A 28-week, Randomized, Double-blind, Active Controlled, Multicenter Study to Evaluate the Efficacy of Subcutaneously Administered Secukinumab Compared to Ustekinumab in Adult Patients With Psoriatic Arthritis and Failure of TNFα- Inhibitor Treatment (AgAIN)
Phase: PHASE3
Conditions: Psoriatic Arthritis
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development 
AIN457/Secukinumab 
Clinical Trial Protocol CAIN457FDE04 / NCT04632927
A 28-week, randomized, double-blind, active-controlled, 
multicenter study to evaluate the efficacy of subcutaneously 
administered secukinumab compared to ustekinumab in 
adult patients with psoriatic arthritis and failure of TNFα-
inhibitor treatment (AgAIN) 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
2019‐004246‐15 
Version number: 
01 Amended Protocol Version (clean) 
Clinical trial phase: 
IIIb  
Release date: 
10 Sep-2024  
Property of Novartis.  Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 2.0 (01-Aug-2018) 

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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 6 
List of figures ...................................................................................................................... 6 
Amendment 1 (10-SEP-2024) .................................................................................................... 7 
List of abbreviations ............................................................................................................ 9 
Glossary of terms ............................................................................................................... 13 
1 
Introduction ....................................................................................................................... 22 
1.1 
Background ............................................................................................................ 22 
1.2 
Purpose .................................................................................................................. 23 
2 
Objectives and endpoints ................................................................................................... 24 
3 
Study design ...................................................................................................................... 26 
4 
Rationale ............................................................................................................................ 26 
4.1 
Rationale for study design ..................................................................................... 26 
4.2 
Rationale for dose/regimen and duration of treatment .......................................... 27 
4.3 
Rationale for choice of control drugs (comparator/placebo) ................................. 27 
4.4 
Purpose and timing of interim analyses/design adaptations .................................. 28 
4.5 
Risks and benefits .................................................................................................. 28 
5 
Population .......................................................................................................................... 30 
5.1 
Inclusion criteria .................................................................................................... 30 
5.2 
Exclusion criteria ................................................................................................... 31 
6 
Treatment ........................................................................................................................... 33 
6.1 
Study treatment ...................................................................................................... 33 
6.1.1 
Investigational and control drugs .......................................................... 33 
6.1.2 
Additional study treatments .................................................................. 34 
6.1.3 
Treatment arms...................................................................................... 34 
6.1.4 
Treatment duration ................................................................................ 35 
6.2 
Other treatment ...................................................................................................... 35 
6.2.1 
Concomitant therapy ............................................................................. 35 
6.2.2 
Prohibited medication ........................................................................... 37 
6.2.3 
Rescue medication ................................................................................ 39 
6.3 
Patient numbering, treatment assignment, randomization ..................................... 39 
6.3.1 
Patient numbering ................................................................................. 39 
6.3.2 
Treatment assignment, randomization .................................................. 39 
6.4 
Treatment blinding ................................................................................................ 40 
6.5 
Dose escalation and dose modification.................................................................. 41 
6.6 
Additional treatment guidance ............................................................................... 41 

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6.6.1 
Treatment compliance ........................................................................... 41 
6.6.2 
Emergency breaking of assigned treatment code .................................. 41 
6.7 
Preparation and dispensation ................................................................................. 42 
6.7.1 
Handling of study treatment and additional treatment .......................... 43 
6.7.2 
Instruction for prescribing and taking study treatment ......................... 43 
7 
Informed consent procedures ............................................................................................ 44 
8 
Visit schedule and assessments ......................................................................................... 45 
8.1 
Screening ............................................................................................................... 50 
8.1.1 
Information to be collected on screening failures ................................. 50 
8.2 
Patient demographics/other Baseline characteristics ............................................. 50 
8.3 
Efficacy .................................................................................................................. 50 
8.3.1 
Health assessment questionnaire – disability index .............................. 51 
8.3.2 
Psoriasis area and severity index ........................................................... 51 
8.3.3 
Patient’s assessment of psoriatic arthritis pain ...................................... 53 
8.3.4 
Tender 68 joint count and swollen 66 joint count ................................. 53 
 
 53 
8.3.6 
Patient’s global assessment of disease activity ..................................... 54 
8.3.7 
Patient’s global assessment of psoriasis and arthritis disease activity .. 54 
8.3.8 
Minimal disease activity ....................................................................... 54 
8.3.9 
Leeds enthesitis index ........................................................................... 54 
8.3.10 
Leeds dactylitis index ............................................................................ 54 
 
 55 
8.3.12 
American College of Rheumatology response ...................................... 55 
 
 55 
 
 56 
8.3.15 
Erythrocyte sedimentation rate ............................................................. 56 
8.3.16 
Appropriateness of efficacy assessments .............................................. 56 
8.4 
Safety ..................................................................................................................... 56 
8.4.1 
Physical examination ............................................................................ 57 
8.4.2 
Vital signs.............................................................................................. 57 
8.4.3 
Height and weight ................................................................................. 57 
8.4.4 
Tuberculosis screening .......................................................................... 57 
8.4.5 
Laboratory evaluations .......................................................................... 58 
8.4.6 
Pregnancy and assessments of fertility ................................................. 58 
8.4.7 
Tolerability of investigational treatments ............................................. 59 
8.4.8 
Additional parameters ........................................................................... 59 
8.4.9 
Appropriateness of safety measurements .............................................. 59 

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8.5 
Other assessments .................................................................................................. 59 
8.5.1 
Health-related quality of life ................................................................. 59 
 
 61 
9 
Study discontinuation and completion .............................................................................. 62 
9.1 
Discontinuation ...................................................................................................... 62 
9.1.1 
Discontinuation of study treatment ....................................................... 62 
9.1.2 
Withdrawal of informed consent ........................................................... 63 
9.1.3 
Lost to follow-up ................................................................................... 64 
9.1.4 
Early study termination by the sponsor ................................................. 64 
9.2 
Study completion and post-study treatment .......................................................... 64 
10 Safety monitoring and reporting ........................................................................................ 65 
10.1 
Definition of adverse events and reporting requirements ...................................... 65 
10.1.1 
Adverse events ...................................................................................... 65 
10.1.2 
Serious adverse events .......................................................................... 66 
10.1.3 
SAE reporting........................................................................................ 67 
10.1.4 
Pregnancy reporting .............................................................................. 68 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 69 
10.2 
Additional safety monitoring ................................................................................. 69 
10.2.1 
Liver safety monitoring ......................................................................... 69 
10.2.2 
Renal safety monitoring ........................................................................ 69 
11 Data collection and database management ........................................................................ 70 
11.1 
Data collection ....................................................................................................... 70 
11.2 
Database management and quality control ............................................................ 70 
11.3 
Site monitoring ...................................................................................................... 70 
12 Data analysis and statistical methods ................................................................................ 71 
12.1 
Analysis sets .......................................................................................................... 71 
12.2 
Patient demographics and other Baseline characteristics ...................................... 71 
12.3 
Treatments ............................................................................................................. 72 
12.4 
Analysis of the primary endpoint(s) ...................................................................... 72 
12.4.1 
Definition of primary endpoint(s) ......................................................... 72 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 73 
12.4.3 
Handling of missing values/censoring/discontinuations ....................... 73 
12.4.4 
Sensitivity and Supportive analyses ...................................................... 74 
12.5 
Analysis of secondary endpoints ........................................................................... 74 
12.5.1 
Efficacy endpoint(s) .............................................................................. 74 
12.5.2 
Safety endpoints .................................................................................... 75 
 
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12.7 
Interim analyses ..................................................................................................... 76 
12.8 
Sample size calculation.......................................................................................... 76 
12.8.1 
Primary endpoint(s) ............................................................................... 76 
13 Ethical considerations and administrative procedures ...................................................... 77 
13.1 
Regulatory and ethical compliance ........................................................................ 77 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 77 
13.3 
Publication of study protocol and results............................................................... 77 
13.4 
Quality control and quality assurance.................................................................... 78 
14 Protocol adherence ............................................................................................................ 78 
14.1 
Protocol amendments............................................................................................. 78 
15 References ......................................................................................................................... 79 
16 Appendices ........................................................................................................................ 83 
16.1 
Appendix 1: Classification criteria for psoriatic arthritis (CASPAR) ................... 83 
16.2 
Appendix 2: Guidelines for administering the questionnaires for patient 
reported outcomes .................................................................................................. 84 
16.3 
Appendix 3: American College of Rheumatology (ACR) Measures and 
Criteria of Response .............................................................................................. 87 
16.4 
Appendix 4: Standard reference table for the LDI ................................................ 89 
16.5 
Appendix 5: The Psoriasis Area and Severity Index (PASI) ................................. 90 
16.6 
Appendix 6: Liver event and laboratory trigger definitions and follow-up 
requirements .......................................................................................................... 92 
16.7 
Appendix 7: Clinically notable laboratory values ................................................. 94 
 

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List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 24 
Table 6-1 
Overview of treatment during the study – type and number of 
injections ............................................................................................... 35 
Table 6-2 
Prohibited medication ........................................................................... 37 
Table 8-1 
Assessment Schedule ............................................................................ 46 
Table 8-2 
The PASI scoring system ...................................................................... 52 
 
 56 
Table 16-1 
LDI reference table for hands (in cm) ................................................... 89 
Table 16-2 
LDI reference table for feet (in cm) ...................................................... 89 
Table 16-3 
PASI Scoring Worksheet ...................................................................... 90 
Table 16-4 
Liver event and laboratory trigger definitions ...................................... 92 
Table 16-5 
Follow-up requirements for liver events and laboratory triggers .......... 92 
Table 16-6 
Clinically notable laboratory values...................................................... 94 
List of figures 
Figure 3-1 
 Study Design ........................................................................................ 26 
 
 
 

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IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol require IRB/IEC and Health Authority 
approval according to local regulations prior to implementation.  
 

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List of abbreviations 
ACR 
American College of Rheumatology 
ADA 
Anti-Drug Antibodies 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
ANA 
Antinuclear Antibody 
anti-CCP 
Anti-Cyclic Citrullinated Peptide 
anti-dsDNA 
Anti-Double Stranded DNA Antibodies 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Chronical 
BSA 
Body Surface Area 
BSL 
Baseline 
CASPAR 
Classification Criteria for Psoriatic Arthritis 
CD 
Cluster of Differentiation 
cDMARD 
Conventional Disease Modifying Anti-Rheumatic Drugs (also known as 
non-biologic DMARDs) 
CFR 
Code of Federal Regulations (U.S.)  
cm 
Centimeter 
COX 
Cyclooxygenase 
CPO 
Country Pharma Organization 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
 
 
 
 
DAS 
Disease Activity Score 
dL 
Deciliter 
DLQI 
Dermatology Life Quality Index 
DMARD(s) 
Disease-Modifying Antirheumatic Drug(s) 
DSM 
Drug Supply Management 
DSUR 
Developmental Safety Update Report 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report/Record Form 
EDC 
Electronic Data Capture 
EMA/EMEA 
European Medicines Agency 
EOS 
End of Study 
 
 
ESR 
Erythrocyte Sedimentation Rate 
EU 
European Union 
EULAR 
European League Against Rheumatism 
F/FUP 
Follow-Up 
FACIT-Fatigue©  
Functional Assessment of Chronic Illness Therapy-Fatigue 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
G 
Gram 

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GCP 
Good Clinical Practice 
HAQ-DI© 
Health Assessment Questionnaire – Disability Index 
hCG 
Human Chorionic Gonadotropin 
HDL 
High Density Lipoprotein 
HIV 
Human Immunodeficiency Virus 
HRQoL 
Health-Related Quality of Life 
HTA 
Health Technology Assessment 
IB 
Investigator’s Brochure 
IBD 
Inflammatory Bowel Disease 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
Ig 
Immunoglobuline 
 
 
IL 
Interleukin 
IN 
Investigator Notification 
IR 
Inadequate Responder 
IRB 
Institutional Review Board 
IUD 
Intrauterine Device 
IUS 
Intrauterine System 
JAK 
Janus Kinase 
kg 
Kilogram 
LDI 
Leeds Dactylitis Index 
LDL 
Low Density Lipoprotein 
LEI 
Leeds Enthesitis Index 
LFT 
Liver Function Test  
LLN 
Lower Limit of Normal 
LLOQ 
Lower Limit of Quantification 
MACE 
Major Adverse Cardiovascular Events 
MAR 
Missing at Random 
 
 
MCS 
Mental Component Summary 
MDA 
Minimal Disease Activity 
MedDRA 
Medical Dictionary for Regulatory Activities  
mg 
Milligram 
MI 
Multiple Imputation 
mL 
Milliliter 
mm 
Millimeter 
MMRM 
Mixed-effect Model for Repeated Measures 
 
 
MRI 
Magnetic Resonance Imaging 
MTX 
Methotrexate 
 
 

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NSAID 
Non-Steroidal Anti-Inflammatory Drug 
 
 
PASI 
Psoriasis Area and Severity Index 
PCS 
Physical Component Summary 
PFS 
Prefilled Syringe 
 
 
PRN 
Pro re nata / As Required 
PRO 
Patient Reported Outcome 
PsA 
Psoriatic Arthritis 
PsAQoL 
Psoriatic Arthritis Quality of Life 
 
 
PUVA 
Psoralen Ultraviolet Light A 
QMS 
Quality Management System 
QoL 
Quality of Life 
QTcF 
Fridericia QT Correction Formula 
R 
Randomization 
RAS 
Randomized Analysis Set 
RBC 
Red Blood Cell 
RF 
Rheumatoid Factor 
SAE 
Serious Adverse Event 
s.c. 
Subcutaneous(ly) 
 
 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamic Pyruvic Transaminase 
SJC 
Swollen Joint Count 
SmPC 
Summary of Product Characteristics 
SMQ 
Standardized MedDRA Query 
SOP 
Standard Operating Procedures 
 
 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
SV 
Screening Visit 
TB 
Tuberculosis 
Th 
T helper 
t.i.d. 
Three Times Daily 
TJC 
Tender Joint Count 
TNF 
Tumor Necrosis Factor 
TNFα 
Tumor Necrosis Factor Alpha 
tsDMARD 
Targeted Synthetic Disease Modifying Anti-Rheumatic Drug 
ULN 
Upper Limit of Normal 
UV 
Ultraviolet 
UVA 
Ultraviolet Light A 
UVB 
Ultraviolet Light B 
V 
Visit 
VAS 
Visual Analog Scale 

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WBC 
White Blood Cell 
WHO 
World Health Organization  
 
  

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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 patient  
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 
DMARDs 
Disease modifying anti-rheumatic drugs. This drug class includes biological 
DMARDs (bDMARDs), conventional (systemic) DMARDs (cDMARDs, csDMARDs) 
and targeted systemic DMARDs (tsDMARDs). 
Dosage 
Dose of the study treatment given to the patient in a time unit (e.g. 100 mg once a 
day, 75 mg twice a day) 
Electronic data capture 
(EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical study data 
using data collection systems, such as Web-based applications, interactive voice 
response systems and clinical laboratory interfaces. EDC includes the use of 
Electronic Case Report Forms (eCRFs) which are used to capture data transcribed 
from paper source forms used at the point of care 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last patient or at a later 
point in time as defined by the protocol  
Enrollment 
Point/time of patient entry into the study at which informed consent must be obtained  
Investigational drug/ 
treatment 
The drug whose properties are being tested in the study 
Medication number 
A unique identifier on the label of medication kits 
Mis-randomized 
patients 
Mis-randomized patients are those who were not qualified for randomization and 
who did not take study treatment, but have been inadvertently randomized into the 
study  
Other treatment 
Treatment that may be needed/allowed during the conduct of the study (i.e. 
concomitant or rescue therapy) 
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 patients with established disease and in those with newly-
diagnosed disease 
Patient 
An individual with the condition of interest for the study 
Period 
The subdivisions of the trial design (e.g. Screening, Treatment, Follow-up) which are 
described in the Protocol. Periods define the study phases and will be used in 
clinical trial database setup and eventually in analysis 
Personal data 
Patient information collected by the Investigator that is transferred to Novartis for the 
purpose of the clinical trial. This data includes patient identifier information, study 
information and biological samples.  
Premature patient 
withdrawal 
Point/time when the patient exits from the study prior to the planned completion of all 
study drug administration and/or assessments; at this time all study drug 
administration is discontinued and no further assessments are planned 
Randomization number 
A unique identifier assigned to each randomized patient 
Screen failure 
A patient who did not meet one or more criteria that were required for participation in 
the study 
Source data/document 
Source data refers to the initial record, document, or primary location from where 
data comes. The data source can be a database, a dataset, a spreadsheet or even 
hard-coded data, such as paper or eSource 

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Start of the clinical trial 
The start of the clinical trial is defined as the signature of the informed consent by 
the first patient 
Study treatment 
Any single drug or combination of drugs or intervention administered to the patient 
as part of the required study procedures 
Study treatment 
discontinuation 
When the patient permanently stops taking any of the study drug(s) prior to the 
defined study treatment completion date (if any) for any reason; may or may not also 
be the point/time of study discontinuation  
Patient ID/number 
A unique number assigned to each patient upon signing the informed consent. This 
number is the definitive, unique identifier for the patient and should be used to 
identify the patient throughout the study for all data collected, sample labels, etc. 
Treatment arm/group  
A treatment arm/group defines the dose and regimen or the combination, and may 
consist of 1 or more cohorts. 
Variable 
A measured value or assessed response that is determined from specific 
assessments and used in data analysis to evaluate the drug being tested in the 
study 
Withdrawal of study 
consent (WoC) 
Withdrawal of consent from the study occurs only when a patient does not want to 
participate in the study any longer and does not allow any further collection of 
personal data  
 

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Protocol summary 
Protocol number 
CAIN457FDE04 
Full Title 
A 28-week, randomized, double-blind, active controlled, multicenter study to 
evaluate the efficacy of subcutaneously administered secukinumab compared 
to ustekinumab in adult patients with psoriatic arthritis and failure of TNFα- 
inhibitor treatment (AgAIN) 
Brief title 
Efficacy of secukinumab compared to ustekinumab in adults with active 
psoriatic arthritis and failure of TNFα-inhibitor treatment 
Sponsor and 
Clinical Phase 
Novartis, Phase IIIb 
Investigation type 
Biological 
Study type 
Interventional 
Purpose and 
rationale 
Secukinumab has already been shown to be superior to ustekinumab in the 
treatment of moderate-to-severe skin psoriasis. To date, no results are 
available for psoriatic arthritis (PsA) in this setting. Additionally, data regarding 
the tumor necrosis factor α inadequate responder (TNFα-IR) population using 
the aforementioned treatment in a dedicated clinical trial are lacking. This 
head-to-head study will close this gap and generate valuable insights into the 
mechanistic process after anti-TNFα failure. 
In addition, secukinumab and ustekinumab were just recently listed as 
appropriate comparators within the German Health Technology Assessment 
(HTA) process for the subpopulation of PsA patients who failed biologics 
treatment.  
The overall study design is intended to reflect efficacy insights, prescription 
information, treatment guidelines and clinical practice in the targeted patient 
population, thereby supporting future HTAs of secukinumab in Germany. 
Primary objective 
• 
To demonstrate that secukinumab 300 mg s.c. is superior to ustekinumab 
45/90 mg s.c. at week 28 based on the proportion of patients achieving an 
improvement 
in 
health 
assessment 
questionnaire-disability 
index  
(HAQ-DI©) score ≥ 0.35 versus Baseline. 
Secondary 
objectives 
To demonstrate 
• 
The efficacy of secukinumab 300 mg s.c. is higher to ustekinumab 
45/90 mg s.c. at Week 28 based on the proportion of patients achieving a 
psoriasis area and severity index (PASI) 90 response. 
• 
Secukinumab 300 mg s.c. shows a beneficial effect compared to 
ustekinumab 45/90 mg s.c. at Week 28 based on the proportion of patients 
achieving an improvement of ≥ 10 mm for the patient’s assessment of pain 
(visual analog scale, VAS). 
• 
The mean change from Baseline on secukinumab 300 mg s.c. is higher to 
ustekinumab 45/90 mg s.c. at week 28 for the tender joint count (TJC) 68. 
• 
The mean change from Baseline on secukinumab 300 mg s.c. is higher to 
ustekinumab 45/90 mg s.c. at week 28 for the swollen joint count (SJC) 66. 
• 
Efficacy of secukinumab 300 mg s.c. is higher to ustekinumab 45/90 mg 
s.c. at week 28 based regarding the proportion of patients achieving a PASI 
100 response. 
• 
Efficacy of secukinumab 300 mg s.c. is higher to ustekinumab 45/90 mg 
s.c. at week 28 based on the proportion of patients achieving a PASI 75 
response. 

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• 
Secukinumab 300 mg s.c. shows a beneficial effect compared to 
ustekinumab 45/90 mg s.c. at Week 28 based on the proportion of patients 
achieving an improvement of 10 mm on patient’s global assessment of 
disease activity (VAS). 
• 
Secukinumab 300 mg s.c. shows a beneficial effect compared to 
ustekinumab 45/90 mg s.c. at Week 28 based on the proportion of patients 
achieving an improvement of 10 mm on patient’s global assessment of 
psoriasis and arthritis disease activity (VAS). 
• 
Efficacy of secukinumab 300 mg s.c. is higher to ustekinumab 45/90 mg 
s.c. at week 28 based on the proportion of patients achieving minimal 
disease activity (MDA). 
• 
The mean change from Baseline on secukinumab 300 mg s.c. is higher to 
ustekinumab 45/90 mg s.c. at week 28 for the Leeds enthesitis index (LEI). 
• 
The mean change from Baseline on secukinumab 300 mg s.c. is higher to 
ustekinumab 45/90 mg s.c. at week 28 for the Leeds dactylitis index (LDI).  
• 
The mean change from baseline on secukinumab 300 mg s.c. is higher to 
ustekinumab 45/90 mg s.c. at week 28 for Psoriatic Arthritis Quality of Life 
(PsAQoL). 
• 
The efficacy of secukinumab 300 mg s.c. is higher to ustekinumab 45/90 
mg s.c. at week 28 based on the proportion of patients achieving an 
improvement of ≥ 4 points for Functional Assessment of Chronic Illness 
Therapy – fatigue (FACIT-Fatigue©).  
• 
The efficacy of secukinumab 300 mg s.c. is higher to ustekinumab 45/90 
mg s.c. at week 28 based on the proportion of patients achieving a 
Dermatology Life Quality Index (DLQI) 0/1 response. 
• 
To evaluate the safety and tolerability of secukinumab 300 mg s.c. 
compared with ustekinumab 45/90 mg s.c. as assessed by vital signs, 
clinical laboratory values, and AE monitoring. 
Study design 
This randomized, double-blind, active-controlled, multicenter, study will assess 
the superiority of secukinumab to ustekinumab for treating patients with active 
PsA who failed TNFα-inhibitor treatment. The study will include a screening 
period of up to 10 weeks, a treatment period of 28 weeks, and a follow-up 
period of 8 weeks. 
Population 
The study population will consist of 310 patients fulfilling Classification criteria 
for Psoriatic Arthritis (CASPAR) and have shown previous inadequate 
response to TNFα-inhibitors. 
Inclusion criteria 
1. Informed consent must be obtained before any assessment is 
performed. 
2. Male or non-pregnant, non-lactating female subjects at least 18 years 
of age. 
3. Diagnosis of PsA as classified by CASPAR criteria for at least 6 
months before randomization. 
4. Active PsA at Baseline defined as ≥3 tender joints out of 68 and ≥3 
swollen joints out of 66 (dactylitis of a digit counts as one joint each). 
5. Inadequate response or intolerance to previous or current treatment 
with at least one TNFα-inhibitor administered at an approved dose for 
the given duration according to the respective Summary of Product 
Characteristics (SmPC). 
6. Inadequate response or intolerance to conventional disease modifying 
anti-rheumatic drugs (cDMARDs) and to at least one TNFα-inhibitor 

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must have been documented in the patient’s medical history or 
reported by the patient or determined by the investigator at Screening. 
7. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) 
antibodies negative at screening. 
8. Diagnosis of active plaque psoriasis, with at least one psoriatic plaque 
or nail changes consistent with psoriasis or documented history of 
plaque psoriasis. 
9. Patients taking methotrexate (MTX) (≤ 30 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 28. 
10. Patients on MTX must be on folic acid supplementation at 
randomization. 
11. Patients who are on a disease modifying anti-rheumatic drug 
(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 wash-out has been performed. 
12. Patients who are regularly receiving non-steroidal anti-inflammatory 
drugs (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 
not increase the dose up to Week 28. 
13. Patients receiving 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 28. 
Exclusion criteria 
1. Pregnant or nursing (lactating) women, where pregnancy is defined as 
the state of a female after conception and until the termination of 
gestation, confirmed by a positive human chorionic gonadotropin 
(hCG) laboratory test. 
2. Women of childbearing potential, defined as all women physiologically 
capable of becoming pregnant, unless they are using effective 
methods of contraception during dosing of study treatment and 
minimum 16 weeks or longer if local label requires it after the last dose 
(e.g. 20 weeks for secukinumab, 15 weeks for ustekinumab in the 
European Union (EU)). 
Effective contraception methods include: 
a. Total abstinence (when this is in line with the preferred and 
usual lifestyle of the patient). Periodic abstinence (e.g. 
calendar, ovulation, symptothermal, post-ovulation methods) 
and withdrawal are not acceptable methods of contraception. 
b. Female sterilization (have had surgical bilateral oophorectomy 
with or without hysterectomy), total hysterectomy or tubal 
ligation at least 6 weeks before taking investigational drug. In 
case of oophorectomy alone, only when the reproductive 
status of the woman has been confirmed by follow up hormone 
level assessment. 
c. Male sterilization (at least 6 months prior to Screening). For 
female patients on the study, the vasectomized male partner 
should be the sole partner for that patient. 
d. Barrier methods of contraception: condom or occlusive cap 
(diaphragm or cervical/vault caps).  
e. Use of oral, (estrogen and progesterone), injected or 
implanted hormonal methods of contraception or other forms 

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of hormonal contraception that have comparable efficacy 
(failure rate <1%), for example hormone vaginal ring or 
transdermal hormone contraception or placement of an 
intrauterine device (IUD) or intrauterine system (IUS). In case 
of use of oral contraception, women should have been stable 
on the same pill for a minimum of 3 months before taking the 
investigational drug. 
In case local regulations deviate from the methods listed, local 
regulations apply and will be described in the informed consent form 
(ICF). 
Women are considered post-menopausal and not of child-bearing 
potential if they have had at least 12 months of natural (spontaneous) 
amenorrhea with an appropriate clinical profile (e.g. age appropriate, 
history of vasomotor symptoms) or have had surgical bilateral 
oophorectomy (with or without hysterectomy), total hysterectomy or 
tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, 
only when the reproductive status of the woman has been confirmed 
by follow up hormone level assessment is she considered not of child-
bearing potential.  
3. Previous exposure to secukinumab, ustekinumab or any other biologic 
drug directly targeting IL-17, IL-17 receptor, IL-12 or IL-23. 
4. Patients for whom the use of secukinumab or ustekinumab is 
contraindicated. 
5. Use of any other investigational drug within 4 weeks or within a period 
of 5 half-lives of the investigational treatment prior to the Baseline Visit, 
whichever is longer, until the expected pharmacodynamic effect has 
vanished. Previous treatment with any cell-depleting therapies 
including but not limited to anti-CD20 or investigational agents (e.g., 
alemtuzumab (Campath®), anti-CD4, anti-CD5, anti-CD3, and anti-
CD19). 
6. 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. 
7. Patients receiving high potency opioid analgesics including but not 
limited to methadone, hydromorphone, and morphine. 
8. Ongoing use of prohibited psoriasis treatments/medications (e.g., 
topical corticosteroids or ultraviolet therapy at randomization). The 
following wash out periods need to be observed: 
a. Oral or topical retinoids: 4 weeks 
b. Photochemotherapy (e.g. PUVA): 4 weeks 
c. Phototherapy (UVA or UVB): 2 weeks 
d. Topical skin treatment (except in face, eyes, scalp and genital 
area during screening; only corticosteroids with mild to 
moderate potency): 2 weeks. 
9. History of hypersensitivity to any of the study drugs or excipients or to 
drugs of similar chemical classes. 
10. Any intramuscular or intravenous corticosteroid treatment within  
4 weeks before randomization. 
11. Any therapy by intra-articular injections (e.g., corticosteroid) within  
4 weeks before randomization. 
12. Active ongoing inflammatory diseases other than PsA that might 
confound the evaluation of the benefit of secukinumab therapy. 

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13. 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. 
14. Significant medical problems or diseases, including but not limited to 
the following: uncontrolled hypertension (≥160/95 mmHg), congestive 
heart failure (New York Heart Association status of class III or IV) and 
uncontrolled diabetes. 
15. History of clinically significant liver disease or liver injury as indicated 
by abnormal liver function tests (LFTs) such as aspartate 
aminotransferase/serum 
glutamic 
oxaloacetic 
transaminase 
(AST/SGOT), alanine aminotransferase / serum glutamic pyruvic 
transaminase (ALT/SGPT), alkaline phosphatase or serum bilirubin. 
The investigator should be guided by the following criteria: 
a. Any single parameter may not exceed 2 x upper limit of normal 
(ULN). A single parameter elevated up to and including 2 x 
ULN should be re-checked once more as soon as possible and 
in all cases, at least prior to enrollment/randomization, to rule 
out any possible lab error. 
b. If the total bilirubin concentration is increased above 2 x ULN, 
total bilirubin should be differentiated into the direct and 
indirect reacting bilirubin. 
16. History of renal trauma, glomerulonephritis, or subjects with one kidney 
only, or a serum creatinine level exceeding 1.8 mg/dL (159.12 μmol/L). 
17. Screening total white blood cell (WBC) count <3,000/μL, or platelets 
<100,000/μL or neutrophils <1,500/μL or hemoglobin <8.5 g/dL (85 
g/L). 
18. Active systemic infections during the last two weeks (exception: 
common cold) prior to randomization. 
19. History of ongoing, chronic or recurrent infectious disease or evidence 
of tuberculosis (TB) infection as defined by a positive QuantiFERON 
TB-Plus test. Patients 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 TB. If presence 
of latent TB is established then treatment according to local country 
guidelines must have been initiated prior to enrollment. 
20. Live vaccinations within 6 weeks prior to Baseline or planned 
vaccination during study participation until 12 weeks after last study 
treatment administration. 
21. Proven infection with human immunodeficiency virus (HIV), hepatitis B 
or hepatitis C at screening or randomization. 
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). 

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The primary analysis will be performed comparing treatments with respect to 
the primary efficacy variable, the proportion of patients achieving a HAQ-DI© 
score ≥ 0.35 versus Baseline, by means of a logistic regression model with 
treatment and randomization strata as factors and HAQ-DI© score as 
covariates.  
The main measure of effect, the odds ratio, with corresponding 95% confidence 
interval (CI) and the p-value (both Wald) will be given. The null hypothesis of 
equal odds will be rejected, if the two-sided p-value from the logistic regression 
model for the factor treatment is below the significance threshold of 0.05.  
Sensitivity as well as supportive subgroup analyses will be conducted in order 
to provide evidence for the robustness of the main results. These analyses will 
center on the deviations in model assumptions and the treatment of missing 
values.  
Key words 
psoriatic arthritis, secukinumab, ustekinumab, monoclonal antibody, CASPAR 

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1 
Introduction 
1.1 
Background 
Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory disease that can affect 
peripheral and axial joints, entheses and the skin. Additional common manifestations are nail 
dystrophy, dactylitis or spine involvement accompanied by comorbidities with impact e.g. on 
cardiovascular risk. PsA is associated with impaired physical function and poor quality of life 
(QoL) and thus constitutes a major socioeconomic burden (Gladman 2005, Rosen et al 2012). 
The majority of patients will have psoriasis prior to the occurrence of the associated arthritis 
and are typically under treatment for their skin disease. 
Pathogenesis-based interventions, particularly therapies targeting tumor necrosis factor alpha 
(TNFα) show improved outcomes in patients with PsA. Effectiveness and safety have been 
demonstrated over many years (Ramiro et al 2016). However, despite this progress, 
approximately 30% of patients fail TNFα inhibitor treatment through inadequate response (IR). 
They might never achieve a response due to a dominant non-TNFα inflammatory pathway 
(primary non-responder), show loss of efficacy over time (secondary inefficacy) or have to 
discontinue treatment because of adverse events (AEs) including intolerance. Switching to a 
second- or even third-line anti-TNFα therapy (“anti-TNF cycling”) may be successful, but most 
studies show an insufficient response as the same molecular and inflammatory pathways are 
targeted. The probability of exhibiting a good response within the same treatment class is lower 
than for the first treatment. As seen not only in rheumatoid arthritis but also in PsA, only a small 
number of primary non-responsive patients switching to a second anti-TNFα achieve a 
significant clinical response and the number of patients achieving a sufficient response on the 
third anti-TNFα is negligible. These patients are in need of further therapeutic options (Gomez-
Reino et al 2006, Cantini et al 2017). Real world evidence obtained from national registries and 
observational studies indicates a discontinuation of first-line TNFα inhibitor treatment ranging 
between 17.1% and 67.5% (Cantini et al 2017).    
Alternative biological treatment options besides TNFα inhibitors include inhibitors for 
Interleukin (IL)-12/IL-23 (ustekinumab) and IL-17A (secukinumab and ixekizumab).  
The IL-17/IL-23 axis plays a central role in the pathogenesis of psoriasis, PsA and axial 
spondyloarthritis (McGonagle et al 2019). The cytokine IL-17A and its receptor are highly 
expressed in psoriatic diseases including PsA. IL-17A is one of the main cytokines involved in 
the inflammatory process in PsA finally leading to destruction, loss of joint function and poor 
quality of life of affected patients. It is produced by a variety of immune cells during the course 
of the disease including T helper (Th) 17 cells, γδT cells, macrophages and type 3 innate 
lymphoid cells (Ivanov et al 2006, Lombes et al 2015). Additionally, IL-23 belongs to the major 
molecules leading to a damaging course of the disease by inducing differentiation, activation 
and expansion of Th17 cells which are an effector of the inflammatory process and the main 
source of IL-17A (Gaffen et al 2014).  
Secukinumab, a human monoclonal antibody that inhibits the effector function of IL-17A, has 
shown better efficacy compared to placebo in several phase III trials for PsA including the 
FUTURE-study program which involved over 2700 patients. Rapid improvement of key 
clinical domains of the disease signs and symptoms could be demonstrated not only for anti-

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TNFα naive patients but also for patients showing an inadequate response regarding prior anti-
TNFα treatment (McInnes et al 2015; Kavanaugh et al 2016). 
Just recently secukinumab and ustekinumab have been added to the list of appropriate 
comparators within the German health technology assessment (HTA) process for the 
subpopulation of PsA patients who fail TNFα inhibitor treatment. Previously, only TNFα 
inhibitors were listed as an appropriate comparator.  
Within the context of the life cycle management of secukinumab including several planned new 
indications in the next years this update of the list of appropriate comparators provides – besides 
important scientific data – an additional opportunity to conduct a study to support the upcoming 
HTAs.  
1.2 
Purpose 
Secukinumab has already been shown to be superior to ustekinumab in the treatment of 
moderate-to-severe psoriasis (Blauvelt et al 2017, Bagel et al 2018). To date, no equivalent data 
are available for the TNFα-IR population in PsA using the aforementioned treatment in a 
dedicated clinical trial. This 28-week study will close this scientific gap and generate valuable 
insights into the mechanistic process in PsA patients after failure of TNFα inhibition. 
In addition to the scientific aspect, secukinumab and ustekinumab were just recently listed as 
appropriate comparators – only TNFα inhibitors until now – within the German HTA process 
for the subpopulation of PsA patients who failed TNFα inhibition. Therefore, this study will 
evaluate the efficacy and safety of secukinumab compared to ustekinumab in a head-to-head 
setting. The overall study design is intended to reflect prescription information, treatment 
guidelines and clinical practice in the targeted patient population, thereby supporting future 
HTAs. 

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2 
Objectives and endpoints 
The study objectives and related endpoints are presented in Table 2-1.  
Table 2-1 
Objectives and related endpoints  
Objectives 
Endpoints 
Primary objective 
Endpoint for primary objective 
• 
To demonstrate that secukinumab 300 mg s.c. is 
superior to ustekinumab 45/90 mg s.c. at Week 28 
based on the proportion of patients achieving an 
improvement in HAQ-DI© score ≥ 0.35 versus 
Baseline.  
• 
Proportion of patients achieving a HAQ-DI© 
response at Week 28. 
Secondary objectives 
Endpoints for secondary objectives 
To demonstrate that: 
• 
The efficacy of secukinumab 300 mg s.c. is higher 
compared to ustekinumab 45/90 mg s.c. at Week 
28 based on the proportion of patients achieving a 
PASI 90 response. 
 
• 
  Proportion of patients achieving a PASI 90 
response at Week 28. 
• 
Secukinumab 300 mg s.c. shows a beneficial 
effect compared to ustekinumab 45/90 mg s.c. at 
Week 28 based on the proportion of patients 
achieving an improvement of ≥ 10 mm for the 
patient’s assessment of pain on VAS.. 
• 
Proportion of patients achieving an improvement 
on VAS at Week 28 for patient’s assessment of 
pain. 
 
• 
The mean change from Baseline on secukinumab 
300 mg s.c. is higher compared to ustekinumab 
45/90 mg s.c. at Week 28 for the TJC 68. 
• 
Between-treatment difference in change from 
baseline to Week 28 for the TJC. 
 
• 
The mean change from Baseline on secukinumab 
300 mg s.c. is higher compared to ustekinumab 
45/90 mg s.c. at Week 28 for the SJC 66. 
• 
Between-treatment difference in change from 
baseline to Week 28 for the SJC. 
• 
Secukinumab 300 mg s.c. is shows a beneficial 
effect compared to ustekinumab 45/90 mg s.c. at 
Week 28 based on the proportion of patients 
achieving a PASI 100 response. 
• 
Proportion of patients achieving a PASI 100 
response at Week 28. 
• 
Secukinumab 300 mg s.c. shows a beneficial 
effect compared to ustekinumab 45/90 mg s.c. at 
Week 28 based on the proportion of patients 
achieving a PASI 75 response. 
• 
Proportion of patients achieving a PASI 75 
response at Week 28. 
• 
Secukinumab 300 mg s.c. shows a beneficial 
effect compared to ustekinumab 45/90 mg s.c. at 
Week 28 based on the proportion of patients 
achieving an improvement of 10 mm for the 
patient’s global assessment of disease activity 
(VAS). 
• 
Proportion of patients achieving an improvement 
on VAS at Week 28 for patient’s global disease 
activity. 
 
• 
Secukinumab 300 mg s.c. shows a beneficial 
effect compared to ustekinumab 45/90 mg s.c. at 
Week 28 based on the proportion of patients 
achieving an improvement of 10 mm for patient’s 
global assessment of psoriasis and arthritis 
disease activity (VAS). 
• 
Proportion of patients achieving an improvement 
on VAS at Week 28 for patient’s global 
assessment of psoriasis and arthritis disease 
activity.  
• 
Secukinumab 300 mg s.c. shows a beneficial 
effect compared to ustekinumab 45/90 mg s.c. at 
Week 28 based on the proportion of patients 
achieving MDA. 
• 
Proportion of patients achieving MDA at Week 28. 

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Objectives 
Endpoints 
• 
The mean change from Baseline on secukinumab 
300 mg s.c. is higher compared to ustekinumab 
45/90 mg s.c. at Week 28 for the LEI.  
• 
Between-treatment difference in change from 
baseline to Week 28 for the LEI. 
• 
The mean change from Baseline on secukinumab 
300 mg s.c. is higher compared to ustekinumab 
45/90 mg s.c. at Week 28 for the LDI. 
• 
Between-treatment difference in change from 
baseline to Week 28 for the LDI. 
 
• 
The mean change from Baseline on secukinumab 
300 mg s.c. is higher compared to ustekinumab 
45/90 mg s.c. at Week 28 for PsAQoL.  
• 
Between-treatment difference in change from 
baseline to Week 28 in the PsAQoL. 
• 
Secukinumab 300 mg s.c. shows a beneficial 
effect compared to ustekinumab 45/90 mg s.c. at 
Week 28 based on the proportion of patients 
achieving an improvement of ≥ 4 points for FACIT-
Fatigue©. 
• 
Proportion of patients achieving a FACIT-Fatigue 
response at Week 28. 
• 
Secukinumab 300 mg s.c. shows a beneficial 
effect compared to ustekinumab 45/90 mg s.c. at 
Week 28 based on the proportion of patients 
achieving a DLQI 0/1 response. 
• 
Proportion of patients achieving a DLQI response 
of 0/1 at Week 28. 
• 
To evaluate the safety and tolerability of 
secukinumab 
300 
mg 
s.c. 
compared 
to 
ustekinumab 45/90 mg s.c. as assessed by vital 
signs, 
clinical 
laboratory 
values, 
and 
AE 
monitoring. 
• 
Number and proportion of patients with treatment-
emergent AEs as well as descriptive description of 
vital signs and clinical laboratory values. 
E: adverse event, BSA: body surface area,
 DLQI: Dermatology Life Quality Index, 
EULAR: European League Against Rheumatism, FACIT-Fatigue©: Functional Assessment of Chronic 
Illness Therapy-fatigue, HAQ-DI©: Health Assessment Questionnaire-Disability Index,  LDI: Leeds Dactylitis 
Index, LEI: Leeds Enthesitis Index, , MDA: Minimal Disease Activity, PASI: Psoriasis Area Severity Index
PsAQoL: Psoriatic Arthritis Quality of Life, s.c.: subcutaneously
SJC: Swollen Joint Count,
TJC: Tender Joint Count, VAS: Visual Analog Scale,  

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3 
Study design 
This is a randomized, double-blind, active-controlled, multicenter study involving 310 adult 
patients with PsA who failed TNFα inhibitor treatment. The aim of the study is to demonstrate 
that the efficacy of secukinumab is superior to ustekinumab in terms of achieving an 
improvement in health assessment questionnaire-disability index (HAQ-DI©) response ≥ 0.35 
versus Baseline. Patients will be randomized equally to one of the following treatment groups 
(see Figure 3-1): 
• Secukinumab 300 mg s.c. for administration at Week 0, 1, 2, 3, 4 followed by dosing every 
4 weeks thereafter (i.e. at Week 8, 12, 16, 20 and 24). 
• Ustekinumab 45 mg s.c. (or 90 mg s.c. if body weight > 100 kg) for administration at 
Week 0 and Week 4 followed by dosing 12 weeks later at Week 16. Placebo to secukinumab 
will be administered at the respective secukinumab dosing time points, i.e. at Week 1, 2, 3, 
8, 12, 20 and 24.  
The study will include a Screening period of up to 10 weeks, a treatment period of 28 weeks 
with the primary endpoint at Week 28, and a follow-up period of 8 weeks. 
Figure 3-1 
 
Study Design 
 
BSL: Baseline, F: Follow-up 
4 
Rationale 
4.1 
Rationale for study design 
The randomized, double-blind, active control, multicenter, parallel-group design used in this 
study is in alignment with clinical trials in the development program for secukinumab, as well 
as with other biologics in this disease area, and is also in compliance with the European 
Medicines Agency (EMA) guidelines on PsA trials (EMA 2005). As described in Section 1.1, 
this study aims to demonstrate the superiority of secukinumab to ustekinumab for treating 
patients with PsA who have failed at least one initial TNFα inhibitor treatment based on the 
proportion of patients achieving a HAQ-DI© response ≥ 0.35 versus Baseline. The trial will 
close the scientific gap regarding this population in a head-to-head setting and support treatment 

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decisions in light of recent German HTA process recommendations. Secukinumab has already 
been shown to be superior to ustekinumab in the treatment of moderate-to-severe psoriasis 
(Blauvelt et al 2017, Bagel et al 2018).  
4.2 
Rationale for dose/regimen and duration of treatment 
The dose regimens selected for secukinumab and ustekinumab are as per the approved label for 
the respective drugs in various countries i.e. 300 mg for secukinumab (the recommended dose 
within approved product labelling in the anti-TNF-IR population), and dosing per weight group 
for ustekinumab. 
Secukinumab will be administered at a dose of 300 mg administered subcutaneously with a 
weekly loading regimen (Baseline/randomization, Week 1, Week 2, and Week 3) followed by 
treatment every 4 weeks thereafter (starting at Week 4) per approved dose of secukinumab in 
PsA for anti-TNF-IR. The dosage of 300 mg has been reported to be effective and safe in all 
approved indications including PsA (McInnes et al 2017, Mease et al 2018). 
Ustekinumab will be administered at Baseline, Week 4 and then every 12 weeks as per the 
approved dose regimen for treatment of patients with PsA: for patients weighing ≤ 100 kg, the 
recommended dose is 45 mg initially and 4 weeks later, followed by 45 mg every 12 weeks; for 
patients weighing >100 kg, alternatively a dose of 90 mg can be applied initially and 4 weeks 
later, followed by 90 mg every 12 weeks. Safety and efficacy have been positively proven in 
several trials including anti-TNF-IR patients (Ritchlin et al 2014). 
In previous studies, 24 weeks served as duration for the primary endpoint at which significant 
results vs. placebo were shown in PsA secukinumab trials as well as in ustekinumab trials 
(McInnes et al 2017, Mease et al 2018, Ritchlin et al 2014). 28 weeks for the primary endpoint 
were chosen in this trial as this is the first time point beyond 24 weeks where secukinumab and 
ustekinumab treatment would be applied according to the approved application interval of 
secukinumab and ustekinumab (every 4 weeks for secukinumab and every 12 weeks for 
ustekinumab).  With the primary endpoint at week 28, the injection interval is at the end for 
both drugs without having an advantage/a disadvantage for either of the drugs.  
Formulation to be used 
Secukinumab 300 mg (2 x 150 mg/1 mL), placebo liquid, and ustekinumab 45 mg/0.5 mL and 
90 mg/1 mL (formulation approved for PsA) will be provided in single-use pre-filled syringes 
(PFS).  
4.3 
Rationale for choice of control drugs (comparator/placebo) 
An active comparator group is necessary to evaluate whether secukinumab is superior to an 
approved therapy in PsA after anti-TNFα failure. The parallel-group controlled design is the 
most appropriate method to compare the two therapies and is consistent with the study of other 
biologics in the treatment of PsA.  
Ustekinumab has been selected as the active comparator in this study. Ustekinumab is a fully 
human monoclonal anti-human IL-12/23 antibody of the IgG1/κ-class, which has been 
commercially available for a number of years and has proven to be a safe and efficacious 

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treatment for PsA in anti-TNFα naive and IR patients (PSUMMIT 1, PSUMMIT 2; Ritchlin et 
al 2014, McInnes et al 2019). 
Superiority of secukinumab to ustekinumab has already been demonstrated in the treatment of 
moderate-to-severe psoriasis (Blauvelt et al 2017, Bagel et al 2018). Up to date, no data are 
available comparing secukinumab with ustekinumab in a head-to-head setting in PsA patients 
who failed prior anti-TNFα treatment. Additionally, ustekinumab is now listed as an 
appropriate comparator in the German HTA process for PsA anti-TNF-IR. 
In order to maintain the study blind, patients assigned to ustekinumab will receive placebo 
secukinumab PFS injections at the corresponding secukinumab administration time points. An 
additional placebo injection will accompany the respective ustekinumab injection as 
ustekinumab is administered in one syringe compared to 300 mg secukinumab which is applied 
in two 150 mg syringes. 
4.4 
Purpose and timing of interim analyses/design adaptations 
Not applicable. 
4.5 
Risks and benefits 
Secukinumab demonstrated clinically meaningful sustained and statistically significant efficacy 
for the treatment of patients with active PsA through all components of joint and skin disease, 
physical function, health-related quality of life (HRQoL) and structural damage. Pre-specified 
endpoints adjusted for multiple testing demonstrated the superiority of secukinumab 150 mg 
and 300 mg regimens compared to placebo. The American College of Rheumatology (ACR)20 
response achieved at 24 weeks with 150 mg s.c. regimen was comparable to the responses with 
300 mg s.c. regimen in anti-TNFα naive patients (FUTURE 2, FUTURE 5; McInnes et al 2015, 
Mease et al 2018). As in the psoriasis program, secukinumab 150 mg s.c. and 300 mg s.c. 
provided greater improvements than placebo in PsA patients with concomitant psoriasis. 
Overall, secukinumab is efficacious and demonstrates a rapid onset of response in achieving 
clinically meaningful improvements in key clinical domains of PsA disease. These domains 
include signs and symptoms, skin disease, structural damage, physical function and QoL. The 
150 mg s.c. regimen provides rapid, superior efficacy for most patients, and the 300 mg s.c. 
regimen offers increased benefit for anti-TNFα IR patients and in patients with 
moderate-to-severe psoriasis. Efficacy results were sustained over time in all studies. 
The safety profile observed in the latest Developmental Safety Update Report (DSUR No. 9) 
period (covering 26-Jun-2018 to 25-Jun-2019) is in line with the current known safety profile 
of secukinumab in PsA, moderate-to-severe psoriasis, and axial spondyloarthritis. 
For all 3 indications, secukinumab has shown an imbalance vs. placebo in total AEs, which was 
driven by infections, mainly non-serious upper respiratory tract infections during the placebo-
controlled epoch of the trials (12 to 16 weeks depending on the protocol). This imbalance was 
not translated into infection serious AEs (SAEs) and there was also no difference between 
300 mg and 150 mg secukinumab in the overall rate of infections or in upper respiratory tract 
infections. In all indications, Candida infections, mainly oral candidiasis, were more frequent 
with secukinumab when compared to placebo, but the cases were generally mild or moderate 
in severity, non-serious with no reports of chronic or systemic disease in any treatment group 

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and responsive to standard treatment. No serious opportunistic infections were reported. No 
tuberculosis (TB) reactivation or viral hepatitis reactivation were observed in clinical trials, 
regardless of indication (PsA, psoriasis or axial spondyloarthritis).  
There is a small increase in neutropenia cases with secukinumab compared to placebo, but most 
cases were mild, transient and spontaneously reversible and without a temporal relationship to 
serious infections.  
The incidence of hypersensitivity AEs was slightly higher with secukinumab compared with 
placebo, with the difference being mostly due to mild to moderate urticaria and eczema, which 
were not associated with systemic symptoms.  
The incidence of selected rare events of interest (major adverse cardiovascular events (MACE) 
and malignancies) adjusted for exposure over 52 weeks was comparable to placebo in clinical 
trials across multiple indications.  
There was no clear association between treatment with secukinumab and new onset of 
inflammatory bowel disease (IBD). A pooled secukinumab safety analysis of over 7300 patients 
across 21 clinical trials showed only uncommon cases of IBD (Schreiber et al 2019). But, due 
to the potential involvement of the IL-17 pathway in the pathogenesis of the disease, it is not 
possible to rule out a potential increased risk of exacerbation.  
The immunogenicity potential, i.e. of eliciting anti-drug antibodies (ADA), is higher for 
ustekinumab (up to 12.4%) than for secukinumab (<1%) (Stelara® package insert; Cosentyx® 
package insert). However, the presence of ADAs does not appear to be associated with 
development of adverse reactions or lack of efficacy for both ustekinumab and secukinumab. 
Secukinumab has an acceptable safety profile for the intended use in adult patients. 
Secukinumab 300 mg was comparable to 150 mg and both doses showed comparable safety to 
placebo and etanercept over 52 weeks of treatment for psoriasis indication (Langley et al 2014). 
No dedicated head-to-head study was conducted with etanercept for spondyloarthritis 
indications.  
Infections, neutropenia and hypersensitivity are important identified risks, while malignancies, 
MACE, Crohn’s disease, and hepatitis B reactivation are important potential risks. Interaction 
with live vaccines is an important potential interaction (and also included as an important 
potential risk).  
No new safety signal was identified in the reporting period. 
The benefit-risk relationship for secukinumab remains positive for the treatment of PsA, as well 
as other indications, and justifies unaltered continuation of the development program. 
The risk to patients in this trial may be minimized by compliance with the eligibility criteria 
and study procedures, as well as close clinical monitoring. Refer to the Investigator’s Brochure 
(IB) for further details. 
Women of child bearing potential and sexually active males must be informed that taking the 
study treatment may involve unknown risks to the fetus if pregnancy were to occur during the 
study, and agree that in order to participate in the study they must adhere to the contraception 
requirements outlined in the exclusion criteria. If there is any question that the patient will not 
reliably comply, they should not be entered or continue in the study. 

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Taking into account the individual risks as outlined above, the expected risk profile of 
secukinumab from its mechanism of action is anticipated to be similar or improved compared 
to the other approved inflammatory cytokine-targeting therapies. The risk to subjects in this 
trial will be minimized by compliance with the eligibility criteria, close clinical monitoring, and 
extensive guidance to the investigators provided by Novartis and in the current version of the 
IB for secukinumab. Based on the overall favorable risk-benefit assessment, the current trial 
with secukinumab (and the comparator ustekinumab) is justified. 
5 
Population 
The study population will consist of a representative group of 310 male or female patients at 
least 18 years of age, fulfilling the Classification criteria for Psoriatic Arthritis (CASPAR) 
(Appendix 1) and who have shown previous inadequate response or intolerance to TNFα 
inhibitors.  
The study population will be comprised of the subjects who have passed screening assessments 
and who comply with eligibility criteria. Subjects can be re-screened, no study related re-
screening procedures should be performed before re-consent by the subject. Mis-randomized 
subjects will not be re-screened. 
 
5.1 
Inclusion criteria 
Patients eligible for inclusion in this study must meet all of the following criteria: 
1. Informed consent must be obtained before any assessment is performed. 
2. Male or non-pregnant, non-lactating female patients at least 18 years of age. 
3. Diagnosis of PsA as classified by CASPAR criteria (see Appendix 1) for at least 6 months 
before randomization. 
4. Active PsA at baseline defined as ≥ 3 tender joints out of 68 and ≥ 3 swollen joints out of 
66 (dactylitis of a digit counts as one joint each). 
5. Inadequate response or intolerance to previous or current treatment with at least one TNFα 
inhibitor administered at an approved dose for the given duration according to the respective 
Summary of Product Characteristics (SmPC). 
6. Inadequate response or intolerance to conventional disease modifying anti-rheumatic drugs 
(cDMARDs) and to at least one TNFα inhibitor must have been documented in the patient’s 
medical history or reported by the patient or determined by the investigator at Screening. 
7. Diagnosis of active plaque psoriasis, with at least one psoriatic plaque of ≥ 2 cm diameter 
and/or nail changes consistent with psoriasis and/or documented history of plaque psoriasis. 
8. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (CCP) antibodies negative at 
screening. 
9. Patients taking methotrexate (MTX) ≤ 30 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 28. 
10. Patients on MTX must be on folic acid supplementation at randomization. 

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11. Patients who are on a disease modifying anti-rheumatic drug (DMARD) other than MTX 
must discontinue the DMARD 4 weeks prior to the randomization visit except for 
leflunomide, which has to be discontinued for 8 weeks prior to randomization unless a 
cholestyramine wash-out has been performed. 
12. Patients who are regularly receiving non-steroidal anti-inflammatory drugs (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 not increase the dose up to Week 28. 
13. Patients receiving 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 28. 
5.2 
Exclusion criteria 
Patients meeting any of the following criteria are not eligible for inclusion in this study. 
1. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive human 
chorionic gonadotropin (hCG) laboratory test. 
2. Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during dosing 
of study treatment and minimum 16 weeks or longer if local label requires it after the last 
dose (e.g. 20 weeks for secukinumab, 15 weeks for ustekinumab in the European Union 
(EU)). 
Effective contraception methods include: 
• Total abstinence (when this is in line with the preferred and usual lifestyle of the 
patient). Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
• Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking 
investigational drug. In case of oophorectomy alone, only when the reproductive status 
of the woman has been confirmed by follow up hormone level assessment. 
• Male sterilization (at least 6 months prior to Screening). For female patients on the 
study, the vasectomized male partner should be the sole partner for that patient. 
• Barrier methods of contraception: condom or occlusive cap (diaphragm or 
cervical/vault caps).  
• Use of oral, (estrogen and progesterone), injected or implanted hormonal methods of 
contraception or other forms of hormonal contraception that have comparable efficacy 
(failure rate <1%), for example hormone vaginal ring or transdermal hormone 
contraception or placement of an intrauterine device (IUD) or intrauterine system 
(IUS). In case of use of oral contraception, women should have been stable on the same 
pill for a minimum of 3 months before taking the investigational drug. 
In case local regulations deviate from the methods listed, local regulations apply and will 
be described in the informed consent form (ICF). 
Women are considered post-menopausal and not of child-bearing potential if they have had 
at least 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile 
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral 

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oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least 
6 weeks ago. In the case of oophorectomy alone, only when the reproductive status of the 
woman has been confirmed by follow up hormone level assessment is she considered not 
of child-bearing potential.  
3. Previous exposure to secukinumab, ustekinumab or any other biologic drug directly 
targeting IL-17, IL-17 receptor, IL-12 or IL-23. 
4. Patients for whom the use of secukinumab or ustekinumab is contraindicated. 
5. Use of any other investigational drug within 4 weeks or within a period of 5 half-lives of 
the investigational treatment prior to the Baseline Visit, whichever is longer, until the 
expected pharmacodynamic effect has vanished. Previous treatment with any cell-depleting 
therapies including but not limited to anti-CD20 or investigational agents (e.g., 
alemtuzumab (Campath®), anti-CD4, anti-CD5, anti-CD3, and anti-CD19). 
6. 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. 
7. Patients receiving high potency opioid analgesics including but not limited to methadone, 
hydromorphone, and morphine. 
8. Ongoing use of prohibited psoriasis treatments/medications (e.g., topical corticosteroids or 
ultraviolet therapy at randomization). The following wash out periods need to be observed: 
a. Oral or topical retinoids: 4 weeks 
b. Photochemotherapy (e.g. PUVA): 4 weeks 
c. Phototherapy (UVA or UVB): 2 weeks 
d. Topical skin treatment (except in face, eyes, scalp and genital area during screening; 
only corticosteroids with mild to moderate potency): 2 weeks. 
9. History of hypersensitivity to any of the study drugs or excipients or to drugs of similar 
chemical classes. 
10. Any intramuscular or intravenous corticosteroid treatment within 4 weeks before 
randomization. 
11. Any therapy by intra-articular injections (e.g., corticosteroid) within 4 weeks before 
randomization. 
12. Active ongoing inflammatory diseases other than PsA that might confound the evaluation 
of the benefit of secukinumab therapy. 
13. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal conditions which in the opinion of the investigator 
immunocompromises the subject and/or places the subject at unacceptable risk for 
participation in an immunomodulatory therapy. 
14. Significant medical problems or diseases, including but not limited to the following: 
uncontrolled hypertension (≥160/95 mmHg), congestive heart failure (New York Heart 
Association status of class III or IV) and uncontrolled diabetes. 
15. History of clinically significant liver disease or liver injury as indicated by abnormal liver 
function tests (LFTs) such as aspartate aminotransferase/serum glutamic oxaloacetic 
transaminase (AST/SGOT), alanine aminotransferase/serum glutamic pyruvic transaminase 
(ALT/SGPT), alkaline phosphatase or serum bilirubin. The investigator should be guided 
by the following criteria: 

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a. Any single parameter may not exceed 2 x upper limit of normal (ULN). A single 
parameter elevated up to and including 2 x ULN should be re-checked once more as 
soon as possible and in all cases, at least prior to enrollment/randomization, to rule out 
any possible lab error. 
b. If the total bilirubin concentration is increased above 2 x ULN, total bilirubin should 
be differentiated into the direct and indirect reacting bilirubin. 
16. History of renal trauma, glomerulonephritis, or subjects with one kidney only, or a serum 
creatinine level exceeding 1.8 mg/dL (159.12 μmol/L). 
17. Screening total white blood cell (WBC) count <3,000/μL, or platelets <100,000/μL or 
neutrophils <1,500/μL or hemoglobin <8.5 g/dL (85 g/L). 
18. Active systemic infections during the last two weeks (exception: common cold) prior to 
randomization. 
19. History of ongoing, chronic or recurrent infectious disease or evidence of TB infection as 
defined by a positive QuantiFERON TB-Plus test. Patients 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 TB. If presence of latent TB is 
established then treatment according to local country guidelines must have been initiated 
prior to enrollment. 
20. Live vaccinations within 6 weeks prior to Baseline or planned vaccination during study 
participation until 12 weeks after last study treatment administration. 
21. Proven infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at 
screening or randomization. 
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. 
6 
Treatment 
6.1 
Study treatment 
6.1.1 
Investigational and control drugs 
The following study drugs will be used: 

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• Investigational treatment 
o Secukinumab 300 mg, 2 x 1 mL liquid formulation in a PFS 
• Control treatment 
o Secukinumab placebo, 1 mL liquid formulation in a PFS 
o Ustekinumab 45 mg, 0.5 mL or 90 mg, 1 mL liquid formulation in a PFS 
Investigational treatment: 
Secukinumab for s.c. injection is provided in a PFS containing 150 mg secukinumab. Each  
300 mg dose is given as 2 s.c. injections of 150 mg. 
Control treatment: 
• Secukinumab placebo: secukinumab placebo to 150 mg secukinumab for s.c. injection is 
provided in a matching PFS. Each PFS contains a mixture of inactive excipients, matching 
the composition of the secukinumab 150 mg dose. 
• Ustekinumab is provided in a PFS containing 45 mg or 90 mg of ustekinumab for s.c. 
injection. Patients weighing ≤ 100 mg at Baseline will receive a dose of 45 mg, patients 
weighing > 100 kg at Baseline 90 mg according to the label. 
 
Secukinumab 150 mg PFS and secukinumab placebo PFS will be supplied by Novartis.  
Ustekinumab 45 mg and 90 mg PFS will be supplied by Novartis. 
All study drugs will be labelled appropriately. 
The removable cap of the secukinumab PFS contains a derivative of natural rubber latex. 
Although no natural rubber latex is detected in the cap, the safe use of the secukinumab 1 mL 
PFS in latex-sensitive individuals has not been studied. 
6.1.2 
Additional study treatments 
No other treatment beyond the investigational drug and control drug is included in this trial. 
6.1.3 
Treatment arms 
Patients will be randomized to one of the following 2 treatment arms in a ratio of 1:1. In order 
to achieve a balanced weight distribution in each treatment arm, randomization in these 2 arms 
will be stratified by body weight (≤ 100 kg and > 100 kg) at Baseline. The weight must be 
ascertained using a calibrated scale and the correct dosage determined by the PI. 
• Secukinumab arm: will receive a dose of secukinumab 300 mg s.c. which consists of 
2 injections of the 150 mg PFS at a frequency shown in Table 6-1.  
• Ustekinumab arm:  
• Patients weighing ≤ 100 kg at Baseline will receive a dose of 45 mg ustekinumab s.c., 
which consists of one injection of the 45 mg PFS + one placebo s.c. injection at a 
frequency shown in Table 6-1. 
• Patients weighing >100 kg at Baseline will receive a dose of 90 mg ustekinumab s.c., 
which consists of one injection of the 90 mg PFS + one placebo s.c. injection at a 
frequency shown in Table 6-1. 

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report form (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 
randomizing a patient or allowing a new medication to be started. If the patient is already 
enrolled, Novartis should be contacted to determine if the patient should continue participation 
in the study. Guidelines for the use of specific medications are provided below. 
The patient is not allowed to participate in other clinical trials during the duration of the actual 
study. 
 
6.2.1.1 
Permitted concomitant therapy requiring caution and/or action 
Methotrexate 
Patients taking MTX (up to 30 mg/week) are allowed to continue their medication. They must 
be on a stable dose for at least 4 weeks before randomization and should remain on this dose 
until Week 28. 
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 patient should remain on a stable dose until Week 28. Higher-dose, time-limited 
corticosteroid courses (bursts) may be permitted for exacerbations of medical conditions 
unrelated to PsA (e.g., asthma, chronic obstructive pulmonary disease, contact dermatitis) after 
randomization.  
Corticosteroid dose reductions below 10 mg prednisone equivalent are permitted during the 
study.  
However, any change in the dose of oral corticosteroids during the trial should be recorded on 
the corresponding eCRF. 
Intra-articular corticosteroids are not permitted within 4 weeks prior to Baseline and up to  
Week 28. The joints injected with intra-articular corticosteroids will be assessed as both swollen 
and tender in the SJC and TJC, from injection time onwards.  
Non-steroidal anti-inflammatory drugs (including selective COX-2 inhibitors), 
low strength opioids and acetaminophen/paracetamol 
Patients on regular use of NSAIDs or paracetamol/acetaminophen should be on stable dose for 
at least 2 weeks before randomization to allow inclusion.   
Patients taking NSAIDs, low strength opioids, or paracetamol/acetaminophen pro re nata/as 
required (PRN) within the 2 weeks before randomization can continue to do so after 
randomization, however, they have to refrain from any intake during at least 24 hours before a 
visit with disease activity assessment. 
When indicated, a reduction of NSAIDs is permitted during the study.  

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After Week 28, 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. 
6.2.2 
Prohibited medication 
Use of the treatments displayed in Table 6-2 is NOT allowed after the start of the washout 
period unless specified otherwise below or in Section 9.1.1. 
Live vaccines should not be given until 12 weeks after last study treatment administration. 
Table 6-2 
Prohibited medication 
Medication 
Action 
(after randomization) 
Washout period 
(before randomization) 
Any biologic drugs, including but not 
limited to biologic drugs targeting IL-
17, IL-17 receptor, IL-12 or IL-23 
(except study medication) 
Discontinue investigational 
treatment 
Biologics for PsA and 
psoriasis: never 
Biologics for other 
indications: 16 weeks  
Any cell-depleting therapies including 
but not limited to anti-CD20 or 
investigational agents [e.g., 
alemtuzumab (Campath), anti-CD4, 
anti-CD5, anti-CD3, and anti-CD19] 
Discontinue investigational 
treatment  
Never 
cDMARDs other than MTX (≤ 30 
mg/week) including apremilast and 
tsDMARDs (JAK inhibitors) 
Discontinue investigational 
treatment 
4 weeks 
Leflunomide 
Discontinue investigational 
treatment 
8 weeks 
Leflunomide with cholestyramine 
washout 
Discontinue investigational 
treatment 
4 weeks 
Any investigational treatment or 
participation in any interventional trial 
Discontinue investigational 
treatment 
4 weeks or 5 half-lives 
(whichever is longer) 
Increasing dose of NSAIDs (selective 
COX-2 inhibitors) 
Discontinuation of 
investigational treatment may 
be required on a case by case 
basis. (Dose increase allowed 
after Week 28) 
2 weeks 
Analgesics other than NSAIDs, 
paracetamol/acetaminophen, and low 
strength opioids PRN  
Discontinue investigational 
treatment 
2 weeks 

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Medication 
Action 
(after randomization) 
Washout period 
(before randomization) 
Systemic corticosteroids > 10 mg 
prednisone equivalent (until Week 
28)* 
If administered due to a medical 
urgency unrelated to the 
patient’s arthritis, study 
treatment should be interrupted 
until the steroid is discontinued. 
If administered not for a medical 
urgency or related to the 
patient’s arthritis, then 
discontinuation of 
investigational treatment may 
be required on a case by case 
basis 
2 weeks 
Increasing dose of systemic 
corticosteroids ≤ 10 mg prednisone 
equivalent (until Week 28)* 
Discontinuation of 
investigational treatment may 
be required on a case by case 
basis. (Dose adjustments 
allowed after Week 28) 
2 weeks 
Intra-articular corticosteroids 
injections, (until Week 28)* 
Discontinue investigational 
treatment, (see Section 9.1.1) 
4 weeks 
Intramuscular or intravenous 
corticosteroid treatment  
Discontinuation of 
investigational treatment may 
be required on a case by case 
basis 
4 weeks 
Live vaccinations 
If administered due to a medical 
urgency, study treatment should 
be interrupted for 4 months. If 
administered not for a medical 
urgency then discontinue 
investigational treatment  
6 weeks 
Oral or topical retinoids 
Discontinue investigational 
treatment 
4 weeks 
Photochemotherapy (e.g. PUVA) 
Discontinue investigational 
treatment 
4 weeks 
Phototherapy (UVA or UVB) 
Discontinue investigational 
treatment 
2 weeks 
Topical skin treatments (except in 
face, eyes, scalp, genital area; only 
cortico-steroids with mild to moderate 
potency) 
Discontinue investigational 
treatment 
2 weeks 
Medical cannabis 
Discontinue investigational 
treatment 
2 weeks 
CD: Cluster of Differentiation, COX: cyclooxygenase, cDMARDs: conventional synthetic Disease Modifying Anti-
Rheumatic Drugs, IL: Interleukin, JAK: Janus Kinase, NSAIDs: Non-Steroidal Anti-Inflammatory Drugs, PRN: pro 
re nata (as required), PsA: psoriatic arthritis, PUVA: psoralen ultraviolet light A, TNFα: tumor necrosis factor 
alpha, tsDMARDs: targeted synthetic Disease Modifying Anti-Rheumatic Drugs, UVA: ultraviolet A, UVB: 
ultraviolet B 
* see details about corticosteroid management in Section 6.2.1 

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6.2.2.1   Leflunomide wash-out with cholestyramine 
In case of leflunomide treatment before study randomization, a drug wash-out of 8 weeks must 
be performed. However, another wash-out procedure can be considered. Cholestyramine may 
be given orally at a dose of 8 g three times daily (t.i.d) to wash out leflunomide. Cholestyramine 
has been shown to reduce plasma levels of the active leflunomide metabolite by approximately 
40% in 24 hours and by 49% to 65% in 48 hours, in 3 healthy volunteers. The administration 
of cholestyramine is recommended in patients who require a drug elimination procedure. If a 
patient receives 8 g t.i.d. for 11 days, the patient can be safely randomized 4 weeks after the 
beginning of the 11-day treatment period.  
6.2.3 
Rescue medication 
Rescue medication is defined as any new therapeutic intervention or a significant change to 
ongoing therapy made because a patient 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 28 assessments (see Section 3). 
Please see Section 6.2.1 and Section 6.2.2 for details. No patient will be restricted from 
receiving necessary rescue medications for lack of benefit or worsening of disease and may  
continue investigational treatment if treated with prohibited medications (please see 
Section 6.2.2). Patients who discontinue investigational treatment should continue to attend all 
subsequent scheduled visit assessments unless informed consent is withdrawn. If study 
investigational treatment is discontinued, patients may take study prohibited medication under 
the investigator’s guidance and per locally approved prescribing information. 
Efficacy and safety will be assessed in detail at every study visit and patients who are deemed 
by the investigator not to be benefiting from study treatment, or for any reason on the patient’s 
own accord, will be free to discontinue study participation at any time. 
Use of rescue medication must be recorded on the corresponding eCRF. 
6.3 
Patient numbering, treatment assignment, randomization 
6.3.1 
Patient numbering 
Each patient is uniquely identified in the study by a combination of his/her center number and 
patient number (Patient ID). The center number is assigned by Novartis to the investigative site. 
When the patient has signed the informed consent form, the investigator or his/her staff will 
create a new patient record in the eCRF and provide the identifying information for the patient. 
The eCRF will then assign the patient number. Once assigned to a patient, the patient number 
will not be reused. If the patient fails to be randomized, the reason must be documented in the 
eCRF immediately. In addition, the Screening Log should be completed for these patients. 
6.3.2 
Treatment assignment, randomization 
At the randomization visit (Baseline) all eligible patients will be given an available 
randomization number that assigns them to one of the two treatment arms. It is ensured that 
treatment assignment is unbiased and concealed from patients and investigator staff. 
Subsequently, the investigator will enter the randomization number in the eCRF.  

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A patient randomization list will be produced by or under the responsibility of Novartis 
Biometrics Department using a validated system ensuring random assignment of treatment 
groups to randomization numbers in the specified 1:1 ratio (secukinumab group, ustekinumab 
group). The randomization scheme will be reviewed and locked after approval. According to 
the recommendations given in the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) E9 Guideline “Statistical Principles 
for Clinical Trials”, the used block length is specified in a separate document which will be 
with-held from the study centers. The randomization list will be kept sealed in a secure location. 
All study sites will be provided with a given set of sealed allocation cards. 
At the Randomization Visit, the investigator will assign each patient who meets all the inclusion 
criteria and does not fulfill any of the exclusion criteria to the lowest available randomization 
number, open the corresponding treatment allocation card and treat the patient with the 
treatment noted on this card (i.e. secukinumab treatment or ustekinumab treatment). 
In order to achieve a balanced weight distribution in each treatment arm, randomization in these 
2 arms will be stratified by body weight assessed at Day 1 (Baseline visit). The weight will not 
be further controlled in following visits. Stratification ensures a balanced allocation of patients 
to treatment groups within the 2 weight strata: “body weight ≤ 100 kg” or “body weight 
> 100 kg”. It is expected that approximately 40% of the patients will be in the upper weight 
stratum. 
6.4 
Treatment blinding 
All data up to Week 36 (Final Visit) will be collected with the Novartis clinical trial team (or 
delegates), investigators/site personnel evaluating patients and patients blinded to treatment 
allocation. All blinded site personnel, including the assessor performing the study assessments 
will remain blinded to individual treatment allocation until after final database lock using the 
following methods:  
• Randomization data will be kept strictly confidential until the time of unblinding, and will 
not be accessible by anyone else involved in the study with the following exceptions: 
• DSM (Drug Supply Management)  
• Study medication will be dispensed by an unblinded qualified site personnel who is 
independent of those involved in the assessment of study patients. In addition, the unblinded 
qualified site personnel will store study medication and keep medication records containing 
unblinded information in a separate area to which blinded staff would not have access. 
• Study treatments will be administered by an “independent study drug administrator”: 
an unblinded suitably qualified individual (nurse, physician, or other unblinded 
qualified site personnel) who is not responsible for any aspect of patient assessment or 
follow-up. The “Independent study drug administrator” could be the same person 
dispensing the drug if suitably qualified to perform both activities.  
• Prior to the administration, the unblinded site personnel will put in place all methods 
e.g. physical barriers as agreed with the patient and being available at the site to prevent 
patient seeing the appearance of their study treatment. 

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• The individual administering study treatment will be advised to refrain from making 
any comments to study staff or to other patients regarding the appearance of study 
treatments. 
• The procedural details relating to treatment blinding and blinded drug administration 
will be described in a manual which will be provided separately. 
In the event that the packaging of a study treatment has a broken seal, this information will be 
documented, along with a reason (if applicable) and the medication number so that the syringe 
will not be available to dispense to another patient. 
The appropriate personnel from the study site and Novartis will assess whether the study 
treatment should be discontinued for any patient whose treatment code has been broken 
inadvertently for any reason. Study treatment must be discontinued after emergency 
unblinding. 
Unblinding will occur in the case of patient emergencies and at the conclusion of the study. 
6.5 
Dose escalation and dose modification 
Investigational treatment dose adjustments are not permitted. For patients who are unable to 
tolerate the protocol-specified dosing scheme (including patients who in the opinion of the 
investigator are at significant safety risk unless dosing is temporarily interrupted), 
investigational treatment interruption is permitted in order to keep the patient on study drug. In 
such cases, investigational treatment should be interrupted only during the time that a risk is 
present and ongoing. Investigational treatment can be restarted at the next scheduled visit after 
resolution of the safety risk. 
The effect of secukinumab or ustekinumab on live vaccines is unknown; therefore live vaccines 
should not be administered during participation in the study. The elimination of ustekinumab 
may take up to 15 weeks (STELARA SmPC); in case a live vaccine has been administered due 
to a medical urgency, study treatment should be interrupted for 15 weeks.  
Any investigational treatment interruption must be recorded on the corresponding eCRF. 
6.6 
Additional treatment guidance 
6.6.1 
Treatment compliance 
All dates and times of study treatment administration will be recorded on the appropriate 
Dosage Administration Record eCRF. Up to the final database lock, compliance will be 
assessed by unblinded field monitor at each visit using PFS (secukinumab, ustekinumab and 
placebo) counts and empty medication boxes/outer packaging and information provided by the 
unblinded qualified site personnel responsible for treatment dispensation and preparation of the 
study treatment. 
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 
patient safely. Most often, study treatment discontinuation and knowledge of the possible 
treatment assignments are sufficient to treat a study patient who presents with an emergency 
condition. Two complete sets of emergency code break cards are provided by Novartis. One set 

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is to be retained by Novartis and one set is to be distributed to the investigators. They must be 
stored in a secure place but accessible in case of emergency. The investigator will receive a 
blinded code break card for each patient, with the details of drug treatment covered by a sealed 
tear-off cover. In an emergency, the tear-off cover can be removed to determine the treatment. 
The tear-off covers are not to be removed for any reason other than an emergency. When the 
investigator removes the tear-off cover he/she must note the date, time, and reason for removing 
it and retain this information with the case report form documentation.  
The unblinded treatment code should not be recorded on the eCRF. The investigator must also 
immediately inform the Novartis monitor that the code has been broken.  
It is the investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the emergency code break cards at any time in case of emergency.  
Furthermore he/she needs to provide a telephone number (e.g. a mobile number) by which 
he/she can be reached throughout the trial in case of an emergency unblinding request for one 
of his/her patients code break cards in case of emergency. The investigator will inform the 
patient how to contact his/her backup in cases of emergency when he/she is unavailable. The 
protocol number, study drug name if available, patient number, and instructions for contacting 
Novartis (or any entity to which it has delegated responsibility for emergency code breaks) will 
be provided to the patient in case emergency unblinding is required at a time when the 
investigator and backup are unavailable. As per Novartis standard operating procedures (SOPs) 
it is one of the primary responsibilities of each investigator to be available in case of an urgent 
emergency unblinding for one of his/her patients. 
In addition, oral and written information to the patient 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. 
Study drug must be discontinued after emergency unblinding. 
6.7 
Preparation and dispensation 
Each study site will be supplied by Novartis with secukinumab and placebo treatment in 
packaging of identical appearance. 
Ustekinumab 45 mg and 90 mg PFS will be supplied by the Novartis DSM team.  
The secukinumab and ustekinumab and placebo treatment packaging has a 2-part label. A 
unique medication number is printed on each part of this label which corresponds to one of the 
2 treatment arms. The unblinded qualified site personnel will identify the study drug package(s) 
to dispense to the patient using the medication number on the label. Immediately before 
dispensing the study drug to the patient, the unblinded qualified site personnel will detach the 
outer part of the label from the packaging and affix it to the source document (Drug Label Form) 
containing the patient’s unique Patient ID. Immediately after dispensing the study drug to the 
patient, investigator staff will access the eCRF to confirm administration of the assigned 
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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 immediately 
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 Country Pharma Organization (CPO) Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of 
Germany. They will include storage conditions for the study treatment but no information about 
the patient except for the medication number. 
The study treatments, i.e. secukinumab PFS 150 mg, ustekinumab 45 mg / 90 mg PFS 
(uninterrupted cold chain) and placebo must be stored in a locked refrigerator at 2-8°C, and 
protected from light and must be carefully controlled in accordance with regulations governing 
investigational medicinal products and local regulations. Study treatments should not be frozen. 
The unblinded qualified site personnel 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 unblinded monitors during site visits or remotely and at the completion of 
the trial.  
At the conclusion of the study and as appropriate during the course of the study, the unblinded 
qualified site personnel will return all partly used and unused investigational treatment, 
packaging, drug labels and a copy of the completed drug accountability log to the Novartis 
monitor or to the Novartis address provided in the investigator folder at each site. 
6.7.1.2 
Handling of additional treatment 
Not applicable.  
6.7.2 
Instruction for prescribing and taking study treatment 
All dosages prescribed and dispensed to the patient and all dose changes during the study must 
be recorded on the eCRF. 
Secukinumab solution, placebo solution and ustekinumab solution will be provided in PFSs for 
s. c. injection. 
All doses of study treatment are to be administered by an unblinded qualified person at the study 
site and should be performed after the study assessments for the visit have been completed. The 
first study treatment administration will occur at the randomization visit after 
inclusion/exclusion criteria have been confirmed, all study scheduled assessments have been 
performed and the scheduled blood samples have been drawn. 
At all study site visits when pre-dose blood samples have to be drawn (Table 8-1), the study 
treatment will be injected only after the blood samples have been taken. At all site visits when 
study assessments need to be done, all study assessments, should be completed prior to the 
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Prior to administration, the boxes containing the PFS with study treatment solution should be 
allowed to come to room temperature, unopened. 
Used PFS should be disposed immediately after use in a sharps container OR according to the 
regulatory needs of the respective countries. 
The investigator must promote compliance by instructing the patient to attend the study visits 
as scheduled and by stating that compliance is necessary for the patient’s safety and the validity 
of the study. 
Study treatment administration  
All study treatment must be administered at the site and will be administered by unblinded site 
personnel not responsible for any aspect of patient assessment or follow-up (Section 6.4). The 
study treatment solution must be injected in non-affected areas of the skin into the appropriate 
body site (thigh, abdomen, upper outer arm). If possible, throughout the trial administer the 
study treatment rotating the injection site from visit to visit and also for each injection at a given 
visit. 
Instructions mentioned in Section 6.4 must be followed to avoid unblinding. The type and 
number of injections to be administered are detailed in Table 8-1.  
7 
Informed consent procedures 
Eligible patients may only be included in the study after providing Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC)-approved informed consent. 
Informed consent must be obtained before conducting any study-specific procedures (e.g. all of 
the procedures described in the protocol). The process of obtaining informed consent must be 
documented in the patient source documents. 
Novartis will provide to investigators in a separate document a proposed ICF that complies with 
the International Conference on Harmonization of Technical Requirements for Registration of 
Pharmaceuticals for Human Use (ICH) Good Clinical Practice (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 IB and/or Core Data Sheet. This information will be included in the patient 
informed consent and should be discussed with the patient during the study as needed. Any new 
information regarding the safety profile of the investigational drug that is identified between 
Investigator’s Brochure updates will be communicated as appropriate, for example, via an 
investigator notification or an aggregate safety finding. New information might require an 
update to the informed consent and then must be discussed with the patient. 
Women of 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. 

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8 
Visit schedule and assessments 
The Assessment Schedule (Table 8-1) lists all of the study assessments and when they are 
performed. All data obtained from these assessments must be supported in the patient’s source 
documentation. 
Patients should be seen for all visits/assessments as outlined in the assessment schedule (Table 
8-1) or as close to the designated day/time as possible. Missed or rescheduled visits should not 
lead to automatic discontinuation. Every effort should be made to respect the time frame for the 
Week 28 visit. If for any reason the subject is a screen failure, the subject may be rescreened. 
There is no restriction on the number of times a potential subject may be re-screened or on how 
much time must pass from the date of screen failure and the date of re-screening. If a subject 
re-screens for the study, a new ICF has to be signed. The initial subject number allocated to the 
patient when signing the ICF is reused throughout the study excluding further re-screenings. 
For all subjects, the investigator/qualified site staff will record if the subject was re-screened 
and the reason for previous screen failure on the re-screening CRF. No screening failure log 
will be filled out for patients that finally were enrolled into study. 
Patients who prematurely discontinue the study treatment (s.c. secukinumab or ustekinumab) 
are encouraged to remain in the study to continue the study-related assessments until completion 
of the study. 
Patients who prematurely discontinue completely from the study for any reason other than 
withdrawal of informed consent should be scheduled for the final visit to conduct the Week 28 
assessments (4 weeks after the last study treatment administration of secukinumab, 12 weeks 
after the last administration of ustekinumab), then also return after additional 8 weeks for a final 
follow-up visit, corresponding to week 36 assessments.  
At this final visit, all dispensed investigational product should be reconciled, and any AEs and 
concomitant medications recorded on the CRF.  

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Table 8-1 
 
Assessment Schedule 
Visit Name 
Screening 
Baseline 
Treatment Period 
EOS 
FUP 
Visit Number 
SV 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
Week 
-10 to 
Baseline 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
36 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Information and informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant medical history/current 
medical condition 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Drug washout evaluation/instruction 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Smoking history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiovascular medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Psoriatic arthritis/psoriasis medical 
history and previous therapies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
S 
S 
 
 
 
S 
S 
S 
S 
S 
S 
S 
 
Vital signs 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X1 
 
 
 
 
 
 
 
 
 
 
 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERON TB-Plus test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray/MRI‡ 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test2 
 
X 
 
 
 
 
X 
 
X 
 
X 
 
X 
Prior/concomitant medication/non-
drug therapy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse events/serious adverse 
events (including injection site 
reactions)3 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Clinical laboratory variables 
(hematology, blood chemistry, 
urinalysis)4, 5 
 
X 
X 
 
 
 
X 
X 
 
X 
 
X 
X 
X 
Lipids5 
 
X 
 
 
 
 
X 
 
X 
 
X 
X 
 
ANA 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
Anti-dsDNA 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
Anti-CCP 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Rheumatoid factor 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Administration of s.c. study 
treatment at study site6, 7, 8 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Psoriatic arthritis assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
CASPAR criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
 
68 TJC/66 SJC 
X 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Psoriasis assessment 
X 
 
 
 
 
 
 
 
 
 
 
 
 
PASI 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
BSA 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
HAQ-DI© 
 
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 
 
Patient’s assessment of PsA pain 
(VAS) 
 
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 
 
LEI 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
LDI  
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 
MDA 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
 

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8.1 
Screening 
8.1.1 
Information to be collected on screening failures 
Patients who sign an ICF may discontinue from the study prior to randomization. These patients 
are considered Screening failures. The reason for Screen failure should be recorded on the 
appropriate eCRF. The demographic information, informed consent, and Inclusion/Exclusion 
pages must also be completed for Screen failure patients. No other data will be entered into the 
clinical database for patients who are Screen failures, unless the patient experienced a SAE 
during the Screening phase. 
Patients who are randomized and fail to start treatment, e.g. patients randomized in error, will 
be considered early terminators. The reason for early termination should be recorded on the 
appropriate CRF. 
All patients who have signed informed consent and are randomized into the Treatment Period 
of the study will have all AEs occurring after informed consent is signed 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 
Patient demographics/other Baseline characteristics 
All Baseline assessments should be performed prior to first study drug administration. These 
may occur during the Screening period or at the Baseline Visit depending on the assessment.  
Patient demographic and Baseline characteristic data to be collected on all patients and recorded 
in the eCRF include: 
• Date of birth, age, sex, race and source of patient referral. 
• All relevant PsA/psoriasis and general medical history/current medical condition data 
until the start of investigational treatment, such as date of diagnosis of PsA/psoriasis, 
previous PsA/psoriasis therapies including treatment duration, cardiovascular medical 
history, smoking history and surgical sterilization for females if applicable. 
• Documentation of inadequate response or intolerance to anti-TNFα treatment, type of 
used anti-TNFα, treatment duration and reason for discontinuation of the treatment 
Whenever possible, diagnoses and not symptoms will be recorded. 
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. 
8.3 
Efficacy 
The efficacy outcome measures used in this study are standard measures used across all PsA 
trials. 
• Health Assessment Questionnaire - Disability Index (HAQ-DI©) 

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on each body region is estimated as a percentage of the total area of that particular body region. 
Further practical details help the assessment: 
• The neck is assessed as part of the head. 
• The axillae and groin are assessed as part of the trunk.  
• The buttocks are assessed as part of the lower limbs. 
When scoring the severity of erythema, scales should not be removed. 
Table 8-2 
The PASI scoring system 
Body  
region 
Erythema (E) 
 
Thickening 
(plaque 
elevation, 
induration, I) 
Scaling  
(desquamation, 
D) 
Area score 
(based on true area%, 
A)* 
Head (H)† 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0 = no involvement 
1 = > 0-< 10% 
2 = 10-< 30% 
3 = 30-< 50% 
4 = 50-< 70% 
5 = 70-< 90% 
6 = 90-100% 
Trunk (T)‡ 
 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0 = no involvement 
1 = > 0-< 10% 
2 = 10-< 30% 
3 = 30-< 50% 
4 = 50-< 70% 
5 = 70-< 90% 
6 = 90-100% 
Upper  
limbs (U) 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0 = no involvement 
1 = > 0-< 10% 
2 = 10-< 30% 
3 = 30-< 50% 
4 = 50-< 70% 
5 = 70-< 90% 
6 = 90-100% 
Lower  
limbs (L)§ 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0=none  
1=slight  
2=moderate  
3=severe 
4=very severe 
0 = no involvement 
1 = > 0-< 10% 
2 = 10-< 30% 
3 = 30-< 50% 
4 = 50-< 70% 
5 = 70-< 90% 
6 = 90-100% 
* Percentage (not score) of body region (not whole body) affected will be entered in the eCRF 
† Neck is assessed as part of the Head (H) body region. 
‡ Axillae and groin are assessed as part of the Trunk (T) body region. 
§ Buttocks are assessed as part of the Lower limbs (L) body region. 

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8.3.6 
Patient’s global assessment of disease activity 
The patient’s global assessment of disease activity will be performed using a 100 mm (VAS) 
ranging from ‘very good’ to ‘very poor’ after the question ‘Considering all the ways Psoriatic 
Arthritis affects you, please indicate with a vertical mark ( | ) through the horizontal line how 
well you are today’. 
8.3.7 
Patient’s global assessment of psoriasis and arthritis disease activity 
Global disease activity: The patient’s assessment of psoriasis and arthritis will be performed 
using a 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’. 
8.3.8 
Minimal disease activity 
Proportion of patients achieving MDA (Coates et al 2010), defined as 5 and 7 (very low disease 
activity) of the following 7 criteria:  
• ≤ 1 tender joint 
• ≤ 1 swollen joint 
• PASI ≤ 1 or BSA < 3% 
• Patient’s assessment of pain on VAS ≤ 15 
• Patient’s global assessment of disease (VAS) ≤ 20 
• HAQ-DI© ≤ 0.5 
• Tender entheseal points ≤ 1 
8.3.9 
Leeds enthesitis index 
The LEI assessment 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. 
The LEI is a validated enthesitis index that uses 6 sites for evaluation of enthesitis: lateral 
epicondyle humerus left (L) + right (R), proximal achilles L + R and medial condyle femur 
L+R. The LEI demonstrated substantial to excellent agreement with other scores in the 
indication of PsA (Healy and Helliwell 2008). 
Presence of enthesitis 
If enthesitis is present with any of the 6 sites, the patient is counted as a patient with enthesitis. 
8.3.10 
Leeds dactylitis index  
The LDI assessments 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. 
The LDI basic measures the ratio of the circumference of the affected digit to the circumference 
of the digit on the opposite hand or foot, using a minimum difference of 10% to define a 
dactylitic digit (Helliwell et al 2005). The ratio of circumference is multiplied by a tenderness 

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• Pregnancy and assessment of fertility 
8.4.1 
Physical examination 
The physical examination will include the examination of general appearance, skin, neck, eyes, 
ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular and 
neurological system. 
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present before signing the ICF must be included in the 
relevant medical history eCRF. Significant findings made after signing the ICF which meet the 
definition of an AE must be recorded in the Adverse Event eCRF. 
8.4.2 
Vital signs  
Vital signs will include blood pressure and pulse rate measurements after 5 minutes rest in 
sitting position. If possible, vital signs assessments should be performed by the same study site 
staff member using the same validated device throughout the study. 
8.4.3 
Height and weight  
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 calibrated scale throughout the study. 
8.4.4 
Tuberculosis screening 
A QuantiFERON TB-Plus test is to be performed at Screening and the results should be known 
prior to randomization to determine the patient’s eligibility for the trial. The test will be used to 
screen the patient population for latent tuberculosis infection.  
Patients with a positive test may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that 
• The patient has no evidence of active TB 
• If presence of latent TB is established then treatment according to local country 
guidelines must have been initiated. 
The QuantiFERON TB-Plus test will be analyzed by the central laboratory. Details on the 
collection, processing and shipment of samples and reporting of results by the central laboratory 
are provided in the laboratory manual. 
X-ray or MRI of the chest 
A chest X-ray (posteroanterior view) or MRI at Screening (or within 3 months prior to 
Screening) will be performed to rule out the presence of a pulmonary malignancy or infectious 
process, in particular, TB. The results must be known prior to randomization to determine the 
patient’s eligibility for the study. These assessments will be documented in source records only 
and will not be entered into the CRF. 

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8.4.5 
Laboratory evaluations 
A central laboratory will be used for analysis of all specimens listed below (except urinalysis). 
Details on the collection, shipment of samples and reporting of results by the central laboratory 
are provided in the laboratory manual. For the identification of clinically notable values, see 
Appendix 6 and Appendix 7. All patients with laboratory tests containing clinically significant 
abnormal values are to be followed until the values return to normal ranges or until a valid 
reason, other than treatment related AE, is defined. 
8.4.5.1 
Hematology 
Hemoglobin, platelets, red blood cell (RBC), white blood cell (WBC) and differential white 
blood cell counts will be measured at scheduled visits. 
8.4.5.2 
Clinical chemistry 
Serum chemistries will include glucose, urea, creatinine, total bilirubin, aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), gamma glutamyl transferase (GGT), 
alkaline phosphatase, sodium, potassium, bicarbonate, calcium, phosphorus, total protein, 
albumin, and uric acid. 
8.4.5.3 
Urinalysis 
Dipsticks will be provided by the central laboratory to the sites for local urinalysis assessments. 
The urinalysis results for standard parameters such as protein, glucose, blood, and WBCs will 
be recorded in the appropriate eCRF. 
8.4.5.4 
Lipid panel 
A lipid profile including high density lipoprotein (HDL), low density lipoprotein (LDL), total 
cholesterol, and triglycerides will be measured from a fasting blood sample. 
8.4.6 
Pregnancy and assessments of fertility  
The study treatment must not be given to pregnant women; therefore, effective methods of birth 
control must be used for women of childbearing potential (see exclusion criteria definitions, 
Section 5.2). 
A serum β-hCG test will be performed in all women at Screening. All women who are not 
surgically sterile or post-menopausal (as defined in Section 5.2) at Screening, will have local 
urine pregnancy tests as indicated in Table 8-1. A positive urine pregnancy test requires 
immediate interruption of study treatment until serum β-hCG is performed and found to be 
negative. If positive, the patient must discontinue 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 

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2. Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile. 
In the absence of the above medical documentation, FSH testing is required of any female 
patient regardless of reported reproductive/menopausal status at Screening/Baseline. 
8.4.7 
Tolerability of investigational treatments 
Tolerability will be assessed by AEs, laboratory values, injection site reaction, and 
immunogenicity. 
8.4.8 
Additional parameters 
Blood will be obtained at the first Screening Visit (Visit 1) for anti-cyclic citrullinated peptide 
(anti-CCP) antibodies and the rheumatoid factor (RF) assessment. Antinuclear antibody (ANA) 
and anti-double stranded deoxyribonucleic acid antibody (anti-dsDNA) antibodies will also be 
assessed at visits/time points indicated in Table 8-1.  
8.4.9 
Appropriateness of safety measurements  
The safety measures used in this study are standard measures for assessing the safety of a 
biological drug in patients with PsA. A chest X-ray or MRI at Screening (or within 3 months 
prior to Screening) is performed to rule out the presence of a pulmonary malignancy of 
infectious process (in particular TB). 
The total amount of radiation exposure that results from the Screening X-ray measurement is 
considered to involve minimal risk and is necessary to ensure reliable safety measures before 
the treatment with a biologic. 
The safety assessments selected are standard and adequate for this indication/patient population. 
8.5 
Other assessments 
The other assessments planned for the study are: 
• Quality of life questionnaires/patient reported outcomes (PROs) 
 
 
8.5.1 
Health-related quality of life  
The impact of PsA on various aspects of patients’ HRQoL will be assessed using the following 
validated instruments: 
• Health assessment questionnaire – disability index (HAQ-DI©) (see Section 8.3.1) 
• 
 
• 
 
• Psoriatic Arthritis Quality of Life (PsAQoL) 
• Functional assessment of chronic illness therapy© – Fatigue (FACIT©-Fatigue) 
• Dermatology life quality index (DLQI) 
All questionnaires will be available, where possible, in the local languages of the participating 
countries and should be completed by patients before they see the study physician. All 

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of their symptoms, or if on balance, the investigator believes that continuation would be 
detrimental to the patient’s well-being. 
If discontinuation of study treatment occurs, the investigator should make a reasonable effort 
to understand the primary reason for the patient’s premature discontinuation of study treatment 
and record this information. 
Patients who discontinue study treatment or who decide they do not wish to participate in the 
study further should NOT be considered withdrawn from the study UNLESS they withdraw 
their consent (see Section 9.1.2). Where possible, they should return for the assessments 
indicated in the assessment schedule. If they fail to return for these assessments for unknown 
reasons, every effort (e.g. telephone, e-mail, letter) should be made to contact the patient/pre-
designated contact as specified in the lost to follow-up section. This contact should preferably 
be done according to the study visit schedule. 
If the patient cannot or is unwilling to attend any visit(s), the site staff should maintain regular 
telephone contact with the patient, or with a person pre-designated by the patient. This telephone 
contact should preferably be done according to the study visit schedule. 
After study treatment discontinuation, at a minimum, in abbreviated visits, the following data 
should be collected at clinic visits or via telephone/email contact: 
• New/concomitant treatments 
• AEs/SAEs 
For patients who discontinue study treatment, a Dosage Administration Record eCRF should 
be completed, giving the date and primary reason for stopping study treatment. 
If discontinuation occurs because treatment code has been broken, please refer to Emergency 
breaking of treatment code section. 
9.1.2 
Withdrawal of informed consent 
Patients may voluntarily withdraw consent to participate in the study for any reason at any time. 
Withdrawal of consent occurs only when a patient: 
• Does not want to participate in the study anymore, and 
• Does not allow further collection of personal data 
In this situation, the investigator should make a reasonable effort (e.g. telephone, e-mail, letter) 
to understand the primary reason for the patient’s decision to withdraw his/her consent and 
record this information. 
Study/reference treatment must be discontinued and no further assessments conducted, and the 
data that would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the patient’s study withdrawal should be made as detailed in the 
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Novartis will continue to keep and use collected study information (including any data resulting 
from the analysis of a patient’s samples until the time of withdrawal) according to applicable 
law. 
All biological samples not yet analyzed at the time of withdrawal will no longer be used, unless 
permitted by applicable law. They will be stored according to applicable legal requirements. 
9.1.3 
Lost to follow-up 
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the investigator must show “due diligence” by 
documenting in the source documents steps taken to contact the patient, e.g. dates of telephone 
calls, registered letters, etc. A patient should not be considered as lost to follow-up until due 
diligence has been completed or until the end of the study. 
9.1.4 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time 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 patient welfare and safety. Should early termination be 
necessary, patients must be seen as soon as possible (provide instruction for contacting the 
patient, when the patient should stop taking drug, when the patient should come for a final visit) 
and treated as a prematurely withdrawn patient. The investigator may be informed of additional 
procedures to be followed in order to ensure that adequate consideration is given to the 
protection of the patient’s interests. The investigator or sponsor depending on the local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial. 
9.2 
Study completion and post-study treatment 
A patient will be considered to have completed the study when the patient has completed the 
last visit planned in the protocol i.e. Follow-up visit (week 36). Information on the patient’s 
completion or discontinuation of the study and the reason for discontinuation of the study will 
be recorded on the appropriate Study Phase Completion in the eCRF. 
The investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care. This care may 
include initiating another treatment outside of the study as deemed appropriate by the 
investigator. Based on the individual risk/benefit profile of a patient, treatment options may 
include DMARDs. 
In case of follow-up medical care with a biologic treatment the waiting period before initiating 
treatment will be at the discretion of the investigator or a minimum of 5 half-lives of the selected 
biologic treatment, whichever is longer. 

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10 
Safety monitoring and reporting 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign 
(including abnormal laboratory findings), symptom or disease) in a patient or clinical 
investigation patient after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. In addition, all reports of intentional misuse and abuse of 
the study treatment are also considered as an AE irrespective of a clinical trial event has 
occurred. See Section 10.1.5 for an overview of the reporting requirements. 
The investigator has the responsibility for managing the safety of individual patient and 
identifying AEs. 
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
The occurrence of AEs must be sought by non-directive questioning of the patient at each visit 
during the study. Adverse events also may be detected when they are volunteered by the patient 
during or between visits or through physical examination findings, laboratory test findings, or 
other assessments. 
Adverse events must be recorded under the signs, symptoms, or diagnosis associated with them, 
accompanied by the following information (as far as possible) (if the event is serious refer to 
Section 10.1.2): 
1. The severity grade  
• mild: usually transient in nature and generally not interfering with normal activities 
• moderate: sufficiently discomforting to interfere with normal activities 
• severe: prevents normal activities 
2. Its relationship to the study treatment and other investigational 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 patient. 
3. Its duration (start and end dates) or if the event is ongoing, an outcome of not recovered/not 
resolved must be reported. 
4. Whether it constitutes a SAE (see Section 10.1.2 for definition of SAE) and which 
seriousness criteria have been met. 
5. Action taken regarding study treatment or other treatment. 
All AEs must be treated appropriately. Treatment may include one or more of the 
following: 
• Dose not changed 

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• Dose Reduced/increased 
• Drug interrupted/withdrawn 
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 the 
patient’s medical history. 
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 (secukinumab) or 20 weeks 
(ustekinumab) following the last dose of study treatment. 
Once an AE is detected, it must be followed until its resolution or until it is judged to be 
permanent (e.g. continuing at the end of the study), and assessment must be made at each visit 
(or more frequently, if necessary) of any changes in severity, the suspected relationship to the 
interventions required to treat it, and the outcome. 
Information about adverse drug reactions for the investigational drug can be found in the 
Investigator’s Brochure. This information will be included in the patient informed consent and 
should be discussed with the patient during the study as needed. Any new information regarding 
the safety profile of the medicinal product that is identified between IB updates will be 
communicated as appropriate, for example, via an investigator notification (IN) or an aggregate 
safety finding. New information might require an update to the informed consent and has then 
to be discussed with the patient. 
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria: 
• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
Baseline or the previous visit, or values which are considered to be non-typical in patients with 
the underlying disease. Alert ranges for laboratory and other test abnormalities are included in 
Appendix 7. 
10.1.2 
Serious adverse events 
An SAE is defined as any AE (appearance of (or worsening of any pre-existing)) undesirable 
sign(s), symptom(s) or medical conditions(s)) which meets any one of the following criteria: 
• Fatal 
• Life-threatening 
Life-threatening in the context of a SAE refers to a reaction in which the patient was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to the ICH-E2D Guidelines). 
• Results in persistent or significant disability/incapacity 

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• Constitutes a congenital anomaly/birth defect 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:  
• Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition. 
• Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent. 
• Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition. 
• Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission. 
• Is medically significant, e.g. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention to prevent one of the outcomes listed above. 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the patient or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant”. Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do 
not result in hospitalization or development of dependency or abuse (please refer to the ICH-
E2D Guidelines). 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All reports of intentional misuse and abuse of the product are also considered SAEs irrespective 
if a clinical event has occurred.  
 
10.1.3 
SAE reporting 
Randomized patients 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until Week 36 (12 weeks (secukinumab) or 20 weeks 
(ustekinumab) after the last dose 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. 
Screen failures  
SAEs occurring after the patient has provided informed consent until the time the patient is 
deemed a Screen Failure must be reported to Novartis. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 

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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. 
Information about all SAEs is collected and recorded on the SAE Report Form (this may be a 
paper or electronic SAE CRF); all applicable sections of the form must be completed in order 
to provide a clinically thorough report. The investigator must assess the relationship of each 
SAE to each specific component of study treatment, (if study treatment consists of several 
components) complete the SAE Report Form in English, and submit the completed form within 
24 hours to Novartis. Detailed instructions regarding the submission process and requirements 
for signature are to be found in the investigator folder provided to each site. 
Follow-up information is submitted as instructed in the investigator folder. Each re-occurrence, 
complication, or progression of the original event must be reported as a follow-up to that event 
regardless of when it occurs. The follow-up information should describe whether the event has 
resolved or continues, if and how it was treated, whether the blind was broken or not, and 
whether the patient continued or withdrew from study participation. 
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert (new 
occurrence) and is thought to be related to the study treatment, a CMO & PS Department 
associate may urgently require further information from the investigator for health authority 
reporting. Novartis may need to issue an Investigator Notification (IN) to inform all 
investigators involved in any study with the same study treatment that this SAE has been 
reported. 
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with EU Guidance 
2011/C 172/01 or as per national regulatory requirements in participating countries. 
Any SAEs experienced after the 24-week follow-up period should only be reported to Novartis 
Safety if the investigator suspects a causal relationship to study treatment. 
Treatment-emergent elevations in AST or ALT (>3x ULN) in combination with total bilirubin 
>2x ULN or jaundice in the absence of cholestasis (defined as ALP < 2 ULN) or other causes 
of hyperbilirubinemia can be an indicator of severe drug induced liver injury (Hy’s Law).  For 
this reason, a potential Hy’s Law case requires expedited reporting, and will be handled as a 
serious unexpected adverse event (assessing it as medically significant in the absence of any 
other seriousness criteria). It must be reported as an SAE to the sponsor promptly (i.e., even 
before all other possible causes of liver injury have been excluded), study drug should be 
discontinued immediately, patient should be hospitalized, if clinically appropriate, and causality 
needs to be established. Reporting should include all available information, especially that 
needed for evaluating the diagnosis, severity and likelihood that the study treatment caused the 
reaction. For patient monitoring and to better understand potential etiologies, the investigator 
must initiate a close follow-up until complete resolution of the problem and completion of all 
attempts to obtain supplementary data. 
10.1.4 
Pregnancy reporting 
To ensure patient safety, each pregnancy occurring after signing the informed consent must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 

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followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications. 
Pregnancy should be recorded and reported by the investigator to the Novartis Chief Medical 
Office and Patient Safety (CMO&PS). Pregnancy follow-up (birth, 1, 3, and 12 months after 
the expected delivery) 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. 
Pregnancy outcomes (birth, 1, 3, and 12 months after the expected delivery) should be collected 
for the female partners of any males who took study treatment in this study. Consent to report 
information regarding these pregnancy outcomes should be obtained from the mother. 
10.1.5 
Reporting of study treatment errors including misuse/abuse 
Study treatment errors are unintentional errors in the prescribing, dispensing, and administration 
of study treatment. 
Study treatment misuse refers to situations where the study treatment is intentionally and 
inappropriately used not in accordance with the protocol. 
Study treatment abuse corresponds to the persistent or sporadic, intentional excessive use of 
study treatment, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol, including misuse or 
abuse, must be reported on the AE (or SAE, if the event meets the definition of an SAE) CRF. 
10.2 
Additional safety monitoring 
10.2.1 
Liver safety monitoring 
There has been no safety signal for liver toxicity with secukinumab to date in approximately 
13000 patients and healthy patients exposed, and from a mechanism of action standpoint there 
is no known effect of blocking IL-17A on the liver. Standard liver function tests will be obtained 
at regular intervals, but special measures for liver safety monitoring are not planned. For further 
information on notable laboratory values, see Appendix 7. 
10.2.2 
Renal safety monitoring 
To date, there has been no safety signal for nephrotoxicity with secukinumab in over 12,000 
patients and healthy patients exposed, and from a mechanism of action standpoint there is no 
known effect of blocking IL-17A on the kidney. All patients with laboratory tests resulting in 
clinically significant abnormal values (see Appendix 7 for notable laboratory values) are to be 
followed until the values return to normal ranges or until a valid reason, other than treatment 
related AE, is defined. Standard renal function tests (blood urea nitrogen, serum creatinine) will 
be obtained at regular intervals, but special measures for renal safety monitoring are not 
planned. 

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11 
Data collection and database management 
11.1 
Data collection 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation and verification 
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRF). The eCRFs have been built using fully validated secure web-
enabled software that conforms to 21 CFR Part 11 requirements, Investigator site staff will not 
be given access to the electronic data capture (EDC) system until they have been trained. 
Automatic validation programs check for data discrepancies in the eCRFs, allow modification 
and/or verification of the entered data by the investigator staff. 
The investigator/designee is responsible for assuring that the data (recorded on CRFs) (entered 
into eCRF) is complete, accurate, and that entry and updates are performed in a timely manner. 
The Investigator must certify that the data entered are complete and accurate 
After final database lock, the investigator will receive copies of the patient data for archiving at 
the investigational site. 
11.2 
Database management and quality control 
Novartis personnel (or designated clinical research organization [CRO]) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated investigator 
site staff are required to respond promptly to queries and to make any necessary changes to the 
data. 
Concomitant treatments and prior medications entered into the database will be coded using the 
World Health Organization (WHO) Drug Reference List, which employs the anatomical 
therapeutic chemical (ATC) classification system. Medical history/current medical conditions 
and AEs will be coded using the medical dictionary for regulatory activities (MedDRA) 
terminology. 
Randomization codes and data about all study treatment(s) dispensed to the patient and all 
dosage changes will be tracked.  
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked. Any changes to the database after that time can only 
be made after written agreement by Novartis development management. 
11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a 
Novartis/delegated CRO representative will review the protocol and data capture requirements 
(i.e. eCRFs) with the investigators and their staff. During the study, Novartis employs several 
methods of ensuring protocol and GCP compliance and the quality/integrity of the sites’ data. 
The field monitor will visit the site to check the completeness of patient records, the accuracy 
of data capture / data entry, the adherence to the protocol and to Good Clinical Practice, the 

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progress of enrollment, and to ensure that study treatment is being stored, dispensed, and 
accounted for according to specifications. Key study personnel must be available to assist the 
field monitor during these visits. Continuous remote monitoring of each site’s data may be 
performed by a centralized Novartis/delegated CRO. Additionally, a central analytics 
organization may analyze data and identify risks and trends for site operational parameters, and 
provide reports to Novartis clinical teams to assist with trial oversight. 
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, and the results of any other tests or assessments. All information 
on CRFs must be traceable to these source documents in the patient’s file. The investigator must 
also keep the original ICF signed by the patient (a signed copy is given to the patient). 
The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. Novartis monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the CRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
patients will be disclosed. 
12 
Data analysis and statistical methods 
The data will be analyzed by Novartis and/or a designated CRO.  
The analyses will be conducted on all patient data after data base lock for the trial. Any data 
analysis carried out independently by the investigator should be submitted to Novartis before 
publication or presentation. 
The primary analyses for all efficacy and safety endpoints will be carried out after the last 
patient completed Week 28 assessment. 
12.1 
Analysis sets 
The Randomized Analysis Set (RAS) consists of all randomized patients. Unless otherwise 
specified, miss-randomized patients will be excluded from the RAS. 
The Full Analysis Set (FAS) comprises all patients to whom study treatment has been assigned 
by randomization. According to the intent to treat principle, patients will be analyzed according 
to the treatment and strata they have been assigned to during the randomization procedure. 
The Safety Set includes all patients who received at least one dose of study treatment. Patients 
will be analyzed according to the study treatment received, where treatment received is defined 
as the randomized/assigned treatment if the patient took at least one dose of that treatment or 
the first treatment received if the randomized/assigned treatment was never received. 
12.2 
Patient demographics and other Baseline characteristics 
Demographic and other Baseline data including disease characteristics will be listed and 
summarized descriptively by treatment group for the FAS and Safety set.  

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Categorical data will be presented as frequencies and percentages. For continuous data, mean, 
standard deviation, median, minimum, and maximum will be presented.  
Relevant medical histories and current medical conditions at Baseline will be summarized by 
system organ class, preferred term and by treatment group. 
12.3 
Treatments 
The Safety set will be used for the analyses below. Categorical data will be summarized as 
frequencies and percentages. For continuous data, mean, standard deviation, median, 25th and 
75th percentiles, minimum, and maximum will be presented. 
The duration of exposure to study treatment by treatment group will be summarized by means 
of descriptive statistics using the safety set. In addition, the number of patients with exposure 
of certain thresholds will be displayed. Compliance will be calculated based on documented 
study drug administrations and syringe counts and displayed by treatment group and study 
phase. 
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be listed and summarized according to the ATC classification system, by 
treatment group. Prior treatments are defined as treatments taken and stopped prior to first dose 
of study treatment. Any treatment given at least once between the day of first dose of 
randomized study treatment and the last day of study visit will be a concomitant treatment, 
including those which were started pre-baseline and continued into the treatment period of the 
study. Treatments will be presented in alphabetical order, by ATC codes and grouped by 
anatomical main group. Tables will also show the overall number and percentage of patients 
achieving at least one treatment of a particular ATC. 
12.4 
Analysis of the primary endpoint(s) 
The primary aim of the study is to demonstrate that secukinumab 300mg is superior to 
ustekinumab 45mg/90mg in terms of achieving a HAQ-DI response ≥ 0.35 in change from 
baseline to week 28 in adult patients with psoriatic arthritis, who failed previous TNFα inhibitor 
treatment. 
12.4.1 
Definition of primary endpoint(s)   
The primary endpoint variable is the proportion of patients achieving treatment response as 
defined by a change in HAQ-DI ≥ 0.35 from baseline to week 28.  
The analysis of the primary variable will be based on the treatment-policy estimand: 
• Analysis set: FAS, 
• Variable of interest: proportion of patients achieving treatment response as defined by 
a change in HAQ-DI ≥ 0.35 from baseline to week 28, 
• Intervention effect: effect between secukinumab 300mg vs. ustekinumab 45mg/90mg 
regardless of adherence to randomized treatment, 
• Summary measure: Odds ratio (OR). 

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12.4.2 
Statistical model, hypothesis, and method of analysis 
Initially, statistics were planned as described below. However, due to recruitment issues of 
study CAIN457FDE04 („AgAIN“), screening has been discontinued as of 31 Jan 2024. Patients 
who were successfully screened through 31 Jan 2024 were all allowed to be randomized and 
could complete the study. A total of 119 patients were randomized, which led to 59 patients in 
one arm and 60 patients in the other arm – herein not further specified due to ongoing blinding. 
The resulting power under previous assumptions will be approximately 55%. Therefore, only a 
descriptive analysis will be performed, as inferential analyses would be underpowered (no 
formal tests will be performed).  Missing data for HAQ-DI response and other binary efficacy 
endpoints (e.g. response of PASI 90, PASI 100, PsAQoL, etc.) for data up to Week 28 will be 
replaced once by last-observation-carried forward (LOCF) or as non-responders in the sense of 
worst-case analysis. 
The statistical hypothesis to be tested is that there is no difference in the proportion of subjects 
fulfilling the HAQ-DI responder definition at Week 28 between the two treatment arms in the 
FAS population. 
Let pj denote the proportion of HAQ-DI responders at Week 28 for treatment group j, j = 0,1, 
where 
• 0 corresponds to the ustekinumab 45mg/90mg treatment arm, 
• 1 corresponds to the secukinumab 300mg arm. 
The following hypotheses will be tested: 
H0: (p1 / (1-p1)) / (p0 / (1-p0)) = 1 vs. HA: (p1 / (1-p1)) / (p0 / (1-p0)) ≠ 1 
In other words:  
HA: The odds ratio of achieving a HAQ-DI response at Week 28 for the comparison of 
secukinumab 300mg vs. ustekinumab 45mg/90mg is different from 1. 
The primary endpoint of HAQ-DI response at Week 28 will be analyzed via a multiple logistic 
regression model with treatment and randomization strata as factors and baseline HAQ-DI 
score as a covariate. Odds ratios will be computed for comparisons of secukinumab versus 
ustekinumab regimen utilizing the logistic model fitted to the data. Superiority in favor of 
secukinumab for the primary efficacy variable will be claimed if the two-sided p-value for the 
factor treatment is ≤ 0.05. 
12.4.3 
Handling of missing values/censoring/discontinuations 
Missing data for HAQ-DI response and other binary efficacy endpoints (e.g. response of  
PASI 90, PASI 100, PsAQoL etc.) for data up to Week 28 will be handled by Multiple 
Imputation (MI) utilizing all accumulated patient data irrespective of on- or off-treatment. All 
considered endpoints should be imputed separately. 
Multiple Imputation (MI) is a simulation based approach where missing values are replaced by 
multiple Bayesian draws from the conditional distribution of missing data given the observed 
data and covariates, creating multiple completed data sets. These completed data sets can then 
be analyzed using standard methods. Within this analysis the composites of e.g. the ACR or the 

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HAQ-DI score will be imputed and response variables will be derived based on the imputed 
scores. In the multiple imputation analysis the response status will be imputed based on the 
individual treatment arm information.   
Patients who were unblinded prior to the scheduled time point will be considered non-
responders from the time of unblinding up to Week 28. 
Continuous variables (e.g. VAS of patient’s assessment of pain) up to Week 28 will be analyzed 
by means of a mixed-effect model for repeated measures (MMRM), which is valid under the 
missing at random (MAR) assumption. Missing data for continuous efficacy endpoints due to 
missed or skipped visits will therefore not be applicable to multiple imputation. Analysis visits 
up to Week 28 will be analyzed in this fashion. 
12.4.4 
Sensitivity and Supportive analyses 
Sensitivity analyses and supportive analyses 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. 
Supportive analyses 
Supportive analyses to be conducted are primarily related to investigating possible subgroup-
by-treatment interaction effects for the following subgroups: 
• Age (≤ 65 vs. > 65) 
• Gender (male vs. female) 
• Number of previous TNFα treatment regimens (≤ 2 vs. > 2) 
 
12.5 
Analysis of secondary endpoints 
The analyses of secondary endpoints will be performed when all patients have completed the 
Week 28 assessment. For evaluation of secondary efficacy outcomes, no formal statistical 
testing procedure will be applied. 
12.5.1 
Efficacy endpoint(s) 
Binary secondary efficacy endpoints like the proportion of patients with a PASI 90 response or 
Minimal Disease Activity at Week 28 will be evaluated using the same multiple logistic 
regression model utilized for the primary efficacy endpoint with treatment and randomization 
stratum as factors and the respective baseline score value, if applicable, as a covariate.  

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For continuous endpoint variables like the patient’s assessment of pain (VAS) or tender and 
swollen joint count, the between-treatment difference in change from baseline will be evaluated 
using a MMRM. Treatment group, randomization stratum and analysis visit will be included as 
factors in the models. Additionally, each respective baseline score value of the endpoint variable 
will be included as a covariate. Treatment group by analysis visit and baseline score by analysis 
visit will be included as interaction terms in the model. An unstructured covariance matrix will 
be assumed. The treatment effect for the secukinumab 300 mg regimen at different analysis 
visits will be determined from the pairwise comparison performed between the two treatment 
groups.  
12.5.2 
Safety endpoints 
For all safety analyses, the safety set will be used. All listings and tables will be presented by 
treatment group. 
Safety summaries (tables, figures) include only data from the on-treatment period with the 
exception of Baseline data which will also be summarized where appropriate (e.g. change from 
Baseline summaries). In addition, a separate summary for death including on treatment and post 
treatment deaths will be provided. In particular, summary tables for AEs will summarize only 
on-treatment events, with a start date during the on-treatment period (treatment-emergent AEs). 
The on-treatment period lasts from the date of first administration of study treatment to 30 days 
after the date of the last actual administration of any study treatment. 
Adverse events 
All information obtained on AEs will be displayed by treatment group and patient. 
The number (and percentage) of patients with treatment emergent AEs (events started after the 
first dose of study medication or events present prior to start of double-blind treatment but 
increased in severity based on preferred term) will be summarized in the following ways: 
• by treatment, primary system organ class and preferred term. 
• by treatment, primary system organ class, preferred term and maximum severity. 
• by treatment, Standardized MedDRA Query (SMQ) and preferred term 
Separate summaries will be provided for study medication related AEs, death, SAEs, other 
significant AEs leading to discontinuation. 
Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of patients having any AE, having any AE in each primary system organ class and 
having each individual AE (PT). Summaries will also be presented for AEs by severity and for 
study treatment related AEs. If a patient reported more than one AE with the same PT; the AE 
with the greatest severity will be presented. If a patient reported more than one AE within the 
same primary system organ class, the patient will be counted only once with the greatest severity 
at the system organ class level, where applicable. Serious adverse events will also be 
summarized. 

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equal proportions. In order to account for some uncertainties in the underlying assumptions and 
to compensate for some expected drop-out, a total of 310 patients (155 in the secukinumab 300 
mg and 155 in the ustekinumab 45 mg / 90 mg arm) should be randomized into the study.  
Furthermore, this number of patients will allow a power of around 90% in order to claim a 
significant benefit of secukinumab 300 mg vs. ustekinumab 45 mg / 90 mg in TNFα-IR PsA 
patients, using the PASI 90 responder definition. Available data from the FUTURE5 trial within 
the TNFα-IR subpopulation showed a PASI 90 response of secukinumab 300 mg of 62.9% and 
57.1% at Weeks 24 and 32, respectively (Non-Responder Imputation). Conservatively, 
assuming a PASI 90 response of at least 57.1% at Week 28 seems therefore justifiable for 
secukinumab 300 mg. Following results from the PSUMMIT2 trial of ustekinumab 45 mg / 90 
mg, the proportion of PASI 90 responders at Week 24 was 37.3% and remained stable over 
time. 
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 GCP, with applicable local regulations 
(including European Directive 2001/20/EC, US CFR 21), and with the ethical principles laid 
down in the Declaration of Helsinki. 
13.2 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from 
the IRB/IEC for the trial protocol, written ICF, consent form updates, patient recruitment 
procedures (e.g. advertisements) and any other written information to be provided to patients. 
Prior to study start, the investigator is required to sign a protocol signature page confirming 
his/her agreement to conduct the study in accordance with these documents and all of the 
instructions and procedures found in this protocol and to give access to all relevant data and 
records to Novartis monitors, auditors, Novartis Quality Assurance representatives, designated 
agents of Novartis, IRBs/IECs, and regulatory authorities as required. If an inspection of the 
clinical site is requested by a regulatory authority, the investigator must inform Novartis 
immediately that this request has been made. 
13.3 
Publication of study protocol and results 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required in EudraCT. In addition, after study completion (defined as last patient last visit) 
and finalization of the study report the results of this trial will be submitted for publication and 
posted in a publicly accessible database of clinical trial results, such as the Novartis clinical trial 
results website and all required Health Authority websites (e.g. Clinicaltrials.gov, EudraCT 
etc.) . 
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the trial investigator 
meetings. 

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

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Yellen SB, Cella DF, Webster K, et al (1997) Measuring fatigue and other anemia-related 
symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J 
Pain Symptom Manage; 13:63-74.  

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16 
Appendices 
16.1 
Appendix 1: Classification criteria for psoriatic arthritis 
(CASPAR) 
To meet the Classification of Psoriatic Arthritis (CASPAR) criteria for diagnosis of psoriatic 
arthritis (Taylor et al 2006), a subject must have inflammatory articular disease (joint, spine or 
entheseal) and at least 3 points from the following 5 categories: 
• 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) 
• 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 point) 
• A family history of psoriasis is defined as a history of psoriasis in a first- or second- 
degree relative according to patient report. (1 point) 
• Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis observed 
on current physical examination (1 point) 
• A negative test result for the presence of rheumatoid factor by any method except latex (1 
point) 
• Either current dactylitis, defined as swelling of an entire digit, or a history of dactylitis 
recorded by a rheumatologist (1 point) 
• Radiographic evidence of juxta-articular new bone formation appearing as ill-defined 
ossification near joint margins (but excluding osteophyte formation) on plain radiographs 
of the hand or foot (1 point) 
Total score:  
(The CASPAR criteria eCRF will autopopulate the total number of points of the CASPAR 
criteria met by the subject. If the total score ≥ 3, the subject meets CASPAR criteria for PsA 
diagnosis.) 
* Current psoriasis is assigned a score of 2; all other features are assigned a score of 1 
 

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respondent has filled in the past. If the patient still declines, retrieve the questionnaires. Record 
the reason for the decline and thank the patient. 
The patient is too ill or weak to complete the questionnaire(s) 
In these instances, the coordinator may obtain patient responses by reading out loud each 
question, followed by the corresponding response categories, and entering the patient’s 
response. No help should be provided to the patient by any person other than the designated 
study coordinator. The coordinator should not influence patient responses. The study 
coordinator cannot translate the question into simpler language and has to be read verbatim. 
The patient wants someone else to complete the questionnaire(s) 
In no case should the coordinator or anyone other than the patient provide responses to the 
questions. Unless specified in the study protocol, proxy data are not an acceptable substitute for 
patient self-report. Patients should be discouraged from asking a family member or friend for 
help in completing a questionnaire. 
The patient does not want to finish completing the questionnaire(s) 
If non-completion is a result of the patient having trouble understanding particular items, ask 
the patient to explain the difficulty. Re-read the question for them verbatim but do not rephrase 
the question. If the respondent is still unable to complete the questionnaire, accept it as 
incomplete. Thank the patient. 
The patient is concerned that someone will look at his/her responses 
Emphasize that all responses are to be kept confidential. Point out that their names do not appear 
anywhere on the questionnaire, so that their results will be linked with an ID number and not 
their name. Tell the patient that his/her answers will be pooled with other patients’ answers and 
that they will be analyzed as a group rather than as individuals. Tell the patient that completed 
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 patient asks the meaning of a question/item 
While completing the questionnaire, some patients might ask the meaning of specific items so 
that they can better understand and respond. If this happens, assist the patient by rereading the 
question for them verbatim. If the patient asks to interpret the meaning of an item, do not try to 
explain it, but suggest that he/she use his/her own interpretation of the question. Patients should 
answer the questions based on what they think the questions mean. 
A General Information about all questionnaire(s): 
All questionnaires have to be completed by the patients in their local languages using an 
electronic device. The questionnaires should be completed by the patients in a quiet area free 
from disturbance, and before any visit assessments. Patients should receive no help from family 
members; if questions cannot be answered alone (due to problems with reading or 
understanding), then the doctor or nurse should read the questions and record the patient’s 
responses without influencing their answers. The information provided is strictly confidential 

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and will be treated as such. If a patient has missed a question or given more than one response 
per question, then this should be brought to patient. Incomplete questions should not be accepted 
without first encouraging the patient to complete unanswered questions. 
The investigator must complete the patient/visit information and ensure that the center number, 
patient’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 patient/visit information. 

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16.4 
Appendix 4: Standard reference table for the LDI 
Table 16-1 
LDI reference table for hands (in cm) 
Digit 
Men 
Women 
Thumb 
7.0 
5.8 
Index 
6.3 
5.4 
Middle 
6.3 
5.4 
Ring 
5.9 
5.0 
Little 
5.2 
4.4 
Table 16-2 
LDI reference table for feet (in cm) 
Digit 
Men 
Women 
Central toe 
8.2 
7.2 
Second 
5.2 
4.6 
Middle 
5.0 
4.4 
Fourth 
5.0 
4.4 
Little 
5.2 
4.5 
 

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16.5 
Appendix 5: The Psoriasis Area and Severity Index (PASI) 
The PASI is a system used for assessing and grading the severity of psoriatic lesions and their 
response to therapy. The PASI produces a numeric score that can range from 0 to 72. The 
severity of disease is calculated as follows. In the PASI system, the body is divided into 4 
regions: the head (h), trunk (t), upper extremities (u), and lower extremities (l), which account 
for 10%, 30%, 20% and 40% of the total BSA, respectively. Each of these areas is assessed 
separately for erythema, induration and desquamation (scaling), which are each rated on a scale 
of 0 to 4. The scoring system for the signs of the disease (erythema, induration, and 
desquamation (scaling)) are: 
0 = none; 1= slight; 2 = moderate; 3 = severe; and 4 = very severe.  
The scale for estimating the area of involvement for psoriatic lesions is outlined below. 
0 = no involvement 
1 = 1% to 9% involvement 
2 = 10% to 29% involvement 
3 = 30% to 49% involvement 
4 = 50% to 69% involvement 
5 = 70% to 89% involvement 
6 = 90% to 100% involvement 
To help with the area assessments, the following conventions should be noted: 
• the neck is considered part of the head 
• the axillae and groin are part of the trunk 
• the buttocks are part of the lower extremities 
The PASI formula is: PASI = 0.1 (Eh + Ih + Dh) Ah + 0.3 (Et +It+ Dt) At+ 0.2 (Eu + Iu + Du) 
Au+ 0.4 (El +II+ Dl) AI (where E= erythema, I = induration, D = desquamation and A = area) 
Table 16-3 
PASI Scoring Worksheet 
 
Head 
Upper 
extremities 
Trunk 
Lower 
extremities 
Redness † 
 
 
 
 
Thickness † 
 
 
 
 
Scale † 
 
 
 
 
Sum of rows 1, 2, and 
3 
 
 
 
 
Area score ‡ 
 
 
 
 
Score of row 4 x row 5 
x the area multiplier 
Row 4 x row 5  
x 0.1 
Row 4 x row 5 
 x 0.2 
Row 4 x row 5 
 x 0.3 
Row 4 x row 5 
 x 0.4 
Sum row 6 for each 
column for PASI score 
 
 
 
 
a. Divide body into four areas: head, arms, trunk to groin, and legs to top of buttocks. 

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b. Generate an average score for the erythema, thickness, and scale for each of the 4 areas (0=clear, 
1-4=increasing severity). 
c. Sum scores of erythema, thickness, and scale for each of the 4 area. 
d. Generate a percentage for skin covered with psoriasis for each area and convert that to a 0-6 scale. 
‡ 
e. Multiply score of item c above times item d above for each area and multiply that by 0.1, 0.2, 0.3 
and 0.4 for head, arms, trunk, and legs, respectively. 
f. Add these scores to get the PASI score. 
† Erythema, thickness, and scale are measured on a 0-4 scale (none, slight, mild, moderate, severe) 
‡ Area scoring criteria (score: % involvement). 
 
 
0: 0% (clear) 
 
 
1: <10% 
 
 
2: 10-<30% 
 
 
3: 30-<50% 
 
 
4: 50-<70% 
 
 
5: 70-<90% 
 
 
6: 90-100% 
Derived from Feldman SR, Krueger GG (2005). Psoriasis assessment tool in clinical trials. Ann 
Rheum Dis; 64 (Suppl 2);ii65-8. 
 

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16.6 
Appendix 6: Liver event and laboratory trigger definitions and 
follow-up requirements 
Table 16-4 
Liver event and laboratory trigger definitions 
 
Definition/ threshold 
Liver 
laboratory 
triggers 
3 x ULN < ALT / AST ≤ 5 x ULN 
1.5 x ULN < TBL ≤ 2 x ULN 
Liver events 
ALT or AST > 5 × ULN 
 
ALP > 2 × ULN (in the absence of known bone pathology) 
 
TBL > 2 × ULN (in the absence of known Gilbert syndrome) 
 
ALT or AST > 3 × ULN and INR > 1.5  
 
Potential Hy’s Law cases (defined as ALT or AST > 3 × ULN and TBL > 2 × 
ULN [mainly conjugated fraction] without notable increase in ALP to > 2 × 
ULN) 
 
Any clinical event of jaundice (or equivalent term) 
 
ALT or AST > 3 × ULN accompanied by (general) malaise, fatigue, abdominal 
pain, nausea, or vomiting, or rash with eosinophilia 
 
Any adverse event potentially indicative of a liver toxicity *  
* These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver damage-
related conditions; non-infectious hepatitis; benign, malignant and unspecified liver neoplasms 
TBL: total bilirubin; ULN: upper limit of normal 
Table 16-5 
Follow-up requirements for liver events and laboratory triggers 
Criteria 
Actions required 
Follow-up monitoring 
Potential 
Hy’s 
Law casea 
Discontinue the study drug immediately 
Hospitalize, if clinically appropriate 
Establish causality 
Complete liver eCRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion) 
 
ALT or AST 
> 8 × ULN 
Discontinue the study drug immediately 
Hospitalize if clinically appropriate 
Establish causality 
Complete liver eCRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion) 
> 3 × ULN and 
INR > 1.5 
Discontinue the study drug immediately 
Hospitalize, if clinically appropriate 
Establish causality 
Complete liver eCRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion) 
> 5 to ≤ 8 × ULN 
Repeat LFT within 48 hours 
If elevation persists, continue follow-up 
monitoring 
If elevation persists for more than 
2 weeks, discontinue the study drug 
Establish causality 
Complete liver eCRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion) 

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Criteria 
Actions required 
Follow-up monitoring 
> 3 × ULN 
accompanied by 
symptomsb 
Discontinue the study drug immediately 
Hospitalize if clinically appropriate 
Establish causality 
Complete liver eCRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion) 
> 3 to ≤ 5 × ULN  
(patient is 
asymptomatic) 
Repeat LFT within the next week 
If elevation is confirmed, initiate close 
observation of the patient 
Investigator discretion 
Monitor LFT within 1 to 4 weeks  
ALP (isolated) 
 
 
> 2 × ULN (in the 
absence of 
known bone 
pathology) 
Repeat LFT within 48 hours 
If elevation persists, establish causality 
Complete liver eCRF 
Investigator discretion 
Monitor LFT within 1 to 4 weeks or at 
next visit 
TBL (isolated) 
 
 
> 2 × ULN (in the 
absence of 
known Gilbert 
syndrome) 
Repeat LFT within 48 hours 
If elevation persists, discontinue the study 
drug immediately 
Hospitalize if clinically appropriate 
Establish causality 
Complete liver eCRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion) 
Test 
for 
hemolysis 
(e.g., 
reticulocytes, haptoglobin, uncon-
jugated [indirect] bilirubin) 
> 1.5 to ≤ 2 × 
ULN 
(patient is 
asymptomatic) 
Repeat LFT within the next week 
If elevation is confirmed, initiate close 
observation of the patient  
Investigator discretion 
Monitor LFT within 1 to 4 weeks or at 
next visit 
Jaundice 
Discontinue the study drug immediately 
Hospitalize the patient 
Establish causality 
Complete liver eCRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc (frequency 
at investigator discretion) 
Any AE 
potentially 
indicative of a 
liver toxicity* 
Consider study drug interruption or 
discontinuation  
Hospitalization if clinically appropriate 
Establish causality 
Complete liver eCRF 
Investigator discretion 
* These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver damage-
related conditions; non-infectious hepatitis; benign, malignant and unspecified liver neoplasms 
TBL: total bilirubin; ULN: upper limit of normal 
a Elevated ALT/AST > 3 × ULN and TBL > 2 × ULN but without notable increase in ALP to > 2 × ULN 
b (General) malaise, fatigue, abdominal pain, nausea, or vomiting, or rash with eosinophilia  
c Resolution is defined as an outcome of one of the following: (1) return to Baseline values, (2) stable 
values at three subsequent monitoring visits at least 2 weeks apart, (3) remain at elevated level after 
a maximum of 6 months, (4) liver transplantation, and (5) death. 
 
 
 
 

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16.7 
Appendix 7: Clinically notable laboratory values 
• The following guidance will be used to define expanded limits and notable abnormalities of 
key laboratory outcomes.  
• Clinically notable values will be forwarded to Novartis in the same time as sent to the 
investigators. Any intervention based on these laboratory values should be discussed with 
Novartis personnel. 
Table 16-6 
Clinically notable laboratory values 
Laboratory variable 
Notable criteria 
Liver function and related variables 
SGOT (AST) 
>3 x ULN 
SGPT (ALT) 
>3 x ULN 
Bilirubin 
>2 x ULN 
Alkaline phosphatase 
>2.5 x ULN 
Renal function, metabolic and electrolyte variables 
Creatinine (serum) 
>2 x ULN 
Hematology variables 
Hemoglobin 
20 g/L decrease from Baseline 
Platelet count 
<100 x 109/L 
White blood cell count 
<0.8 x LLN 
Neutrophils 
<0.9 x LLN