 to 
-4 
≤-4 to 
BSL 
Base 
line 
Wk 
1 
Wk 
2 
Wk 
3 
Wk 
4 
Wk 
8 
Wk 
12 
Wk16/ 
End of 
TP1/TD 2 
Wk 
20 
Wk 
24 
Wk 
28 
Wk 
32 
Wk 
36 
Wk 
40 
Wk 
44 
Wk 
48 
Wk52/ 
End of 
TP2/TD2 
F60 (End of 
study/PSW)2 
Weeks -10 to 
-4 
-4 to 0 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
60 
Days -70 to 
-28 
-28 to 0 
1 
7 
14 
21 
28 
56 
84 
112 
140 
168 
196 224 
252 
280 308 336 
364 
420 
X Assessment to be recorded in the clinical database or received electronically from a vendor 
1 If subject’s washout period is ≤ 4 weeks, two screening visits can be performed on the same day. 
2 These assessments are also to be conducted for patients who discontinue from the treatment- Treatment Discontinuation (TD): Patients who prematurely discontinues 
during Treatment Period 1 has to return for assessments associated with End of TP1  visit (4 weeks after the last study treatment) and End of study visit (12 weeks after 
the last administration of the study treatment). Patients who prematurely discontinues during Treatment Period 2 has to return and complete assessments associated 
with End of TP2 visit (4 weeks after the last study treatment) and End of study visit (12 weeks after the last administration of the study treatment). 
3 To determine the duration of the washout period, and if the second screening visit will be performed (see Section 8.1). 
4 assessment to be recorded on source documentation only 
5 Either a QuantiFERON TB-Gold test or a PPD skin test must be performed at Screening. A QuantiFERON TB-Gold test is to be performed at the second screening 
visit. The PPD skin test can be performed at any time during the screening period but it has to be read within 72 hrs and before randomization. 
6 Sample will be analyzed locally 
7 If patients do not have a chest X-ray available within 3 months of screening, an X-ray is to be performed after it is certain the subject meets inclusion/exclusion criteria 
in order to minimize unnecessary exposure to X-ray radiation. The x-ray might be replaced by an MRI assessment. 
8 Patients will be re-randomized at Week 16. 
9 Recommended to perform urine pregnancy test at designated visits in local lab, if not feasible alternatively the serum pregnancy test should be performed.  A positive 
urine test requires immediate interruption of study drug and needs to be confirmed with a serum Beta human chorionic gonadotropin (β-hCG test) (serum pregnancy 
test). If positive, the participant must be discontinued from the study treatment.  
10 AEs/SAEs occurring after the participant has signed the informed consent must be captured on the appropriate eCRF page. 
11 Since the results of this test may unblind study personnel, results from the central lab will be provided for SCR and BSL only. The hsCRP results from samples 
collected during the treatment period will be revealed following database lock only 
12 BSA evaluation at BSL to determine if 
should be done or not. 
13 Sample has to be obtained fasting. 
14 Optional 


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Protocol No. CAIN457F2367 
 
8.1 
Screening 
Screening 
Screening will be flexible in duration based on the time required to wash out prior anti-
rheumatic medications and have duration of 4-10 weeks, during which time the participant will 
sign the ICF, be evaluated for eligibility and allowed sufficient time for potential medication 
washout (see Table 6-2, in addition to all other assessments indicated in Table 8-1). 
Screening will consist of two consecutive visits. During the first screening visit, initial 
assessments will be performed as outlined in Table 8-1. At that visit the duration of the washout 
period will be determined. The second screening visit will be performed as follows: 
• If the washout period is ≤ 4 weeks the investigator should proceed directly to second 
screening visit on the same day and complete all assessments in the next 4 weeks prior to 
randomization. 
• If the washout period is more than 4 weeks, the participant will be instructed to initiate 
necessary washout regimen and return for screening visit 2 at 4 weeks prior to 
randomization. 
The rationale is that in all cases second screening visit must occur within the 4 weeks prior to 
randomization. 
If participants do not have a chest X-ray obtained within 3 months preceding the screening visit, 
a chest X-ray should be performed. In order to minimize unnecessary exposure to radiation, the 
chest X-ray should only be performed after confirming that the participant meets all 
inclusion/exclusion criteria. In some sites selected by Novartis, the X-ray assessment may be 
replaced by MRI assessment. 
All participants evaluated at both screening visits for eligibility should not be screen failed on 
the basis of a medication requiring washout, unless the participant will be unable to complete 
the washout in the appropriate time frame before randomization. 
Participants who prematurely withdraw from the study will not be replaced. 
In the case where a safety laboratory assessment at screening and/or initial BSL is outside of 
the range specified in the exclusion criteria, the assessment may be repeated once prior to 
randomization. If the repeat value remains outside of the specified ranges, the participant must 
be excluded from the study. 
It is permissible to re-screen a participant if she/he fails the initial screening. Participants can 
be rescreened only once, and no study-related re-screening procedure should be performed prior 
to written re-consent by the participant. 
If a participant rescreens for the study, then the participant must sign a new ICF and be issued 
a new participant number prior to any screening assessment being conducted for the participant 
under the new screening participant number. For all participant s, the investigator/qualified site 
staff will record if the participant was rescreened on the rescreening CRF and any applicable 
screening numbers the participant was issued prior to the current screening number. 


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Clinical Trial Protocol (Version No. 00) 
 
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The date of the new informed consent signature must be entered on the Informed consent CRF 
to correspond to the new screening participant number. Informed Consent for a rescreened 
participant must be obtained prior to performing any study-related assessment or collecting any 
data for the Screening Visit.  
For rescreening, all screening assessments must be performed as per protocol.  
8.1.1 
Information to be collected on screening failures 
Participants who sign an informed consent form and subsequently found to be ineligible prior 
to randomization will be considered a screen failure. The reason for screen failure should be 
recorded on the appropriate CRF. The demographic information, informed consent, and 
Inclusion/Exclusion pages must also be completed for screen failure participants. No other data 
will be entered into the clinical database for participants who are screen failures, unless the 
participant experienced a serious adverse event during the screening phase (see SAE 
Section 10.1.3 for reporting details). 
Adverse events that are not serious will be followed by the investigator and collected only in 
the source data. 
If the participant fails to be randomized, the IRT must be notified within 2 days of the screen 
fail that the participant was not randomized, and the reason for not being randomized will be 
entered on the screening phase dispostion CRF page. 
Participants who are randomized and fail to start treatment, e.g. participants randomized in 
error, will be considered an early terminator. The reason for early termination should be 
recorded on the appropriate CRF. All AEs occurring after informed consent is signed should be 
recorded on the Adverse Event eCRF. 
Investigators will have the discretion to record abnormal test findings on the medical history 
CRF whenever in their judgment, the test abnormality occurred prior to the informed consent 
signature. 
8.2 
Participant demographics/other baseline characteristics 
Country-specific (China) regulations should be considered for the collection of demographic 
and BSL characteristics in alignment with eCRF. 
Participant demographic and BSL characteristic data to be collected on all participants include: 
age, sex, race, ethnicity, smoking history, relevant medical history/current medical condition 
present before signing informed consent. Where possible, diagnoses instead of symptoms will 
be recorded. 
Investigators will have the discretion to record abnormal test findings on the medical history 
eCRF if, in their judgment, the test abnormality occurred prior to the informed consent 
signature. 
8.3 
Efficacy 
The efficacy outcome measures used in this study are the standard measures, which are used 
across all PsA trials and required for filing. 
• ACR 20, 50 
 responses  


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Clinical Trial Protocol (Version No. 00) 
 
Protocol No. CAIN457F2367 
 
x Swollen Joint Count (SJC)/Tender Joint Count (TJC) 
x Patient's global assessment of disease activity (VAS) 
x Physician's global assessment of disease activity (VAS) 
x Patient's assessment of PsA pain intensity (VAS) 
x HAQ-DI© 
x hsCRP) and ESR 
x Disease Activity Score (DAS28) and EULAR response criteria 
x PASDAS 
 
 
 
 
 
 
 
 
All efficacy assessments should be performed prior to administration of study treatment. 
Details relating to the administration of all PROs are provided in Section 16.8 
8.3.1 
American College of Rheumatology (ACR) response 
The ACR response Section 16.5 will be used to determine efficacy (Felson et al 1995). A 
participant is defined as an ACR20 responder if, and only if, the following three conditions 
hold: 
x WKH\KDYHDLPSURYHPHQWLQWKHQXPEHURIWHQGHUMRLQWVEDVHGRQMRLQWV 
x WKH\KDYHDLPSURYHPHQWLQWKHQXPEHURIVZROOHQMRLQWVEDVHGRQMRLQts) 
x WKH\KDYHDLPSURYHPHQWLQWKUHHRIWKHIROORZLQJILYHGRPDLQV 
x Patient's global assessment of disease activity (PaGA) (measured on a VAS scale, 0-
100) 
x Physician's global assessment of disease activity (PhGA) (measured on a VAS scale, 
0-100) 
x Patient's assessment of PsA pain (measured on a VAS scale, 0-100) 
x Health Assessment Questionnaire – Disability Index (HAQ-DI©) score 
x Acute phase reactant (hsCRP or ESR) 
ACR50 = 50% improvement in at least 3 of the 5 measures and 50% improvement in the swollen 
and tender joint count. 
 
 
The components of ACR response are to be assessed at the visits/time points shown in 
Table 8-1. 
P
P


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Clinical Trial Protocol (Version No. 00) 
 
Protocol No. CAIN457F2367 
 
8.3.1.1 
Tender 78 joint count and swollen 76 joint count 
Joint counts will be performed by the independent 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. Refer Section 16.5 
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. 
 
 
Data is recorded for tender and swollen joints (right or left side), i.e. a box (yes, no or not 
applicable) needs to be ticked for all joints. 
8.3.1.2 
Patients global assessment of disease activity 
The patient's global assessment of disease activity will be performed using a Visual Analog 
Scale (VAS) of 100 mm ranging from "0 -very good" to "100= 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 today'. 
8.3.1.3 
Physicians global assessment of disease activity 
The PhGA 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 participant. 
8.3.1.4 
Patients assessment of PsA pain 
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'. 
8.3.1.5 
Health Assessment Questionnaire  Disability Index (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 participant's level of 
functional ability and activity restriction. The disability assessment component of the HAQ, the 
HAQDI©, assesses a participant'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. 


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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 participants with 
PsA. 
8.3.1.6 
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 BSL only. The hsCRP results from samples collected during the 
treatment period will be revealed following database lock only. 
8.3.1.7 
Erythrocyte sedimentation rate (ESR) 
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 8-1. 
Local ESR test will be performed. 
8.3.2 
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 of Disease Activity. 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. Refer Section 16.6. 
The components of DAS28 are to be assessed at the visits/time points shown in Table 8-1. 
8.3.3 
Psoriatic Arthritis Disease Activity Score (PASDAS) 
PASDAS is a new composite measure developed to access disease activity in Psoriasis 
(GRACE Project) Helliwell et al 2012 . It is calculated by utilizing seven measures; the seven 
components are: Patient reported measures
 
skin, peripheral joint counts (Tender 
and Swollen joint counts),
 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) 
+ (0.102 x LN (CRP + 1)) +2)*1.5 


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8.3.3.1 
VAS for PASDAS assessment 
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 ’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’. 


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8.3.8 
Appropriateness of efficacy assessments 
The efficacy outcome measures used in this study are the standard measures used across many 
PsA trials and they are required for regulatory filing. 
8.4 
Safety 
Safety assessments are specified below with the assessment schedule detailing when each 
assessment is to be performed. 
For details on AE collection and reporting, refer to AE section. 
PPD


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Evaluation of all AEs and SAEs including injection site reactions, electrocardiograms (ECGs), 
physical examination, and vital signs and laboratory assessments. 
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 
• ECG 
• Local tolerability (Injection site reactions) 
• Laboratory evaluations (Hematology, Clinical Chemistry, Lipid Panel, Urinalysis) 
• Pregnancy and assessment of fertility 
• Tolerability of secukinumab 
Table 8-4 
General safety assessments 
Assessment 
Specification 
Physical examination 
A complete physical examination will include the examination of general appearance, 
skin, neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, 
lymph nodes, extremities, vascular, and neurological system.If indicated based on 
medical history and/or symptoms, rectal, external genitalia, breast, and pelvic exams 
will be performed.  
A physical exam will be at all visits starting from visit 2 (i.e. the screening 2 visit) until 
the follow-up visit at Week F60 as indicated in Table 8-1. Whenever possible, 
assessments for an individual participant should be performed by the same member 
of the study site staff throughout the study. 
Information for all physical examinations must be included in the source 
documentation at the study site. Clinically relevant findings that are present prior to 
signing informed consent must be recorded on the appropriate CRF that captures 
medical history. Significant findings made after signing informed consent which meet 
the definition of an Adverse Event must be recorded as an adverse event. 
Vital signs 
Vital signs include blood pressure and pulse measurements. Vital signs will be 
assessed at every scheduled visit from visit 2 (i.e. the screening 2 visit) until the 
follow-up visit at Week F60 as indicated in Table 8-1. Whenever possible, 
assessments should be performed by the same member of the study site staff using 
the same validated device throughout the study. 
After the participant has been sitting for five minutes, with back supported and both 
feet placed on the floor, systolic and diastolic blood pressure will be measured three 
times using an automated validated device, e.g. OMRON, with an appropriately sized 
cuff. The repeat sitting measurements will be made at 1 - 2 minute intervals and the 
mean of the three measurements will be used. In case the cuff sizes available are not 
large enough for the participant's arm circumference, a sphygmomanometer with an 
appropriately sized cuff may be used. Three measurements will be recorded in the 
source documentation and should be entered on the Vital Signs eCRF. 
No specific action is pre-defined within this protocol to respond to specific abnormal 
vital signs, as it will be decided by the investigator whether and which specific action 
needs to be taken to respond to any abnormal values, taking into account the overall 
status of the participant. 


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Assessment 
Specification 
Height and weight 
Height and body weight will be measured as indicated in Table 8-1. 
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram (kg) in indoor 
clothing but without shoes) will be measured. 
If possible, body weight assessments should be performed by the same study site 
staff member using the same scale throughout the study.  
8.4.1 
Laboratory evaluations 
A central laboratory will be used for analysis of all specimens listed below (except for ESR, 
pregnancy test, Hepatitis B Virus (HBV), Hepatitis B Virus (HCV) and Human 
immunodeficiency virus (HIV ). Details on the collection, shipment of samples and reporting 
of results by the central laboratory are provided in the laboratory manual. Refer to the 
Laboratory Manual for identification of laboratory reference range values and the schema for 
notification of site staff and Novartis for out of range values. 
Blood withdrawals and safety assessments should be done prior to study treatment 
administration and should be taken as shown in Table 8-1. 
Laboratory evaluations listed below are to be measured at scheduled visit as indicated in 
Table 8-1. 
Table 8-5 
Laboratory evaluations 
Test Category 
Test Name 
Hematology 
Hemoglobin, Red blood cells (RBC), Platelets, White blood cells, Differential 
(Basophils, Eosinophils, Lymphocytes, Monocytes, Neutrophils including 
Bands). 
Chemistry 
Albumin (Alb), Alkaline phosphatase (ALP), Alanine Aminotransferase (ALT) , 
Aspartate Aminotransferase (AST) , Gamma-glutamyl-transferase (GGT), 
Lactate dehydrogenase (LDH), Bicarbonate, Calcium, Magnesium, Phosphorus, 
Chloride, Sodium, Potassium, Creatinine, , Total Bilirubin, Total Protein, Blood 
Urea Nitrogen (BUN) or Urea, Uric Acid and Glucose. 
Urinalysis  
Macroscopic Panel: pH, Glucose, Protein, Blood, Bilirubin, Urobilinogen, 
Ketones, , Specific Gravity, White Blood Cells (WBC). 
A midstream urine sample (approx. 30 mL) will be obtained, in order to avoid 
contamination with epithelial cells and sediments, and allow proper 
assessments. 
Urine sample should be collected and sent to central lab for analysis.  
If the results are not in the normal ranges, the investigator will evaluate whether 
further testing is required or not. This testing will be done at the local lab. 
Lipid panel 
High-density Lipoprotein (HDL), Low-density Lipoprotein (LDL), total cholesterol 
and triglycerides. 
The lipid panel will be measured from a fasting sample. 
Autoantibodies 
Anti-nuclear antibodies (ANA) and anti-dsDNA will be assessed at the visits/time 
points indicated in Table 8-1. 
In addition, RF and anti-CCP must be tested negative for a participant being 
eligible in this study as per inclusion criteria 5. 
Hepatitis markers & HIV 
(locally, as applicable) 
Hepatitis and HIV testing is to be performed at the second Screening visit and 
the results to be known prior to randomization to determine the participant's 
eligibility for the trial. 
Hepatitis testing will include hepatitis B surface antigen (HBsAg) and anti-HCV 
antibodies. 
Pregnancy Test  
(locally) 
Serum / Urine pregnancy test for Women of Childbearing Potential (WoCBP). 
Recommended to perform urine pregnancy test at designated visits in local lab, 
if not feasible alternatively the serum pregnancy test should be performed. 


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Clinically significant abnormalities must be recorded as either medical history/current medical 
conditions or adverse events as appropriate. All participants 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.   
Clinically notable lab values are defined in Section 16.1. 
8.4.2 
Electrocardiogram (ECG) 
A standard 12 lead ECG will be performed as indicated in Table 8-1. In this study, local 
electrocardiogram (ECG) will be used. ECGs must be recorded after 10 minutes rest in the 
supine position to ensure a stable BSL. The preferred sequence of cardiovascular data collection 
during study visits is ECG collection first, followed by vital signs, and blood sampling. 
The original ECGs on non-heat-sensitive paper appropriately signed, must be collected and 
archived at the study site.  
Each ECG tracing must be labeled with study number, subject initials, subject number, date and 
time, and filed in the study site source documents. Investigator should document clinical 
evaluation in source. For any ECGs with subject safety concerns, two additional ECGs must be 
performed to confirm the safety finding 
Although there is no exclusion criterion based on ECG results, the BSL ECG at the 
Randomization Visit must be reviewed locally for major abnormalities prior to dosing. 
Clinically significant abnormalities must be recorded on the CRF as either medical 
history/current medical conditions or adverse events as appropriate. 
8.4.3 
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 for the entire study period (see exclusion 
criteria definitions, Section 5.2). 
All pre-menopausal women who are not surgically sterile will have local urine pregnancy tests, 
as indicated in Table 8-1. Additional pregnancy testing might be performed if requested by local 
requirements. A positive urine test requires immediate interruption of study drug and needs to 
be confirmed with a serum β-hCG test (serum pregnancy test to be done locally). If positive, 
the participant must be discontinued from the study treatment. 
Assessments of fertility  
Medical documentation of oophorectomy, hysterectomy, or tubal ligation must be retained as 
source documents. Subsequent hormone level assessment to confirm the woman is not of child-
bearing potential must also be available as source documentation in the following cases: 
1. Surgical bilateral oophorectomy without a hysterectomy 
2. Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile. 


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In the absence of the above medical documentation, follicle stimulating hormone (FSH) testing 
is required of any female participant regardless of reported reproductive/menopausal status at 
screening/BSL. 
8.4.4 
Other safety evaluations 
8.4.4.1 
Chest X-ray 
Standard chest X-ray (PA view) will be performed except for those who have had a valid X-ray 
done within 3 months of screening. If participants do not have a chest X-ray obtained within 3 
months preceding the Screening visit, a chest X-ray should be performed. In order to minimize 
unnecessary exposure to radiation, the chest X-ray should only be performed after confirming 
that the participant meets all inclusion/exclusion criteria. In some sites selected by Novartis, the 
X-ray assessment may be replaced by MRI assessment. 
8.4.4.2 
QuantiFERON TB-Gold test 
Either a QuantiFERON TB-Gold test or a PPD skin test must be performed at Screening. 
participants with a positive test may participate in the study if further work up (according to 
local practice/guidelines) establishes conclusively that the participant has no evidence of active 
tuberculosis, or if presence of latent tuberculosis is established then treatment according to local 
country guidelines must have been initiated. 
A QuantiFERON TB-Gold test is to be performed at the second screening visit and the results 
to be known prior to randomization to determine the participant’s eligibility for the trial. The 
test will be used to screen the participant population for latent tuberculosis infection. 
The test will be analyzed by the central laboratory. Details on the collection, processing and 
shipment of samples and reporting of results by the central laboratory are provided in the 
laboratory manual. 
8.4.4.3 
PPD skin test 
A PPD skin test is to be performed at screening and read within 72 hours and before 
randomization to determine the participant's eligibility for the trial. The test dose is 
bioequivalent to 5 tuberculin units of standard PPD injected intradermally, usually into the volar 
surface of the forearm. The site is cleaned and the PPD extract is then injected into the most 
superficial layer under the skin. If given correctly, the injection should raise a small wheal of 
about 5 mm, which resolves within 10-15 minutes. 
Because the reaction (induration) will take 48-72 hours to develop, the participants must return 
to the investigators’ site within that time for a proper evaluation of the injection site. This will 
determine whether the participant has had a significant reaction to the PPD test. A reaction is 
measured in millimeters of induration (hard swelling) at the site. A PPD skin induration ≥5 mm 
(or according to local practice/guidelines) is interpreted as a positive result. 
8.4.5 
Appropriateness of safety measurements 
The safety assessments selected are standard for this indication/participant population. 12-week 
period following the last administration of study treatment should be reported. 


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8.5 
Additional assessments 
8.5.1 
Clinical Outcome Assessments (COAs) 
8.5.1.1 
Clinician Reported Outcomes (ClinRO) 
The impact of study treatment on participant's disease activity will be assessed by the following 
measures: 
x Swollen Joint Count (SJC)/Tender Joint Count (TJC) - Refer to Section 8.3.1.1 for details 
x Physician's global assessment of disease activity (PhGA, VAS) – Refer to 
Section 8.3.1.3 for details 
 
 
 
 
 
 
 
 
8.5.1.2 
Patient reported outcomes (PRO) 
Participant will be asked to complete the following PRO measures: 
2. Medical Outcome Short Form Health Survey (SF-36 v2) version 2 (Acute form) 
3. HAQ-DI© 
4. Patient's Global Assessment of Disease Activity 
5. Patient’s assessment of PsA Pain 
The participant must be given the PRO measure(s) to be completed at the scheduled visit before 
any clinical assessments are conducted. Participant's refusal to complete all or any part of a 
PRO measure should be documented in the study data capture system and should not be 
captured as a protocol deviation. Handling of protocol deviations can be modified if needed per 
study protocol. 
 Participant questionnaires should be completed in the language most familiar to the participant. 
The participants should be given sufficient space and time to complete the PRO measures. 
The site personnel should check PRO measures for completeness and ask the participant to 
complete any inadvertently missing responses. The responses stored electronically in the 
database will be considered the source file. 
Completed questionnaires must be reviewed and assessed by the investigator for responses 
which may indicate potential AEs or SAEs before any clinical study examinations. This 
assessment should be documented in study source records. If AEs or SAEs are confirmed, study 
investigators should not encourage the participant to change responses reported in the 
completed questionnaires. Study investigators must follow reporting instructions outlined in 
section 10 of the study protocol. 
HAQ-DI© , Patient’s assessment of PsA Pain and Patient's Global Assessment of Disease 
Activity are already described in Efficacy Section 8.3.1.5 , Section 8.3.1.4 and Section 8.3.1.2, 
respectively. 
PPD
PPD


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Trial Feedback 
This trial will include an option for participants to complete an anonymized questionnaire, ‘Trial 
Feedback Questionnaire’ (TFQ) for participants to provide feedback on their experience in a 
Novartis clinical trial. The TFQ is a validated web-based questionnaire. The TFQ has been 
tested and validated by research conducted by Adelphi, PatientsLikeMe and HRM using 
established PRO methodology and is based on feedback from 400 adult participants across 
different therapeutic areas. 
The optional questionnaire will be completed at the site at Week F60, end of the study period. 
TFQ questions relate to both protocol-specified and site-specific components, including study 
burden and interaction with site staff. 
Feedback is anonymous. Individual participant level responses will not be reviewed by 
Investigators. Responses will be used by Novartis to understand where improvements can be 
made in the clinical trial process. This questionnaire does not collect data about the participant's 
disease, symptoms, treatment effect or adverse events and therefore the TFQ data is not trial 
data. 
The TFQ data will be stored in the Electronic Clinical Outcome Assessment (eCOA) vendor 
provider database, separate from the clinical trial database. 
8.5.1.4 
Medical outcome short form health survey (SF-36), Version 2 (acute 
form) 
The SF-36 is a widely used and extensively studied instrument to measure HRQoL among 
healthy participants and participants with acute and chronic conditions. It consists of eight 
subscales that can be scored individually: Physical Functioning, Role- Physical, Bodily Pain, 
General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health 
Ware et al 1993. Two overall summary scores, the Physical Component Score (PCS) 
 
also can be computed Ware et al 1994. The SF-36 has proven 
useful in monitoring general and specific populations, comparing the relative burden of 
different disease, differentiating the health benefits produced by different treatments, and in 
screening individual participants. 
The purpose of the SF-36 in this study is to assess the Health-Related Quality of Life (HRQoL) 
of participants. Given the acute nature of this disease, version 2, with a one week recall period, 
will be used in this study. 


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9 
Study discontinuation and completion 
9.1 
Discontinuation and completion 
9.1.1 
Study treatment discontinuation and study discontinuation 
Discontinuation of study treatment for a participant occurs when study treatment is stopped 
earlier than the protocol planned duration and can be initiated by either the participant or the 
investigator. 
Participants may voluntarily discontinue from the study treatment for any reason at any time. 
They may be considered discontinued if they state an intention to withdraw, fail to return for 
visits, or become lost to follow-up for any other reason. 
If premature discontinuation of study treatment occurs for any reason, the investigator must 
make every effort to determine the primary reason for a participant’s premature discontinuation 
from the study treatment and record this information on the appropriate Study Phase 
Completion eCRF. 
Study treatment must be discontinued if the investigator determines that continuation of study 
treatment would result in a significant safety risk for a participant. 
The following circumstances require study treatment discontinuation: 
• Participant/guardian decision 
• participant's request to terminate treatment 
• Use of prohibited treatment as per recommendations in the prohibited treatment section 
(Section 6.2.2) 
• Any situation in which study participation might result in a safety risk to the participant 
• Following emergency unblinding of the treatment arm (Section 6.6.2) 
• Emergence of the following AEs: 
• Any severe or serious AE that is not compatible with administration of study medication, 
including AEs that require treatment with an unacceptable co-medication 
• Onset of lymphoproliferative disease or any malignancy except for treated basal cell 
carcinoma, treated actinic keratoses, treated in situ carcinoma of the cervix or non- 
invasive malignant colon polyps which are being or have been removed 
• Life-threatening infection 
• Severe hypersensitivity reaction or anaphylactic reaction 
• Any laboratory abnormalities that in the judgment of the investigator are clinically 
significant and are deemed to place the participant at a safety risk for continuation in the 
study (A general guidance on clinically notable laboratory values is provided in 
Section 16.1). 
• Pregnancy 
• Use of any biologic immunomodulating agent except secukinumab 
• Any protocol deviation that results in a significant risk to the participant’s safety. 


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The appropriate personnel from the site and Novartis will assess whether study treatment should 
be discontinued for any participant whose treatment code has been broken inadvertently for any 
reason. 
Participants who prematurely discontinued from study treatment during Treatment Period 1 had 
to return for assessments associated with End of TP1 visit (4 weeks after the last study 
treatment) and the End of study visit (12 weeks after the last study treatment). Participants who 
prematurely discontinued during Treatment Period 2 had to return and complete assessments 
associated with End of TP2 visit (4 weeks after the last study treatment) and End of study visit 
(12 weeks after the last study treatment), see Table 8-1 
• Participants unwilling to continue attending further study visits after prematurely 
discontinuing the study treatment should return for the end of study (EOS) visit 12 weeks 
after the last administration of the study treatment. 
• Participants willing to continue attending study visit should continue attending all 
subsequent scheduled site visits for clinical and safety study assessments, except study 
treatment administration. 
• Participants initially continue attending site visits after premature study treatment 
discontinuation may decide to discontinue study at any time. For those participants, the 
EOS visit will be performed at time of study discontinuation. Note: the EOS visit must 
always be completed at least 12 weeks after the last study treatment administration. 
If discontinuation of study treatment occurs, the investigator should make a reasonable effort 
to understand the primary reason for the participant‘s premature discontinuation of study 
treatment and record this information. For participants who discontinue study treatment, a 
Dosage Administration Record eCRF should be completed, giving the date and primary reason 
for stopping study treatment. 
Participants who discontinue study treatment or who decide they do not wish to participate in 
the study further should NOT be considered withdrawn from the study UNLESS they withdraw 
their consent (see 'Withdrawal of Informed Consent' Section 9.1.2). Where possible, they 
should return for the follow-up assessments indicated in the Assessment Schedule. If they 
fail to return for these assessments for unknown reasons, every effort (e.g., telephone, e-mail, 
letter) should be made to contact the participant/pre-designated contact as specified in the lost 
to follow-up section. This contact should preferably be done according to the study visit 
schedule. 
If the participant cannot or is unwilling to attend any visit(s), the site staff should maintain 
regular telephone contact with the participant, or with a person pre-designated by the 
participant. This telephone contact should preferably be done according to the study visit 
schedule. 
After study treatment discontinuation, at a minimum, in abbreviated visits, the following data 
should be collected at clinic visits or via telephone/email contact: 
• New / concomitant treatments 
• Adverse Events / Serious Adverse Events 
The investigator must also contact the IRT to register the participant’s discontinuation from 
study treatment. 


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If discontinuation occurs because treatment code has been broken, please refer to Emergency 
breaking of treatment code section (Section 6.6.2). 
9.1.2 
Withdrawal of informed consent 
Participants may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent (WoC) occurs only when a participant: 
• 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 
In this situation, the investigator should make a reasonable effort (e.g. telephone, e-mail, letter) 
to understand the primary reason for the participant’s decision to withdraw his/her consent and 
record this information. 
Where consent to the use of personal and coded data is not required, participant therefore cannot 
withdraw consent. They still retain the right to object to the further use of personal data. 
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study discontinuation. A final 
evaluation at the time of the participant’s study discontinuation should be made as detailed in 
the assessment table. 
Novartis will continue to retain and use all research results (data) that have already been 
collected for the study evaluation. 
9.1.3 
Lost to follow-up 
For participants whose status is unclear because they fail to appear for study visits without 
stating an intention to discontinue or withdraw, the investigator must show "due diligence" by 
documenting in the source documents steps taken to contact the participant, e.g. dates of 
telephone calls, registered letters, etc. A participant should not be considered as lost to follow-
up until due diligence has been completed or until his/her scheduled End of Study visit would 
have occurred. 
9.1.4 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit/ risk assessment of participating in the study, practical reasons (including 
slow enrollment), or for regulatory or medical reasons. In taking the decision to terminate, 
Novartis will always consider the participant welfare and safety. Should early termination be 
necessary, participants must be seen as soon as possible and treated as a prematurely withdrawn 
participant. 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 participant’s interests. The 
investigator or sponsor depending on the local regulation will be responsible for informing 
IRBs/IECs of the early termination of the trial. 


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9.2 
Study completion and post-study treatment 
A participant will be considered to have completed the study if he/she received a total of 52 
weeks of study treatment and upon completion of the scheduled study assessments and 
procedures up to and including Week F60. 
Information on the participant’s completion or discontinuation of the study and the reason for 
discontinuation of the study will be recorded on the appropriate Study Phase Completion eCRF 
page. 
In any case, the investigator or site staff must contact the IRT as soon as possible to record the 
participant’s study completion (Week F60) and/or discontinuation. 
The investigator must provide follow-up medical care for all participants who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care. This care may 
include initiating another treatment outside of the study as deemed appropriate by the 
investigator. This treatment may be any non-biologic DMARD. In case of a biologic treatment, 
a waiting period of 3 months before initiating the treatment is recommended. 
Continuing care should be provided by investigator and/or referring physician based on 
participant availability for follow-up. This care may include enrollment in a roll over study or 
equivalent program, as applicable, provided the participant completed end of study visit 
(treatment period and follow up visits) and could still deriving benefit from the study treatment 
based on investigator’s decision. 
10 
Safety monitoring and reporting 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a participant 
or clinical investigation participant after providing written informed consent for participation 
in the study. Therefore, an AE may or may not be temporally or causally associated with the 
use of a medicinal (investigational) product. 
The investigator has the responsibility for managing the safety of individual participant and 
identifying adverse events. 
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
The occurrence of adverse events must be sought by non-directive questioning of the participant 
at each visit during the study. Adverse events also may be detected when they are volunteered 
by the participant during or between visits or through physical examination findings, laboratory 
test findings, or other assessments. 
Adverse events must be recorded under the signs, symptoms, or diagnosis associated with them, 
accompanied by the following information (as far as possible) (if the event is serious refer to 
Section 10.1.2): 


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1. 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 
2. Its relationship to the study treatment. If the event is due to lack of efficacy or progression 
of underlying illness (i.e. progression of the study indication) the assessment of causality 
will usually be 'Not suspected'. The rationale for this guidance is that the symptoms of a 
lack of efficacy or progression of underlying illness are not caused by the trial drug, they 
happen in spite of its administration and/or both lack of efficacy and progression of 
underlying disease can only be evaluated meaningfully by an analysis of cohorts, not on a 
single participant 
3. Its duration (start and end dates) or if the event is ongoing, an outcome of "not 
recovered/not resolved" or "recovering/resolving" must be reported based on the 
investigator's judgment 
4. Whether it constitutes a SAE (see Section 10.1.2 for definition of SAE) and which 
seriousness criteria have been met 
5. Action taken regarding with study treatment. 
All adverse events must 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 drug(s) permanently discontinued; 
• Concomitant medication given; 
• Non-drug therapy given. 
6. Its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown) 
Conditions that were already present at the time of informed consent should be recorded in 
medical history of the participant. 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Adverse event monitoring should be continued for at least 12 weeks following the last dose of 
study treatment. 
Once an adverse event is detected, it must be followed until its resolution or until it is judged to 
be permanent (e.g. continuing at the end of the study), and assessment must be made at each 
visit (or more frequently, if necessary) of any changes in severity, the suspected relationship to 
the interventions required to treat it, and the outcome. 
Information about adverse drug reactions for the investigational drug can be found in the 
Investigator's Brochure (IB). 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria: 


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• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
BSL or the previous visit, or values which are considered to be non-typical in participant with 
the underlying disease. Alert ranges for laboratory and other test abnormalities are included in 
Section 16.1. 
10.1.2 
Serious adverse events 
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing) 
undesirable sign(s), symptom(s), or medical condition(s)] which meets any one of the following 
criteria: 
• fatal 
• life-threatening 
Life-threatening in the context of a SAE refers to a reaction in which the participant was at risk 
of death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to the ICH-E2D Guidelines). 
• results in persistent or significant disability/incapacity 
• constitutes a congenital anomaly/birth defect 
• requires in participant hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:  
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
• elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
• social reasons and respite care in the absence of any deterioration in the participant’s 
general condition 
• treatment on an emergency out participant basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
• is medically significant, e.g. defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as "medically significant". Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that 
do not result in hospitalization or development of dependency or abuse (please refer to the ICH-
E2D Guidelines). 


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All new malignant neoplasms will be assessed as serious under "medically significant" if other 
seriousness criteria are not met . 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All reports of intentional misuse and abuse of the product are also considered serious adverse 
event irrespective if a clinical event has occurred. 
10.1.3 
SAE reporting 
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
has provided informed consent and until 12 weeks following the last administration of study 
treatment  must be reported to Novartis safety within 24 hours of learning of its occurrence. 
Detailed instructions regarding the submission process and requirements are to be found in the 
investigator folder provided to each site. 
Detailed instructions regarding the submission process and requirements are to be found in the 
investigator folder provided to each site. Any SAEs experienced after the 12 week period 
following the last administration of study treatmen should only be reported to Novartis safety 
if the investigator suspects a causal relationship to study treatment. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at a 
different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event. 
If the SAE is not previously documented in the IB or Package Insert (new occurrence) and is 
thought to be related to the study treatment, a Chief Medial Office & Patient Safety (CMO & 
PS) department associate may urgently require further information from the investigator for 
health authority reporting. Novartis may need to issue an Investigator 
Notification (IN) to inform all investigators involved in any study with the same study treatment 
that this SAE has been reported. 
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with EU Guidance 
2011/C 172/01 or as per China national regulatory requirements. 
Note: SAEs must be reported to Novartis within 24 hours of the investigator learning of its 
occurrence/receiving follow-up information 
10.1.4 
Pregnancy reporting 
Pregnancies 
To ensure subject safety, each pregnancy occurring after signing the informed consent must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications. 


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Pregnancy should be recorded and reported by the investigator to the Novartis Chief Medical 
Office and Patient Safety (CMO&PS). Pregnancy follow-up should be recorded on the same 
form and should include an assessment of the possible relationship to the study treatment. Any 
SAE experienced during pregnancy must be reported. Information will be collected at three 
time points after the estimated date of delivery and for a period of 12 months.  
Follow up of the pregnancy (female participant) should be according to the following schedule: 
Tracking of pregnancy cases occurs until after Expected Delivery Date (EDD) for all 
prospective pregnancy cases received from clinical studies (including pregnancies where the 
participant was exposed to placebo and pregnancies due to the conduct of the study). 
• EDD + 1 month (mandatory for all cases). Requesting the pregnancy outcome and other 
clinically relevant pregnancy data or changes in data. 
• EDD + 2 month (mandatory if no answer is obtained after request at EDD+1 month). A 
reminder letter for the outcome. 
• The follow-up at EDD + 3 months is mandatory for all cases of live birth. Information on 
the status of the baby 3 months after delivery and information on any development issue 
or abnormality that would not be seen at birth must be collected. 
• The follow up at EDD + 12 months is mandatory for all cases of live birth. Information on 
the status of the baby 12 months after delivery and information on any development issue 
or abnormality that would not be seen at birth must be collected. If the pregnancy case is 
lost to follow-up (e.g., no response after 3 attempts) this information must be transferred 
to the Safety Desk of the Country participant Safety. 
10.1.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate CRF irrespective of whether or not associated with an AE/SAE and reported to 
Safety only if associated with an SAE. Misuse or abuse will be collected and reported in the 
safety database irrespective of it being associated with an AE/SAE within 24 hours of 
Investigator’s awareness. 


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Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error type 
Document in Dosing 
CRF (Yes/No) 
Document in AE eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated with an 
AE 
Only if associated with an 
SAE 
Misuse/Abuse 
Yes 
Yes 
Yes, even if not 
associated with a SAE 
For more information on AE and SAE definition and reporting requirements, please see the 
respective sections. 
10.2 
Additional Safety Monitoring 
10.2.1 
Liver safety monitoring 
To ensure participant safety and enhance reliability in determining the hepatotoxic potential of 
an investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed 
The following two categories of abnormalities / AEs have to be considered during the course 
of the study (irrespective of whether classified/reported as AE/SAE): 
• Liver laboratory triggers, which will require repeated assessments of the abnormal 
laboratory parameter 
• Liver events, which will require close observation, follow-up monitoring and completion 
of the standard base liver CRF pages 
Please refer to Section 16.2 for complete definitions of liver laboratory triggers and liver events. 
Once a participant is exposed to study treatment, every liver event defined 
in Section 16.2 should be followed up by the investigator or designated personnel at the trial 
site, as summarized below. Additional details on actions required in case of liver events are 
outlined in Section 16.2. Repeat liver chemistry tests (i.e. ALT, AST, total bilirubin (TBL), 
prothrombin time(PT)/international Normalized Ratio (INR), ALP and GGT) to confirm 
elevation. 
• These liver chemistry repeats will be performed using the central laboratory. If results will 
not be available from the central laboratory, then the repeats can also be performed at a 
local laboratory to monitor the safety of the participant. If a liver event is subsequently 
reported, any local liver chemistry tests previously conducted that are associated with this 
event should have results recorded on the appropriate CRF. 
• If the initial elevation is confirmed, close observation of the participant will be initiated, 
including consideration of treatment interruption if deemed appropriate. 
• Discontinuation of the investigational drug (refer to the Discontinuation of study treatment 
section), if appropriate 
• Hospitalization of the participant if appropriate 
• Causality assessment of the liver event 
• Thorough follow-up of the liver event should include  


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• These investigations can include based on investigator's discretion: serology tests, 
imaging and pathology assessments, hepatologist's consultancy; obtaining more 
detailed history of symptoms and prior or concurrent diseases, history of concomitant 
drug use, exclusion of underlying liver disease 
All follow-up information and procedures performed must be recorded as appropriate in the 
eCRF. 
10.2.2 
Renal safety monitoring 
There has been no safety signal for nephrotoxicity with secukinumab to participants and healthy 
participants exposed, and from a mechanism of action standpoint there is no known effect of 
blocking IL-17A on the kidney. All participants with laboratory tests containing clinically 
significant abnormal values (see Section 16.1) are to be followed until the values return to 
normal ranges or until a valid reason, other than treatment related AE, is defined. Standard renal 
function tests (blood urea nitrogen, serum creatinine) will be obtained at regular intervals, but 
special measures for renal safety monitoring are not planned. 
11 
Data Collection and Database management 
11.1 
Data collection 
Designated investigator staff will enter the data required by the protocol into the eCRF. The 
eCRFs have been built using fully validated secure web enabled software that conforms to 21 
CFR (Code of Federal Regulation) Part 11 requirements, Investigator site staff will not be given 
access to the EDC system until they have been trianed. Automatic validation programs check 
for data discrepancies in the eCRFs. The EDC system allows modification and/or verification 
of the entered data by the investigator staff. 
The investigator/designee is responsible for assuring that the data (entered into eCRF) is 
complete, accurate, and that entry and updates are performed in a timely manner. The 
Investigator must certify that the data entered are complete and accurate. After final database 
lock, the investigator will receive copies of the participant data for archiving at the 
investigational site. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
11.2 
Database management and quality control 
Novartis personnel will review the data entered by investigational staff for completeness and 
accuracy. Electronic data queries stating the nature of the problem and requesting clarification 
will be created for discrepancies and missing values and sent to the investigational site via the 
EDC system. Designated investigator site staff are required to respond promptly to queries and 
to make any necessary changes to the data. 
Concomitant medications and prior medications entered into the database will be coded using 
the World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions, 


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concomitant and prior procedures/non-drug therapies, and adverse events will be coded using 
the Medical Dictionary for Regulatory Activities (MedDRA) terminology. 
Randomization/re-randomization codes and data about all study treatment(s) dispensed to the 
participant and all dosage changes will be tracked using an IRT. The system will be supplied 
by a vendor, who will also manage the database. The data will be sent electronically to Novartis 
at specific timelines. 
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. The 
code break functionality will remain available until study shut down or upon request of 
Novartis. 
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked and the treatment codes will be unblinded and made 
available for data analysis. Any changes to the database after that time can only be made after 
written agreement by Novartis development management. 
11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and data capture requirements (i.e., eCRFs) with the 
investigators and their staff. During the study, Novartis employs several methods of ensuring 
protocol and GCP compliance and the quality/integrity of the sites’ data. The field monitoring 
will be performed according to relevant sections of the monitoring plan. Monitors will visit the 
site to check the completeness and appropriate storage of investigator site files, participant 
records, the accuracy of data capture / data entry, the adherence to the protocol, to the study 
procedures and to Good Clinical Practice. The monitor is also responsible to report any 
deviation from the protocol or defined procedures and to follow the progress of enrollment. 
Monitors are responsible 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 monitors during these visits. Continuous remote monitoring of each site’s data may be 
performed by a centralized Novartis/CRA (Clinical Research Associate) organization. 
Additionally, a central analytics organization may analyze data and identify risks and trends for 
site operational parameters, and provide reports to Novartis clinical teams to assist with trial 
oversight. 
The investigator must maintain source documents for each participant 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 eCRFs must be traceable to these source documents in the 
participant’s file. The investigator must also keep the original informed consent forms signed 
by the participant (a signed copy is given to the participant). The investigator must give the 
monitor access to all relevant source documents in paper or electronic format to confirm their 
consistency with the data capture and/or data entry. Novartis monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the eCRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
participants will be disclosed. 


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12 
Data analysis and statistical methods 
The primary endpoint analysis will be performed after all participants complete Week 16 as 
described in Section 12.7 and the final analysis will be conducted on all participant data at the 
time the study ends. Any data analysis carried out independently by the investigator should be 
submitted to Novartis before publication or presentation. 
Summary statistics for continuous variables will generally include the number of participants 
(N), minimum, lower quartile, mean, standard deviation (SD), median, upper quartile, and 
maximum. For binary or discrete variables the absolute number of participants in each category 
and relative frequencies will be provided. 
In case of a global health disruptive event, such as pandemic/epidemic (e.g., COVID-19), 
affecting the ability of the patient or the site to adhere to protocol requirements and assessments 
and therefore leading to a potential increase in the number of missing measurements, additional 
anyalysis populations may be defined as per the instructions and procedures outlined 
in Section 16.9. 
The efficacy evaluation of secukinumab relative to placebo will generally focus on the first 16 
weeks of treatment unless otherwise specified. 
Data analyses will be presented by treatment group. Efficacy and safety data for the 16-week 
placebo-controlled period and the entire treatment period as appropriate will be presented by 
the following two treatment groups. participants may be included in more than one treatment 
group for some analyses (e.g., exposure adjusted adverse events over the entire treatment 
period). 
These treatment groups represent the regimens to which participants will be eligible to be 
randomized: 
• Secukinumab 150 mg regimen 
• Placebo regimen 
Note that the treatment groups above for a participant may differ depending on the time period 
of the analysis and whether one assesses the participant for efficacy or safety (see Section 12.1 
for details).  
Data may also be presented by a combination of the ‘original’ and ‘switch’ treatment groups. 
These treatment groups represent the treatment combinations the participants experience over 
the course of the entire trial. 
12.1 
Analysis sets 
The following analysis sets will be used in this study: 
Randomized set: The randomized set will be defined as all participants who were randomized. 
Unless otherwise specified, mis-randomized participants (mis-randomized in IRT) will be 
excluded from the randomized set. 
Mis-randomized participants are defined as those participants who were mistakenly randomized 
into the IRT prior to the site confirming all eligibility criteria had been met and to whom no 
study medication was given. Mis-randomized participants are treated as screen failures. 


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Full analysis set (FAS): The FAS will be comprised of all participants from the randomized 
set to whom study treatment has been assigned. Following the intent-to-treat principle, 
participants will be evaluated according to the treatment assigned to at randomization. Three 
subsets of FAS are defined as follows: 
• Psoriasis subset: The psoriasis subset will include all FAS participants who have ≥ 3% of 
theBSA affected by psoriatic skin involvement at BSL. 
Safety set: The safety set includes all participants who took at least one dose of study treatment 
during the treatment period. participants will be evaluated according to treatment received. 
12.2 
Participant demographics and other baseline characteristics 
Demographics and BSL characteristics 
Summary statistics will be presented for continuous demographic and BSL characteristic 
variables for each treatment group and for all participants in the randomized set. The number 
and percentage of participants in each category will be presented for categorical variables for 
each treatment group and all participants. 
The following demographic variables and BSL disease characteristics will be summarized by 
treatment groups: 
• Gender, age, race, ethnicity, weight, height, and Body Mass Index (BMI) 
• Anti-TNF treatment history (naïve or inadequate responder), ACR components and other 
disease-related measures (e.g., DAS28, presense of dactylitis, presense of enthesitis, time 
since first diagnosis of PsA, participant with psoriasis ≥ 3%), etc., number of prior 
biologic PsA therapies, dose of MTX or other DMARD at randomization. 
Medical history 
A history of PsA with focus on previous extra-articular involvement and past therapies for PsA 
will be obtained and summarized by treatment group. Any other significant prior or active 
medical condition at the time of signing informed consent will be recorded and coded using the 
MedDRA dictionary. These medical conditions will be summarized by primary system organ 
class and preferred term. 
To establish a BSL level of cardiovascular risk, the number and percentage of participants with 
pre-solicited cardiovascular risk factors will be summarized by treatment group. The number 
of cardiovascular risk factors that each participant has will also be summarized by treatment 
group. If it is unknown whether or not a participant currently or previously experienced a 
specific cardiovascular risk factor, it will be assumed that cardiovascular risk factor did not 
occur for that participant. 


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12.3 
Treatments 
Study treatment 
The analysis of study treatment data will be based on the safety set. The number of visits with 
active and placebo injections received will be presented by treatment group. 
The duration of exposure to study treatment will also be summarized by treatment group. In 
addition, the number and percentage of participants with cumulative exposure levels (e.g., any 
exposure, ≥ 1 weeks, ≥ 2 weeks, ≥ 3 weeks, ≥ 4 weeks, ≥ 8 weeks, etc.) will be presented. 
Prior and concomitant medication 
Prior and concomitant medications will be summarized in separate tables by treatment group. 
Prior medications are defined as treatments taken and stopped prior to first dose of study 
treatment. Any medication given at least once between the day of first dose of randomized study 
treatment and the date of the last study visit will be a concomitant medication, including those 
which were started pre-BSL and continued into the period where study treatment is 
administered. 
Medications will be presented in alphabetical order, by Anatomical Therapeutic Classification 
(ATC) codes and grouped by anatomical main group. Tables will show the overall number and 
percentage of participants receiving at least one treatment of a particular ATC code and at least 
one treatment in a particular anatomical main group. 
Significant prior and concomitant non-drug therapies and procedures will be summarized by 
primary system organ class and MedDRA preferred term. 
Prior surgeries and procedures are defined as surgeries and procedures done prior to first dose 
of study treatment. Any surgeries and procedures done between the day of first dose of study 
treatment and within the date of the last study visit will be a concomitant surgeries and 
procedures, including those which were started pre-BSL and continued into the period where 
study treatment is administered. 
The number and percentage of participants receiving prior and concomitant PsA therapy will 
be presented by randomized treatment group as well as the reasons for stopping their therapies 
(primary lack of efficacy, secondary lack of efficacy, lack of tolerability, other) and the total 
duration of exposure to PsA therapies previously. NSAID, glucocorticoid and DMARD (MTX, 
Leflunomide, Sulfasalazine) use will be summarized. 
12.4 
Analysis of the primary endpoint(s)/estimand(s) 
The primary objective of this study is to assess the efficacy of secukinumab relative to placebo 
at week 16 based on the proportion of participants achieving an ACR20 response. The 
consistency of the treatment difference between this bridging study and the global study will be 
evaluated. 


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12.4.1 
Definition of primary endpoint(s)/estimand(s) 
The primary efficacy variable will be ACR20 response at Week 16. The analysis of the primary 
efficacy variable will be based on the FAS . Primarily, CRP will be used instead of ESR to 
calculate ACR response; ESR will only be used in the event CRP is missing. 
12.4.2 
Statistical model, hypothesis, and method of analysis 
The primary analysis of ACR20 at Week 16 in the FAS will be evaluated using a logistic 
regression with treatment as a factor and weight as a covariate. Difference in response 
proportions between secukinumab regimen and placebo regimen and the corresponding 95% 
confidence interval (CI) will be computed utilizing the logistic regression model fitted. 
12.4.3 
Handling of missing values/censoring/discontinuations 
Missing data for ACR20 response and other binary efficacy variables (e.g., ACR50, etc.) for 
data up to Week 16 will be handled as follows: 
1. participants who discontinue from treatment or study for any reason will be considered as 
non-responders from the time of discontinuation through Week 16 
2. participants who do not have the required data to compute ACR responses (i.e., tender and 
swollen joint counts and at least three of the five ACR core set variables) at BSL and at 
the specific timepoint will be classified as non-responders at the specific timepoint. 
participants who are unblinded prior to the scheduled time point will be considered non-
responders from the time of unblinding up to Week 16. The primary analysis will use the non-
responder imputation. 
Continuous variables (e.g., ACR components, etc.) will be analyzed using a mixed-effects 
model repeated measures (MMRM) which is valid under the missing at random (MAR) 
assumption. As such, single-point imputation of missing data will not be performed (e.g., 
LOCF). For analyses of these parameters, if all post-BSL values are missing then these missing 
values will not be imputed and this participant will be removed from the analysis of the 
corresponding variable, i.e., it might be that the number of participants providing data to an 
analysis is smaller than the number of participants in the FAS. 
12.4.4 
Sensitivity analyses for primary endpoint/estimand 
Sensitivity analysis will be conducted in order to provide evidence that the results seen from 
the primary analysis are robust. These analyses will center on the deviations in model 
assumptions and the handlingof missing data. 
In order to determine the robustness of the logistic regression model used for the primary 
analysis, ACR20 response in active PsA participants at Week 16 will also be evaluated using a 
non-parametric regression (Koch et al (1998) model with the same independent variables as the 
logistic regression model.
 
 
 


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The impact of missing data on the analysis results of ACR20 in active PsA participants will be 
assessed as well by repeating the logistic regression model using different ways to handle 
missing data. This may include, but are not limited to: 
• Multiple imputation 
• Observed data analysis 
12.4.5 
Supplementary analysis 
Supplementary analysis will be conducted in order to fully investigate and understand the 
treatment effects as well as demonstrate the consistency between the bridging study and the 
global study.  
The analyses may include, but are not limited to: 
• Meta-analysis: it combines the estimates of the treatment effect from the historical studies 
and delivers an overall treatment effect as well as the corresponding confidence interval. 
The consistency can be claimed if the treatment effect estimated from the bridging study is 
located within the confidence interval. 
• Bayesian Meta-Analytic-Predictive (MAP) approach: it is similar as the meta-analysis, but 
priors should be specified carefully.  
• Logistic regression: same logistic regression model will be used as the primary 
analysis.The odds ratio bewteen the secukinumab regime and the placebo regimen and the 
corresponding 95% confidence interval will be presented. 
Subgroup analysis of the primary endpoint will be conducted by selected subgroup groups. The 
subgroups to be considered will be defined in the SAP. 
12.5 
Analysis of secondary endpoints/estimands 
12.5.1 
Efficacy and/or Pharmacodynamic endpoint(s) 
The secondary efficacy variables are described below. Secondary efficacy variables will be 
analyzed using the FAS population. Handling of missing data for secondary variables will be 
the same as for the primary variable. 
ACR50 at Week 16 
Response at Week 16 to ACR50 in the FAS will be evaluated using a logistic regression model 
with treatment group as a factor and weight as a covariate. 
DAS28-CRP at Week 16 
Between-treatment differences in the change from BSL in DAS28-CRP will be evaluated using 
MMRM with treatment group and analysis visit as factors and BSL DAS28-CRP score and 
weight as continuous covariates. Treatment by analysis visit and BSL DAS28-CRP score by 
analysis visit will be included as interaction terms in the model. An unstructured covariance 
structure will be assumed for the model. 


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PASDAS at Week 16 
Between-treatment differences in the change from BSL in PASDAS will be evaluated using 
MMRM with treatment group and analysis visit as factors and BSL PASDAS score and weight 
as continuous covariates. Treatment by analysis visit and BSL PASDAS score by analysis visit 
will be included as interaction terms in the model. An unstructured covariance structure will be 
assumed for the model. 
SF-36 PCS at Week 16 
See Section 12.5.7 PROs. 
Physical function (HAQ-DI©) at Week 16 
Between-treatment differences in the change from BSL in HAQ-DI© will be evaluated using 
MMRM with treatment group and analysis visit as factors and BSL HAQ-DI© score and weight 
as continuous covariates. Treatment by analysis visit and BSL HAQ-DI© score by analysis visit 
will be included as interaction terms in the model. An unstructured covariance structure will be 
assumed for the model. 
12.5.2 
Safety endpoints 
Adverse events 
Treatment-emergent adverse events (i.e., events started after the first dose of study treatment or 
events present prior to the first dose of study treatment but increased in severity based on 
preferred term and on or before last dose + 84 days) will be summarized. 
Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of participants having any AE, having an AE in each primary system organ class 
and having each individual AE (preferred term). Summaries will also be presented for AEs by 
severity and for study treatment related AEs. If a participant reported more than one adverse 
event with the same preferred term, the adverse event with the greatest severity will be 
presented. If a participant reported more than one adverse event within the same primary system 
organ class, the participant will be counted only once with the greatest severity at the system 
organ class level, where applicable. Serious adverse events will also be summarized. 
These summaries may be presented separately by study periods. 
As appropriate, the incidence of AEs will be presented per 100 patient years of exposure 
(exposure-adjusted incidence rates). 
Separate summaries will be provided for death, serious adverse event, other significant adverse 
events leading to discontinuation and adverse events leading to dose adjustment (including 
study treatment discontinuation). 
A graphical display of relative frequencies within system organ classes and relative risks, as 
appropriate, will be presented. 
When adjudication is required of major cardiovascular events, a summary of those types of 
events as reported by the investigator and confirmed by adjudication will be provided. 


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Laboratory data 
The summary of laboratory evaluations will be presented for three groups of laboratory tests 
(hematology and serum chemistry). Descriptive summary statistics for the change from BSL to 
each study visit will be presented. These descriptive summaries will be presented by test group, 
laboratory test and treatment group. Change from BSL will only be summarized for participants 
with both BSL and post BSL. 
For each parameter, the maximum change from BSL within each study period will be evaluated 
analogously. 
In addition, shift tables will be provided for all parameters to compare a participant’s BSL 
laboratory evaluation relative to the visit’s observed value. For the shift tables, the normal 
laboratory ranges will be used to evaluate whether a particular laboratory test value was normal, 
low, or high for each visit value relative to whether or not the BSL value was normal, low, or 
high. These summaries will be presented by laboratory test and treatment group. Shifts will be 
presented by visit as well as for most extreme values post-BSL. 
Vital signs 
Analysis of the vital sign measurements using summary statistics for the change from BSL for 
each post-BSL visit will be performed. These descriptive summaries will be presented by vital 
sign and treatment group. Change from BSL will only be summarized for participants with both 
BSL and post-BSL values. 
ECG 
Summary statistics will be presented for ECG variables by visit and treatment group. Qualitative 
changes will be summarized. 
12.5.3 
Patient reported outcomes 
SF-36 
The following variables will be evaluated: 
x SF-36 domain scores (based on a scale of 0-100) 
x SF-36 PCS 
 (norm-based scores) 
x 
 
For the change in SF-36 summary scores (PCS 
), summary statistics will be provided 
using observed data for each treatment regimen. 
 
The SF-36 domain scores will be summarized by treatment. 
PPD
PPD
PPD
PPD


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12.7 
Interim analyses 
Interim analysis is not applicable in this study. 


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The primary endpoint analysis will be performed after all participants have completed the Week 
16 visit or discontinued earlier. The primary endpoint analysis will be used for regulatory 
submission.The investigators, site personnel and monitors will continue to remain blinded to 
the original treatment assignment that each participant received at randomization until after the 
database lock for Week F60 analysis.  
Subsequent to the primary endpoint analysis, the final analysis is planned after participants have 
completed the Week F60 assessments and may be used for regulatory submission and/or 
publication purposes. Additional analyses may be performed to support interactions with health 
authorities, as necessary. 
12.8 
Sample size calculation 
12.8.1 
Primary endpoint(s) 
As it is a bridging study for China registration, this study will pursue an estimation strategy 
rather than formal hypothesis testing of treatment difference. 
Analysis of the pooled data of global pivotal studies (CAIN457F2312, CAIN457F2318, 
CAIN457F2336 and CAIN457F2342) showed an active drug response rate of about 51.4% and 
a placebo response rate of 23.1% after 16 weeks for ACR20. With 40 participants (1:1 ratio to 
two arms), there are approximately 86.0% probability to show at least 50% global treatment 
difference (14.15%) and approximately 96.0% probability to show positive treatment 
difference. 
Table 12-1 shows the probability of success with different observed response rates. 
Table 12-1 
Probability of Success with Different Observed Response Rates 
 
Observed Response Rate 
Criterion 1 
Criterion 2 
Secukinuma
b (p1) 
Placeb
o (p2) 
p1-p2 
95% CI 
of (p1-p2) 
Aimed 
Treatment 
Difference 
PoS 
Aimed 
Treatment 
Difference 
PoS 
Scenario 1 
0.464 
0.231 
0.233 
(-0.053, 
0.519) 
> 0.1415 
0.772 
> 0 
0.922 
Scenario 2 
0.514 
0.231 
0.283 
(-0.003, 
0.569) 
> 0.1415 
0.860 
> 0 
0.960 
Scenario 3 
0.564 
0.231 
0.333 
(0.048, 
0.618) 
> 0.1415 
0.922 
> 0 
0.981 
Scenario 4 
0.614 
0.231 
0.383 
(0.101, 
0.665) 
> 0.1415 
0.961 
> 0 
0.992 
13 
Ethical considerations and administrative procedures 
13.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations (including European Directive 2001/20/EC, US CFR 21), and with the ethical 
principles laid down in the Declaration of Helsinki. 


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13.2 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, 
written informed consent form, consent form updates, participant recruitment procedures (e.g., 
advertisements) and any other written information to be provided to participants. Prior to study 
start, the investigator is required to sign a protocol signature page confirming his/her agreement 
to conduct the study in accordance with these documents and all of the instructions and 
procedures found in this protocol and to give access to all relevant data and records to Novartis 
monitors, auditors, Novartis Quality Assurance representatives, designated agents of Novartis, 
IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site is 
requested by a regulatory authority, the investigator must inform Novartis immediately that this 
request has been made. 
13.3 
Publication of study protocol and results 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required by local regulation. In addition, after study completion and finalization of the study 
report the results of this trial will be submitted for publication and posted in a publicly accessible 
database of clinical trial results, such as the Novartis clinical trial results website and all required 
Health Authority websites (e.g., Clinicaltrials.gov). 
For details on the Novartis publication policy including authorship criteria, please refer to the 
publication policy training materials that will be provided to you at the investigator portal. 
13.4 
Quality Control and Quality Assurance 
Novartis maintains a robust Quality Management System (QMS) that includes all activities 
involved in quality assurance and quality control, to ensure compliance with written Standard 
Operating Procedures as well as applicable global/local Good Clinical Practice (GCP) 
regulations and ICH Guidelines. 
Audits of investigator sites, vendors, and Novartis systems are performed by auditors, 
independent from those involved in conducting, monitoring or performing quality control of the 
clinical trial. The clinical audit process uses a knowledge/risk based approach. 
Audits are conducted to assess GCP compliance with global and local regulatory requirements, 
protocols and internal SOPs, and are performed according to written Novartis  processes. 
14 
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of participants should be 
administered as deemed necessary on a case by case basis. Under no circumstances including 
incidental collection is an investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the investigator shall immediately disclose it to 


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Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by 
Novartis and approved by the IRB/IEC and Health Authorities, where required, it cannot be 
implemented. 
14.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. 
Only amendments that are required for participant safety may be implemented immediately 
provided the health authority 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 participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations. 


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15 
References 
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secukinumab in treatment of ankylosing spondylitis: a randomised, double-blind, placebo-
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Barrett et al (2008); Genome-wide association defines more than thirty distinct susceptibility 
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Curran SA, FitzGerald OM, Costello PJ, et al. (2004); Nucleotide sequencing of psoriatic 
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T cell infiltrate with very few clones exhibiting features that suggest they drive the 
inflammatory process by recognizing autoantigens. J Immunol; 172:1935-44. 
Deodhar AA, Dougados M, Baeten DL, et al. (2016); Effect of Secukinumab on Patient- 
Reported Outcomes in Patients With Active Ankylosing Spondylitis: A Phase III Randomized 
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Dominique Baeten, Joachim Sieper, Jürgen Braun, et al. (2015): 373(26); Secukinumab, an 
Interleukin-17A Inhibitor, in Ankylosing Spondylitis. N Engl J Med; 373:2534-48. 
European Medicines Agency (2006) Guideline On Clinical Investigation of Medicinal Products 
for the Treatment of Psoriatic Arthritis (Internet) Available from:  (Accessed 15 NOV 2020). 
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sedimentation rate in patients with rheumatoid arthritis. J Rheumatol; 24(8):1477-85. 
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Development Programs for Drugs, Devices, and Biological Products for the Treatment of 
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Fredriksson T, Pettersson U, et al (1978); Severe psoriasis-oral therapy with a new retinoid. 
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Gladman DD et all (2004); Psoriatic arthritis. Dermatol Ther; 17:350–63. 
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moderate to severe chronic plaque-type psoriasis: a double-blind, multicentre, randomized, 
dose-finding trial. Br J Dermatol; 152:1219-27. 
Healy PJ, Helliwell PS, et al (2008)59(5); Measuring clinical enthesitis in psoriatic arthritis: 
assessment of existing measures and development of an instrument specific to psoriatic 
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Helena Marzo-Ortega, Joachim Sieper, Alan Kivitz, et al. (2017); Secukinumab provides 
sustained improvements in the signs and symptoms of active ankylosing spondylitis with high 
retention rate: 3-year results from the phase III trial, MEASURE 2. RMD Open; 3:e000592. 
Helliwell PS, Firth J, Ibrahim GH, et al (2005):32(9): 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 (2013); The development of candidate composite 
disease activity and responder indices for psoriatic arthritis (GRACE project). Ann Rheum 
Dis 2013; 72:986-991. 
Helliwell et al (2005); Development of an assessment tool for dactylitis in patients with PsA. J 
Rheumatol 2005; 32:1745–50. 
Jürgen Braun, Xenofon Baraliakos, Atul Deodhar, et al. (2017); Effect of secukinumab on 
clinical and radiographic outcomes in ankylosing spondylitis: 2-year results from the 
randomised phase III MEASURE 1 study. Ann Rheum Dis; 76:1070-7. 
Kane D, Stafford L, Bresnihan B, et al. (2003); A prospective, clinical and radiological study 
of early psoriatic arthritis - an early synovitis clinic experience. Rheumatology 2003; 
42:1460-8. 
Kavanaugh A, Mease PJ, Reimold AM, et al. (2017) Secukinumab for Long-Term Treatment 
of Psoriatic Arthritis: A Two-Year Followup From a Phase III, Randomized, Double-Blind 
Placebo-Controlled Study. Arthritis Care Res; 69:347-55. 
Koch GG, Tangen CM, Jung J-W IA, et al (1998); Issues for covariance analysis of 
dichotomous and ordered categorical data from randomized clinical trials and non-parametric 
strategies for addressing them. Statist Med; 17:1863-92. 
Koenders MI, Lubberts E, Oppers-Walgreen B, et al. (2005):167(1); 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 et al (1991); C-reactive protein in rheumatology. Arthritis Rheum; 34(8):1065-8. 
Li R et al (2012); Epidemiology of eight common rheumatic diseases in China: a large-scale 
cross-sectional survey in Beijing. Rheumatology 2012; 51:721-29. 
 
M A van Leeuwen, M H van Rijswijk, DMFM van der Heijde, 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. 
M. Acosta Felquer, O. FitzGerald, et al (2015);Peripheral joint involvement in psoriatic 
arthritis patients. Clin Exp Rheumatol;33 (93 Suppl):S26-S30. 
Mallya et al(1982); Correlation in RA of concentration of plasma C3d, serum RF, immune 
complexes and CRP with each other and with clinical features of disease activity. Clin. Exp. 
Immunol. (1982); 48:747-753. 
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McInnes IB, Sieper J, Braun J, et al. (2013); Efficacy and safety of secukinumab, a fully 
human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe 
psoriatic arthritis: a 24-week, randomised, double-blind, placebo-controlled, Phase II proof-
of-concept trial. Ann Rheum Dis; 73:349-56. 
Mease PJ et all (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. 
Mease PJ, Goffe BS, Metz, J, et al. (2000); Etanercept in the treatment of psoriatic arthritis 
and psoriasis: a randomized trial. Lancet; 356:385-90. 
R K Mallya, D Vergani, D.E.H. TEE, et al. (1982); Correlation in rheumatoid arthritis of 
concentrations of plasma C3d, serum rheumatoid factor, immune complexes and C-reactive 
protein with each other and with clinical features of disease activity. Clin Exp Immunol; 
48(3):747-53. 
R. Li, J. Sun, L.M. Ren, et al. (2012); Epidemiology of eight common rheumatic diseases in 
China: a large-scale cross-sectional survey in Beijing. Rheumatology (Oxford); 51:721-9. 
Ritchlin CT, Kavanaugh A, Gladman DD, et al. (2009); Treatment recommendations for 
psoriatic arthritis. Ann Rheum Dis; 68:1387-94. 
Strand V, Mease P, Gossec L, et al. (2017) Secukinumab improves patient-reported outcomes 
in subjects with active psoriatic arthritis: results from a randomised phase III trial (FUTURE 
1). Ann Rheum Dis; 76:203-7. 
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; 60:479-91. 
Taylor W, Gladman D, Helliwell P, et al (2006):54(8); Classification criteria for psoriatic 
arthritis. Arthritis Rheum; 54:2665-73. 
Turkiewicz AM, Moreland LW, et al (2007); Psoriatic arthritis: current concepts on 
pathogenesis-oriented therapeutic options. Arthritis Rheum; 56(4):1051-66. 
Van et al 1993; The acute phase response in relation to radiographic progression in early RA. 
J Rheumatol 1993; 32 (suppl 3):9-13. 
Ware J, Kosinki M, Gandeck B, et al (1993); SF-36 Health Survey: manual and interpretation 
guide. Boston: The Health Institute, New England Medical Center. Reference available upon 
request. 
Ware JE, Snow KK, Kosinki M, et al (1994); SF-36 Health Survey: manual and interpretation 
guide. Update. Boston: The Health Institute, New England Medical Center. Reference 
available upon request. 
Weisman S, Pollack CR, Gottschalk RW, et al(2003):14(3); Psoriasis disease severity 
measures: comparing efficacy of treatments for severe psoriasis. J Dermatolog Treat; 14:158-
65. 
Wolfe et all (1997); Comparative usefulness of C-reactive protein and erythrocyte 
sedimentation rate in patients with RA. J Rheumatology 1997; 24:8. 


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X. Baraliakos, A.J. Kivitz, A.A. Deodhar, et al. (2018); Long-term effects of interleukin-17A 
inhibition with secukinumab in active ankylosing spondylitis: 3-year efficacy and safety results 
from an extension of the Phase 3 MEASURE 1 trial. Clin Exp Rheumatol; 36(1):50-55. 
Yang Q et al 2011; Prevalence and characteristics of psoriatic arthritis in Chinese patients 
with psoriasis. JEADV 2011; 25:1409-14. 
Yang Q, Qu L, Tian H, et al. (2011); Prevalence and characteristics of psoriatic arthritis in 
Chinese patients with psoriasis. J Eur Acad Dermatol Venereol; 25(12):1409-14. 
Yellen SB, Cella DF, Webster K, et al. (1997):13(2); Measuring Fatigue and Other Anemia-
Related Symptoms with the Functional Assessment of Cancer Therapy (FACT) Measurement 
System. Journal of Pain and Symptom Management; 13:63-74. 


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16 
Appendices 
16.1 
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. 
Table 16-1 
Clinically notable laboratory values and vital signs 
Laboratory variable 
Standard units 
SI units 
Liver function and related variables 
Serum Glutamic Oxaloacetic 
Transaminase (SGOT) (AST) 
≥ 3 × upper limit of normal 
(ULN) 
≥ 3 × ULN 
Serum Glutamic Pyruvic 
Transaminase (SGPT) (ALT) 
≥ 3 × ULN 
≥ 3 × ULN 
Bilirubin 
≥ 2 × ULN 
≥ 2 × ULN 
Alkaline phosphatase 
≥ 2 × ULN 
≥ 2 × ULN 
GGT 
≥ 2 × ULN 
≥ 2 × ULN 
Renal function, metabolic and electrolyte variables  
Urea 
≥ 5 × ULN 
≥ 5 × ULN 
Creatinine 
≥ 3 mg/dL 
≥ 265 μmol/L 
Uric acid 
M ≥ 12 mg/dL 
M ≥ 714 μmol/L 
  
F ≥ 9 mg/dL 
F ≥535 μmol/L 
Glucose 
< 45 mg/dL 
< 2.5 mmol/L 
  
> 250 mg/dL 
> 13.9 mmol/L 
Cholesterol 
≥ 350 mg/dL 
≥ 9.1 mmol/L 
Triglycerides 
≥ 750 mg/dL 
≥ 8.5 mmol/L 
CK (MB) 
None 
None 
Potassium 
< or = 3.0 mEq/L 
< or = 3 mmol/L 
  
< or = 6.0 mEq/L 
> or = 6 mmol/L 
Calcium 
< or = 6 mg/dL 
< or = 1.5 mmol/L 
  
> or = 13 mg/dL 
> or = 3.2 mmol/L 
Magnesium 
< 1.0 mg/dL 
< 0.4 mmol/L 
  
> 3.6 mg/dL 
> 1.5 mmol/L 
Amylase 
≥ 2 x ULN 
≥ 2 x ULN 
Lipase 
≥ 2 x ULN 
≥ 2 x ULN 
Hematology variables  
Hemoglobin 
< 7 g/dL 
< 4.39 mmol/L 
Platelets (thrombocytes) 
< 50 k/mm3 
< 50 × 109/L 
  
≥ 700 k/mm3 
≥ 700 × 109/L 
Leukocytes (WBCs) 
≤ 2.0 k/mm3 
≤ 2.0 × 109/L 
  
≥ 16 k/mm3 
≥ 16 × 109/L 


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Laboratory variable 
Standard units 
SI units 
Liver function and related variables 
Hematology variables: Differential 
Granulocytes (poly, 
neutrophils)  
≤ 1,000/mm3 
≤ 1 x 109/L 
Eosinophils 
≥ 12%  
≥ 12% 
Lymphocytes 
≤ 1,000/mm3 
≤ 1 × 109/L 
Vital sign variables 
Notable criteria 
Systolic Blood Pressure (BP) 
(mm/Hg) 
Either an increase of ≥ 30 that results in ≥ 180 or > 200 (mm/Hg) 
OR a decrease of ≥30 that results in ≤ 90 or < 75 (mm/Hg) 
Diastolic BP (mm/Hg) 
Either an increase of ≥ 20 that results in ≥ 105 or > 115(mm/Hg) 
OR a decrease of ≥20 that results in ≤ 50 or < 40 (mm/Hg) 


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16.2 
Appendix 2: Liver event and laboratory trigger definitions & 
follow-up requirements 
Table 16-2 
Liver event and laboratory trigger definitions 
LIVER LABORATORY TRIGGERS 
LIVER EVENTS 
Definition/ threshold 
· 3 x ULN < ALT / AST ≤ 5 x ULN 
· 1.5 x ULN < TBL ≤ 2 x ULN 
· ALT or AST > 5 × ULN 
· ALP > 2 × ULN (in the absence of known bone 
pathology) 
· TBL > 2 × ULN (in the absence of known 
Gilbert syndrome) 
· ALT or AST > 3 × ULN and INR > 1.5 
· Potential Hy’s Law cases (defined as ALT or 
AST > 3 × ULN and TBL > 2 × ULN [mainly 
conjugated fraction] without notable increase in 
ALP to > 2 × ULN) 
· Any clinical event of jaundice (or equivalent 
term) 
· ALT or AST > 3 × ULN accompanied by 
(general) malaise, fatigue, abdominal pain, 
nausea, or vomiting, or rash with eosinophilia 
· Any adverse event potentially indicative of a 
liver toxicity* 
*These events cover the following: Hepatic failure, fibrosis and cirrhosis, and other liver damage- 
related conditions; the non-infectious hepatitis; the benign, malignant and unspecified liver neoplasms 
TBL: total bilirubin; ULN: upper limit of normal 
Table 16-3 
Follow up requirements for liver events and laboratory triggers 
Criteria 
Actions required 
Follow-up monitoring 
Potential Hy’s Law casea  
· Discontinue the study 
treatment immediately 
Hospitalize, if clinically 
appropriate 
· Establish causality 
· Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in the 
appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at investigator 
discretion) 
ALT or AST 
> 8 × ULN 
· Discontinue the study 
treatment immediately 
· Hospitalize if clinically 
appropriate 
· Establish causality 
· Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in the 
appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until 
resolutionc  (frequency at 
investigator discretion) 


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Criteria 
Actions required 
Follow-up monitoring 
> 3 × ULN and INR > 1.5 
· Discontinue the study 
· treatment immediately 
· Hospitalize, if clinically 
appropriate 
· Establish causality 
· Record the AE and 
contributing factors (e.g. 
conmeds, med hx, lab) in the 
appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at investigator 
discretion) 
> 5 to ≤ 8 × ULN 
· Repeat LFT within 48 hours 
· If elevation persists, continue 
follow-up monitoring 
· If elevation persists for more 
than 2 weeks, discontinue the 
study drug 
· Establish causality 
· Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in the 
appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at investigator 
discretion) 
> 3 × ULN accompanied by 
symptomsb 
· Discontinue the study 
treatment immediately 
· Hospitalize if clinically 
appropriate 
· Establish causality 
· Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in the 
appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at investigator 
discretion) 
> 3 to ≤ 5 × ULN (participant is 
asymptomatic) 
· Repeat LFT within the next 
week 
· If elevation is confirmed, 
initiate close observation of the 
participant 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks 
ALP (isolated) 
> 2 × ULN (in the absence of 
known bone pathology) 
· Repeat LFT within 48 hours 
· If elevation persists, establish 
causality 
· Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in the 
appropriate CRF 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
TBL (isolated) 
> 2 × ULN (in the absence of 
known Gilbert syndrome) 
· Repeat LFT within 48 hours 
· If elevation persists, 
discontinue the study drug 
immediately 
· Hospitalize if clinically 
appropriate 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at investigator 
discretion) 


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Criteria 
Actions required 
Follow-up monitoring 
· Establish causality 
· Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in the 
appropriate CRF 
Test for hemolysis (e.g. 
reticulocytes, haptoglobin, 
unconjugated [indirect] 
bilirubin) 
> 1.5 to ≤ 2 × ULN (participant 
is asymptomatic) 
· Repeat LFT within the next 
week 
· If elevation is confirmed, 
initiate close observation of the 
participant 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
Jaundice 
· Discontinue the study 
treatment immediately 
· Hospitalize the participant 
· Establish causality 
· Record the AE and 
contributing factors (e.g., 
conmeds, med hx, lab) in the 
appropriate CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at investigator 
discretion) 
Any AE potentially indicative of 
a liver toxicity* 
· Consider study treatment 
interruption or discontinuation 
· Hospitalization if clinically 
appropriate 
· Establish causality 
· Record the AE and 
contributing factors (e.g. 
conmeds, med hx, lab) in the 
appropriate CRF 
Investigator discretion 
*These events cover the following: Hepatic failure, fibrosis and cirrhosis, and other liver damage- 
related conditions; the non-infectious hepatitis; the benign, malignant and unspecified liver neoplasms 
TBL: total bilirubin; ULN: upper limit of normal. aElevated ALT/AST > 3 × ULN and TBL > 2 × ULN but 
without notable increase in ALP to > 2 × ULN b(General) malaise, fatigue, abdominal pain, nausea, or 
vomiting, or rash with eosinophilia cResolution is defined as an outcome of one of the following: (1) 
return to BSL values, (2) stable values at three subsequent monitoring visits at least 2 weeks apart, (3) 
remain at elevated level after a maximum of 6 months, (4) liver transplantation, and (5) death.Based 
on investigator’s discretion investigation(s) for contributing factors for the liver event can include: 
Serology tests, imaging and pathology assessments, hepatologist’s consultancy; obtaining more 
detailed history of symptoms and prior or concurrent diseases, history of concomitant drug use, 
exclusion of underlying liver disease. 


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16.3 
Appendix 3: Specific Renal Alert Criteria and Actions and Event 
Follow-up 
Table 16-4 
Specific Renal Alert Criteria and Actions and Event Follow -up 
Serum Event 
Serum creatinine increase 25 – 49% compared 
to BSL 
Confirm 25% increase after 24-48h Follow up 
within 2-5 days 
Acute Kidney Injury: Serum creatinine increase ≥ 
50% compared to BSL 
Follow up within 24-48h if possible 
Consider study treatment interruption 
Consider participant hospitalization /specialized 
treatment 
Urine Event 
New dipstick proteinuria ≥3+ 
OR 
Protein-creatinine ratio > or =150 mg/g or > or 
=15 mg/mmol  
Consider causes and possible interventions 
• Assess serum albumin & serum total protein 
• Repeat assessment to confirm 
• Consider drug interruption or discontinuation 
unless other causes are diagnosed and 
corrected 
New dipstick hematuria ≥3+ on urine dipstick 
Repeat assessment to confirm 
• Distinguish hemoglobinuria from hematuria 
• Urine sediment microscopy 
• Assess sCr 
• Exclude infection, trauma, bleeding from the 
distal urinary tract/bladder, menstruation 
• Consider bleeding disorder 
For all renal events: 
Document contributing factors in the CRF: co-medication, other co-morbid conditions, and additional 
diagnostic procedures performed 
Monitor participant regularly (frequency at investigator’s discretion) until either: 
Event resolution: sCr within 10% of BSL or protein-creatinine ratio within 50% of BSL, or 
Event stabilization: sCr level with ±10% variability over last 6 months or protein-creatinine ratio 
stabilization at a new level with ±50% variability over last 6 months. 
16.4 
Appendix 4: The classification criteria for psoriatic arthritis 
(CASPAR) 
To meet the Classification of Psoriatic Arthritis (CASPAR) criteria for diagnosis of psoriatic 
arthritis according to Taylor et al (2006), a participant 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 
• Current psoriasis is defined as psoriatic skin or scalp disease present today as judged by a 
rheumatologist or dermatologist.* (2 points) 


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• 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. (1 points) 
• A family history of psoriasis is defined as a history of psoriasis in a first- or second- 
degree relative according to patient report. (1 points) 
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) 
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 participant. If the total score ≥ 3, the participant meets CASPAR criteria for 
PsA diagnosis.) 
* Current psoriasis is assigned a score of 2; all other features are assigned a score of 1. 
16.5 
Appendix 5: American College of Rheumatology (ACR) Measures 
and Criteria of Response 
Number of tender joints 
Seventy-eight joints (78) are scored as either tender or not tender: 8 distal interphalangeal, 10 
proximal interphalangeal, 10 metacarpophalangeal and 2 first carpometacarpal joints of the 
hands, 8 distal interphalangeal, the 10 metatarsophalangeal and 10 proximal interphalangeal 
joints of the feet, the 2 wrists, 2 elbows, 2 shoulders, 2 acromioclavicular, 2 sternoclavicular, 2 
temporomandibular, 2 hip, 2 knee, 2 talo-tibial, and 2 mid-tarsal joints. 
Joint tenderness is to be scored present (1) or absent (0). 
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". 


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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
 
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)/ESR. 
ACR50 = 50% improvement in at least 3 of the 5 measures and 50% improvement in the 
swollen and tender joint count. 
 
Reference: (Felson et al 1995) 
16.6 
Appendix 6 Disease Activity Score (DAS) 
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: 
Table 16-5 
EULAR response criteria 
Present DAS28 
DAS28 improvement 
>1.2 0.6 - 1.2 <0.6 
>1.2 0.6 - 1.2 <0.6 
>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: 


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· The number of swollen joints and tender joints should be assessed using 28-joint count (TJC28 
and SJC28). 
· The 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-ESR = 0.56 * sqrt(TJC28) + 0.28 * sqrt(SJC28) + 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 (RA) 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 et all 1991. CRP production is associated 
with radiological progression in RA Van et al 1993, and is considered at least as valid as ESR 
to measure RA disease activity Mallya et al(1982)Wolfe et all (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-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. 


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16.8 
Appendix 8: Guidelines for administering the questionnaires for 
patient reported outcomes 
Before trial start 
Study coordinators should familiarize themselves with the PRO questionnaire(s) in the trial and 
identify any items where a participant’s response might highlight issues of potential concern. 
At BSL, BSA involvement with psoriasis should be determined before completing PRO 
questionnaire(s) to ensure that 
 is completed only for participants who 
have BSA≥3%. 
Before completion 
1. participants should be provided with the correct questionnaire at the appropriate visits and in 
the appropriate language 
2. participants should have adequate space and time to complete the forms 
3. participants should be provided with a firm writing surface (such as a table or a clip board) 
4. Questionnaire should be administered before the clinical examination 
During completion 
1. Administrator may clarify the questions but should not influence the response 
2. Only one response for each question 
3. Also see “Addressing Problems and Concerns” 
After completion 
1. Check for completeness and not for content* 
2. Data should be sent from the eCRF / electronic device 
*However, any response which may directly impact or reflect the participant’s medical 
condition (e.g. noting of depression) should be communicated by the study coordinator to the 
investigator). 
Addressing Problems and Concerns 
Occasionally a participant may have concerns or questions about the questionnaires 
administered. Guidance related to some of the most common concerns and questions are given 
below. 
The participant does not want to complete the questionnaire(s) 


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Tell the participant that the goal is to better understand the physical, mental and social health 
problems of participants. Emphasize that such information is as important as any 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 
participant still declines, record the reason for the decline and thank the participant. 
The participant is too ill or weak to complete the questionnaire(s) 
In these instances, the coordinator may obtain participant responses by reading out loud each 
question, followed by the corresponding response categories, and entering the participant’s 
response. No help should be provided to the participant by any person other than the designated 
study coordinator. The coordinator should not influence participant responses. The study 
coordinator cannot translate the question into simpler language and has to be read verbatim. 
The participant wants someone else to complete the questionnaire(s) 
In no case should the coordinator or anyone other than the participant provide responses to the 
questions. Unless specified in the study protocol, proxy data are not an acceptable substitute for 
participant self-report. participants should be discouraged from asking a family member or 
friend for help in completing a questionnaire. 
The participant does not want to finish completing the questionnaire(s) 
If non-completion is a result of the participant having trouble understanding particular items, 
ask the participant 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, accept it 
as incomplete. Thank the participant. 
The participant 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 participant that his/her answers will be pooled with other participants’ 
answers and that they will be analyzed as a group rather than as individuals. Tell the participant 
that completed forms are not routinely shared with treating staff and that their responses will 
only be seen by you (to check for completeness) and by 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 participant asks the meaning of a question/item 
While completing the questionnaire, some participants might ask the meaning of specific items 
so that they can better understand and respond. If this happens, assist the participant by 
rereading the question for them verbatim. If the participant 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. participants should answer the questions based on what they think the questions mean. 
A General Information about all questionnaire(s): 
All questionnaires have to be completed by the participants in their local languages using an 
electronic device. The questionnaires should be completed by the participants in a quiet area 
free from disturbance, and before any visit assessments. participants should receive no help 
from family members; if questions cannot be answered alone (due to problems with reading or 


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understanding), then the doctor or nurse should read the questions and record the participant’s 
responses without influencing their answers. The information provided is strictly confidential 
and will be treated as such. If a participant has missed a question or given more than one 
response per question, then this should be brought to participant. Incomplete questions should 
not be accepted without first encouraging the participant to complete unanswered questions. 
The investigator must complete the participant/visit information on the electronic device and 
ensure that the center number, participant’s number and initials are identical to the CRF. As 
there are no source data for this questionnaire, the data queries will be restricted to 
participant/visit information. 
16.9 
Appendix 9: Study management during potential future 
pandemic/epidemic (e.g. COVID-19) 
Scope 
The instructions and procedures outlined in this appendix are applicable only in case of global 
health disruptive event, such as pandemic/epidemic [e.g. severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) or coronavirus disease/COVID-19]. In order to maintain the 
study data integrity and ensure the safety of participants, investigators should inform and 
discuss with the sponsor’s monitor about its applicability prior to implementing any of the 
following procedures, 
Screening (Screening to Randomization) 
In case of a global health disruptive event, such as pandemic/epidemic (e.g. COVID-19), 
affecting the ability of the patient or the site to adhere to protocol requirements and assessments, 
investigators should only randomize patients if they expect them to be able to adhere to 
assessments and protocol-related activities. Evaluation of the eligibility of the subject should 
consider the ability to attend study visits and adhere to protocol assessments. If the latter is not 
anticipated, screening and randomization should not proceed, and re-screening (as allowable 
per protocol) should be considered when conditions allow for proper trial management. 
During Treatment Period (BSL to EOT) 
In case of a global health disruptive event, such as pandemic/epidemic (e.g. COVID-19), 
affecting the ability of the patient or the site to adhere to protocol requirements and assessments 
and therefore leading to a potential increase in the number of missing measurements, the 
Sponsor may consider recruiting additional patients to restore the sample size only after 
consultation with local regulatory authority.Risks and Benefits 
Active infection should be excluded in order to comply with eligibility criteria (Section 5.2). 
The potential of secukinumab to increase the risk of infections has been identified (see IB 
Section 7.1). COVID-19 has similar impact on risk-benefit as other infections. No additional 
risks is anticipated due to COVID-19 infection. 


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Visits 
If the COVID-19 pandemic or similar situations that limits or prevents on-site study visits, 
alternative methods of providing continuing care may be implemented only for the visits 
outlined in the Table 8-1 . Phone calls, virtual contacts (e.g. teleconsult) or visits by site staff to 
the participant´s home depending on local regulations and capabilities, can replace on-site study 
visits, for the duration of the pandemic until it is safe for the participant to visit the site again. 
Any safety or efficacy assessments which could not be feasible to perform or evaluate conduct 
remotely or virtually, the protocol deviation need to be recorded. Such data will treated as 
missing data. 
This will not apply to Screening, BSL, Week 16, Week 52 and Week 60 visit. For remaining 
visits per protocol, the above exceptions may be implemented, however, every effort need to be 
made to ensure on-site visit. If on-site visit is prevented at Screening or BSL visit, the 
participants should not be randomized.   
Laboratory assessments 
If the designated central laboratory is unable to operate, collection of samples may be modified 
by Novartis and if modified, will be communicated to the investigator. In such cases, it is 
acceptable to collect and perform laboratory tests at local laboratories that are certified for these 
diagnostics. Similarly, sites should inform to the Sponsor of proposed changes to sample 
management/collection. 
IMP (administration and dispensation) 
In case of a major health care event (e.g., COVID-19 pandemic, epidemic) that limits or 
prevents on-site study visits, delivery of IMP directly to a participant’s home is generally 
permitted (if allowed by local regulations) in the event the Investigator has decided that an on-
site visit by the participant is no longer appropriate or possible, and that it is in the interest of 
the participant’s health to administer the study treatment even without performing an on-site 
visit. For changes in the distribution of trial drugs, the primary goal is to provide IMP to 
participants based on protocol to ensure participant safety and the integrity of clinical trials. 
Implementation will need to be discussed with Novartis. The dispatch of IMP from the site to 
the participant’s home remains under the accountability of the Investigator. Each 
shipment/provisioning will be for a maximum of 1-month supply. In this case, regular phone 
calls or virtual contacts (every 4 weeks or more frequently if needed) will occur between the 
site and the participant for instructional purposes, safety monitoring, and discussion of the 
participant´s health status until the participants can again visit the site. 
IMP home administration is allowed only for the scheduled dosing visits (outlined in table 8-1) 
if the participant or caregiver is trained on subcutaneous self-administration. 
Changes in transportation and storage arrangements will not violate the blind design of 
treatment. The investigator should make relevant records such as the inventory and storage 
conditions of trial drugs. 


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Efficacy and Clinical Outcome Assessments (COAs) 
In 
the 
event 
of 
a 
pandemic/epidemic 
that limits 
or 
prevents 
on-site study 
visits, selected efficacy assessments including PROs can alternatively be done via  web-based 
backup portal or visits of site staff to the subject´s home, depending on local regulations and 
capabilities, and following any applicable training in the required process. 
Exceptionally, if the electronic device is not working, the efficacy assessments and PROs may 
be completed using web backup portal for PROs. The data would then be transcribed in the 
vendor database. 
For individual cases where the efficacy endpoint is not collected, the reasons for not obtaining 
the efficacy evaluation should be documented. 
Safety 
During the COVID-19 pandemic that limits or prevents on-site study visits, regular phone or 
virtual calls will occur (every 4 weeks or more frequently if needed) for safety monitoring and 
discussion of the participant´s health status until the participant can again visit the site.  
Female participants would be advised to perform the urine pregnancy test at home and report 
the result to the site. It is important that participants are instructed to perform the urine 
pregnancy test first and only if the test result is negative proceed with the administration of the 
study treatment. 
Informed Consent Procedures 
During the COVID-19 pandemic that may challenge the ability to obtain a standard written 
informed consent due to limits that prevent an on-site visit, the Investigator may conduct the 
informed consent discussion remotely (e.g. telephone, videoconference). Guidance issued by 
local regulatory bodies on this aspect prevail and must be implemented and appropriately 
documented (e.g. the presence of an impartial witness, sign/dating separate ICFs by trial 
participant and person obtaining informed consent, etc.). Remote informed consent should be 
appropriately documented and confirmed by way of standard informed consent procedures at 
the earliest opportunity when the subject will be back at the trial sites.   
Site monitoring 
In the event of a major health care disruption (e.g. pandemic, epidemic), requiring social 
distancing or limited travel/attendance to the clinical trial site, remote site initiation and 
monitoring could be considered. 
Note: The details on operationalizing above-mentioned study management aspects during 
potential future pandemic/epidemic will be supplemented by dedicated instructions / manual to 
the clinical trial sites.  

SAP_001.pdf: 
Clinical Development 
CAIN457/Secukinumab/Cosentyx® 
CAIN457F2367 / NCT04711902  
A phase III randomized, double-blind, placebo controlled, multicenter, 
bridging study of subcutaneous secukinumab, to demonstrate efficacy 
after sixteen weeks of treatment and to assess safety, tolerability and 
long-term efficacy follow-up to one year in Chinese participants with 
active psoriatic arthritis 
Statistical Analysis Plan (SAP) for Final Analysis 
Document type: 
SAP Documentation 
Document status: 
Final 
Release date: 
06-April-2023
Number of pages: 
44 
Property of Novartis 
For business use only 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 
Template Version 3.0, Effective from 01-Jul-2020 


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SAP 
 
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Document History – Changes compared to previous final version of SAP 
 
Date 
Time 
point 
Reason for 
update 
Outcome for update 
Section and 
title impacted 
(Current) 
6-Apr-2023 
Prior 
to 
DBL 
Amendment 1 
Removed “AIN457 150 mg” group 
in the entire period  
2.1.1.1 
Treatment 
groups 
6-Apr-2023 
Prior 
to 
DBL 
Amendment 1 
Added a paragraph for disclosure 
purpose 
2.7.1
 
Adverse 
events (AEs) 
6-Apr-2023 
Prior 
to 
DBL 
Amendment 1 
Added a sentence for potential 
additional analysis 
 
 as appropriate 
 


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Table of contents 
Table of contents ................................................................................................................. 3 
List of abbreviations ............................................................................................................ 5 
1 
Introduction ......................................................................................................................... 9 
1.1 
Study design............................................................................................................. 9 
1.2 
Study objectives and endpoints ............................................................................. 10 
2 
Statistical methods ............................................................................................................. 12 
2.1 
Data analysis general information ......................................................................... 12 
2.1.1 
General definitions ................................................................................ 13 
2.2 
Analysis sets .......................................................................................................... 14 
2.2.1 
Subgroup of interest .............................................................................. 15 
2.3 
Patient disposition, demographics and other baseline characteristics ................... 15 
2.3.1 
Patient disposition ................................................................................. 16 
2.4 
Treatments (study treatment, rescue medication, concomitant therapies, 
compliance) ............................................................................................................ 16 
2.4.1 
Study treatment / compliance ................................................................ 16 
2.4.2 
Prior, concomitant and post therapies ................................................... 17 
2.5 
Analysis of the primary objective .......................................................................... 17 
2.5.1 
Primary endpoint ................................................................................... 17 
2.5.2 
Statistical hypothesis, model, and method of analysis .......................... 18 
2.5.3 
Handling of missing values/censoring/discontinuations ....................... 18 
2.5.4 
Supportive analyses ............................................................................... 18 
2.6 
Analysis of the secondary objectives ..................................................................... 18 
2.6.1 
Secondary endpoints ............................................................................. 18 
2.6.2 
Statistical hypothesis, model, and method of analysis .......................... 19 
2.6.3 
Handling of missing values/censoring/discontinuations ....................... 20 
2.7 
Safety analyses ....................................................................................................... 20 
2.7.1 
Adverse events (AEs) ............................................................................ 20 
2.7.2 
Deaths .................................................................................................... 22 
2.7.3 
Laboratory data ..................................................................................... 22 
2.7.4 
Other safety data ................................................................................... 24 
2.8 
Patient-reported outcomes ..................................................................................... 26 
 
 26 
2.10 
Interim analysis ...................................................................................................... 27 
3 
Sample size calculation ..................................................................................................... 27 
3.1 
Primary endpoint(s) ............................................................................................... 27 


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4 
Change to protocol specified analyses .............................................................................. 28 
5 
Appendix ........................................................................................................................... 28 
5.1 
Visit window .......................................................................................................... 28 
5.1.1 
Visit window ......................................................................................... 28 
5.1.2 
Multiple assessments within visit windows .......................................... 30 
5.2 
Description of efficacy variables ........................................................................... 32 
5.2.1 
American College of Rheumatology (ACR) response .......................... 32 
5.2.2 
DAS28 and EULAR response ............................................................... 35 
5.2.3 
Psoriatic Arthritis Disease Activity Score (PASDAS) .......................... 36 
 
 37 
 
 37 
 
 37 
 
 39 
5.3 
Imputation rules ..................................................................................................... 39 
5.3.1 
Study drug ............................................................................................. 39 
5.3.2 
AE date imputation ............................................................................... 40 
5.3.3 
Concomitant medication date imputation ............................................. 41 
5.4 
AEs coding/grading ............................................................................................... 42 
 
 42 
 
 42 
 
 43 
 
 43 
 
 43 
6 
Reference ........................................................................................................................... 44 


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List of abbreviations 
ACR 
AE 
ALB 
ALP 
ALT 
ANA 
Anti-CCP 
anti-dsDNA 
AS 
AST 
ATC 
β-hCG 
BMI 
BP 
BSA 
BSL 
BUN 
°C 
CASPAR 
CD4 
CD8 
CFDA 
CFR 
CI 
ClinRO 
CMO&PS 
CO 
COA 
COVID-19 
COX-1 
COX-2 
CRA 
CRF 
CRP 
csDMARDs 
CSR 
CTLA4 Ig 
DAS 
DAS28-CRP 
DLT 
DMARDs 
DMS 
American College of Rheumatology 
Adverse Event 
Albumin 
Alkaline Phosphatase 
Alanine Aminotransferase 
Antinuclear antibody 
Anti-cyclic citrullinated peptide 
anti-double stranded DNA antibodies 
Ankylosing Spondylitis 
Aspartate Aminotransferase 
Anatomical Therapeutic Classification 
Beta human chorionic gonadotropin 
Body Mass Index 
Blood Pressure 
Body Surface Area 
Baseline 
Blood Urea Nitrogen 
degree Celsius 
Classification of Psoriatic Arthritis 
Cluster of differentiation 4 
Cluster of differentiation 8 
China Food and Drug Administration 
Code of Federal Regulation 
Confidence Interval 
Clinician Reported Outcomes 
Chief Medical Office and Patient Safety 
Country Organization 
Clinical Outcome Assessment 
Coronavirus disease 2019 
Cyclooxygenase 1 
Cyclooxygenase 2 
Clinical Research Associate 
Case Report Form 
C-Reactive Protein 
Conventional Synthetic Disease-Modifying Antirheumatic Drugs 
Clinical Study Report 
Cytotoxic T lymphocyte associated antigen-4 immunoglobulin fusion proteins 
Disease Activity Score 
Disease Activity Score for 28 joints - C reactive protein 
Dose Limiting Toxicity 
Disease modifying antirheumatic drug(s) 
Document Management System 
DNA 
EC 
Deoxyribonucleic Acid 
Ethics Committee 


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ECG 
eCRF 
EDC 
EMA 
EOS 
eSAE 
ESR 
EULAR 
°F 
 
FAS 
FDA 
FSH 
GCP 
GCS 
h 
HAQ-DI 
HBsAg 
HBV 
HCV 
HDL 
HIV 
HRQoL 
hs-CRP 
IA 
Electrocardiogram 
electronic Case Report Form 
Electronic Data Capture 
European Medicines Agency 
End of study 
Electronic Serious Adverse Event 
Erythrocyte sedimentation rate 
European League Against Rheumatism 
degree Fahrenheit  
 
Full Analysis Set 
Food and Drug Administration 
Follicle-stimulating hormone 
Good Clinical Practice 
Gamma-glutamyl transferase 
Hour 
Health Assessment Questionnaire – Disability Index  
Hepatitis B surface antigen 
Hepatitis B Virus 
Hepatitis C Virus 
High-density lipoprotein 
Human immunodeficiency virus 
Health-Related Quality of Life 
high-sensitivity C-reactive protein  
Interim Analyses 
IB 
ICF 
ICH 
 
IEC 
IFU 
 
IL-17 
i.v. 
IVR 
IWR 
 
LDL 
 
LLN 
LLOQ 
MAR 
MCR 
MCS 
MedDRA 
Investigator’s Brochure 
Informed Consent Form 
International Council for Harmonization of Technical Requirements for 
Pharmaceuticals for Human Use 
Independent Ethics Committee 
Instructions for Use 
  
Interleukin-17  
Intravenous(ly) 
Interactive Voice Response 
Interactive Web Response 
 
Low Density Lipoprotein 
 
Lower Limit Normal 
Lower Limit of Quantification 
Missing at Random 
Major Clinical Response 
Mental Component Summary 
Medical Dictionary for Drug Regulatory Affairs 
PP
D
PPD


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MMRM 
MRI 
MTX 
NSAIDs 
PaGA 
 
PSOC 
PCS 
PD 
PFS 
PhGA 
PK 
Mixed-effects model repeated measures  
Magnetic resonance imaging 
Methotrexate  
Non-steroidal anti-inflammatory drugs  
Patient's Global Assessment of disease activity 
  
Primary system organ classes 
Physical component score 
Pharmacodynamic(s) 
Prefilled syringe 
Physician's global assessment of disease activity 
Pharmacokinetics 
PMDA 
PoC 
PPD 
PPS 
Pharmaceuticals and Medical Devices Agency 
Proof of concept 
Purified protein derivative 
Per-Protocol Set 
PRO 
Patient-reported Outcomes 
PsA 
PSD 
PSO 
PT 
PUVA 
q1w 
q4w 
QMS 
RA 
RAP 
Psoriatic arthritis 
Premature Subject Discontinuation 
Psoriasis 
Prothrombin time 
Psoralen and ultraviolet A 
every week 
every 4 weeks  
Quality Management System 
Rheumatoid Arthritis 
Reporting & Analysis Process 
RBC 
RF 
SAE 
SAP 
SAS 
Red Blood Cell(s) 
Rheumatoid Factor 
Serious Adverse Event 
Statistical Analysis Plan 
Statistical Analysis System 
SBP 
s.c. 
sCR 
SD 
SF36-PCS 
SGOT 
SGPT 
SJC 
SUSAR 
t.i.d 
TBL 
TD 
TEAE 
Systolic Blood Pressure 
subcutaneous 
serum creatinine 
Standard deviation 
Short form health survey -physical component summary 
Serum Glutamic Oxaloacetic Transaminase 
Serum Glutamic Pyruvic Transaminase 
Swollen Joint Count 
Suspected Unexpected Serious Adverse Reaction 
3 times a day 
Total bilirubin 
Study Treatment Discontinuation 
Treatment Emergent Adverse Events 


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TFLs 
TFQ 
TJC 
TNFα 
ULN 
Tables, Figures, Listings 
Trial Feedback Questionnaire 
Tender Joint Count  
Tumor Necrosis Factor alpha  
Upper Limit of Normal 
ULQ 
UVA 
UVB 
VAS 
WBC 
WHO 
WoC 
WoCBP 
Upper Limit of Quantification 
Ultraviolet A  
Ultraviolet B 
Visual Analog Scale 
White Blood Cell(s) 
World Health Organization 
Withdrawal of Consent 
Women of Childbearing Potential 


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1 
Introduction 
Data will be analyzed by Novartis according to this SAP and the data analysis Section 12 of the 
clinical study protocol. The statistical methodology is described below and any deviations from 
the protocol are documented. Additional detailed information regarding the analysis 
methodology is contained in the Appendix section.  
This version of SAP covers the statistical and analytical plans of the CAIN457F2367 trial 
regarding the final DBL. Analyses pertaining to Week 16 will not be repeated. 
1.1 
Study design 
This bridging study uses a randomized, double-blind, placebo-controlled, parallel-group design 
to assess the efficacy, safety, and tolerability of secukinumab 150 mg s.c. in Chinese 
participants with active PsA.  
A screening period running up to 10 weeks before randomization will be used to assess 
participant eligibility followed by 52 weeks of treatment.  
At BSL, approximately 40 Chinese participants whose eligibility are confirmed will be 
randomized to one of two treatment groups in 1:1 ratio: 
• Group 1 – secukinumab 150mg s.c.: 
Secukinumab 150 mg (1.0 mL PFS of 150 mg dose) administered at BSL, Weeks 1, 2, and 3 
followed by dosing every four weeks starting at Week 4. 
• Group 2 – placebo s.c. 
Placebo (1.0 mL PFS) administered at BSL, Weeks 1, 2 and 3, followed by dosing every four 
weeks starting at Week 4. 
At Week 16 the participants in Group 1 and Group 2 will be re-randomized in a blinded manner 
in 1:1 ratio separately.  
• The participants in Group 1 will be re-randomized in 1:1 ratio to secukinumab 150 mg 
s.c. q4w regimen (1.0 mL PFS of 150 mg dose + 1.0 mL PFS of placebo) or 
secukinumab 
 s.c. q4w regimen (
) 
• The participants in Group 2 will be re-randomized in 1:1 ratio to secukinumab 150 mg 
s.c. q4w regimen (1.0 mL PFS of 150 mg dose + 1.0 mL PFS of placebo) or 
secukinumab 
 s.c. q4w regimen (
) 
Stratification is not applicable in the study. 
A primary endpoint analysis was conducted after all participants complete Week 16 visit. 
Rescue medication was not allowed before the completion of Week 16 assessments (protocol 
Section 6.2.3). Although no participant will be restricted from receiving necessary rescue 
medications for lack of benefit or worsening of disease, if rescue with prohibited biologics (as 
described in section 6.2.2) occurs prior to completion of Week 16 assessments, participants will 
be discontinued from the study treatment. Efficacy will be assessed in detail at every study visit, 
and participants who are deemed not to be benefiting from the study treatment based upon safety 


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and efficacy assessments by the investigator, or for any reason of their own accord, are free to 
discontinue participation in the study at any time.  
A follow-up visit will be done 12 weeks after last study treatment administration for all 
participants, regardless of whether they complete the entire study as planned or discontinue 
prematurely.  
The total combined duration of treatment for this Phase III study is 52 weeks.  
1.2 
Study objectives and endpoints 
 
Objective(s) 
Endpoint(s) 
Primary objective(s) 
Endpoint(s) for primary objective(s) 
• 
To demonstrate the treatment effect of secukinumab 
150 mg s.c. (q1w×4, followed by dosing q4w) in Chinese 
participants with active PsA is consistent with global 
population 
by 
assessing 
American 
College 
of 
Rheumatology 20 (ACR20) response rates in participants 
treated with secukinumab 150 mg s.c. compared to 
placebo s.c. at Week 16. 
• 
ACR20 response at Week 16. 
A patient will be considered as improved according 
to the ACR20 criteria if he/she has at least 20% 
improvement in the three following measures: 
• Tender joint count; 
• Swollen joint count; 
• and at least 3 of the following 5 domains: 
a. Patient's assessment of PsA pain 
b. Patient's global assessment of disease activity 
c. Physician's global assessment of disease 
activity 
d. Health Assessment Questionnaire Disability 
Index (HAQ-DI©) score 
e.  Acute phase reactant (hsCRP or ESR) 
Secondary objective(s) 
Endpoint(s) for secondary objective(s) 
• 
To evaluate the efficacy of secukinumab 150 mg s.c. 
(q1w×4, followed by dosing q4w) at Week 16 
compared with placebo by assessing the proportion of 
participants achieving an ACR50 response. 
• 
ACR50 response rate at Week 16. 
• 
To evaluate the efficacy of secukinumab 150 mg s.c. 
(q1w×4, followed by dosing q4w) at Week 16 
compared with placebo by assessing the changes 
from baseline in Disease Activity Score for 28 joints 
(DAS28-CRP). 
• 
Change from baseline in DAS28-CRP at Week 
16. 
• 
To evaluate the efficacy of secukinumab 150 mg s.c. 
(q1w×4, followed by dosing q4w) at Week 16 
compared with placebo by assessing change from 
baseline in PASDAS (Psoriatic Arthritis Disease 
Activity Score). 
• 
Change from baseline in PASDAS at Week 
16. 
• 
To evaluate the efficacy of secukinumab 150 mg s.c. 
(q1w×4, followed by dosing q4w) at Week 16 
compared with placebo by assessing the changes 
• 
Change from baseline in SF36-PCS at Week 
16. 


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Objective(s) 
Endpoint(s) 
from baseline in medical outcome short form health 
survey (SF36-PCS). 
• 
To evaluate the efficacy of secukinumab 150 mg s.c. 
(q1w×4, followed by dosing q4w) at Week 16 
compared with placebo by assessing the changes 
from baseline in Health Assessment Questionnaire - 
Disability Index (HAQ-DI©). 
• 
Change from baseline in HAQ-DI© at Week 
16. 
• 
To evaluate the overall safety and tolerability of 
secukinumab 150 mg s.c. (q1w×4, followed by dosing 
q4w). 
• 
Physical examination, vital signs, laboratory 
values, AEs/SAEs. 


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2 
Statistical methods 
2.1 
Data analysis general information 
The primary endpoint analysis was performed after all participants complete Week 16. The 
Final analysis will be conducted when all participants have either withdrawn or completed the 
study. Any data analysis carried out independently by the investigator should be submitted to 
Novartis before publication or presentation. 
Summary statistics for continuous variables will generally include the number of participants 
(N), mean, standard deviation (SD), minimum, lower quartile, median, upper quartile, and          
maximum. For binary or discrete variables, the absolute number of participants in each category 
and relative frequencies will be provided.  
Unless otherwise specified, two-sided 95% confidence intervals will be displayed.  
In case of a global health disruptive event, such as pandemic/epidemic (e.g., COVID-19), 
affecting the ability of the patient or the site to adhere to protocol requirements and assessments 
and therefore leading to a potential increase in the number of missing measurements, additional 
analysis populations may be defined as per the instructions and procedures outlined in Section 
16.9 in the protocol. 
The inferential efficacy evaluation of secukinumab relative to placebo was generally focus on 
the first 16 weeks of treatment unless otherwise specified. 
Participants may be included in more than one treatment group for some analysis (e.g. exposure 
adjusted adverse events over the entire treatment period). 
Note that the treatment groups for a participant may differ depending on the time period of the 
analysis and whether one assesses the participant for efficacy or safety. 
Data may also be presented by a combination of the ‘original’ and ‘switch’ treatment groups. 
These treatment groups represent the treatment combinations the subjects experience over the 
course of the entire trial. 


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Efficacy data following re-randomization 
Data will also be presented after Week 16, by a combination of the ‘original’ and ‘switch’ 
treatment groups and will be referred to as treatment sequence. These treatment sequences 
represent the treatment combinations the subjects experience over the course of the entire trial 
in case of re-randomization (refer to Section 2.1.1.1).  
At the primary endpoint analysis, efficacy and safety data for the placebo-controlled period up 
to Week 16 were presented.  Additional aspects of efficacy, safety and tolerability of 
secukinumab of the data collected up to the final database lock at the end of study will be 
investigated in the final analysis. Data collected after Week 16 will generally be summarized 
descriptively on the FAS population using treatment sequence.  
2.1.1 
General definitions  
2.1.1.1 
Treatment groups 
In the final analysis, the summaries by treatment will be performed by the treatment sequence.  
• Treatment sequence: 
o AIN457 150 mg – AIN457 150 mg 
o AIN457 150 mg – AIN457 
 
o Placebo – AIN457 150 mg 
o Placebo – AIN457 
 
For some safety summaries (e.g., exposure-adjusted) the ‘switch’ treatment may be summarized 
separately:  
• 
Entire study: Placebo, Any AIN457 150 mg, Any AIN457 
, Any AIN457. 
In the safety and efficacy listings, the groups will be presented by treatment sequence. 
2.1.1.2 
 Study Day 1 and other study days 
The first day of administration of randomized study treatment (first dose) is defined as Study 
Day 1 or Day 1.  
All other study days will be labeled relative to Day 1. For event dates on or after Day 1, study 
day for a particular event date is calculated as [Date of event] – [Date of first dose] + 1, i.e., 
Day 2, Day 3, etc., will be one day, two days, etc., after Day 1, respectively. For the dates before 
Day 1, study day for an event date is calculated as [Date of event] – [Date of first dose], i.e., 
Day -1, Day -2, etc., will be one day, two days, etc., before Day 1, respectively. Duration of an 
event will be calculated as (Event end date – Event start date + 1). 
The descriptor “Day 0” will not be used. 


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2.1.1.3 
Screening, baseline and post-baseline definitions 
Screening refers to any procedures (e.g., checking inclusion and exclusion criteria) performed 
prior to the date of first dose of study treatment (for safety analysis) or prior to the randomization 
date (for efficacy analysis). Per protocol, subject informed consent must be obtained prior to 
performing any study related activity. The date of signing informed consent is the start date of 
screening period. Any assessment obtained during the screening period will be labeled 
screening assessment. Assessments made on Day 1 may occur before or after the randomization 
or the first dose. Further information will be found in Programming Datasets Specifications 
(PDS). 
For efficacy analyses, baseline is the last assessment (including unscheduled visits) obtained 
(on or) before randomization (day). All assessments obtained after randomization (day) are 
considered as post-baseline unless otherwise specified. 
For safety analyses, baseline is the last assessment (including unscheduled visits) obtained (on 
or) before the first dose of study treatment. All assessments obtained after the first dose (day) 
of study treatment are considered as post-baseline unless otherwise specified. 
Of note, baseline will be derived based on the randomization day or first dose day, exact 
randomization/dosing time is not considered. 
In general, a baseline value refers to the last measurement made prior to administration of the 
first dose of study treatment. However, for patient reported outcomes, laboratory assessments 
and ECG if no pre-treatment value exists, values obtained after first dose of treatment can be 
used as baseline only if it was collected on the same day as first dose. 
2.1.1.4 
Day of last dose of randomized study treatment 
The date of last dose will be collected via the electronic case report form (eCRF). The subject’s 
exposure will be calculated considering the end of treatment period visit (e.g., treatment 
completion visit). If a subject discontinued early, then the last dose + 84 days or the last visit 
during the follow-up period whichever occurs earlier is considered. 
2.2 
Analysis sets 
The following analysis sets will be used in this study: 
Randomized set: The randomized set will be defined as all participants who were randomized. 
Unless otherwise specified, mis-randomized participants (mis-randomized in IRT) will be 
excluded from the randomized set. 
Mis-randomized participants are defined as those participants who were mistakenly randomized 
into the IRT prior to the site confirming all eligibility criteria had been met and to whom no 
study medication was given. Mis-randomized participants are treated as screen failures. 
Full analysis set (FAS): The FAS will be comprised of all participants from the randomized 
set to whom study treatment has been assigned. Following the intent-to-treat principle, 
participants will be evaluated according to the treatment assigned to at randomization.  
Three subsets of FAS are defined as follows: 


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• Psoriasis subset: The psoriasis subset will include all FAS participants who have ≥ 3% of 
the BSA affected by psoriatic skin involvement at BSL. 
Safety set: The safety set includes all participants who took at least one dose of study treatment 
during the treatment period. Participants will be evaluated according to treatment received. 
2.2.1 
Subgroup of interest 
Not applicable. 
2.3 
Patient disposition, demographics and other baseline 
characteristics 
Summary statistics will be presented for continuous demographic and BSL characteristic 
variables for each treatment sequence and for all participants in the randomized set. The number 
and percentage of participants in each category will be presented for categorical variables for 
each treatment group and all participants. 
The following demographic variables and BSL disease characteristics, if collected, will be 
analyzed: 
Continuous variables: 
• Age  
• Height 
• Weight 
• Body mass index (BMI) = (body weight in kilograms) / (height in meters)2 
Categorical variables: 
• Age categories (<65 years, 65-74, 75 years and older) 
• Gender  
• Race  
• Ethnicity  
• Smoking status at baseline 
The following disease specific baseline characteristics and history of disease will be 
summarized. 
• Anti-TNF treatment history (naïve or inadequate responder), ACR components and other 
disease-related measures (e.g., DAS28, presense of dactylitis, presense of enthesitis, time 


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since first diagnosis of PsA, participant with psoriasis ≥ 3%), etc., number of prior biologic 
PsA therapies, dose of MTX or other DMARD at randomization. 
Medical history 
A history of PsA with focus on previous extra-articular involvement and past therapies for PsA 
will be obtained and summarized by treatment group for all patients in the Randomized set. 
Any other significant prior or active medical condition at the time of signing informed consent 
will be recorded and coded using the MedDRA dictionary. These medical conditions will be 
summarized by primary system organ class and preferred term. 
Data on baseline and demographic characteristics will be summarized by treatment sequence at 
Final Analysis. 
2.3.1 
Patient disposition 
The number of participants screened and the reasons for screen failures were presented in the 
previous primary endpoint analysis thus will not be repeated. The number and percentage of 
participants in the randomized set who completed the study periods and who discontinued from 
treatment or study prematurely (including the reason for discontinuation) will be presented at 
the end of each treatment period (e.g., Week 52 and entire treatment period), if appropriate, for 
each treatment sequence and all participants.  
For each protocol deviation (PD), the number and percentage of participants for whom the PD 
applied will be tabulated by treatment sequence on the randomized set.   
2.4 
Treatments (study treatment, rescue medication, concomitant 
therapies, compliance) 
2.4.1 
Study treatment / compliance 
The analysis of study treatment data will be based on the safety set. The number of visits with 
active and placebo injections received will be presented by treatment group. 
The duration of exposure to study treatment will also be summarized by treatment group. In 
addition, the number and percentage of participants with cumulative exposure levels (e.g. any 
exposure, ≥ 1 week, ≥ 2 weeks, ≥ 3 weeks, ≥ 4 weeks, ≥ 8 weeks, etc.) will be presented. 
Duration of exposure is defined as the time from first dose of study treatment to the time of 
treatment switch (for participants who switch treatment) or minimum of (last dose of the 
treatment + 84 days) and (last visit date). Participants who switch treatment during the study 
(e.g., from placebo to active treatment) will have exposure to both medications/doses using the 
appropriate start and stop dates. 
Duration of exposure (years) = duration of exposure (days) / 365.25 
Duration of exposure (100 subject years) = duration of exposure (years) / 100 
The analysis of duration of exposure described above will be done for the entire study treatment 
period by treatment group. 


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2.4.2 
Prior, concomitant and post therapies 
Prior and concomitant treatments will be summarized in separate tables by treatment group for 
the safety set.  
Prior medications are defined as treatments taken and stopped prior to first dose of study 
treatment. Any medication given at least once between the day of first dose of randomized study 
treatment and the date of the last study visit will be a concomitant medication, including those 
which were started pre-BSL and continued into the period where study treatment is 
administered. 
Medications will be presented in alphabetical order, by Anatomical Therapeutic Classification 
(ATC) codes and grouped by anatomical main group. Tables will show the overall number and 
percentage of participants receiving at least one treatment of a particular ATC code and at least 
one treatment in a particular anatomical main group. 
Significant prior and concomitant non-drug therapies and procedures will be summarized by 
primary system organ class and WHODrug preferred term. 
Prior surgeries and procedures are defined as surgeries and procedures done prior to first dose 
of study treatment. Any surgeries and procedures done between the day of first dose of study 
treatment and within the date of the last study visit will be a concomitant surgeries and 
procedures, including those which were started pre-BSL and continued into the period where 
study treatment is administered.  
The number and percentage of participants receiving prior and concomitant PsA therapy will 
be presented by randomized treatment group as well as the reasons for stopping their therapies 
(primary lack of efficacy, secondary lack of efficacy, lack of tolerability, other) and the total 
duration of exposure to PsA therapies previously. NSAID, glucocorticoid and DMARD (MTX, 
Leflunomide, Sulfasalazine) use will be summarized. 
Prior therapies have been summarized at Primary endpoint analysis; therefore, no summary 
tables or listings will be reproduced at the Final Analysis. 
2.5 
Analysis of the primary objective 
The primary objective of this study is to assess the efficacy of secukinumab relative to placebo 
at week 16 based on the proportion of participants achieving an ACR20 response. The 
consistency of the treatment difference between this bridging study and the pooled efficacy data 
of global pivotal studies (CAIN457F2312, CAIN457F2318, CAIN457F2336 and 
CAIN457F2342) were evaluated at the Primary endpoint analysis and will not be repeated at 
the Final Analysis. 
2.5.1 
Primary endpoint 
The primary efficacy variable was ACR20 response at Week 16. The analysis of the primary 
efficacy variable was based on the FAS. Primarily, CRP will be used instead of ESR to calculate 
ACR response; ESR will only be used in the event CRP is missing. 


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The clinical question of interest is: What is the effect of secukinumab 150 mg s.c. versus placebo 
on the composite endpoint ACR20 response at Week 16 and the completion of 16 week- 
treatment in Chinese patients with active PsA? 
The primary estimand is described by the following attributes: 
a. Population: defined through appropriate inclusion/exclusion criteria to reflect the targeted 
PsA population 
b. Variable: composite of remaining on the study and on randomized treatment through 16 
weeks and achieving ACR20 response at 16 weeks 
c. Treatment of interest: Secukinumab 150 mg s.c. and Placebo 
d. Intercurrent event: the intercurrent event of discontinuation from treatment or study prior to 
Week 16 has been addressed via the composite variable definition 
e. Population-level summary: difference in proportions of responders between secukinumab 
and placebo groups 
The estimand of binary variables is (s.c. secukinumab regimen vs placebo) obtained from a 
logistic regression model with treatment as a factor and weight as a covariate at week 16 in the 
FAS population. Difference in marginal response proportions were computed for s.c. 
secukinumab regimen and placebo regimen utilizing the logistic regression model fitted. In the 
analysis subjects discontinued study drug, dropping out or being unblinded before week 16 or 
having missing response data at week 16 are considered as non-responders.  
2.5.2 
Statistical hypothesis, model, and method of analysis  
The statistical hypothesis, model and method of analysis have been presented in the SAP for 
Primary endpoint analysis and will not be repeated in this document. 
2.5.3 
Handling of missing values/censoring/discontinuations 
The handling of missing values has been presented in the SAP for Primary endpoint analysis 
and will not be repeated in this document. 
 
2.5.4 
Supportive analyses 
The supportive analyses have been presented in the SAP for Primary endpoint analysis and will 
not be repeated in this document. 
2.6 
Analysis of the secondary objectives 
2.6.1 
Secondary endpoints 
The secondary efficacy variables are described below. Secondary efficacy variables were 
analyzed using the FAS population. Handling of missing data for secondary variables were the 
same as for the primary variable. 
• ACR50 response rate at Week 16 


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• Change from baseline in DAS28-CRP at Week16 
• Change from baseline in PASDAS at Week 16 
• Change from baseline in SF36-PCS at Week 16 
• Change from baseline in HAQ-DI© at Week 16 
The clinical questions of interest are: 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the composite endpoint 
ACR50 response at week 16 and the completion of 16 week-treatment in Chinese patients 
with active PsA? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on change from BSL in 
DAS28-CRP at week 16 in Chinese patients with active PsA had patients completed 16 
week-treatment? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on change from BSL in 
PASDAS at week 16 in Chinese patients with active PsA had patients completed 16 week- 
treatment? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on change from BSL in SF- 
36 PCS at week 16 in Chinese patients with active PsA had patients completed 16 week- 
treatment? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on change from BSL in HAQ-
DI at week 16 in Chinese patients with active PsA had patients completed 16 week- 
treatment? 
 
The justification for targeting the treatment effect is that we wish to estimate the effect of the 
study drug for the full duration when administered without dose changes. 
The estimand definition of all secondary objectives related to response (e.g., ACR50, ets.) will 
have the same attributes as that for the primary estimand, except for the variable of interest.  
Estimand definition for the secondary continuous variables (e.g., HAQ-DI©, etc.) is the 
following: 
a. Population: defined through appropriate inclusion/exclusion criteria to reflect the targeted 
PsA population 
b. Variable: change from baseline in the variable of interest 
c. Treatment of interest: Secukinumab 150 mg s.c. and Placebo 
d. Intercurrent event: discontinuation from treatment or study prior to Week 16  
e. Population-level summary: difference in variable means between secukinumab and placebo 
groups 
2.6.2 
Statistical hypothesis, model, and method of analysis 
The statistical hypothesis, model and method of analysis have been presented in the SAP for 
Primary endpoint analysis and will not be repeated in this document. 


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2.6.3 
Handling of missing values/censoring/discontinuations 
The statistical hypothesis, model and method of analysis have been presented in the SAP for 
Primary endpoint analysis and will not be repeated in this document. 
2.7 
Safety analyses 
Summaries will be performed for the entire treatment period on the Safety Set. 
Safety analysis will be performed on treatment received or actual treatment as described below: 
The actual treatment or treatment received for summaries of safety data would differ to the 
treatment assigned at randomization only if a subject received the wrong treatment during the 
entire study. 
For those subjects who received not the treatment assigned at randomization, i.e., who received 
erroneously the wrong treatment at least once, an additional AE listing will be prepared 
displaying which events occurred after the treatment errors.  
Subjects who switch treatment during the study (e.g. from placebo to active treatment) will be 
counted to both groups using the appropriate start and stop exposure date. 
The safety variables to be analyzed include Adverse events (AEs)/Serious Adverse Events 
(SAEs), clinical laboratory tests (hematology, chemistry and urinalysis), physical examination 
results, ECGs, vital signs and deaths. Safety variables are to be tabulated by descriptive statistics 
(n, mean, median, standard deviation, minimum, and maximum; or n and percent). No formal 
statistical testing is planned. 
2.7.1 
Adverse events (AEs) 
Treatment-emergent adverse events (i.e., events started after the first dose of study treatment or 
events present prior to the first dose of study treatment but increased in severity based on 
preferred term and on or before last dose + 84 days) will be summarized. 
Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of participants having any AE, having an AE in each primary system organ class 
and having each individual AE (preferred term). Summaries will also be presented for AEs by 
severity and for study treatment related AEs. If a participant reported more than one adverse 
event with the same preferred term, the adverse event with the greatest severity will be presented. 
If a participant reported more than one adverse event within the same primary system organ 
class, the participant will be counted only once with the greatest severity at the system organ 
class level, where applicable. Serious adverse events will also be summarized. 
These summaries may be presented separately by placebo controlled period and entire study. 
As appropriate, the incidence of AEs will be presented per 100 patient years of exposure 
(exposure-adjusted incidence rates). 
Separate summaries will be provided for death, serious adverse event, other significant adverse 
events leading to discontinuation and adverse events leading to dose adjustment (including 
study treatment discontinuation). 


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A graphical display of relative frequencies within system organ classes and relative risks, as 
appropriate, will be presented. 
Adverse events will also be reported separately by Standardized MedDRA Query (SMQ) 
according to MedDRA. The MedDRA version used for reporting the study will be described in 
a footnote. 
Treatment emergent and non-treatment emergent adverse events will be listed.  
Algorithms for date imputations will be provided in Programming Datasets Specifications. 
For serious adverse events (SAEs) occurred during screening a listing were prepared for all 
subjects screened including screening failures at the primary endpoint analysis. 
The safety analysis that will be performed for treatment emergent AEs and on treatment labs 
and vital signs for each analysis period is described in Table 2-1.  
The data in the period of Day 1 – Week 16 were presented at the primary endpoint analysis; the 
data in the period of Entire treatment will be presented at the Final Analysis. 
 
Table 2-1 Overview of analysis on some safety endpoints 
Analysis 
period 
AEs & SAEs 
AEs-SMQ 
AEs by 
severity 
study drug 
related AEs 
notables for 
(vitals/ 
ECG), lab 
criteria 
Risk 
Day 1 – 
Week 16 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
Entire 
Treatment  
• crude 
incidence 
• exp.time 
adjusted 
incidence 
• exp.time 
adjusted 
incidence 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
• crude 
incidence 
• exp.time 
adjusted 
incidence 
* Exposure-adjusted incidence rates will be done for the following: 
At the PSOC for AE and SAE and Level 1 for Risks and SMQ analysis 
 
For the legal requirements of ClinicalTrials.gov and EudraCT, two required tables on treatment 
emergent adverse events which are not serious adverse events with an incidence greater than 2% 
and on treatment emergent serious adverse events and SAE suspected to be related to study 
treatment will be provided by system organ class and preferred term on the safety set population. 
If for a same patient, several consecutive AEs (irrespective of study treatment causality, 
seriousness and severity) occurred with the same SOC and PT: 
• a single occurrence will be counted if there is  ≤ 1 day gap between the end date of the 
preceding AE and the start date of the consecutive AE 
• more than one occurrence will be counted if there is > 1 day gap between the end date of 
the preceding AE and the start date of the consecutive AE 


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For occurrence, the presence of at least one SAE / SAE suspected to be related to study 
treatment / non SAE has to be checked in a block e.g., among AE's in a ≤ 1 day gap block, if at 
least one SAE is occurring, then one occurrence is calculated for that SAE. 
The number of deaths resulting from SAEs suspected to be related to study treatment and SAEs 
irrespective of study treatment relationship will be provided by SOC and PT. 
2.7.1.1 
Adverse events of special interest / grouping of AEs 
Safety topics of interest, such as risks defined in the Safety Profiling Plan (SPP), Risk 
Management Plan (RMP) or topics of interest regarding signal detection or routine analysis are 
defined in the Program Case Retrieval Sheet.  
Number and percentage of subjects with an event for SPP/RMP risks will be summarized. 
2.7.2 
Deaths 
 Separate summaries will be provided for deaths.  
2.7.3 
Laboratory data 
The summary of lab data will only include on treatment data, which are defined as those lab 
assessments after the first dose of study treatment and on or before last dose +84 days. 
The summary of laboratory evaluations will be presented for three groups of laboratory tests 
(hematology, serum chemistry and urinalysis).  
For urinalysis, frequency tables will be presented. Specifically, the urine specific gravity will 
be presented in the following categories: <1.001, 1.001-1.005, 1.006-1.010, 1.011-1.015, 1.016-
1.020, 1.021-1.025, 1.026-1.030, 1.031-1.035, >1.035. Descriptive summary statistics for the 
change from BSL to each study visit will be presented. These descriptive summaries will be 
presented by test group, laboratory test and treatment group. Change from BSL will only be 
summarized for participants with both BSL and post BSL. 
For each parameter, the maximum change from BSL within each study period will be evaluated 
analogously. 
In addition, shift tables will be provided for all parameters to compare a participant’s BSL 
laboratory evaluation relative to the visit’s observed value. For the shift tables, the normal 
laboratory ranges will be used to evaluate whether a particular laboratory test value was normal, 
low, or high for each visit value relative to whether the BSL value was normal, low, or high. 
These summaries will be presented by laboratory test and treatment group. Shifts will be 
presented as well as for most extreme values post-BSL. 
The following laboratory parameters will be analyzed with respect to numerical Common 
Terminology Criteria for Adverse Events (CTCAE) grades, given in hemoglobin, platelets, 
white blood cell count, neutrophils, lymphocytes, creatinine, total bilirubin (TBL), gamma-
glutamyl transferase (GGT), alanine aminotransferase (ALT), aspartate aminotransferase 
(AST), alkaline phosphatase (ALP), glucose, cholesterol, triglycerides (TG). These summaries 
will be split into hematology and chemistry. 


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Table 2-2 CTCAE grades for laboratory parameters to be analyzed 
CTCAE v4.0 Term 
Grade 1    
Grade 2    
Grade 3    
Grade 4    
HGB decreased 
(Anemia) 
<LLN - 100 g/L  
<100 - 80 g/L 
<80 g/L 
Life-threatening 
consequences; 
urgent 
intervention 
Platelet count 
decreased 
<LLN – 75.0 x10e9 /L 
<75.0 - 50.0 x10e9 
/L 
<50.0 – 25.0 x10e9 
/L 
<25.0 x 10e9 /L 
White blood cell 
decreased 
<LLN - 3.0 x 10e9 /L 
<3.0 - 2.0 x 10e9 /L 
<2.0 - 1.0 x 10e9 /L 
<1.0 x 10e9 /L 
Neutrophil count 
decreased 
<LLN - 1.5 x 10e9 /L 
<1.5 - 1.0 x 10e9 /L 
<1.0 - 0.5 x 10e9 /L 
<0.5 x 10e9 /L 
Lymphocyte count 
decreased 
<LLN - 0.8 x 10e9/L 
<0.8 - 0.5 x 10e9 /L 
 
<0.5 - 0.2 x 10e9 /L 
<0.2 x 10e9 /L 
Creatinine increased* 
 
>1 - 1.5 x baseline;  
>ULN - 1.5 x ULN 
>1.5 - 3.0 x 
baseline;  
>1.5 - 3.0 x ULN 
>3.0 baseline;  
>3.0 - 6.0 x ULN 
>6.0 x ULN 
TBL increased 
>ULN - 1.5 x ULN 
>1.5 - 3.0 x ULN 
>3.0 - 10.0 x ULN 
>10.0 x ULN 
GGT increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALT increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
AST increased 
>ULN - 3.0 x ULN 
>3.0 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
ALP increased 
>ULN - 2.5 x ULN 
>2.5 - 5.0 x ULN 
>5.0 - 20.0 x ULN 
>20.0 x ULN 
Glucose increased 
(Hyperglycemia)  
>ULN - 8.9 mmol/L 
>8.9 - 13.9 mmol/L 
>13.9 - 27.8 mmol/L 
>27.8 mmol/L 
Glucose decreased 
(Hypoglycemia) 
<LLN - 3.0 mmol/L 
<3.0 - 2.2 mmol/L 
<2.2 - 1.7 mmol/L 
<1.7 mmol/L 
Cholesterol high 
>ULN - 7.75 mmol/L 
>7.75 - 10.34 
mmol/L 
>10.34 - 12.92 
mmol/L 
>12.92 mmol/L 
Hypertriglyceridemia 
1.71 - 3.42 mmol/L 
>3.42 - 5.7mmol/L 
>5.7 - 11.4 mmol/L 
>11.4 mmol/L 
* Note: for “creatinine increased” the baseline criteria do not apply 
Shift tables will be presented comparing baseline laboratory result (CTCAE grade) with the 
worst results (expressed in CTCAE grade) during the treatment phase (either initial up to week 
16 or entire) analyzed. Of note, baseline will be defined as last assessment prior to first dosing 
in initial treatment phase. 
Summaries for newly occurring or worsening clinically notable lipid abnormalities will also be 
provided cumulatively for each of the following parameters and categories: 
• HDL: 
o <=LLN 
o <0.8x LLN 
• LDL, cholesterol, triglycerides: 
o >=UNL 
o >1.5 x ULN 


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o > 2.5 x ULN 
Newly occurring or worsening liver enzyme abnormalities will also be summarized based on 
the event criteria given in Table 2-3: 
 
Table 2-3 Liver-related events 
Parameter 
Criterion 
ALT 
>3xULN; >5xULN; >8xULN;>10xULN, >20xULN 
AST 
>3xULN; >5xULN; >8xULN >10xULN; >20xULN 
ALT or AST 
>3xULN; >5xULN; >8xULN >10xULN; >20xULN 
TBL 
>1.5xULN; >2xULN; >3xULN 
ALP 
>2xULN; >3xULN; >5xULN 
ALT or AST & TBL  
ALT or AST>3xULN & TBL >2xULN; 
ALT or AST >5xULN & TBL >2xULN; 
ALT or AST >8xULN & TBL >2xULN; 
ALT or AST >10xULN & TBL >2xULN; 
ALP & TBL 
ALP >3xULN & TBL >2xULN 
ALP >5xULN & TBL >2xULN 
ALT or AST & TBL 
& ALP 
ALT or AST>3xULN & TBL >2xULN & ALP <2xULN (Potential Hy’s Law) 
Note: elevated ALP may suggest obstruction as a consequence of gall bladder or bile duct 
disease; ALP may also be increased in malignancy. FDA therefore terms Hy’s Law cases 
as indicators of pure hepatocellular injury. This does not mean that cases of ALT or 
AST >3xULN & TBL >2xULN & ALP  ≥ 2xULN may not result in severe DILI. 
Notes: 
1) In studies which enroll subjects with pre-existing liver disease, baseline LFT may be increased above ULN; in such a case it 
is meaningful to add the condition “and worse than baseline” to the abnormality criteria 
For a combined criterion to be fulfilled, all conditions have to be fulfilled on the same visit. The 
criteria are not mutually exclusive, e.g., a subject with ALT = 6.42xULN is counted for ALT > 
3xULN and ALT>5x ULN. 
Individual subject data listing may be provided for subjects with abnormal laboratory data. Data 
of subjects with newly occurring or worsening liver enzyme abnormalities may be listed in an 
additional listing. 
The laboratory values below Lower Level of Quantification (LLQ) or above Upper Level of 
Quantification (ULQ) will be imputed as LLQ or ULQ, respectively. The numerical part of the 
reported result will be treated as the actual LLQ or ULQ.  
2.7.4 
Other safety data 
2.7.4.1 
ECG and cardiac imaging data 
The summary of ECG will only include treatment emergent data, which are defined as those 
ECG measurements after the first dose of study treatment and on or before last dose + 84 days. 
Analysis in ECG parameters using descriptive summary statistics for the change from baseline 
for each post-baseline visit will be performed. These descriptive summaries will be presented 
by ECG parameter and treatment group. Change from baseline will only be summarized for 
subjects with both baseline and post-baseline values and will be calculated as: 


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Change from baseline = post-BSL - BSL 
The following quantitative variables will be summarized: ECG mean heart rate, RR interval, 
PR interval, QRS duration, QT interval, and corrected QT interval (QTc). Fridericia (QTcF) 
corrections will be presented for QTc. 
QTc will be summarized by computing the number and percentage of subjects (including 95% 
confidence intervals for pooled analysis, e.g., DMC or SCS) with: 
• QTcF > 500 msec  
• QTcF > 480 msec 
• QTcF > 450 msec 
• QTcF changes from baseline > 30 msec 
• QTcF changes from baseline > 60 msec 
• PR > 250 msec 
Summary statistics will be presented for ECG variables by visit and treatment group. 
In addition, shift tables comparing baseline ECG interpretation (normal, abnormal, not available, 
total) with the worst on-study interpretation (normal, abnormal, not available, total) will be 
provided. 
A listing of all newly occurring or worsening abnormalities will be provided, as well as a by-
subject listing of all quantitative ECG parameters. 
Qualitative changes will be summarized. 
2.7.4.2 
Vital signs 
The summary of vital signs will only include on treatment data, which are defined as those vital 
sign measurements after the first dose of study treatment and on or before last dose + 84 days. 
Analysis of the vital sign measurements using summary statistics for the change from BSL for 
each post-BSL visit will be performed. These descriptive summaries will be presented by vital 
sign and treatment group. Change from BSL will only be summarized for participants with both 
BSL and post-BSL values and will be calculated as: 
change from BSL = post-BSL – BSL 
the number and percentage of subjects with newly occurring notable vital signs will be 
presented. Criteria for notable vital sign abnormalities are provided in Table 2-4 below 
 
Table 2-4 Criteria for notable vital sign abnormalities 
Vital sign (unit) 
Notable abnormalities 
Systolic blood pressure (mmHg) 
>= 140 mmHg or < 90 mmHg 
Diastolic blood pressure (mmHg) 
>=90 mmHg or <60 mmHg 
Pulse (bpm) 
> 100 bpm or <60 bpm 
 
 


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2.8 
Patient-reported outcomes 
SF-36 
The following variables will be evaluated: 
x SF-36 domain scores (based on a scale of 0-100) 
x SF-36 PCS 
 scores (norm-based scores) 
x 
 
For the change in SF-36 summary scores (PCS 
), summary statistics will be provided 
using observed data for each treatment regimen. 
 
The SF-36 domain scores will be summarized by treatment. 
 
 
Patient’s global assessment of disease activity (PaGA) 
Summary statistics of observed data by visit and change from BSL in PaGA will be provided 
for each treatment. 
Patient’s assessment of PsA pain 
Summary statistics of observed data by visit and change from BSL in Patient’s assessment of 
PsA pain will be provided for each treatment. 
PPD
PPD
PPD
PPD


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2.10 
Interim analysis 
Interim analysis is not applicable in this study. 
The primary endpoint analysis was performed after all participants have completed the Week 
16 visit or discontinued earlier. The primary endpoint analysis was used for regulatory 
submission. The investigators, site personnel and monitors will continue to remain blinded to 
the original treatment assignment that each participant received at randomization until after the 
database lock for Week F60 analysis. 
Subsequent to the primary endpoint analysis, the final analysis is planned after all participants 
have completed the Week F60 assessments and may be used for regulatory submission and/or 
publication purposes. Additional analyses may be performed to support interactions with health 
authorities, as necessary. 
3 
Sample size calculation 
3.1 
Primary endpoint(s) 
As it is a bridging study for China registration, this study will pursue an estimation strategy 
rather than formal hypothesis testing of treatment difference. 
Analysis of the pooled data of global pivotal studies (CAIN457F2312, CAIN457F2318, 
CAIN457F2336 and CAIN457F2342) showed an active drug response rate of about 51.4% and 
a placebo response rate of 23.1% after 16 weeks for ACR20. With 40 participants (1:1 ratio to 
two arms), there are approximately 86.0% probability to show at least 50% global treatment 
difference (14.15%) and approximately 96.0% probability to show positive treatment difference. 


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Table 3-1 shows the probability of success with different observed response rates. 
Table 3-1 Probability of Success with Different Observed Response Rates 
  
Observed Response Rate 
Criterion 1 
Criterion 2 
  
Secukinumab 
(p1) 
Placebo 
(p2) 
p1-p2 
95% CI of 
(p1-p2) 
Aimed 
Treatment 
Difference 
PoS 
Aimed 
Treatment 
Difference 
PoS 
Scenario 1 
0.464 
0.231 
0.233 
(-0.053, 
0.519) 
> 0.1415 
0.772 
> 0 
0.922 
Scenario 2 
0.514 
0.231 
0.283 
(-0.003, 
0.569) 
> 0.1415 
0.860 
> 0 
0.960 
Scenario 3 
0.564 
0.231 
0.333 
(0.048, 
0.618) 
> 0.1415 
0.922 
> 0 
0.981 
Scenario 4 
0.614 
0.231 
0.383 
(0.101, 
0.665) 
> 0.1415 
0.961 
> 0 
0.992 
 
4 
Change to protocol specified analyses 
In the protocol, Table 16-1 Clinically notable laboratory values and vital signs summarizes the 
criteria that will be used to define expanded limits and notable abnormalities of key laboratory 
tests. The notable BP levels defined in protocol are considered as severe clinical significance 
that may require follow-up action and reporting as appropriate. In this SAP we use the criteria 
as defined in Table 2-4. Therefore, the SAP will list all events that BP is out of normal range 
for reporting purpose. 
5 
Appendix 
Summary statistics for continuous variables will include N, mean, standard deviation, minimum, 
lower quartile, median, upper quartile, maximum. Summary statistics for discrete variables will 
be presented in contingency tables and will include absolute and relative frequencies. 
5.1 
Visit window 
5.1.1 
Visit window 
When visit windows are used, all visits will be re-aligned, i.e., they will be mapped into one of 
the visit windows. E.g., if the Week 4 visit of a subject is delayed and occurs on Day 46 instead 
of on Day 29, say, it will be re-aligned to visit window Week 8. In case of major deviations 
from the visit schedule, or due to unscheduled visits, several assessments of a subject may fall 
in a particular visit window (either scheduled or unscheduled). Statistical approaches to handle 
multiple assessments in a given visit window are specified in Table 5-2.  
For lab/ECG/vital signs, as for follow-up (F/U) visits, only assessments that come as F/U 
nominal visit will be directly assigned as analysis F/U visit. Other assessments that are beyond 
the last on-treatment visit (Week 60) or after nominal F/U visit date will be listed under label 
“Week 60” in the listing. 


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For chemistry, hematology, urinalysis and lipids, the F/U visit will be presented in the summary 
table to present long-term safety of AIN. Of note, participants are allowed to have gaps in visits. 
All data collected will be displayed in listings. 
 
Table 5-1 Analysis visit windows 
Analysis 
visit 
Target 
Day 
Group 
1 
Group 
2 
Group 
3 
Group 
4 
Group 
5 
Group 
6 
Group 
7 
Group 
8 
Group 
9 
Baseline 
1 
 
 
 
 
 
 
 
 
 
Week 1 
8 
2-11 
 
 
 
 
 
2-11 
 
 
Week 2 
15 
12-18 
 
 
 
 
 
12-18 
 
 
Week 3 
22 
19-25 
 
 
 
 
 
19-25 
 
 
Week 4 
29 
26-43 
 
2-43 
2-43 
2-57 
 
26-43 
 
 
Week 8 
57 
44-71 
 
44-71 
44-71 
 
 
44-71 
2-85 
 
Week 12 
85 
72-99 
2-99 
72-99 
72-99 
58-99 
 
72-99 
 
 
Week 16 
113 
100-
127 
100-
155 
100-
141 
100-
141 
100-
141 
2-239 
100-
127 
86-
141 
2-239 
Week 20 
141 
128- 
155 
 
 
 
 
 
128- 
155 
 
 
Week 24 
169 
156- 
183 
 
142-
267 
142-
197 
142-
197 
 
156- 
183 
142-
267 
 
Week 28 
197 
184- 
211 
156-
239 
 
 
 
 
184- 
211 
 
 
Week 32 
225 
212- 
239 
 
 
198-
253 
198-
253 
 
212- 
239 
 
 
Week 36 
253 
240- 
267 
 
 
 
 
 
240- 
267 
 
 
Week 40 
281 
268- 
295 
240-
323 
 
254-
323 
254-
323 
 
268- 
295 
 
 
Week 44 
309 
296- 
323 
 
 
 
 
 
296- 
323 
 
 
Week 48 
337 
324- 
351 
 
 
 
 
 
324- 
351 
 
 
Week 52 
365 
352- 
435 
324-
393 
268-
435 
324-
435 
324-
393 
240-
393 
352- 
393 
268-
393 
240-
435 
*The first administration of randomized study treatment (first dose) is defined as Day 1. 
Group 1: ACR components, ESR, High sensitivity C-Reactive protein 
Group 2: Hematology, blood chemistry, urinalysis  
Group 3: SF-36 v2
Group 4: 
 
 
, Patient’s global assessment of psoriasis and arthritis disease activity (VAS) 
Group 5: Pregnancy test 
Group 6: ECG, Body weight 
Group 7: Vital signs 
Group 8: Lipids  
Group 9: ANA, anti-dsDNA 
The following rules are used to determine the window for an applicable visit post baseline 
“Lower limit” = “upper limit of prior applicable visit” + 1. “Upper limit” = “target day of current 
visit” + integer part of (“target day of next applicable visit” - “target day of current visit”)/2. 
Lower limit of the first applicable visit is always Day 2. Day 1 is the date of the first dose of 
randomized study treatment. 
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The mapping described above applies to all visits (not just scheduled visits). Repeat and/or 
unscheduled visits (which will be numbered in the database according to new NCDS standards) 
will be mapped for analysis purposes in the same way as scheduled visits. This leaves the 
possibility, then, for multiple measurements within an analysis window. If more than one 
assessment falls into the interval, the rules defined in Section 5.1.2 below are applied. 
Re-randomization will be performed at the end of treatment period 1, assessment from treatment 
period 2 will not be considered for treatment period 1, e.g., if a Week 20 (scheduled visit) 
measurement would fall into the Week 16 visit window, this measurement would not be 
analyzed as treatment period 1 value. Of note, for subjects who discontinue in treatment period 
1, i.e., not moving into treatment period 2, measurements taken in follow-up period would still 
be considered for treatment period 1. 
5.1.2 
Multiple assessments within visit windows 
When there are multiple assessments in a particular visit window, the following rules are 
applied to select one value “representing” the subject in summary statistics in a visit window 
(See Table 5-2). 
For baseline assessment definition, please see Section 2.1.1.3. For post-baseline visit windows, 
the following applies (unless otherwise specified)： 
• for quantitative variables, the closest to the actual visit is chosen (if two assessments have 
the same distance, then the earlier one will be chosen);  
• for qualitative variables, the worst record is selected. It is noted that in the analyses 
performed, worst case is always well defined (e.g., for urine protein values “+” and “++”, 
the worst case is defined as “++”), 
• in case qualitative variables are based on quantitative variables, 
, the 
visit will be assigned to the quantitative variable, and this visit will be used for the derived 
qualitative variable.  
 
Table 5-2  Rules for selecting values for analysis within a given visit window 
Timing of   
measurement 
Type of data 
Rule  
Baseline  
All data 
The last non-missing measurement made prior to or on the date 
of administration of the first dose of study treatment (the reference 
start date / Day 1). If a patient did not receive any dose of study 
treatment, then the randomization date will be used. Only date 
part is considered if just one assessment on Day 1.  
If there are multiple assessments on Day 1, following rules will 
apply: 
a. If assessment time exists, 
* select the last available measurement prior to reference start 
date/time considering time; 
* if no measurement prior to reference start data/time considering 
time, select the earliest measurement post reference start 
date/time considering time.  


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b. If assessment time does not exist, select the available 
measurement from the lowest CRF visit number. 
For X-ray, a baseline value is the last measurement prior to 
dosing if available. Otherwise, take the first value within 30 days 
post dosing. 
For MRI, a baseline value is the last measurement prior to dosing 
if available. Otherwise, take the first value within 7 days post 
dosing. 
Post-baseline 
efficacy 
All data 
For visits without switch of treatment in the window, the 
measurement closest to the target will be used. In the event two 
measurements are taken equally apart (e.g., 1 before target date 
and 1 after) the first one will be used. 
For visits during which the patient switches from placebo to AIN 
the following will be done based on whether or not the patient met 
the rescue criteria: 
a. if the analysis visit window is <= week 16, then  
   - if available, the closest measurement to the target date which 
is ON or BEFORE the switch date will be used (i.e., the closest 
measurement to target which is on placebo)  
  - if there are no data on or before the switch then the closest 
measurement to the target date after the switch will be used 
b. if the analysis visit window is > week 16, then 
  - if available, the closest measurement to the target date which is 
AFTER the switch date will be used (i.e., the closest 
measurement to target which is on AIN) 
  - if there are no data AFTER the switch then the closest 
measurement to the target date before the switch will be used 
Cases where the same parameter is recorded more than once on 
the same date will be handled as follows: 
* if time of completion exists the earliest measurement will be 
used; 
* if time does not exist the measurement from the lowest CRF visit 
number will be used 
   
Post-baseline safety  
Summary visit 
information (e.g., 
lab, ECG, etc.) 
For visits without switch of treatment in the window, the 
measurement closest to the target will be used. In the event two 
measurements are taken equally apart (e.g., 1 before target date 
and 1 after) the first one will be used.  
For visits during which the patient switchers from placebo to AIN 
the following will be done based on whether or not the patient met 
the rescue criteria: 
a. if the analysis visit window is <= week 16, then  
   - if available, the closest measurement to the target date which 
is ON or BEFORE the switch date will be used (i.e., the closest 
measurement to target which is on placebo)  
  - if there are no data on or before the switch then the closest 
measurement to the target date after the switch will be used 
b. if the analysis visit window is > week 16, then 
  - if available, the closest measurement to the target date which is 
AFTER the switch date will be used (i.e., the closest 
measurement to target which is on AIN) 
  - if there are no data AFTER the switch then the closest 
measurement to the target date before the switch will be used 
Cases where the same parameter is recorded more than once on 
the same date will be handled as follows: 


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* if time of completion exists the earliest measurement will be 
used; 
* if time does not exist the measurement from the lowest CRF visit 
number will be used 
   
Post-baseline safety 
Notable 
abnormalities  
(e.g. lab) 
The most extreme measurement in the window will be used. Note 
this means a patient can have a notably high and notably low 
measurement within a window. 
 
5.2 
Description of efficacy variables 
5.2.1 
American College of Rheumatology (ACR) response 
A participant is defined as an ACR20 responder if, and only if, the following three conditions 
hold: 
• 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 (PaGA) (measured on a VAS scale, 0-
100) 
• 
Physician's global assessment of disease activity (PhGA) (measured on a VAS scale, 0-
100) 
• 
Patient's assessment of PsA pain (measured on a VAS scale, 0-100) 
• 
Health Assessment Questionnaire – Disability Index (HAQ-DI©) score 
• 
Acute phase reactant (hsCRP or ESR) 
 
ACR50 = 50% improvement in at least 3 of the 5 measures and 50% improvement in the 
swollen and tender joint count. 
 
 
5.2.1.1 
Tender 78 joint count and swollen 76 joint count 
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. 
 


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. These aspects are to be implemented during data capture and will not be addressed 
during programming. 
If the number of joints for which data were available (e.g., T) is less than 78/76 for the 
tender/swollen joint assessment, the number of tender/swollen joints (e.g., t) will be scaled up 
proportionately (i.e., 78*t/T or 76*t/T for tender or swollen joint count). 
Data is recorded for tender and swollen joints (right or left side), i.e., a box (yes, no or not 
applicable) needs to be ticked for all joints. 
5.2.1.2 
Patients’ global assessment of disease activity 
The patient's global assessment of disease activity will be performed using a Visual Analog 
Scale (VAS) of 100 mm ranging from "0 -very good" to "100= 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 today'. 
5.2.1.3 
Physicians’ global assessment of disease activity 
The PhGA 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 participant. 
5.2.1.4 
Patients’ assessment of PsA pain 
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'. 
5.2.1.5 
Health Assessment Questionnaire Disability Index (HAQ- DI©) 
The Health Assessment Questionnaire (HAQ©) 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 (Health Assessment Questionnaire – Disability Index), 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]. 
Scoring of the HAQ-DI© 
The HAQ-DI© will be scored in accordance with the Alternative Disability Index (ADI) scoring 
as described in Wolfe F (2001), Zandbelt et al (2001) and the HAQ instruction [10]. The use of 
ADI scoring is due to how the data was collected for the “use of aids, devices, or help from 


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another person” questions. The ADI scoring does not include data collected from “use of aids, 
devices, or help from another person” questions in the calculation of scores. The ADI is one of 
the two disability indices described in HAQ instruction, to reflect the disability level of a subject 
when using aids and devices to compensate for disability. The HAQ-DI© using ADI scoring 
method was efficient and sensitive to change, and performed well to detect mild functional loss 
(Wolfe F, 2001). 
The following coding is to be used for the 20 items of the 8 categories of the disability outcome 
dimension: 
 
Without ANY Difficulty 
0 
With SOME Difficulty 
1 
With MUCH Difficulty 
2 
UNABLE to do 
3 
The score for each category will be the single response of the item with the highest score 
(greatest difficulty) within that category. For example, in the "Arising" category, there are two 
items: 1. “Are you able to stand up from a straight chair”; 2. “Are you able to get in and out of 
bed”. If “Are you able to stand up from a straight chair” is marked as “3” and “Are you able to 
get in and out of bed” is marked as “0”, then the score for the “Arising” category would be “3”.  
Therefore, the highest score reported by the subject for any component question of the eight 
categories determines the score for that category. If a component question is left blank, then the 
score of that category will be determined by the remaining completed question(s). 
An ADI is computed by summing the computed scores for each category and then divided by 
the number of categories answered. The ADI is not computed if the subject does not have scores 
for at least 6 categories. The ADI is the HAQ-DI© score, which will be used in the statistical 
analyses of this instrument, e.g., ACRn calculation, HAQ-DI© change from baseline. The range 
for HAQ-DI© score is (0, 3).   
HAQ-DI© response is defined by an improvement of at least 0.35 score points compared to 
baseline. 
5.2.1.6 
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 BSL only. The hsCRP results from samples collected during the 
treatment period will be revealed following database lock only. 
5.2.1.7 
Erythrocyte sedimentation rate (ESR) 
Blood for ESR, which is helpful in diagnosing inflammatory disease and is used to monitor 
disease activity and response to therapy, will be obtained at scheduled visits. 


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Local ESR test will be performed. 
5.2.2 
DAS28 and EULAR response 
DAS28, low disease activity and remission 
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. 
The DAS28 is a measure of disease activity based on Swollen and Tender Joint Counts, CRP 
or ESR, and the Patient Global Assessment of PsA disease activity.  
The following 28 joints will be assessed for tenderness and swelling: metacarpophalangeal IV 
(10), thumb interphalangeal (2), hand proximal interphalangeal II-V (8), wrist (2), elbow (2), 
shoulders (2), and knees (2). 
The following formulas can be used to calculate the DAS28 with CRP (mg/L) or ESR 
(mm/hour). 
DAS28-CRP = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.36*ln(CRP+1) + 0.014*PGA + 
0.96 
DAS28-ESR = 0.56*sqrt(TJC28) + 0.28*sqrt(SJC28) + 0.70*ln(ESR) + 0.014*PGA 
TJC28: 28 Tender joint count; SJC28: 28 Swollen joint count; CRP: C-reactive protein; PGA: 
Patient Global Assessment 
If any component measurement is missing, DAS28 will be missing. 
DAS28-CRP will be primarily used for the interpretation of the outcome; DAS-ESR is 
considered supportive. 
DAS28-CRP (or ESR) remission is defined as a DAS28-CRP (or ESR) index score less than 
2.6. Low disease activity is defined as DAS28-CRP (or ESR) index less than or equal to 3.2.  
EULAR response 
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 patient’s clinical response can be assessed. 
Comparing the DAS28-CRP (or ESR) from one patient on two different time-points, it is 
possible to define improvement or response. The EULAR response criteria are defined as 
follows: 
 
Table 5-3 EULAR response criteria 
Present DAS28 
DAS28 improvement 
>1.2 
0.6-1.2 
<0.6 
<3.2 
Good response 
Moderate response 
No response 


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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 above mentioned 
improvement criteria are used to interpret the DAS28 scores. 
5.2.3 
Psoriatic Arthritis Disease Activity Score (PASDAS) 
PASDAS is a new composite measure developed to access disease activity in Psoriasis 
(GRACE Project) (Helliwell et al 2012). It is calculated by utilizing seven measures; the seven 
components are: Patient reported measures
 
skin, peripheral joint counts (Tender 
and Swollen joint counts),
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) 
 
 
+ (0.102 x LN (CRP + 1)) + 2)*1.5 
If any component measurement is missing, PASDAS will be missing. The patient global VAS 
defined in the PASDAS score is “VAS for PASDAS assessment” which measures patient’s 
global assessment of PSORIASIS and ARTHRITIS disease activity. The Physician global VAS 
is the Physician’s global assessment of PsA disease activity. Tender Dactylitis count is from 
“Leeds Dactylitis Instrument” CRF page with “Was dactylitis present?” = “Yes” and 
“Tender/non-tender” = “Tender”. 
66-swollen / 68-tender joint counts for PASDAS assessment: 
There are only 66 swollen and 68 tender joint counts which will be used for PASDAS 
assessment. That is the 10 joints in CRF: CMC1, DIP2 (FOOT), DIP3 (FOOT), DIP4 (FOOT), 
and (DIP5 (FOOT) both left and right, should not be counted in the swollen/tender joint count 
in PASDAS formula. 
If the number of joints for which data were available (e.g., T) is less than 66/68 for the 
swollen/tender joint assessment, the number of swollen/tender joints (e.g., t) will be scaled up 
proportionately (i.e., 66*t/T or 68*t/T for swollen or tender joint count). 


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5.2.3.1 
VAS for PASDAS assessment 
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 ‘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’. 


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5.3 
Imputation rules 
5.3.1 
Study drug 
Any partial dates will be imputed as follows: 
PPD


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We take the earlier day of 
• The last day in the month and 
• The end day of the corresponding epoch 
5.3.2 
AE date imputation 
Impute AE end date: 
1. If the AE end date ‘month’ is missing, the imputed end date should be set to the earliest of 
the (min (last visit date, last dose data + 84 days), 31DECYYYY, date of death). 
2. If the AE end date ‘day’ is missing, the imputed end date should be set to the earliest of the 
(min (last visit date, last dose date + 84 days), last day of the month, date of death) 
3. If AE ‘year’ is missing or AE is ongoing, the end date will not be imputed. 
Impute AE start date: 
Before imputing AE start date, find the AE start reference date. 
1. If the (imputed) AE end date is complete and the (imputed) AE end date < treatment start 
date then AE start reference date = min(informed consent date, earliest visit date). 
2. Else AE start reference date = treatment start date 
1. If the AE start date ‘year’ value is missing, the date uncertainty is too high to impute a rational 
date. Therefore, if the AE year value is missing, the imputed AE start date is set to NULL. 
2. If the AE start date ‘year’ value is less than the treatment starts date year value, the AE started 
before treatment. Therefore: 
a. If AE ‘month’ is missing, the imputed AE start date is set to the mid-year point 
(01JulYYYY). 
b. Else if AE ‘month’ is not missing, the imputed AE start date is set to the mid-month 
point (15MONYYYY). 
3. If the AE start date year value is greater than the treatment starts date year value, the AE 
started after treatment. Therefore: 
a. If the AE month is missing, the imputed AE start date is set to the year start point 
(01JanYYYY). 
b. Else if the AE month is not missing, the imputed AE start date is set to the later of 
(month start point (01MONYYYY), AE start reference date + 1 day). 
4. If the AE start date year value is equal to the treatment start date year value: 
a. And the AE month are missing the imputed AE start date is set to the AE reference 
start date + 1 day. 
b. Else if the AE month is less than the treatment start month, the imputed AE start date 
is set to the mid-month point (15MONYYYY). 


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c. Else if the AE month is equal to the treatment start date month or greater than the 
treatment starts date month, the imputed AE start date is set to the later of (month start 
point (01MONYYYY), AE start reference date + 1 day). 
If complete (imputed) AE end date is available and the imputed AE start date is greater than the 
(imputed) AE end date, then imputed AE start date should be set to the (imputed) AE end date. 
5.3.3 
Concomitant medication date imputation 
Impute CM end date: 
1. If CM end day is missing and CM month/year are non-missing, then impute CM day as the 
minimum of treatment end date and the last day of the month. 
2. If CM end day/month are missing and CM year is non-missing, then impute CM day as the 
minimum of treatment end date and the end of the year (31DECYYYY). 
3. If imputed CM end date is less than the CM start date, use the CM start date as the imputed 
CM end date. 
Impute CM start date: 
1. If the CM start date year value is missing, the imputed CM start date is set to one day prior 
to treatment start date. 
2. If the CM start date year value is less than the treatment starts date year value, the CM 
started before treatment. Therefore: 
a. If the CM month is missing, the imputed CM start date is set to the mid-year point 
(01JULYYYY) 
b. Else if the CM month is not missing, the imputed CM start date is set to the mid-
month point (15MONYYYY) 
3. If the CM start date year value is greater than the treatment starts date year value, the CM 
started after treatment. Therefore: 
a. If the CM month is missing, the imputed CM start date is set to the year start point 
(01JANYYYY) 
b. Else if the CM month is not missing, the imputed CM date is set to the month start 
point (01MONYYYY) 
4. If the CM start date year value is equal to the treatment start date year value: 
a. And the CM month is missing, or the CM month is equal to the treatment start date 
month, then the imputed CM start date is set to one day prior treatment start date 
b. Else if the CM month is less than the treatment starts date month, the imputed CM 
start date is set to the mid-month point (15MONYYYY) 
c. Else if the CM month is greater than the treatment starts date month, the imputed 
CM start date is set to the month start point (01MONYYYY) 


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If complete (imputed) CM end date is available and the imputed CM start date is greater than 
the (imputed) CM end date, then imputed CM start date should be set to the (imputed) CM end 
date. 
5.3.3.1 
Prior therapies date imputation 
See Section 5.3.2.  
5.3.3.2 
Post therapies date imputation 
See Section 5.3.3. 
5.3.3.3 
Other imputations 
5.4 
AEs coding/grading 
Adverse events will also be coded according to MedDRA dictionary, using a narrow search. 
The MedDRA version used for reporting the adverse events will be described in a footnote. 
Safety topics of interest, such as risks defined in the Safety Profiling Plan, Risk Management 
Plan or topics of interest regarding signal detection or routine analysis are defined in the 
Program Case Retrieval Sheet. 


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6 
Reference 
1. Garwood, F (1936); Fiducial limits for the Poisson distribution. Biometrika; 46:441-453. 
2. Ge, M., Durham, L.K., Meyer, R.D. et al (2011); Covariate-Adjusted Difference in 
Proportions from Clinical Trials Using Logistic Regression and Weighted Risk Differences. 
Ther Innov Regul Sci 45, 481–493. 
3. Helliwell PS, Fitzgerald O, Fransen J et al (2013); The development of candidate composite 
disease activity and responder indices for psoriatic arthritis (GRACE project). Ann Rheum 
Dis 2013; 72:986-991. 
4. Koch GG, Tangen CM, Jung J-W IA, et al (1998); Issues for covariance analysis of 
dichotomous and ordered categorical data from randomized clinical trials and non-
parametric strategies for addressing them. Statist Med; 17:1863-92. 
5. Sahai H, Khurshid Anwer (1993); Confidence intervals for the mean of a poisson 
distribution: a review. Biom J, 35 (7); 857-867 
6. Ulm K (1990); A simple method to calculate the confidence interval of a standard mortality 
ratio. American Journal of Epidemiology, 131(2); 373-375. 
7. Wolfe F (2001); Which HAQ is best? A comparison of the HAQ, MHAQ and RA-HAQ, a 
difficult 8 item HAQ (DHAQ), and a rescored 20 item HAQ (HAQ20): analyses in 2,491 
rheumatoid arthritis patients following leflunomide initiation. J Rheumatol. 2001 
May;28(5):982-9. 
8. Zandbelt MM, Welsing PM, van Gestel AM et al (2001); Health Assessment Questionnaire 
modifications: is standardisation needed? Ann Rheum Dis. 2001 Sep;60(9):841-5. 
9. Introduction 
of 
the 
health 
assessment 
questionnaire 
introduction.  
http://www.chcr.brown.edu/pcoc/EHAQDESCRSCORINGHAQ372.PDF