Conditions: Psoriatic Arthritis
Keywords: Power Doppler Ultrasonography Psoriatic Arthritis Enthesitis Synovitis Outcome Measures in Rheumatology Spondyloarthritis Research Consortium of Canada active psoriatic arthritis secukinumab Arthritis GLOESS monoclonal antibody PsA
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 166
Healthy volunteers: no

Brief summary:
This study was designed to leverage the sensitivity of ultrasonography available in clinical practice setting to better describe the time course of response to secukinumab (150 mg and 300 mg) on joint synovitis and enthesitis in PsA patients with an inadequate response to non-biologic DMARDs. PDUS changes in joint synovitis will be assessed using the global Outcome Measures in Rheumatology (OMERACT)-European League against Rheumatism (EULAR) synovitis score (GLOESS) and changes in joint enthesitis were assessed using the OMERACT enthesitis score.

Detailed description:
This was a 52-week, multicenter, international study consisting of a 2 to 4-week Screening period, a 12-week randomized, placebo-controlled double-blind treatment period (Period 1), a 12-week open-label treatment period (Period 2) and a 6-month open-label extension period (Period 3).

Treatment Period 1 is a 12-week placebo-controlled, randomized period primarily designed to demonstrate the early and optimal efficacy of secukinumab vs placebo on joint synovitis using PDUS via the GLOESS and global entheseal score after 12 weeks of treatment.

The main aim of Period 2 was to assess the maintenance or increased magnitude of treatment response on joint synovitis for patients from the original secukinumab groups and to assess the time course of response with secukinumab on joint synovitis in the original placebo group switched to secukinumab from Week 12.

The main aim of Period 3 (extension period) was to allow patients who respond to secukinumab to extend study treatment up to Week 52 or until commercial drug becomes available, whichever occurs sooner.

Arms:
arm 1: In Treatment Period-1:

Patients in this group were administered secukinumab with 12 weeks of treatment from baseline.

In Treatment Period-2:

Patients continued to receive the same active dose of secukinumab every 4 weeks until Week 24

In Treatment Period 3 (extension period):

the extension period allowed responder patients the possibility to continue open-label secukinumab treatment up to Week 52 arm 2: In Treatment Period-1:

Patients received placebo at baseline and same time points as secukinumab until Week 8.

In Treatment Period-2:

Patients commenced open-label secukinumab every 4 weeks from Week 12, as follows, based on their clinical characteristics at Week 12

In Treatment Period-3:

Open-label secukinumab continued to be assigned to patients

Interventions: intervention 1: AIN457 (secukinumab) intervention 2: Placebo
Intervention descriptions: intervention 1: Is a recombinant monoclonal antibody which neutralizes the activity of IL-17A, and has been shown to be effective in treating patients with moderate-to-severe plaque psoriasis.

Secukinumab 150 mg provided in 1 mL pre filled syringes (PFS) for s.c. injection. The 300 mg dose was administered as 2 × PFS injections. intervention 2: Secukinumab placebo was provided in a 1 mL PFS for s.c. injection.

Protocol document:
Prot_000.pdf: 
 
 
Global Clinical Development - General Medicine 
AIN457/Secukinumab 
Clinical Trial Protocol (CAIN457F2354) 
A 52-week, multicenter study to assess the time course of 
response to secukinumab on joint inflammation using 
Power Doppler ultrasonography in patients with active 
psoriatic arthritis 
Document type: 
Amended Clinical Trial Protocol 
EUDRACT number: 
2015-002394-38 
Version number: 
v03 (Clean) 
Development phase: 
Phase IIIb 
Document status: 
Final 
Release date: 
27-Nov-2018 
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed  
without the consent of Novartis 
Template version 02-Dec-2013 


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Table of contents 
Table of contents ............................................................................................................. 2 
List of tables ................................................................................................................... 5 
List of figures .................................................................................................................. 6 
List of abbreviations ........................................................................................................ 7 
Glossary of terms .......................................................................................................... 10 
Amendment 1 ................................................................................................................ 11 
Amendment 2 ................................................................................................................ 13 
Amendment 3 ................................................................................................................ 15 
Protocol summary ......................................................................................................... 20 
1 
Introduction .................................................................................................................. 27 
1.1 
Background ....................................................................................................... 27 
1.1.1 
Overview of psoriatic arthritis ............................................................ 27 
1.1.2 
Treatment of psoriatic arthritis ........................................................... 27 
1.1.3 
Power Doppler ultrasonography for monitoring treatment response 
in psoriatic arthritis ............................................................................ 28 
1.2 
Purpose .............................................................................................................. 30 
2 
Study objectives ............................................................................................................ 30 
2.1 
Primary objective ............................................................................................... 30 
2.2 
Secondary objectives ......................................................................................... 30 
2.2.1 
Key secondary objectives ................................................................... 30 
2.2.2 
Other secondary objectives ................................................................ 30 
2.3 
Exploratory objectives ....................................................................................... 31 
2.3.1 
Sub-study objectives .......................................................................... 31 
3 
Investigational plan ....................................................................................................... 32 
3.1 
Study design ...................................................................................................... 32 
3.2 
Rationale of study design ................................................................................... 37 
3.3 
Rationale of dose/regimen, route of administration and duration of treatment .... 37 
3.4 
Rationale for choice of comparator .................................................................... 39 
3.5 
Purpose and timing of interim analyses/design adaptations ................................ 39 
3.6 
Risks and benefits .............................................................................................. 39 
4 
Population ..................................................................................................................... 41 
4.1 
Inclusion criteria ................................................................................................ 41 
4.2 
Exclusion criteria ............................................................................................... 42 
5 
Treatment ...................................................................................................................... 44 
5.1 
Protocol requested treatment .............................................................................. 44 
5.1.1 
Investigational treatment .................................................................... 44 


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5.1.2 
Additional study treatment ................................................................. 45 
5.2 
Treatment arms .................................................................................................. 47 
5.2.1 
Group 1: secukinumab double-blind followed by secukinumab 
open-label from Week 12 ................................................................... 47 
5.2.2 
Group 2: placebo followed by secukinumab from Week 12 ................ 48 
5.3 
Treatment assignment, randomization ................................................................ 48 
5.4 
Treatment blinding ............................................................................................. 49 
5.5 
Treating the patient ............................................................................................ 50 
5.5.1 
Patient numbering .............................................................................. 50 
5.5.2 
Dispensing the investigational treatment ............................................ 51 
5.5.3 
Handling of study treatment ............................................................... 51 
5.5.4 
Instructions for prescribing and taking study treatment ...................... 52 
5.5.5 
Permitted dose adjustments and interruptions of study treatment ........ 54 
5.5.6 
Rescue medication ............................................................................. 54 
5.5.7 
Concomitant treatment ....................................................................... 54 
5.5.8 
Prohibited Treatment ......................................................................... 55 
5.5.9 
Discontinuation of study treatment ..................................................... 56 
5.5.10 
Withdrawal of informed consent ........................................................ 57 
5.5.11 
Loss to follow-up ............................................................................... 58 
5.5.12 
Emergency breaking of assigned treatment code ................................ 58 
5.5.13 
Study completion and post-study treatment ........................................ 58 
5.5.14 
Early study termination ...................................................................... 59 
5.5.15 
End of study ....................................................................................... 59 
6 
Visit schedule and assessments...................................................................................... 60 
6.1 
Information to be collected on screening failures ............................................... 66 
6.2 
Patient demographics/other baseline characteristics ........................................... 66 
6.3 
Treatment exposure and compliance .................................................................. 66 
6.4 
Efficacy ............................................................................................................. 66 
6.4.1 
Power Doppler Ultrasonography ........................................................ 67 
6.4.2 
American College of Rheumatology response .................................... 69 
6.4.3 
Minimal disease activity .................................................................... 70 
6.4.4 
Spondyloarthritis research consortium of Canada – enthesitis index ... 70 
6.4.5 
Psoriasis area and severity index ........................................................ 71 
6.4.6 
Appropriateness of efficacy assessments ............................................ 73 
6.5 
Safety ................................................................................................................ 73 
6.5.1 
Physical examination ......................................................................... 74 
6.5.2 
Vital signs .......................................................................................... 74 


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6.5.3 
Height and weight .............................................................................. 74 
6.5.4 
QuantiFERON TB-Gold test or PPD skin test .................................... 74 
6.5.5 
Laboratory evaluations ....................................................................... 75 
6.5.6 
Tolerability of secukinumab ............................................................... 76 
6.5.7 
Additional parameters ........................................................................ 76 
6.5.8 
Immunogenicity ................................................................................. 76 
6.5.9 
Appropriateness of safety measurements ............................................ 77 
6.6 
Other assessments .............................................................................................. 77 
6.6.1 
Resource utilization ........................................................................... 77 
6.6.2 
Pharmacokinetics ............................................................................... 77 
6.6.3 
Other biomarkers ............................................................................... 78 
7 
Safety monitoring .......................................................................................................... 78 
7.1 
Adverse events................................................................................................... 78 
7.2 
Serious adverse events ....................................................................................... 79 
7.2.1 
Definition of SAE .............................................................................. 79 
7.2.2 
SAE reporting .................................................................................... 80 
7.3 
Liver safety monitoring ...................................................................................... 82 
7.4 
Renal safety monitoring ..................................................................................... 83 
7.5 
Reporting of study treatment errors including misuse/abuse ............................... 83 
7.6 
Pregnancy reporting ........................................................................................... 84 
8 
Data review and database management ......................................................................... 84 
8.1 
Site monitoring .................................................................................................. 84 
8.2 
Data collection ................................................................................................... 85 
8.3 
Database management and quality control ......................................................... 85 
8.4 
Scientific Committee ......................................................................................... 86 
8.5 
Data Monitoring Committee .............................................................................. 86 
9 
Data analysis ................................................................................................................. 86 
9.1 
Analysis sets ...................................................................................................... 87 
9.2 
Patient demographics and other baseline characteristics ..................................... 87 
9.3 
Treatments ......................................................................................................... 88 
9.4 
Analysis of the primary variable ........................................................................ 88 
9.4.1 
Variable ............................................................................................. 88 
9.4.2 
Statistical model, hypothesis, and method of analysis ......................... 88 
9.4.3 
Handling of missing values/censoring/discontinuations ...................... 89 
9.4.4 
Supportive analyses ........................................................................... 89 
9.5 
Analysis of secondary variables ......................................................................... 89 
9.5.1 
Key secondary efficacy variables ....................................................... 89 


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9.5.2 
Other secondary efficacy variables ..................................................... 91 
9.5.3 
Exploratory efficacy variables ............................................................ 91 
9.5.4 
Substudy ............................................................................................ 92 
9.5.5 
Safety variables .................................................................................. 93 
9.5.6 
Resource utilization ........................................................................... 94 
9.5.7 
Pharmacokinetics ............................................................................... 94 
9.5.8 
Pharmacogenetics/pharmacogenomics ............................................... 94 
9.5.9 
Biomarkers ........................................................................................ 95 
9.5.10 
PK/PD ............................................................................................... 95 
9.6 
Interim analyses ................................................................................................. 95 
9.7 
Sample size calculation ...................................................................................... 95 
10 Ethical considerations ................................................................................................... 97 
10.1 
Regulatory and ethical compliance ..................................................................... 97 
10.2 
Informed consent procedures ............................................................................. 97 
10.3 
Responsibilities of the investigator and IRB/IEC ............................................... 98 
10.4 
Publication of study protocol and results ............................................................ 98 
11 Protocol adherence ........................................................................................................ 98 
11.1 
Protocol Amendments ........................................................................................ 98 
12 References .................................................................................................................... 99 
13 Appendices ................................................................................................................. 103 
13.1 
Appendix 1: Clinically notable laboratory values ............................................. 103 
13.2 
Appendix 2: Liver event and laboratory trigger definitions ............................... 103 
13.3 
Appendix 3: The classification criteria for psoriatic arthritis (CASPAR) .......... 106 
13.4 
Appendix 4: American College of Rheumatology measures and criteria of 
response ........................................................................................................... 106 
13.5 
Appendix 5: Joint assessments ......................................................................... 108 
13.6 
Appendix 6 OMERACT-EULAR Global PDUS OMERACT out of 48 joints .. 108 
13.7 
Appendix 7: OMERACT score of enthesitis..................................................... 110 
 
 111 
13.9 
Appendix 9: PDUS equipment ......................................................................... 113 
13.10 Appendix 10: Health assessment questionnaire ................................................ 113 
13.11 Appendix 11: Standard reference table for the LDI .......................................... 115 
 
List of tables 
Table 5-1 
Corticosteroids conversion table for the equivalence of 1 mg of 
cortisone ............................................................................................ 46 
Table 5-2 
Prohibited treatment ........................................................................... 55 


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Table 6-1 
Assessment schedule .......................................................................... 61 
Table 6-2 
Overview of study drug administration .............................................. 65 
Table 6-3 
Entheses sites comprising the total spondyloarthritis research 
consortium of Canada enthesitis index ............................................... 71 
Table 6-4 
Psoriasis area and severity index scoring system ................................ 72 
Table 6-5 
Immunogenicity sample log ............................................................... 76 
Table 6-6 
Pharmacokinetic sample log ............................................................... 77 
Table 7-1 
Treatment error types ......................................................................... 84 
Table 13-1 
Clinically notable laboratory values ................................................. 103 
Table 13-2 
Liver event and laboratory trigger definitions ................................... 103 
Table 13-3 
Follow-up requirements for liver events and laboratory triggers ....... 104 
Table 13-4 
Ultrasound scoring system ............................................................... 109 
Table 13-5 
Severity grade of enthesitis .............................................................. 111 
 
 
 112 
 
 112 
 
 112 
Table 13-9 
PDUS equipment recommendations ................................................. 113 
 
List of figures 
Figure 3-1 
Study design ...................................................................................... 36 
Figure 9-1 
Testing strategy.................................................................................. 90 
 


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List of abbreviations 
ACR 
 
American College of Rheumatology 
AE 
 
Adverse Event 
ALT 
 
Alanine Aminotransferase 
ANCOVA 
 
Analysis of Covariance 
anti-CCP 
 
Anti Cyclic Citrullinated Peptide 
AS 
 
Ankylosing Spondylitis 
AST 
 
Aspartate Aminotransferase 
BSA 
 
Body Surface Area 
β-hCG 
 
Beta Human Chorionic Gonadotropin 
CASPAR 
 
Classification Criteria for Psoriatic Arthritis 
CHMP 
 
Committee for Medicinal Products for Human Use 
CRF 
 
Case Report Form  
COX-1 
 
Cyclo-oxygenase-1 
COX-2 
 
Cyclo-oxygenase-2 
CPO 
 
Country Pharma Organization 
CRO 
 
Contract Research Organization 
CRP 
 
C-Reactive Protein 
DAR 
 
Dose Administration Record 
DOH 
 
Declaration of Helsinki 
DMARD 
 
Disease Modifying Anti-Rheumatic Drug 
DS&E 
 
Drug Safety & Epidemiology 
DSUR 
 
Developmental Safety Update Report 
eCRF 
 
Electronic Case Report Form  
EEA 
 
European Economic Area 
EMEA 
 
European Medicines Agency 
EULAR 
 
European League Against Rheumatism 
GCP 
 
Good Clinical Practice 
GDPR 
 
General Data Protection Regulation 
GLOESS 
 
Global OMERACT-EULAR Synovitis Score 
GRAPPA 
 
Group for Research and Assessment of Psoriasis and Psoriatic Arthritis  
HAQ-DI© 
 
Health Assessment Questionnaire-Disability Index 
HCG 
 
Human Chorionic Gonadotropin 
hsCRP 
 
High Sensitivity C-Reactive Protein 


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IB 
 
Investigator’s Brochure 
ICH 
 
International Conference on Harmonization  
IEC 
 
Independent Ethics Committee 
IL 
 
Interleukin 
IL-17 
 
Interleukin 17 
IR 
 
Inadequate Response 
IRB 
 
Institutional Review Board 
IRT 
 
Interactive Response Technology 
JE 
 
Joint Effusion 
MAR 
 
Missing at Random 
MCP 
 
Metacarpophalangeal 
MDA 
 
Minimal Disease Activity 
METc 
 
Medical Ethics Committee 
MHLW 
 
Ministry of Health, Labor and Welfare 
MedDRA 
 
Medical Dictionary for Regulatory Activities  
MMRM 
 
Mixed-Effect Model Repeated Measures Model 
MRI 
 
Magnetic Resonance Imaging 
MTP 
 
Metatarsophalangeal 
MTX 
 
Methotrexate 
OC/RDC 
 
Oracle Clinical/Remote Data Capture 
OMERACT 
 
Outcome Measures in Rheumatology 
PASI 
 
Psoriasis Area and Severity Index 
PCS 
 
Physical Component Summary 
PDUS 
 
Power Doppler Ultrasonography 
PFS 
 
Pre-Filled Syringes 
PGA 
 
Physician’s Global Assessment 
PIP 
 
Proximal Interphalangeal 
PPD 
 
Purified Protein Derivative 
PsA 
 
Psoriatic Arthritis 
PUVA 
 
Psoralen and Ultraviolet A 
RA 
 
Rheumatoid Arthritis 
RMP 
 
Risk Management Plan 
SAE 
 
Serious Adverse Event 
s.c. 
 
Subcutaneous 


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SF36 
 
Short Form Health Survey  
SH 
 
Synovial Hyperplasia  
SIB 
 
Suicidal Ideation and Behavior 
SJC 
 
Swollen Joint Count 
SpA 
 
Spondyloarthritides 
SPARCC  
 
Spondyloarthritis Research Consortium of Canada 
SSR 
 
Sample size re-estimation 
TJC 
 
Tender Joint Count 
TNF 
 
Tumor Necrosis Factor  
TNFα 
 
Tumor Necrosis Factor Alpha 
US 
 
Ultrasound 
UVA 
 
Ultraviolet A 
UVB 
 
Ultraviolet B 
VAS 
 
Visual Analog Scale 
WMA 
 
World Medical Association 


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Glossary of terms 
Assessment 
A procedure used to generate data required by the study. 
Control drug 
Any drug (an active drug or an inactive drug, such as a placebo) which is used 
as a comparator to the drug being tested in the study. 
DMARD 
Disease modifying anti-rheumatic drug; in this study this term refers only to non-
biologics. 
Enrollment 
Point/time of patient entry into the study at which informed consent must be 
obtained (i.e. prior to starting any of the procedures described in the protocol). 
Medication number 
A unique identifier on the label of each study drug package in studies that 
dispense medication using an interactive response technology (IRT) system. 
Mis-randomization 
A patient who is randomized to a treatment group, but did not receive any study 
treatment. 
Clinical non-
responder 
A patient with < 20% improvement from Baseline in either tender joint count 
(TJC) or swollen joint count (SJC). 
Period 
The planned stage of the patient’s participation in the study. Each period serves 
a purpose in the study as a whole. In this study, there is a Screening period for 
determination of patient eligibility, Period 1, which is a 12-week double-blind 
placebo-controlled period; Period 2, which is 12-week open-label maintenance 
period and Period 3, which is 6-month open label extension period.  
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. 
Protocol 
A written account of all the procedures to be followed in a trial, which describes 
all the administrative, documentation, analytical and clinical processes used in 
the trial. 
Randomization 
number 
A unique identifier assigned to each randomized patient, corresponding to a 
specific treatment arm assignment. 
Re-screening 
A patient who qualified for all or most eligibility criteria but could not be 
randomized within the Screening period can be considered for re-screening only
once. 
Rescue medication 
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. 
Clinical responder 
A patient with ≥ 20% improvement from Baseline in both TJC and SJC. 
Study drug/treatment Any single drug or combination of drugs administered to the patient as part of 
the required study procedures; includes investigational drug(s), active drug run-
ins or background therapy. 
Study treatment 
discontinuation 
Point/time when patient permanently stops taking study treatment for any 
reason; may or may not also be the point/time of premature patient withdrawal. 
Patient number 
A number assigned to each patient who enrolls into the study. 
Variable 
A measured value or assessed response that is determined in specific 
assessments and used in data analysis to evaluate the drug being tested in the 
study. 
Withdrawal of study 
consent 
Withdrawal of consent from the study occurs only when a 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 No. CAIN457F2354 
Amendment 1 
Amendment rationale 
This protocol amendment is issued for the following reasons: 
 For those countries where it is required, add hepatitis B, hepatitis C and human 
immunodeficiency virus (HIV) serology testing during the Screening Period to the 
assessment schedule (Table 6-1). These tests were already outlined in Exclusion Criterion 
No. 21 and results of these tests determine eligibility for the study. Thus the addition to 
the assessment schedule in this amendment is made in order to clarify and remove 
inconsistencies in the protocol. 
 To add collection of Spondyloarthritis Research Consortium of Canada (SPARCC) at the 
Screening Visit to the assessment schedule as it was previously omitted in error for this 
visit (Table 6-1). This test was already outlined in Inclusion Criterion No.5 and results of 
this test determine eligibility for the study. Thus the addition to the assessment schedule in 
this amendment is made in order to clarify and remove inconsistencies in the protocol. 
 To remove one reference to a placebo injection in Treatment Period 2 that was included in 
error. No placebo injection is administered in Treatment Period 2 as it is open label. 
 To document that the total time required for each PDUS assessment (either in the main 
study or substudy) will be recorded in the eCRF and to add 2 exploratory endpoints (one 
for the main study and one for the sub-study) regarding the time spent on PDUS 
assessments.  
 To document that the name and type of PDUS machine used will be recorded in the eCRF. 
 To updated background information with respect to the most recent Developmental Safety 
Update Report (DSUR). 
Changes to the protocol 
Changes to specific sections of the protocol are shown in the track changes version of the 
protocol using strike through red font for deletions and red underlined for insertions. 
 Section 3.6: Revised statement based on updated DSUR as follows: 
From: “As of 12-Jul-2014 (safety cut-off for latest IB and Developmental Safety Update 
Report (DSUR), approximately 10 900 healthy subjects and patients have been enrolled 
into the secukinumab clinical program and in trials where secukinumab has been used as 
a protocol-specified treatment, of whom approximately 8 600 healthy subjects and 
patients have received at least one dose of secukinumab in Novartis-sponsored clinical 
trials.”  
To: “As of 25-Jun-2015 (safety cut-off for latest Developmental Safety Update Report 
(DSUR), approximately 12000 subjects (which included patients and a small number of 
healthy volunteers) have been enrolled into the secukinumab clinical program (including 
trials where secukinumab has been used as a protocol specified treatment), of which 
approximately 9600 subjects (comprising of patients and healthy volunteers) have 
received at least one dose of secukinumab.”  
 Section 5.2.2: Deletion of the wording “and placebo (1.0 mL PFS)” for Period 2. 


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 Section 6, Table 6-1: Addition of row with wording “hepatitis B, C and HIV serology 
testing (only in countries where required)**” at the Screening Visit, along with footnote 
“** Hepatitis B and/or hepatitis C and/or HIV serology testing to be performed during 
screening period only if required as per local medical practice or local regulations prior 
to initiation of therapy. These assessments will be documented in source records only and 
will not be entered into the eCRF.”  
 Section 6, Table 6-1: Addition of SPARCC assessment at the Screening Visit.  
 Section 6.2: Addition of the wording “The SPARCC will be assessed at both the Screening 
and Baseline Visit.” 
 Section 6.4.1: Addition of the wording “The total time required for each PDUS 
assessment in the study will be recorded in the eCRF” and 
“The name and type of PDUS machine used will also be recorded in the eCRF. PDUS 
equipment recommendations are described in Appendix 9.”  
 Section 6.4.1.1: Addition of the wording “the total time required for each PDUS 
assessment in the sub-study will be recorded in the eCRF,” and 
“The name and type of PDUS machine used will also be recorded in the eCRF. PDUS 
equipment recommendations are described in Appendix 9.”  
 Section 7.4: Revised statement based on updated DSUR as follows: 
From: “There has been no safety signal for nephrotoxicity with secukinumab to date in 
over 8 600 patients and healthy subjects exposed (safety cut-off date of 12-Jul-2014, 
DSUR No. 004), and from a mechanism of action standpoint there is no known effect of 
blocking IL-17A on the kidney.” 
To: “There has been no safety signal for nephrotoxicity with secukinumab to date in over 
9600 patients and healthy subjects exposed (safety cut-off date of 25-Jun-2015, DSUR 
No. 005), and from a mechanism of action standpoint there is no known effect of blocking 
IL-17A on the kidney.” 
 Section 9.4.2: Addition of the words “center, machine type” to the following statement: 
Between-treatment differences in the change in GLOESS will be evaluated using a 
mixed-effect model repeated measures model (MMRM) with treatment regimen, center, 
machine type and analysis visit as factors and weight and baseline GLOESS as continuous 
covariates. 
 Section 9.5.2: Addition of the words “center, machine type” to the following statement: 
The between treatment differences will be compared by means of a MMRM with 
treatment regimen, center, machine type and analysis visit as factors and baseline weight 
and baseline score as continuous covariates. 
 Section 9.5.3: Addition of the exploratory endpoint: “overall time spent on PDUS 
assessments of joint inflammation and enthesitis for the main study and breakdown of 
time spent on these assessments by visit.” 
 
 
 
  
At the time this amendment was written no patient had been enrolled in the study. 


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Amendment 2 
Amendment rationale 
Study CAIN457F2354 is a phase IIIb, 52-week, multicenter, international study to assess the 
time course of response to secukinumab on joint inflammation using Power Doppler 
ultrasonography in patients with active psoriatic arthritis (PsA). The study was started on 
22-Aug-2016 (First Patient First Visit). As of 23-Feb-2017, 12 of 19 patients screened at 
17 active sites were assessed as screen failures mainly because they did not meet inclusion 
criterion 4 related to PDUS entry criteria i.e. they did not present with a total synovitis score 
≥ 2 and enough inflammation on PD signal ≥ 2 for at least 2 affected joints. Of the remaining 
7 patients being screened, 3 were still in screening and 4 patients have been enrolled and 
randomized into the study as of 23-Feb-2017. Some active sites from across EU have also 
suggested that a total of 20 study visits was too demanding for patients given most of them 
continued to work.  
The rationale for the amendment is 
1. To increase the study feasibility and to ease the study visit burden on patients without 
compromising the primary and secondary objectives of the study until Week 12 based on 
the number of screen failures reported to date and feedback received from active centers 
on the number of study visits. 
 To amend inclusion criterion no. 4, an ultrasound entry criterion that is considered too 
restrictive as it has resulted in the most screen failures, to allow inclusion of patients 
with a total synovitis score ≥ 2 and inflammation related to PD signal ≥ 2 for at least 
1 affected joint as observed via PDUS of 48 joints, OR with an inflammation related 
to PD signal ≥ 1 for at least 2 affected joints as observed via PDUS of 48 joints. 
 To remove the study visits and associated study assessments at Week 28, 32, 40, 44 
and 48 from the open-label Extension Period and to introduce home administration of 
study drug at these time points; to remove the clinical efficacy assessments (including 
PDUS assessments) from the double-blind Week 3 visit; and to remove the PDUS 
assessment from the Week 56 follow-up visit. The Extension Period is optional 
according to Investigator’s judgment and patient consent and exploratory study 
objectives only apply to this period. The removal of study visits during the Extension 
Period will not compromise patient safety given the benefit/ risk of secukinumab has 
already been assessed and secukinumab is registered in all participating countries. 
The removal of the Week 3 efficacy assessments is to decrease the burden of weekly 
assessments for patients during the initial period of the study without compromising 
the primary or secondary objectives of the study. Similarly the removal of the 
follow-up PDUS assessments the Week 56 visit is to decrease the burden of 
assessments for patients without compromising the study objectives.  
2. Clarify different aspects of the protocol following the review of different Ethics 
Committees (ECs): 
 Clarification in the patient population that subjects must have had an inadequate 
response to non-biologic DMARDs to be consistent with study rationale and primary 
objective of the study. 


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 To amend the use of rescue medication so it is less restrictive throughout the study 
and notably for the patients randomized to placebo during the first 12 weeks to make 
it more ethical given the risk of potential flare and existence of alternative therapies. 
 To update the following aspects of the protocol: 
 To reference the Medical Research Involving Human Subjects Act in the 
Netherlands (known as the WMO in Dutch) for the Netherlands. 
 To describe specific reporting of SAEs, SUSARs and safety reports to the 
Medical Ethics Committee (METc in Dutch) for the Netherlands. 
 To describe the reporting of the end date of the study/early termination of the 
study to METc for the Netherlands.  
 To reference the latest version of the Declaration of Helsinki.  
 To correct the conversion table for corticosteroids and update source references.  
 To add clinical and ultrasound assessment of the contralateral digit at the same 
time points to allow a descriptive comparison. 
3. To update the risk/benefit section of the protocol based on latest Developmental Safety 
Update Report (DSUR) for secukinumab (covering reporting period 26-Jun-2015 to 
25-Jun-2016).  
4. To include new safety sub-section section on the reporting of study treatment errors, 
including misuse/abuse, and to clarify in the AE reporting section that all reports of 
intentional misuse and abuse of the product are also considered an AE irrespective if a 
clinical event. 
5. To remove all references to Japan as this study will not be conducted in Japan.  
6. To add that a visit window of ± 3 days must be observed for visits with PDUS assessments 
scheduled from Baseline through to the end of study, 
7. To amend the Screening period from “2 to 4 weeks” to “1 to 4 weeks”. 
8. To correct typo in Appendix 6 from “22 paired joints” to “24 paired joints”. 
Changes in the protocol 
Changes to specific sections of the protocol, and newly added sections, are shown in the 
tracked changes version of the protocol using strike through red font for deletions and red 
underlined for insertions. 
A summary of the changes that have been made to the protocol is provided below. 
The wording of various sub-sections to “Protocol Summary”, “Introduction (Section 1.1.2)”, 
“Sub-study objectives (Section 2.3.1)”, “Study design (Section 3.1)”, “Rationale of study 
design” (Section 3.2)”, “Rationale of dose/regimen, route of administration and duration of 
treatment (Section 3.3)”, “Rationale for choice of comparator (Section 3.4)”, “Risks and 
benefits (Section 3.6)”, “Inclusion criteria (Section 4.1)”, “Investigational treatment 
(Section 5.1.1)”, “Systemic corticosteroids, (Table 5-1, Section 5.1.2.3)”, “NSAIDs (including 
COX-1 or COX-2 inhibitors), low strength opioids and acetaminophen/paracetamol 
(Section 5.1.2.4)”, “Treatment Arms (Section 5.2)”, “Group 1: secukinumab double-blind 
followed by secukinumab open-label from Week 12 (Section 5.2.1)”, “Group 2: placebo 
followed by secukinumab from Week 12 (Section 5.2.2),” “Treatment assignment, 
randomization (Section 5.3)”, “Dispensing the investigational treatment (Section 5.5.2)”, 


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“Handling of investigational treatment (Section 5.5.3.1)” “Instructions for prescribing and 
taking study treatment (Section 5.5.4)”, “Rescue medication (Section 5.5.6)”, “Concomitant 
medications (Section 5.5.7)”, “Early study termination (Section 5.5.14)”, “End of study 
(Section 5.5.15)”, “Visit schedule and assessments (Section 6, Table 6-1 and Table 6-2)”, 
“Treatment exposure and compliance (Section 6.3)”, 
 
 “Adverse events (Section 7.1)”, “SAEs 
(Section 7.2)”, “Reporting of study treatment errors including misuse/abuse (Section 7.5)”, 
“Safety reporting specific to the Netherlands (Section 7.2.2.1)”, “Site monitoring 
(Section 8.1)”, 
“Substudy 
(Section 9.5.4)”, 
“Regulatory 
and 
ethical 
compliance 
(Section 10.1)”, “Informed consent procedures (Section 10.2)”, “References (Section 12)”, 
“Appendix 6 (Section 13.6)”, and “Appendix 8 (Section 13.8)” have been amended to reflect 
the rationale given above. In addition, “an overview of study drug administration” (Table 6-2) 
has been added to Section 6 to display the timing of home study drug administrations relative 
to study center drug administrations.  
Review requirements by Independent Ethics Committee and Health Authorities 
A copy of this amended protocol will be sent to the Independent Ethics Committee (IECs) and 
Health Authorities. 
The changes described in this amended protocol require IEC approval prior to 
implementation. 
The changes herein affect the Informed Consent. Sites are required to update and submit for 
approval a revised Informed Consent that takes into account the changes described in this 
protocol amendment. 
Amendment 3 
Amendment rationale 
As of 05-Oct-2018, the study recruitment is still ongoing with a total of 96 enrolled patients 
from 33 active sites in 15 countries. The recruitment in the trial has been longer than expected 
with a screen failure rate of 35% since the implementation of substantial Amendment 2. 
Screen failures are mainly due to ultrasound entry criteria not being met, elevated hepatic 
liver enzymes, or RF+, criteria for disease activity not being met, and withdrawal of informed 
consent. 
The rationale for the amendment is as follows: 
1. To update the sample size calculation in the trial keeping in mind the difficulties of 
recruitment. 
The primary objective of the study is to demonstrate a difference between secukinumab 
and placebo in terms of response to joint inflammation over the time course of 12 weeks 
as measured by Global OMERACT-EULAR Synovitis Score (GLOESS) using Power 
Doppler Ultrasound (PDUS) as a very sensitive imaging technology in PsA patients with 
an inadequate response to non-biologic disease-modifying anti-rheumatic drugs 
(DMARDs). Secukinumab has already proven to be consistently superior to placebo in 
terms of clinical benefit across the FUTURE 1-5 program, so there is no expectation of 
inferiority of secukinumab versus placebo in ultrasound outcomes. The efficacy results 


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will be tested with a 1-sided strategy to maximize sensitivity in the available sample and 
to overcome recruitment difficulties. 
The initial sample size calculation for this trial was extrapolated from an ultrasound study 
assessed to evaluate the early response of abatacept on synovitis in patients with 
rheumatoid arthritis (D’Agostino et al 2016) given the lack of a previous ultrasound PsA 
trial with biologics. A blinded sample size re-estimation was planned in the protocol once 
the first 60 patients had completed Week 12 and has been supplemented with data from 
the first 72 patients who reached their Week 12 visit to provide the most accurate 
estimation. The sample size was re-estimated using the estimated placebo effect of 
roughly 50% of secukinumab based on data from the FUTURE-2 study (CAIN457F2312) 
as in the original sample size calculation and adapting the original sample size calculation 
to be 1-sided with the power relaxed to 80%. The sample size will be adjusted to a new 
target of 164 patients in total (82 patients per arm). This is mid-way point of the range 
plus a 5% adjustment based on the observed drop-out rate of patients prior to Week 12 
observed at the time of this calculation. The reduction of sample size from 218 to 164 
patients will help achieve completion of the last patient first visit by the end of August 
2019.   
2. To clarify different aspects of the protocol following comments from the Health 
Authorities (HA), Ethics Committees and investigators. 
a. To clarify the dose of non-steroidal anti-inflammatory drugs (NSAIDs) as rescue 
therapy prior to assessments in the trial until Week 24. The requirement for patients to 
return to their previous NSAIDs’ dose following a transient increase in dose as rescue 
therapy 48 hours prior to study assessments was considered unethical by investigators 
and not accepted by patients who were in pain, and is therefore being removed from 
the protocol. 
b. To update the entry criteria for the long-term extension period. The entry criteria for 
the long-term extension phase depend on investigator’s judgment on patient clinical 
benefit and patient’s wish given the study drug is registered and commercially 
available. Patients must sign a separate informed consent form (ICF) to confirm their 
agreement to participate in the extension period. 
c. To simplify safety requirements, the Adjudication Committee section is being 
removed as no such committee is required for this study at the current late stage of 
development. 
d. To clarify the conditions of quality control assessment of the GLOESS scoring 
performed at the start of the study (for the first patient from each center) and at the 
end of the study (once the last patient last visit has been completed) in Section 6.4.1 
of the protocol in addition to Appendix 6 to be consistent throughout the protocol. 
e. To protect patient data privacy according to latest recommendations from the EEA 
General Data Protection Regulation (GDPR) requirements, the wording on patient 
withdrawal of informed consent will be amended to reflect the EEA GDPR 
requirements. 
f. To add rationale for recording of total time for each PDUS assessment of joint 
inflammation and enthesitis based on a site audit request. The rationale is to evaluate 
the variability on time spent by ultrasonographers to assess multiple joints and 
entheses across the sites. 


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3. To clarify different aspects of the protocol following clinical trial team review: 
a. To clarify that the 20% improvement in tender joint count (TJC) and swollen joint 
count (SJC) at Week 24 is relative to Baseline. 
b. To correct figure footnote on use of methotrexate (MTX)/other DMARDs. 
c. To update risk/benefit section based on latest Developmental Safety Update Report 
(DSUR).  
d. To update renal safety monitoring section based on latest DSUR.  
e. To amend Exclusion Criterion no. 14 to clarify that uncontrolled diabetes is as per 
investigator’s judgment.  
f. To amend wording on NSAID row in table in line with Inclusion Criterion No. 8.  
g. To remove statement on documentation of whether or not a caregiver administered the 
study treatment in the eCRF as this data is not being collected in this study. 
h. To clarify the timing of the interim and final statistical analyses.  
i. To correct the definition of End of Study.  
j. To include missing sub-section heading on pregnancy and fertility.  
k. To correct details on Interactive Response Technology (IRT) system. 
l. To update list of references.  
m. To define IR on first use and abbreviate throughout the document.  
n. Remove list of authors from title page per latest protocol template.  
Changes in the protocol 
Changes to specific sections of the protocol, and newly added sections, are shown in the 
tracked changes version of the protocol using strike through red font for deletions and red 
underlined for insertions. 
A summary of the changes that have been made to the protocol is provided below: 
 List of abbreviations: Updated.  
 Glossary of terms: Added definition of personal data and withdrawal of consent. 
 Protocol Summary (exclusion criteria): Amended Exclusion Criterion No. 14 to clarify 
that uncontrolled diabetes is as per the investigator’s judgment.  
 Section 1.1.3 (power doppler ultrasonography for monitoring treatment response): Added 
cross reference to Section 6.4.1.  
 Section 3.1 (study design), Section 3.4 (rationale for choice of comparator), 
Section 5.1.2.4 (NSAIDs [including COX-1 or COX-2 inhibitors], low strength opioids 
and acetaminophen/paracetamol) Section 5.5.6 (rescue medication), Section 5.5.7 
(concomitant treatment), and Section 5.5.8 (prohibited treatment): Deleted wording on 
requirement for patients to return to their previous NSAIDs’ dose following a transient 
increase in dose as rescue therapy 48 hours prior to study assessments.  


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 Section 3.1 (study design), Section 3.2 (rationale of study design): Amended wording on 
the long-term extension phase given the study drug is commercially available and 
registered.  
 Section 3.1 (study design), Section 3.2 (rationale of study design), Section 6 (visit 
schedule and assessments): Added wording to clarify that the extension period is from 
Week 24 to Week 52 and follow-up period from Week 52 to Week 64. Also added 
footnote in Table 6-1 to clarify that patients would not be treated at Week 24 unless they 
signed the ICF for the extension period of the study.  
 Section 3.1 (study design), Section 5.2.1 (Group 1: secukinumab double-blind followed by 
secukinumab open-label from Week 12) and Section 5.2.2 (Group 2: placebo followed by 
secukinumab from Week 12): Amended wording to clarify that the 20% improvement in 
TJC and SJC at Week 24 is relative to Baseline.  
 Section 3.1 (study design): Corrected footnote on use of MTX/other DMARDs in 
Figure 3-1.  
 Section 3.1 (study design), Section 3.5 (interim analyses/design adaptations), Section 5.4 
(treatment blinding), Section 9.6 (interim analyses): Amended statements to clarify that 
the timing of the final database lock and final statistical analysis.  
 Section 3.5 (interim analyses/design adaptations) and Section 9.6 (interim analyses): 
Removed stop-go decision rules.  
 Section 3.6 (risks and benefits): Updated section based on the latest Developmental Safety 
Update Report for secukinumab.  
 Section 4 (population): Reduced planned number of randomized patients from 218 
patients (109 per arm) to 164 patients (82 per arm).  
 Section 4.2 (exclusion criteria): Amended exclusion criterion no. 14 to clarify that 
uncontrolled diabetes is as per the investigator’s judgment. 
 Section 5.5.4 (instructions for prescribing and taking study treatment):  Deleted wording 
to clarify that documentation of whether or not a caregiver administered the study 
treatment is not required.  
 Section 5.5.8 (prohibited treatment): Amended wording on NSAID row in Table 5-2 so it 
is aligned with Inclusion Criterion No. 8.   
 Section 5.5.9 (discontinuation of study treatment): Amended wording to clarify the timing 
of end of study and follow-up visit assessments for early withdrawal patients.  
 Section 5.5.10 (withdrawal of informed consent): Amended section on withdrawal of 
informed consent to reflect the EEA GDPR requirements. 
 Section 5.5.15 (end of study): Amended statement to clarify timing of end of study.   
 Section 6.4.1 (power doppler ultrasonography) and Appendix 6 (OMERACT-EULAR 
Global PDUS OMERACT out of 48 joints): Added wording to clarify the requirements for 
quality checks of PDUS assessments. In addition, added rationale for recording of total 
time for each PDUS assessment of joint inflammation and enthesitis.  
 
 
 
  


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 Section 6.5.5.4 (pregnancy and assessments of fertility): Added sub-section heading that 
was missing in error from previous protocol.   
 Section 7.4 (renal safety monitoring): Updated background information on renal safety 
monitoring. 
 Section 8.3 (database management and quality control): Updated details on IRT system.  
 Section 8.6 (adjudication committee) and Section 9.5.5 (safety variables): Deleted 
Section 8.6 and removed statement on adjudication from Section 9.5.5 as no such 
committee is required for this study. 
 Section 9 (data analysis): Amended 2-sided p-values to 1-sided p-values. 
 Section 9.5.1 (key secondary efficacy variables): Amended 2-sided hypothesis analyses to 
1-sided hypothesis analyses. 
 Section 9.6 (interim analyses): Revised details on the blinded sample size re-estimation.  
 Section 9.7 (sample size calculation): Amended the sample size from 218 patients 
(109 per arm) to 164 patients (82 per arm), amended the power of the sample size from 
90% to 80% and amended the statistical test for the primary endpoint from a 2-sided to a 
1-sided test. In addition, amended the statistical test for other endpoints from a 2-sided to a 
1-sided test. Also, removed the wording “treatment difference to placebo of 5.8 will 
remain as originally planned” as the pooled change will now be used to determine the 
difference between the treatment and placebo effect. 
 Section 12: updated list of references. 
Review requirements by Independent Ethics Committee and Health Authorities 
 A copy of this amended protocol will be sent to the Independent Ethics Committee (IECs) 
and Health Authorities. 
 The changes described in this amended protocol require IEC approval prior to 
implementation. 
 The changes herein affect the Informed Consent. Sites are required to update and submit 
for approval a revised Informed Consent that takes into account the changes described in 
this protocol amendment. 


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Protocol summary 
Protocol number 
CAIN457F2354 
Title 
A 52-week, multicenter study to assess the time course of response to 
secukinumab on joint inflammation using Power Doppler ultrasonography 
in patients with active psoriatic arthritis.  
Brief title 
Study of application of Power Doppler ultrasonography (PDUS) to 
measure response to secukinumab treatment in patients with active 
psoriatic arthritis (PsA). 
Sponsor and clinical 
phase 
Novartis, Phase IIIb  
Investigation type 
Drug 
Study type 
Interventional 
Purpose and rationale 
Psoriatic arthritis is an autoimmune-mediated chronic inflammatory 
disease belonging to the spectrum of conditions commonly referred to as 
spondyloarthritides (SpA). Grayscale ultrasound coupled with power 
Doppler (PDUS) has been shown to be a sensitive imaging technology 
for assessing joint and entheseal involvement in PsA; however, there has 
been limited focus on its use for extensive evaluation of these structures 
in randomized controlled trials. The use of PDUS for monitoring 
pathological findings indicative of joint inflammation or enthesitis in 
patients with moderate-to-severe PsA has been demonstrated for 
patients treated with anti-tumor necrosis factor alpha (anti-TNFα) therapy 
in open label studies. This study is designed to leverage the sensitivity of 
ultrasonography available in clinical practice setting to better describe the 
time course of response to secukinumab (150 mg and 300 mg) on joint 
synovitis and enthesitis in PsA patients with an inadequate response (IR) 
to non-biologic DMARDs. PDUS changes in joint synovitis will be 
assessed using the global Outcome Measures in Rheumatology 
(OMERACT)-European League Against Rheumatism (EULAR) synovitis 
score (GLOESS) and changes in joint enthesitis will be assessed using 
the OMERACT enthesitis score.  
Primary objective 
 
To demonstrate that there is a difference between secukinumab and 
placebo in terms of joint synovitis response over 12 weeks as 
measured by the PDUS global OMERACT-EULAR synovitis score 
(GLOESS) of the affected joints (out of 48 joints) in PsA patients with 
an IR to non-biologic DMARDs. 
Secondary objectives 
Key secondary objectives 
 
To demonstrate that the efficacy of secukinumab at Week 12 is 
superior to placebo based on the proportion of patients achieving an 
American College of Rheumatology (ACR) 20 response. 
 
To demonstrate that the efficacy of secukinumab at Week 12 is 
superior to placebo based on the proportion of patients achieving an 
ACR 50 response. 
 
To demonstrate that the clinical response of secukinumab at 
Week 12 is superior to placebo based on the change in 
Spondyloarthritis Research Consortium of Canada (SPARCC) 
enthesitis index from Baseline to Week 12. 
Other secondary objectives 


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 
To evaluate the therapeutic effect of secukinumab versus placebo on 
joint synovitis from Baseline to Week 8 using the GLOESS score out 
of 48 joints. 
 
To evaluate the therapeutic effect of secukinumab versus placebo on 
enthesitis at Week 12 using the OMERACT enthesitis score for each 
affected enthesis. 
 
To evaluate the overall safety, tolerability and immunogenicity of 
secukinumab.  
Exploratory objectives 
 
To evaluate the therapeutic effect on joint synovitis for patients in the 
placebo group once switched to secukinumab from Week 12 to Week 
24 and Week 24 to Week 52, as assessed by the improvement in 
synovitis from Week 12 to 24 and Week 24 to Week 52 using the 
GLOESS score and its components out of 48 joints.  
 
To evaluate the therapeutic effect on joint synovitis in the initial 
secukinumab group as assessed by the improvement in synovitis 
from Baseline to Week 24 and to Week 52 using the GLOESS score 
and its components out of 48 joints. 
 
To evaluate the therapeutic effect on enthesitis for patients in the 
placebo group who switched to secukinumab from Week 12 to Week 
24 and Week 24 to Week 52 using the OMERACT individual 
enthesitis score and its morphologic components.  
 
To evaluate the therapeutic effect on enthesitis for patients in the 
initial secukinumab group from Baseline to Week 24 and from Week 
24 to Week 52 using the OMERACT individual enthesitis score and 
its morphologic components. 
 
To explore the correlation between clinical improvement of each 
enthesitis site as assessed by SPARCC and the improvement in 
enthesitis as assessed by individual PDUS enthesitis scores from 
Baseline to Week 12. 
 
To explore the correlation between the PDUS response versus ACR 
20 response either by an improvement of the total GLOESS score of 
at least 20% from Baseline to 12 weeks or by comparing the clinical 
improvement in the same joints examined to GLOESS score.  
 
To explore the correlation between the PDUS response versus the 
SPARCC score over 12 weeks by comparing the improvement in the 
same entheses examined. 
 
To explore the efficacy of secukinumab at Week 24, during the 
extension period, and other time points for assessments that are not 
part of the primary and secondary objectives as applicable only to: 
 
ACR 20, ACR 50, ACR 70, ACR components, PASI 75, 
PASI 90, dactylitis count, HAQ-DI© response.  
 
Proportion of patients achieving minimal disease activity (MDA) 
at Week 24 and Week 52.  
 
 
 
 
 
 
 
 
 
 
 


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Study design 
This is a 52-week, multicenter, international study consisting of a 1 to 
4-week Screening period, a 12-week, placebo-controlled, double-blind 
treatment period, a 12-week open-label treatment period, and a 6-month 
open-label extension period. 
Population 
The study population will consist of male and female patients aged ≥ 18 
years with PsA as per the classification criteria for PsA (CASPAR),and 
with active PsA for at least 6 months who must have a tender joint count 
(TJC) ≥ 3 out of 78 and swollen joint count (SJC) ≥ 3 out of 76 at 
Baseline and with an IR to non-biologic DMARDs. Patients can be re-
screened only once and ‘no’ re-screening study related procedures 
should be performed prior to written re-consent by the patient. Mis-
randomized patients cannot be re-screened. 
Inclusion criteria 
Patients eligible for inclusion in this study have to fulfill all of the following 
criteria: 
1. Patient must be able to understand and communicate with the 
Investigator and comply with the requirements of the study and must 
provide written, signed and dated informed consent before any study 
assessment is performed.  
2. Male or female patients at least 18 years of age.  
3. Diagnosis of PsA as per CASPAR criteria with active PsA for at least 
6 months and a TJC ≥ 3 of 78 and SJC ≥ 3 of 76 at Baseline.  
4. a) Patients must have a total synovitis PDUS score ≥ 2 and 
inflammation related to PD signal ≥ 2 for at least 1 affected joint (as 
observed via PDUS) of 48 joints at the Screening visit and at the 
Baseline visit (before injection), OR 
b) Patients must have a total synovitis PDUS score ≥ 2 and 
inflammation related to PD signal ≥ 1 for at least 2 affected joints 
(as observed via PDUS) of 48 joints at the Screening visit and at the 
Baseline visit (before injection). 
5. At least 1 clinically-involved enthesitis site at Screening and at the 
Baseline visit (before injection) defined by SPARCC index different 
from 0. 
6. Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) 
negative at Screening.  
7. Patients with PsA who have had an IR to non-biologic DMARDs.  
8. Patients with PsA who are taking NSAIDs should be on a stable dose 
for at least 2 weeks prior to enrollment and remain on a stable dose 
throughout the 24-week study period unless rescue therapy is 
needed. 
9. Patients with PsA who are taking steroids must have received 
steroids at least 3 months prior to the Baseline visit and be on a 


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stable dose of ≤ 10 mg equivalent prednisone for at least 4 weeks 
prior to Baseline visit and remain on a stable dose throughout the 
24-week study period unless tolerance issues are present.  
10. Patients with PsA who are taking MTX or DMARDs must have 
received them at least 3 months prior to Baseline visit and be on a 
stable dose of ≤ 25 mg/week of MTX or stable standard doses of 
other DMARD(s) (according to the Investigator’s judgment) for at 
least 4 weeks prior to the Baseline visit and remain on a stable dose 
throughout the 24-week study period. 
Exclusion criteria 
Patients fulfilling any of the following criteria are not eligible for inclusion 
in this study. No additional exclusions may be applied by the Investigator 
in order to ensure that the study population will be representative of all 
eligible patients. 
1. Chest X-ray or chest MRI with evidence of ongoing infectious or 
malignant process obtained within 3 months prior to Screening and 
evaluated by a qualified physician.  
2. Previous exposure to secukinumab or other biologic drug directly 
targeting interleukin 17 (IL-17) or IL-17 receptor.  
3. Patients taking high-potency opioid analgesics (e.g. methadone, 
hydromorphone, morphine).  
4. Use of any investigational drug and/or devices within 4 weeks before 
randomization or a period of 5 half-lives of the investigational drug, 
whichever is longer. 
5. Any change in the dose of oral corticosteroids in the last 4 weeks 
prior to the Baseline visit or use of i.v. intramuscular or intra-articular 
corticosteroid during the last 4 weeks prior to the enrollment visit.  
6. Patients who have previously been treated with TNFα inhibitors 
(investigational or approved).  
7. History of hypersensitivity to the study drug or its excipients or to 
drugs of similar classes.  
8. Previous treatment with any cell-depleting therapies including but not 
limited to anti-CD20 investigational agents (e.g. CAMPATH, anti-
CD4, anti-CD5, anti-CD3, anti-CD19).  
9. Prohibited psoriasis treatments/medications with topical 
corticosteroids in the last 4 weeks prior to randomization (see 
Section 5.5.8 of main protocol).  
10. Pregnant or nursing (lactating) women, where pregnancy is defined 
as the state of a female after conception and until the termination of 
gestation, confirmed by a positive human chorionic gonadotropin 
(hCG) laboratory test. 
11. Women of child-bearing potential, defined as all women 
physiologically capable of becoming pregnant, unless they are using 
effective methods of contraception during the entire study or longer if 
required by locally approved prescribing information (e.g. 20 weeks in 
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) or tubal ligation at least 6 weeks 
before taking study drug. In case of oophorectomy alone, only 


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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) with spermicidal 
foam/gel/film/cream/vaginal suppository.  
 
Use of oral, injected or implanted hormonal methods of 
contraception or other forms of hormonal contraception that 
have comparable efficacy (failure rate < 1%), for example 
hormone vaginal ring or transdermal hormone contraception. 
 
Placement of an intrauterine device or intrauterine system. 
In case of use of oral contraception, women should have been stable 
on the same pill for a minimum of 3 months before taking study drug. 
Women are considered post-menopausal and not of child bearing 
potential if they have had 12 months of natural (spontaneous) 
amenorrhea with an appropriate clinical profile (e.g. age appropriate, 
history of vasomotor symptoms) or surgical bilateral oophorectomy 
(with or without 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. 
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 
immunocompromise the patient and/or place the patient at 
unacceptable risk for participation in an immunomodulatory therapy.  
14. Significant medical problems or diseases, including but not limited to 
the following: uncontrolled hypertension (≥ 160/95 mmHg), 
congestive heart failure (New York Heart Association status of class 
III or IV), and uncontrolled diabetes (as per Investigator’s judgment). 
15. History of clinically significant liver disease or liver injury as indicated 
by abnormal liver function tests (LFT) such as aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), 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 
laboratory 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. In any case, serum bilirubin should not exceed 
1.6 mg/dL (27 μmol/L). 
16. History of renal trauma, glomerulonephritis, or patients with 1 kidney 
only, or a serum creatinine level exceeding 1.5 mg/dL (132.6 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). 


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18. Active systemic infections during the last 2 weeks (exception: 
common cold) prior to randomization. 
19. History of ongoing, chronic or recurrent infectious disease or 
evidence of tuberculosis infection as defined by either a positive 
purified protein derivative (PPD) skin test (the size of induration will 
be measured after 48-72 hours, and a positive result is defined as an 
induration of ≥ 5 mm or according to local practice/guidelines) or a 
positive QuantiFERON TB-Gold test. 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 tuberculosis. If presence of latent tuberculosis is 
established then treatment according to local country guidelines must 
have been initiated. 
20. Known infection with human immunodeficiency virus, hepatitis B or 
hepatitis C at Screening or randomization. 
21. History of lymphoproliferative disease or any known malignancy or 
history of malignancy of any organ system within the past 5 years 
(except for basal cell carcinoma or actinic keratoses that have been 
treated with no evidence of recurrence in the past 3 months, 
carcinoma in situ of the cervix or non-invasive malignant colon polyps 
that have been removed). 
22. Current severe progressive or uncontrolled disease, which in the 
judgment of the clinical Investigator renders the patient unsuitable for 
the trial. 
23. Inability or unwillingness to undergo repeated venipuncture (e.g. 
because of poor tolerability or lack of access to veins). 
24. Any medical or psychiatric condition which, in the Investigator’s 
opinion, would preclude the participant from adhering to the protocol 
or completing the study per protocol. 
25. Donation or loss of 400 mL or more of blood within 8 weeks before 
randomization. 
26. History or evidence of ongoing alcohol or drug abuse, within the last 
6 months before randomization. 
27. Plans for administration of live vaccines during the study period or 
within 6 weeks preceding randomization. 
Investigational and 
reference therapy 
Investigational treatment secukinumab 150 mg provided in 1 mL prefilled 
syringes (PFSs) or 300 mg provided in (2 × 1.0 mL PFSs of 150 mg 
dose).  
Dosing will be performed based on the severity of skin lesions. Reference 
treatment: secukinumab placebo provided in a 1 mL PFSs.  
Efficacy assessments 
 
OMERACT/EULAR global synovitis score (GLOESS) and its 
components. 
 
OMERACT enthesitis score and its components. 
 
American College of Rheumatology (ACR) 20, 50 and 70 responses. 
 
Swollen joint count (SJC)/tender joint count (TJC). 
 
Patient’s global assessment of disease activity (VAS). 
 
Physician’s global assessment (PGA) of disease activity (VAS). 
 
Patient’s assessment of PsA pain intensity (VAS). 
 
Health assessment questionnaire – disability index (HAQ-DI©). 
 
Minimal disease activity (MDA). 


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 
Spondyloarthritis Research Consortium of Canada (SPARCC). 
 
Psoriasis area and severity index (PASI). 
 
Leeds Dactylitis Index (LDI). 
Safety assessments 
 
Incidence and severity of AEs/ SAEs. 
 
Physical examinations. 
 
Vital signs. 
 
Height and weight. 
 
QuantiFERON TB-Gold test or PPD skin test. 
 
Local tolerability (injection site reactions). 
 
Laboratory evaluations (hematology, clinical chemistry, urinalysis). 
 
Pregnancy and assessment of fertility. 
 
Tolerability of secukinumab. 
 
Immunogenicity. 
Other assessments 
Not applicable. 
Data analysis 
The primary analysis variable is the change from baseline in Global 
PDUS score over 12 weeks. The primary analysis of this study will 
evaluate the superiority of secukinumab compared to placebo in PsA 
patients who have an IR to non-biologic DMARDs with respect to the 
change from Baseline in Global PDUS score over 12 weeks.  
The statistical hypothesis for the primary objective is that secukinumab is 
not different relative to placebo with respect to the change from baseline 
in GLOESS score over 12 weeks. 
Between-treatment differences in the change in GLOESS score will be 
evaluated using a mixed-effect model repeated measures (MMRM) with 
treatment regimen and analysis visit as factors and weight and baseline 
GLOESS score as continuous covariates. Treatment by analysis visit will 
be included as an interaction term in the model. An unstructured 
covariance structure will be assumed for this model. If the model does not 
converge, the compound symmetry covariance structure will be used. 
Key words 
Power Doppler ultrasonography, active psoriatic arthritis, secukinumab, 
enthesitis, synovitis, Phase 3b, monoclonal antibody, GLOESS score, 
ACR, CASPAR, OMERACT enthesitis score, SPARCC, PASI, PFS, 
HAQ-DI©, MDA, TJC, SJC, Physician’s global assessment (PGA) of 
disease activity (VAS), Patient’s assessment of PsA pain intensity (VAS), 
safety and tolerability.  


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1 
Introduction 
1.1 
Background 
1.1.1 
Overview of psoriatic arthritis 
Psoriatic arthritis (PsA) is an immune-mediated chronic inflammatory disease belonging to 
the spectrum of conditions commonly referred to as spondyloarthritides (SpA), which 
encompass a spectrum of overlapping clinical entities (Moll and Wright 1973). PsA is 
characterized by the association of peripheral arthritis, axial involvement and periarticular 
inflammation in patients with psoriasis. In addition to a heterogeneous and variable clinical 
course, PsA is complex and multifaceted and may include prominent involvement in the 
peripheral and axial diarthrodial joints, the skin and nails, and in periarticular structures such 
as the entheses. Simultaneous inflammation in the skin and musculoskeletal structures in a 
single patient, a relatively common scenario, often leads to a marked decrease in function and 
quality of life (Coates et al 2014).  
Synovitis is a key manifestation of PsA and is associated with the development of joint 
erosion and structural damage. Peripheral enthesitis, an important feature that can be observed 
in all forms of SpA, usually manifests as isolated pain or tenderness at physical examination 
but is sometimes only detected by imaging techniques. One major hurdle faced by clinicians 
is their inability to establish an early diagnosis because of the poor specificity of symptoms 
(D’Agostino et al 2011). Peripheral enthesitis is frequently associated with the presence of 
psoriasis even in patients with early SpA (Richette et al 2013). 
1.1.2 
Treatment of psoriatic arthritis 
Typically diseases modifying anti-rheumatic drugs (DMARDs) are used for the treatment of 
PsA including methotrexate (MTX), sulfasalazine, cyclosporine, and leflunomide; however, 
these are often inadequate because DMARDs only partially control established disease 
(Mease 2008). Tumor necrosis factor (TNF) blocking therapy was successfully introduced for 
the treatment of patients with PsA (Mease et al 2000). Interleukin-17 (IL-17) blocking 
therapies have more recently been introduced to provide better disease control and long term 
prevention of structural damage beyond mere abrogation of inflammatory processes. 
Cosentyx® (secukinumab) is a recombinant monoclonal antibody, which neutralizes the 
activity of IL-17A, and has been shown to be effective in treating patients with moderate-to-
severe plaque psoriasis. Secukinumab is approved in Europe (since Nov 2015), the US (since 
Jan 2016) and Canada (since Apr 2016) as well as in other countries including Mexico, 
Argentina, and Columbia for the treatment of PsA and ankylosing spondylitis (AS). 
Additionally, it is approved in Europe (since Jan 2015), the US (since Jan 2015) and Canada 
(since Mar 2015), as well as in other countries including Mexico, Argentina and Columbia, 
for the treatment of moderate-to-severe plaque psoriasis in adults who are candidates for 
systemic therapy or phototherapy (US and Canada only).  
The approval of secukinumab for psoriasis was based on the safety and efficacy results from 
more than 10 Phase 2 and Phase 3 studies which included nearly 4 000 patients with 
moderate-to-severe plaque psoriasis (Langley et al 2014, Blauvelt et al 2014, Paul et al 2014). 
The four Phase 3, randomized, placebo-controlled studies, i.e. ERASURE, FIXTURE 
(Langley et al 2014), FEATURE (Blauvelt et al 2014) and JUNCTURE (Paul et al 2014), 
included 2403 patients with moderate-to-severe plaque psoriasis.  


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The approval of secukinumab for PsA was based on 2 pivotal Phase 3 secukinumab studies, 
i.e. FUTURE 1 (CAIN457F2306) and FUTURE 2 (CAIN457F2312) have been performed in 
1003 patients with PsA (Mease et al 2014, McInnes et al 2015). These studies provided 
evidence that the secukinumab 150 mg regimen has a rapid onset of effect and demonstrates 
sustained improvement in all clinical domains of PsA up to Week 104 in FUTURE 2 
(Mc Innes et al 2016: ACR Abstract No. 2757) and 3 years in FUTURE 1 (Mease et al 2016: 
ACR Abstract No. 961). These domains include signs and symptoms (both for arthritic and 
skin symptoms), structural damage (FUTURE 1 only), patient reported outcomes, physical 
function and QoL. The secukinumab 300 mg s.c. regimen enabled a subgroup of PsA patients 
with concomitant moderate-to-severe plaque psoriasis to achieve clear/almost clear skin, and 
demonstrated clinically meaningful benefit on the primary and multiple secondary endpoints 
in a subgroup of patients who were TNFα inhibitor inadequate responders.  
The FUTURE 1 (i.e. CAIN457F2306) study also demonstrated the ability of secukinumab to 
provide significant and sustained inhibition of joint structural damage at Week 24. Inhibition 
of structural damage was maintained with secukinumab treatment up to Week 104 
(Kavanaugh et al 2016). Patients receiving secukinumab 150 mg s.c. starting at Week 24 
achieved comparable inhibition of structural damage progression at Week 52 as patients 
receiving secukinumab iv-150 mg s.c. regimen up to Week 24.  
In all studies, secukinumab demonstrated a favorable safety profile, with similar incidence 
and severity of adverse events (AEs) between secukinumab treatment arms (150 mg and 
300 mg).  
Further details are provided in Section 3.6.  
1.1.3 
Power Doppler ultrasonography for monitoring treatment response in 
psoriatic arthritis 
In recent years, the International Group for Research and Assessment of Psoriasis and 
Psoriatic Arthritis (GRAPPA) underlined the importance of integrating clinical and imaging 
findings from a rheumatology and dermatology perspective for psoriatic patients 
(Kaeley et al 2011, Gutierrez et al 2012) given the multifaceted nature of the disease. The use 
of Power Doppler and Grayscale ultrasound (PDUS) is a promising, non-invasive imaging 
method to assess peripheral involvement of SpA, including PsA. This technique permits 
visualization of most of the relevant joint pathologies associated with SpA, including 
synovitis, bone erosions, peripheral enthesitis, bursitis, tenosynovitis and dactylitis with 
results from numerous studies suggesting it provides additional information to conventional 
radiographic or clinical examinations (D’Agostino 2012). It may provide a more accessible 
point of care alternative to magnetic resonance imaging (MRI) and is non-invasive for 
patients in clinical practice. It also has the advantage of being able to scan multiple joints in a 
short period of time.  
The Outcome Measures in Rheumatology and the European League Against Rheumatism 
(OMERACT-EULAR) Ultrasound Task Force is a working group since 2004 to standardize 
the use of ultrasonography in rheumatoid arthritis (RA) and in SpA, including PsA 
(Bruyn et al 2015) and has developed a composite scoring system (the OMERACT-EULAR 
global synovitis score (GLOESS) as measured using PDUS) to detect and score synovitis. 
This score combines Grayscale-assessed synovial hyperplasia with an intra-synovial Power 
Doppler signal for evaluating synovial activity. The score has demonstrated validity and intra- 


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and inter-observer reliability in cross-sectional datasets, applicability to all joints and 
consistency between machines. The responsiveness of the OMERACT-EULAR composite 
PDUS score was demonstrated in biologic-naïve patients with RA treated with abatacept plus 
DMARDs during 24 weeks (D’Agostino et al 2012, Wakefield et al 2007). Regardless of the 
differences between PDUS scoring systems, data from published studies indicate these 
systems could be useful in monitoring early response to biologic treatment in patients with 
PsA (Naredo et al 2008, Iagnocco et al 2008, Terslev et al 2003, Filippucci et al 2006, 
Fiocco et al 2005, Fiocco et al 1996). 
PDUS has also proven to be a valid and reliable means of evaluating spondyloarthritis 
enthesitis (de Miguel et al 2009; D’Agostino et al 2002, 2003 and 2011). The hallmark feature 
of enthesitis is an abnormal vascularization of entheses, which was exclusively detected in 
SpA (D’Agostino et al 2003 and 2011). Quantification of entheseal involvement by 
ultrasound is best undertaken using semi-quantitative scoring systems that combine both 
inflammatory and structural damage signs. The OMERACT group has developed an enthesitis 
score which has demonstrated to be reliable and which includes clear definition of each 
elementary component (Tersley et al 2014) Evidence supporting the possibility of using 
ultrasound in combination with PD for monitoring pathological findings indicative of joint or 
soft tissue involvement in patients with PsA has been demonstrated for patients treated with 
anti-TNFα therapy (adalimumab or infliximab) (de Agustin et al 2012, Gutierrez et al 2012). 
Improvements in vascularization and structural changes were shown in the heel and the 
retrocalcaneal bursa with anti-TNFα therapy (D’Agostino et al 2003).  
PDUS has never been used in the secukinumab development studies in PsA (or any other 
secukinumab studies) and presents the advantage to be a sensitive and non-invasive imaging 
technique to fill gaps in imaging data on a multifaceted disease with joints, enthesitis, 
dactylitis and skin manifestations. PDUS will allow an in depth evaluation of joints and 
enthesitis inflammation and their morphological components. A randomized clinical study in 
patients with PsA with an inadequate response (IR) to non-biologic DMARD will provide for 
the first time comparative PDUS data on the early efficacy and time course of response to 
secukinumab versus placebo using the OMERACT-EULAR global synovitis score (GLOESS 
score) and the OMERACT enthesitis score. In an attempt to limit variability of synovitis 
scoring across sites, the completion of a training session will be required by all PDUS 
assessors at each center in order to be qualified for PDUS evaluation in this study as well as a 
quality control assessment of the GLOESS score during the study and at the end of the study 
as described in Section 6.4.1. This study will also confirm clinical response to treatment using 
standard assessment tools, such as the American College of Rheumatology (ACR) response 
and SPARCC enthesitis index.  
 
 
 
 
 
 
 
 
 


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1.2 
Purpose  
The purpose of this study is to provide early efficacy data using ultrasound on joint synovitis 
and enthesitis in addition to clinical efficacy already demonstrated in patients with active PsA 
despite non-biologic DMARDs. This study is designed to leverage the sensitivity of 
ultrasonography available in clinical practice setting to better describe the time course of 
response to secukinumab (150 mg and 300 mg) on joint synovitis and enthesitis in PsA 
patients with an IR to non-biologic DMARDs. 
 
 
 
 
2 
Study objectives 
2.1 
Primary objective 
 To demonstrate that there is a difference between secukinumab and placebo in terms of 
joint synovitis response over 12 weeks as measured by the PDUS Global OMERACT-
EULAR Synovitis Score (GLOESS) of the affected joints (out of 48 joints) in PsA 
patients with an IR to non-biologic DMARDs. 
2.2 
Secondary objectives 
2.2.1 
Key secondary objectives  
 To demonstrate that the efficacy of secukinumab at Week 12 is superior to placebo based 
on the proportion of patients achieving an ACR 20 response. 
 To demonstrate that the efficacy of secukinumab at Week 12 is superior to placebo based 
on the proportion of patients achieving an ACR 50 response. 
 To demonstrate that the clinical response of secukinumab at Week 12 is superior to 
placebo based on the change in SPARCC enthesitis index from Baseline to Week 12. 
2.2.2 
Other secondary objectives  
 To evaluate the therapeutic effect of secukinumab versus placebo on joint synovitis from 
Baseline to Week 8 using the GLOESS score out of 48 joints. 
 To evaluate the therapeutic effect of secukinumab versus placebo on enthesitis at Week 12 
using the OMERACT enthesitis score for each affected enthesis. 
 To evaluate the overall safety, tolerability and immunogenicity of secukinumab.  


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2.3 
Exploratory objectives 
 To evaluate the therapeutic effect on joint synovitis for patients in the placebo group once 
switched to secukinumab from Week 12 to Week 24 and Week 24 to Week 52, as 
assessed by the improvement in synovitis from Week 12 to 24 and Week 24 to Week 52 
using the GLOESS score and its components out of 48 joints.  
 To evaluate the therapeutic effect on joint synovitis in the initial secukinumab group as 
assessed by the improvement in synovitis from Baseline to Week 24 and to Week 52 using 
the GLOESS score and its components out of 48 joints. 
 To evaluate the therapeutic effect on enthesitis for patients in the placebo group who 
switched to secukinumab from Week 12 to Week 24 and Week 24 to Week 52 using the 
OMERACT individual enthesitis score and its morphologic components.  
 To evaluate the therapeutic effect on enthesitis for patients in the initial secukinumab 
group from Baseline to Week 24 and from Week 24 to Week 52 using the OMERACT 
individual enthesitis score and its morphologic components. 
 To explore the correlation between clinical improvement of each enthesitis site as assessed 
by SPARCC and the improvement in enthesitis as assessed by individual PDUS enthesitis 
scores from Baseline to Week 12. 
 To explore the correlation between the PDUS response versus ACR 20 response either by 
an improvement of the total GLOESS of at least 20% as compared to Baseline over 
12 weeks or by comparing the improvement in the same joints examined.  
 To explore the correlation between the PDUS response versus the SPARCC score over 
12 weeks by comparing the improvement in the same entheses examined. 
 To explore the efficacy of secukinumab at Week 24, during the extension period, and 
other time points for assessments that are not part of the primary and secondary objectives 
as applicable only to: 
 ACR 20, ACR 50, ACR 70, ACR components, PASI 75, PASI 90, dactylitis count, 
HAQ-DI© response.  
 Proportion of patients achieving minimal disease activity (MDA) at Week 24 and 
Week 52.  
2.3.1 
Sub-study objectives 
The following exploratory objectives will be evaluated in the substudy: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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3 
Investigational plan 
3.1 
Study design 
This is a 52-week, multicenter, international study consisting of a 1 to 4-week Screening 
period, a 12-week randomized, placebo-controlled double-blind treatment period (Period 1 
[Baseline to Week 12]), a 12-week open-label treatment period (Period 2 [Week 12 to 
Week 24]), a 6-month open-label extension period (Period 3 [Week 24 to Week 52]), and a 
12-week follow-up period (Week 52 to Week 64).  
During the entire study, it is mandatory for the integrity of study data to maintain the blind 
even between the Ultrasonography Investigator and the Clinical Investigator. This ensures that 
the PDUS assessment is performed without the knowledge of current clinical symptoms of the 
patient. The PDUS assessment will be performed by a rheumatologist who is unaware of the 
clinical symptoms, and randomization arm of the study patient.  
Screening period 
Informed consent: Investigators must ensure that patients, or, in those situations where 
consent cannot be given by patients, their legally acceptable representative, are clearly and 
fully informed about the purpose, potential risks, and other critical issues regarding this 
clinical study. Freely given written informed consent must be obtained from every patient or, 
in those situations where consent cannot be given by patients, their legally acceptable 
representative, prior to clinical study participation, including informed consent for any 
Screening procedures conducted to establish patient eligibility for the study. The rights, 
safety, and well-being of the study patients are the most important considerations and should 
prevail over interests of science and society. See Section 10.2 for further details. 
Eligible patients will be enrolled and enter a 1- to 4-week Screening period prior to 
randomization. In the case of leflunomide, the washout period is 8 weeks unless patients take 
cholestyramine according to the manufacturer’s recommendation where the washout period is 
less than 4 weeks. Patients who received MTX or other DMARDs during the last 3 months 
prior to Screening will continue with their previous therapy until Week 24.  
Treatment periods 
During the study, the study treatment (secukinumab 150 mg and 300 mg, and placebo) 
provided as prefilled syringes (PFSs) will be self-administered s.c. (into the appropriate 
injection site of the body) by the patient at the study center during Treatment Period 1 and 
Treatment Period 2 under supervision of the Investigator/ qualified study center staff; and at 
home at Week 28, 32, 40, 44, and 48 (during the Extension Period) as indicated in Table 6-1 
and Table 6-2 and described in Section 5.5.4.   
At each study visit, all patients will receive 2 s.c. injections using PFSs since secukinumab is 
available in 1.0 mL PFSs. Patients assigned to secukinumab 150 mg will receive 1 PFS of 
secukinumab 150 mg and 1 PFS of placebo; patients assigned to secukinumab 300 mg will 


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receive 2 PFS of secukinumab 150 mg; and patients assigned to placebo will receive 2 PFSs 
of placebo. At the study visits preceding home administration, sufficient study drug will be 
supplied to the patient to cover home administrations.  
Treatment period 1 – placebo-controlled double-blind (Baseline to Week 12) 
At Baseline, patients whose eligibility is confirmed will be randomized in 1:1 ratio in a 
double-blinded fashion to one of 2 treatment groups as follows: 
 Group 1: secukinumab (150 mg s.c. or 300 mg s.c. depending on severity of skin lesions) 
(1, 2)  
 secukinumab 150 mg (1.0 mL PFS of 150 mg dose) and placebo (1.0 mL PFS) 
administered at Baseline, Weeks 1, 2 and 3, followed by 4-weekly dosing at Week 4 
and Week 8. 
 secukinumab 300 mg (2 × 1.0 mL PFSs of 150 mg dose) administered at Baseline, 
Weeks 1, 2 and 3, followed by 4-weekly dosing at Week 4 and Week 8. 
1. Secukinumab 150 mg will be administered to patients with PsA (body surface area (BSA) 
≤ 10% as assessed by PASI (Section 6.4.5), corresponding to mild psoriatic skin lesions). 
2. Secukinumab 300 mg s.c. will be administered to patients with PsA (BSA > 10% as 
assessed by PASI (Section 6.4.5), corresponding to moderate-to-severe psoriatic skin 
lesions.  
 Group 2: placebo  
 Placebo (2 × 1.0 mL PFSs) at Baseline, Weeks 1, 2 and 3, followed by 4-weekly 
dosing at Week 4 and Week 8. 
Treatment Period 2 – open-label treatment period (Week 12 to Week 24) 
At Week 12, the assessments to address the primary objective will be performed as outlined in 
Table 6-1. After each patient has completed the Week 12 assessments, the investigator staff 
will notify the Novartis clinical team and the Interactive Response Technology (IRT) system 
that open-label assessments are starting. Patient, relevant study center personnel and data 
analysts will be unblinded to the treatment patient will be getting from this period onwards 
(i.e. open label treatment from this period). From Week 12, secukinumab will be given open-
label in order to eliminate the placebo injection (i.e. only 150 mg or 300 mg secukinumab will 
be dispensed as 1 or 2 PFSs, respectively).  
In Group 1, patients will continue to receive the same active dose of secukinumab every 
4 weeks until Week 24 (i.e. at Week 12, 16 and 20); patients will no longer receive the 
placebo PFS, which was administered to maintain blinding.  
In Group 2, patients will commence open-label secukinumab every 4 weeks from Week 12, 
as follows, based on their clinical characteristics at Week 12: 
 secukinumab (150 mg s.c. or 300 mg s.c. depending on severity of skin lesions)(1, 2)  
 secukinumab 150 mg (1.0 mL PFS of 150 mg dose) every 4 weeks starting from 
Week 12 (i.e. Week 12, 16 and 20).  
 secukinumab 300 mg (2 × 1.0 mL PFSs of 150 mg dose) every 4 weeks starting from 
Week 12 (i.e. Week 12, 16 and 20).  
1. Secukinumab 150 mg will be administered to patients with PsA (BSA ≤ 10% as assessed 
by PASI (Section 6.4.5), corresponding to mild psoriatic skin lesions). 


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2. Secukinumab 300 mg s.c. will be administered to patients with PsA with BSA > 10% as 
assessed by PASI (Section 6.4.5), corresponding to moderate-to-severe psoriatic skin 
lesions).  
A blinded sample size estimation (SSR) will be performed when the first 60 patients have 
completed the Week 12 visit as described in Section 9.6. 
The Week 12 analysis will be performed after all patients complete the Week 12 visit (see 
Section 9.6). Only the data analysts will be unblinded to the Treatment Period 1 
randomization after the Week 12 database lock/analyses. Summary results will be shared 
internally and externally; however, individual unblinded patient data will not be disclosed. 
The Ultrasonography Investigator and the Clinical Investigator will remain blinded from each 
other until the final database lock. 
Treatment Period 3 – extension period (Week 24 to Week 52) 
Treatment Period 3 is an extension period to allow responder patients (if they wish and as per 
clinician’s judgment) the possibility to continue open-label secukinumab treatment up to 
Week 52. Patients must sign a separate ICF to confirm their agreement to participate in the 
extension period (Section 9.6). 
At Week 24, open-label secukinumab will continue to be assigned to patients in Group 1 and 
Group 2 at the same dose every 4 weeks until Week 52 for administration at either the study 
site (i.e. Week 24, 36 and 52) or at home (Week 28, 32, 40, 44, and 48).  
At Week 24, patients who do not reach at least a 20% improvement in tender joint count 
(TJC) and swollen joint count (SJC) with secukinumab (150 mg or 300 mg) from Baseline 
will be withdrawn from the study.  
The Week 24 analysis will be performed after all patients complete the Week 24 visit (see 
Section 9.6). 
The final analysis will be performed after the last patient has completed the Week 64/End of 
Study visit or early withdrawal visit (in case of early withdrawal of last patient from the 
study). After the final database lock and analyses have been completed, site personnel 
(including the Ultrasonography Investigator and Clinical Investigator) will be unblinded to the 
original randomized treatment (sequence) assignment at randomization. Additional study 
treatments (non-biologic DMARDs including MTX, systemic corticosteroids, and NSAIDs, 
low strength opioids, or paracetamol/acetaminophen) permitted for use alongside 
secukinumab in this study are described in Section 5.1.2.  
If, despite concomitant medication, a patient presents with worsening of disease or does not 
seem to benefit from study treatment, necessary rescue medication with low strength opioids 
or paracetamol/acetaminophen is permitted for use alongside secukinumab prior to 
completion of Week 24 assessments. In addition, changes in NSAID concomitant therapy are 
permitted prior to Week 24 assessments as per the Investigator’s clinical judgment and 
following failure of previously authorized rescue medication.  
If there is no patient improvement despite authorized rescue medication and there is a need to 
use prohibited treatments (as described in Table 5-2) prior to completion of Week 24 
assessments, patients will be discontinued from the study and assessed as a prematurely 
withdrawn patient as described in Section 6 (i.e. the patient will return for the final visit 


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within the treatment period (4 weeks after the last study treatment), as well as return for the 
final follow-up visit (F64) 12 weeks after the last study treatment). Efficacy will be assessed 
in detail at every study visit; patients who are deemed not to be benefiting from the study 
treatment based upon safety and efficacy assessments by the Investigator, or for any reason of 
their own accord, will be free to discontinue participation in the study at any time. 
A follow-up visit is to be done 12 weeks after last study treatment administration for all 
patients, regardless of whether they complete the entire study as planned or discontinue 
prematurely. All AEs that occur during this post-treatment follow-up period will be included 
in the evaluation of treatment-emergent AEs.  


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Protocol No. CAIN457F2354 
Figure 3-1 
Study design 
 
Abbreviations: DMARD: disease modifying anti-rheumatic drugs, Fup: follow-up  
1 Secukinumab 150 mg will be administered to patients with PsA (BSA ≤ 10% as assessed by PASI (Section 6.4.5), corresponding to mild skin lesions). 
2 Secukinumab 300 mg s.c. will be administered to patients with PsA (BSA > 10% as assessed by PASI (Section 6.4.5), corresponding to moderate-to-
severe psoriatic skin lesions).  
Note: Study drug will be self-administered by the patient (or caregiver if applicable) at home at Week 28, 32, 40, 44 and 48 (Section 5.5.4).  
* Patients who received MTX/ other DMARDs at a stable dose in the last 3 months prior to Screening should remain on a stable dose until Week 24 
unless there are safety or tolerability issues as described in Section 5.1.2. 
Note: The Ultrasonography Investigator will be blinded from the Clinical Investigator in this study.  


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3.2 
Rationale of study design 
This study will consist of 3 study periods: a 12-week placebo-controlled double-blind period, 
a 12-week open label period and a 6-month open-label extension period. 
Treatment Period 1 is a 12-week placebo-controlled, randomized period primarily designed to 
demonstrate the early and optimal efficacy of secukinumab vs placebo on joint synovitis using 
PDUS, which is a very sensitive imaging technique. It will also compare the improvement in 
joint inflammation response (synovitis and enthesitis) for secukinumab compared to placebo 
using PDUS, specifically via the GLOESS and global entheseal score, after 12 weeks of 
treatment in patients with active PsA with an IR to DMARDs.  
The placebo control arm in the first period of this study is aimed at evaluating the variability 
of joint synovitis using the global OMERACT PDUS synovitis score and will allow the true 
effect of secukinumab treatment to be demonstrated. In addition, the 12-week placebo-
controlled period is aligned with Phase 3 trials of other biologics and is in accordance with 
EMA guidelines (CHMP/EWP/438/04).  
A TNFα inhibitor-naïve population was selected for this study despite efficacy being observed 
with secukinumab in patients previously treated with TNFα inhibitors as this is the first 
exploratory PDUS study in secukinumab; and a homogeneous population with 
biologically-naïve patients will limit data variability and will allow for better assessment of 
ultrasound and clinical outcomes.  
The main aim of Period 2 is to assess the maintenance or increased magnitude of treatment 
response on joint synovitis for patients from the original secukinumab groups and to assess 
the time course of response with secukinumab on joint synovitis in the original placebo group 
switched to secukinumab from Week 12. 
The main aim of Period 3 (Extension Period [Week 24 to Week 52]) is to allow patients who 
respond to secukinumab (if they wish and as per clinician’s judgment) the possibility to 
extend study treatment up to Week 52. Clinical efficacy assessments (including PDUS 
assessments) and safety assessments are also extended to occur at Week 36 and Week 52 
during this period. Other aims are to assess patients who may develop a late ultrasound 
response and/or clinical response to secukinumab and to further evaluate the long term 
maintenance of the clinical and ultrasound response to secukinumab. 
Patients who are experiencing worsening of disease in any of the treatment groups can exit the 
study at their own request or based on the advice of the Investigator at any time. 
3.3 
Rationale of dose/regimen, route of administration and duration 
of treatment 
The doses (150 mg and 300 mg), regimen (once weekly for first 4 weeks, followed by 
4-weekly dosing from Week 4), route of administration (s.c.) and duration of treatment were 
chosen for this study in accordance with the outcomes of the Phase 3 trials in PsA 
(CAIN457F2306 and CAIN457F2312). In addition, 300 mg is approved in Europe for the 
treatment of PsA with concomitant moderate to severe psoriasis (per the EU SmPC) and 
moderate to severe psoriasis may be defined as > 10% BSA as per EMA guideline 
(CHMP/EWP/2454/02 corr). 
In the Phase 3 trials in PsA, CAIN457F2306 assessed the efficacy of both 75 mg and 150 mg 
s.c. maintenance doses (every 4 weeks) after loading regimens consisting of 3 i.v. doses of 


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10 mg/kg given at Baseline, Week 2 and 4, and CAIN457F2312 assessed the efficacy of 
75 mg, 150 mg and 300 mg s.c. maintenance doses (every 4 weeks) after loading regimens 
consisting of s.c. doses of 75 mg, 150 mg or 300 mg given at Baseline, Week 1, 2, and 3. 
Given the similarity of the ACR 20 response seen at the Week 24 primary endpoint for the 
150 mg dose in each of these studies, regardless of whether the loading dosing was i.v. 
(CAIN457F2306: 50.0% for 150 mg vs 17.3% for placebo) or s.c. (CAIN457F2312: 51.0% 
for 150 mg vs 15.3% for placebo), 150 mg is considered a sufficient dose to provide clinically 
and statistically significant efficacy, whereas higher loading doses of secukinumab do not 
appear to confer a greater response on the primary endpoint of ACR 20 at Week 24. This 
study also demonstrated the ability of secukinumab to provide significant and sustained 
inhibition of joint structural damage at Week 24 and Week 52. Patients receiving 
secukinumab 150 mg s.c. starting at Week 24 achieved comparable inhibition of structural 
damage progression at Week 52 as patients receiving secukinumab iv-150 mg s.c. regimen up 
to Week 24. 
In the CAIN457F2312 study, the PASI 75 and PASI 90 response was assessed in the 
subgroup of patients who had ≥ 3% skin involvement with psoriasis at Baseline. For both 
PASI 75 and PASI 90 response rates, the difference to placebo at Week 24 was statistically 
significant for the secukinumab 150 mg and 300 mg doses (PASI 75: 48.3%, p = 0.0006 and 
63.4%, p < 0.0001; PASI 90: 32.8%, p = 0.0029 and 48.8%, p = 0.0002, respectively). The 
percentage of responders increased as the secukinumab dose increased, with the secukinumab 
300 mg dose demonstrating a clinically meaningful improvement over the secukinumab 
150 mg dose (treatment differences between secukinumab 300 mg and 150 mg for PASI 75 
and PASI 90 were 15.1% and 16%, respectively). Of note, the 75 mg s.c. loading/s.c. 
maintenance regimen tested in CAIN457F2312 achieved a statistically significant but 
clinically lower effect size in ACR 20 response of 29.3% and did not achieve statistically 
significant improvements in any of the other pre-specified secondary efficacy endpoints 
which included: PASI 75, PASI 90, DAS28-CRP, SF36 Physical Component Summary, 
HAQ-DI©, ACR 50, resolution of dactylitis and resolution of enthesitis. 
Overall, the Phase 3 studies in PsA (CAIN457F2306 and CAIN457F2312) provide evidence 
that secukinumab 150 mg regimen is efficacious and demonstrates clinically meaningful 
improvement in all clinical domains of PsA. These domains include signs and symptoms 
(both for arthritic and skin symptoms), structural damage, patient reported outcomes, physical 
function, and quality of life. Secukinumab 300 mg s.c. regimen enabled a subgroup of PsA 
patients with concomitant moderate-to-severe plaque psoriasis to achieve clear/almost clear 
skin, and demonstrated clinically meaningful benefit on the primary and multiple secondary 
endpoints in a subgroup of patients who were TNFα inhibitor inadequate responders. 
Pre-filled syringes have been selected for secukinumab s.c. administration in this study as 
these have been successfully used in the Phase 3 clinical studies in moderate-to-severe plaque 
psoriasis, as well as in the completed Phase 3 clinical studies for PsA (CAIN457F2306 and 
CAIN457F2312), which showed the use of PFSs was safe and well tolerated.  


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3.4 
Rationale for choice of comparator 
A placebo group is included in this study up to the Week 12. Due to the nature of the disease 
and the primary outcome measure to evaluate the time course of response to secukinumab for 
joint inflammation synovitis (OMERACT-EULAR global PDUS score out of 48 joints), a 
placebo group is necessary to obtain robust and reliable efficacy measurements for 
comparison between the active treatment groups and placebo in a controlled fashion up to 
12 weeks and differentiate the true therapeutic effect from the variability of the disease. 
Patients assigned to placebo for the first 12 weeks in the study will be assigned to 
secukinumab for the next 12 weeks and will therefore have the opportunity to benefit from the 
proven efficacy of the active study drug.  
Patients are permitted to continue their non-biologic DMARDs (including MTX) and 
systemic corticosteroid medications at a stable dose during the study up to Week 24 as 
described in Section 5.1.2.1, Section 5.1.2.2 and Section 5.1.2.3.  
If, despite concomitant medication, a patient presents with worsening of disease or does not 
seem to benefit from study treatment, necessary rescue medication with low strength opioids 
or paracetamol/acetaminophen is permitted for use alongside secukinumab prior to 
completion of Week 24 assessments. Changes in NSAID concomitant therapy are permitted 
prior to Week 24 assessments as a rescue therapy as per the Investigator’s clinical judgment 
and following failure of previously authorized rescue medication. Changes in NSAID 
concomitant therapy after Week 24 assessments are also permitted as per the Investigator’s 
clinical judgment as described in Section 5.1.2.4.  
3.5 
Purpose and timing of interim analyses/design adaptations 
A blinded sample size re-estimation (SSR) will be performed after the first 60 patients 
complete the Week 12 visit. The objective of the blinded SSR is to evaluate the assumptions 
of the sample size calculation and to decide whether the study should continue as planned. 
Details on the SSR options that will be considered can be found in Section 9.6. 
The analysis of the primary and secondary efficacy variables will be performed after all 
patients complete the Week 12 visit. This analysis will also include exploratory variables 
outlined up to Week 12 and all available safety data. Subsequent to the Week 12 analysis, a 
Week 24 analysis will be performed and a final analysis will be performed after the final 
database lock, i.e. when last patient completes the Week 64/End of Study visit or early 
withdrawal visit. 
3.6 
Risks and benefits  
Secukinumab is approved in Europe (since Nov 2015), the US (since Jan 2016), Canada 
(since Apr 2016), as well as in other countries, including Mexico, Argentina, and Columbia 
for the treatment of PsA and AS. Additionally, it is approved in Europe (since Jan 2015), the 
US (since Jan 2015) and Canada (since Mar 2015), as well as in other countries including 
Mexico, Argentina and Columbia, for the treatment of moderate-to-severe plaque psoriasis in 
adults who are candidates for systemic therapy or phototherapy (US and Canada only).  
Secukinumab has shown either preliminary or confirmed efficacy in several inflammatory 
diseases including PsA, psoriasis and AS. The primary and key secondary efficacy endpoints 
for secukinumab were met in both Phase 3 randomized clinical trials in PsA (CAIN457F2306 
and CAIN457F2312). Both trials were adequately powered to detect clinically meaningful 


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improvement in efficacy compared to placebo. Both trials used pre-specified hierarchical 
testing schemes to control for multiplicity of comparisons. The efficacy of secukinumab 
150 mg and 300 mg s.c. load followed by respective maintenance was robust and similar 
across multiple endpoints, with clinically meaningful improvements in signs and clinical 
symptoms, physical function, disease activity, skin involvement, patient-reported outcomes 
and measures of productivity. The therapeutic effect was rapid (within 3 weeks) and 
sustained. Moreover, these benefits were observed in the overall PsA population comprising 
subpopulations of both PsA patients naïve to anti-TNFα therapy and anti-TNFα IR 
(30% to 40%). The 300 mg s.c. dose provided greater clinical benefit in anti-TNFα IR patients 
and patients with concomitant moderate-to-severe plaque psoriasis. The 75 mg s.c. dose was 
ineffective. 
The safety profile observed in the latest drug safety update report (DSUR) (Issue 008: 26-Jun-
2017 to 25-Jun-2018) is in line with the current known safety profile of secukinumab in PsA, 
moderate to severe psoriasis, and AS. As of 25-Jun-2018, approximately 24279 subjects 
(which included patients and a small number of healthy volunteers) had been enrolled with the 
secukinumab clinical development program (including trials where secukinumab had been 
used as a protocol specified treatment), of which approximately 20000 subjects (comprised of 
patients and healthy volunteers) had received at least 1 dose of secukinumab. Overall, healthy 
subjects and patients suffering from PsA, psoriasis, rheumatoid arthritis, AS, nr-axial SpA, 
multiple sclerosis, uveitis, dry eye, Crohn’s disease, asthma and polymyalgia rheumatica have 
received secukinumab at doses ranging from single and multiple iv doses of 0.1 mg/kg up to 
30 mg/kg and s.c. doses of 25 mg up to 300 mg. The cumulative patient exposure since the 
first launch of secukinumab is estimated to be approximately 212060 patient years.  
Full safety results from all PsA, AS and psoriasis completed studies show that secukinumab 
generally is safe and well tolerated. For these indications, secukinumab has shown a higher 
rate of total AEs, mainly infections, when compared to placebo (placebo-controlled periods of 
12 to 16 weeks depending on the protocol). The majority of infections were upper respiratory 
tract infections. However, no clinically meaningful difference was observed in infectious 
SAEs. In addition, no dose dependency with secukinumab (300 mg and 150 mg) was 
observed in the overall rate of infections or upper respiratory tract infections.  
Adverse drug reactions (ADRs) classified as very common (≥ 1/10 patients) or common 
(≥ 1/100 but < 1/10 patients) included upper respiratory tract infections (nasopharyngitis, 
upper respiratory tract infection, rhinitis and pharyngitis), oral herpes, rhinorrhea, diarrhea 
and urticaria. Uncommon (≥ 1/1000 but  1/100 patients) ADRs included sinusitis, tonsillitis, 
oral candidiasis, tinea pedis, neutropenia and conjunctivitis. 
Infections, neutropenia and hypersensitivity are important identified risks, while 
malignancies, major adverse cardiovascular events, immunogenicity, Crohn’s disease, and 
hepatitis B reactivation (EU only) are important potential risks. Interaction with live vaccines 
is an important potential risk. 
Immunogenicity was low with secukinumab and did not correlate with loss of efficacy in all 
indications studied to date. No new and relevant information from clinical trials was obtained 
for any of the above topics during the reporting interval for the latest DSUR and the overall 
post-marketing experience (including reporting rates across Periodic Safety Update Reports 


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(PSURs) 1, 2, 3 and cumulative period) has been in line with what was observed during the 
clinical program. 
During the reporting interval of the latest DSUR, a Risk Management Plan (RMP) update was 
triggered upon request from Pharmacovigilance Risk Assessment Committee, to include 
suicidal ideation and behavior (SIB) as an important potential risk in the RMP on the basis 
that “although causality has not been established, SIB meets the criteria as important potential 
risk because a potential biological mechanism cannot be completely ruled out since the 
biological role of IL-17 receptor ligands is still largely unknown, and consideration of the 
potential public health impact”. The RMP is currently being updated for this change. At its 
completion SIB will be listed as an important potential risk in the RMP. 
From the standpoint of the overall risk-benefit assessment, the current trial is justified. The 
risk to patients in this study will be minimized by compliance with the eligibility criteria and 
study procedures and close clinical monitoring.  
4 
Population 
The study population will consist of male and female patients aged ≥ 18 years with PsA as per 
the classification criteria for PsA (CASPAR) and with active PsA for at least 6 months and 
must have ≥ 3 tender joint count (TJC) out of 78 and ≥ 3 swollen joint count (SJC) out of 
76 at Baseline and with an IR to non-biologic DMARDs. Patients can be re-screened only 
once and ‘no’ re-screening study related procedures should be performed prior to written re-
consent by the patient. Mis-randomized patients cannot be re-screened. 
The goal is to randomize 164 patients in total (82 patients per arm) at approximately 50 
centers worldwide. 
4.1 
Inclusion criteria 
Patients eligible for inclusion in this study have to fulfill all of the following criteria: 
1. Patient must be able to understand and communicate with the Investigator and comply 
with the requirements of the study and must provide written, signed and dated informed 
consent before any study assessment is performed.  
2. Male or female patients at least 18 years of age.  
3. Diagnosis of PsA as per CASPAR with active PsA for at least 6 months and a TJC ≥ 3 of 
78 and SJC ≥ 3 of 76 at Baseline.  
4. a) Patients must have a total synovitis PDUS score ≥ 2 and inflammation related to PD 
signal ≥ 2 for at least 1 affected joint (as observed via PDUS) of 48 joints at the 
Screening visit and at the Baseline visit (before injection), OR 
b) Patients must have a total synovitis PDUS score ≥ 2 and inflammation related to PD 
signal ≥ 1 for at least 2 affected joints (as observed via PDUS) of 48 joints at the 
Screening visit and at the Baseline visit (before injection). 
5. At least 1 clinically-involved enthesitis site at Screening and at the Baseline visit (before 
injection) defined by SPARCC index different from 0. 
6. Rheumatoid factor and anti-cyclic citrullinated peptide (anti-CCP) negative at Screening.  
7. Patients with PsA who have an IR to non-biologic DMARDs.  


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8. Patients with PsA who are taking NSAIDs should be on a stable dose for at least 2 weeks 
prior to enrollment and remain on a stable dose throughout the 24-week study period 
unless rescue therapy is needed.  
9. Patients with PsA who are taking steroids must have received steroids at least 3 months 
prior to the Baseline visit and be on a stable dose of ≤ 10 mg equivalent prednisone for at 
least 4 weeks prior to Baseline visit and remain on a stable dose throughout the 24-week 
study period unless tolerance issues are present.  
10. Patients with PsA who are taking MTX or DMARDs must have received them at least 
3 months prior to Baseline visit and be on a stable dose of ≤ 25 mg/week of MTX or stable 
standard doses of other DMARD(s) (according to the Investigator’s judgment) for at least 
4 weeks prior to the Baseline visit and remain on a stable dose throughout the 24-week 
study period. 
4.2 
Exclusion criteria 
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the Investigator in order to ensure that the study 
population will be representative of all eligible patients. 
1. Chest X-ray or chest MRI with evidence of ongoing infectious or malignant process 
obtained within 3 months prior to Screening and evaluated by a qualified physician.  
2. Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 
receptor.  
3. Patients taking high-potency opioid analgesics (e.g. methadone, hydromorphone, 
morphine).  
4. Use of any investigational drug and/or devices within 4 weeks before randomization or a 
period of 5 half-lives of the investigational drug, whichever is longer. 
5. Any change in the dose of oral corticosteroids in the last 4 weeks prior to the Baseline 
visit or use of i.v. intramuscular or intra-articular corticosteroid during the last 4 weeks 
prior to the enrollment visit.  
6. Patients who have previously been treated with TNFα inhibitors (investigational or 
approved).  
7. History of hypersensitivity to the study drug or its excipients or to drugs of similar classes.  
8. Previous treatment with any cell-depleting therapies including but not limited to 
anti-CD20 investigational agents (e.g. CAMPATH, anti-CD4, anti-CD5, anti-CD3, 
anti-CD19).  
9. Prohibited psoriasis treatments/medications with topical corticosteroids in the last 4 weeks 
prior to randomization (see Section 5.5.8).  
10. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female 
after conception and until the termination of gestation, confirmed by a positive human 
chorionic gonadotropin (hCG) laboratory test. 
11. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during the 
entire study or longer if required by locally approved prescribing information (e.g. 
20 weeks in EU). Effective contraception methods include: 


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 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) or tubal ligation at least 6 weeks before taking study 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) with spermicidal foam/gel/film/cream/vaginal suppository.  
 Use of oral, injected or implanted hormonal methods of contraception or other forms 
of hormonal contraception that have comparable efficacy (failure rate < 1%), for 
example hormone vaginal ring or transdermal hormone contraception. 
 Placement of an intrauterine device or intrauterine system. 
In case of use of oral contraception women should have been stable on the same pill for a 
minimum of 3 months before taking study drug. 
Women are considered post-menopausal and not of child bearing potential if they have 
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile 
(e.g. age appropriate, history of vasomotor symptoms) or surgical bilateral oophorectomy 
(with or without 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. 
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 
immunocompromise the patient and/or place the patient at unacceptable risk for 
participation in an immunomodulatory therapy.  
14. Significant medical problems or diseases, including but not limited to the following: 
uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure (New York Heart 
Association status of class III or IV), uncontrolled diabetes (as per Investigator’s 
judgment). 
15. History of clinically significant liver disease or liver injury as indicated by abnormal liver 
function tests (LFT) such as aspartate aminotransferase (AST), alanine aminotransferase 
(ALT), 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 laboratory 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. In any case, serum 
bilirubin should not exceed 1.6 mg/dL (27 μmol/L). 


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16. History of renal trauma, glomerulonephritis, or patients with 1 kidney only, or a serum 
creatinine level exceeding 1.5 mg/dL (132.6 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 2 weeks (exception: common cold) prior to 
randomization. 
19. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis 
infection as defined by either a positive purified protein derivative (PPD) skin test (the 
size of induration will be measured after 48-72 hours, and a positive result is defined as an 
induration of ≥ 5 mm or according to local practice/guidelines) or a positive 
QuantiFERON TB-Gold test (as indicated in Section 6.5.4 and Table 6-1). 
20. 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 tuberculosis. If presence of latent tuberculosis is established then treatment 
according to local country guidelines must have been initiated. 
21. Known infection with human immunodeficiency virus, 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 patient 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 6 months before 
randomization. 
28. Plans for administration of live vaccines during the study period or within 6 weeks 
preceding randomization. 
5 
Treatment 
Secukinumab for s.c. injection will be supplied in single boxes each containing PFSs of 
150 mg secukinumab in a 1 mL liquid formulation. The solution for injection in the PFS is 
colorless to slightly yellow.  
Each 300 mg dose will be administered as 2 PFS injections of 150 mg secukinumab. All study 
drugs will be labelled appropriately. 
5.1 
Protocol requested treatment 
5.1.1 
Investigational treatment 
Novartis will supply the following: 


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 Investigational treatment 
Secukinumab 150 mg provided in 1 mL PFS for s.c. injection. The 300 mg dose will be 
administered as 2 × PFS injections. 
 Reference treatment 
Secukinumab placebo provided in a 1 mL PFS for s.c. injection. 
Patients will be instructed by site staff on how to self-administer the s.c. injection using the 
PFS based on the Instructions for Use (IFU). The study treatment (secukinumab (150 mg and 
300 mg) and placebo provided as PFSs) will be self-administered s.c. (into the appropriate 
injection site of the body) by the patient at the study center during Treatment Period 1 and 
Treatment Period 2 under supervision of the Investigator/ qualified study center staff, or at 
home at Week 28, 32, 40, 44, and 48 (during Treatment Period 3: Extension Period) as 
indicated in Table 6-1 and Table 6-2. 
At each study treatment visit, all patients will receive 2 s.c. injections using PFSs since 
secukinumab is available in 1 mL PFSs. Patients assigned to secukinumab 150 mg will 
receive 1 PFS of secukinumab 150 mg and 1 PFS of placebo; patients assigned to 
secukinumab 300 mg will receive 2 PFS of secukinumab 150 mg; and patients assigned to 
placebo will receive 2 PFSs of placebo. At the study visits preceding home administration, 
sufficient study drug will be supplied to the patient to cover home administrations. 
The PFSs are packed in a double-blinded fashion and do not need to be prepared. The study 
treatments will be labeled as follows: 
 Double-blind secukinumab and placebo PFSs will be labeled AIN457 150 mg 
/1 mL/Placebo for dosing until Week 12. 
 Open label secukinumab PFSs will be labeled AIN457 150 mg/1 mL. 
For detailed instructions for storage of the study treatments, please refer to Section 5.5.3. 
5.1.2 
Additional study treatment 
During this study, MTX or other DMARDs, systemic corticosteroids, and NSAIDs, low 
strength opioids, or paracetamol/acetaminophen are permitted as described in the sub-sections 
below.  
5.1.2.1 
Disease-modifying anti-rheumatic drugs 
Background non-biologic DMARDs must have been initiated at least 3 months prior to the 
Baseline visit and should be taken at standard stable doses (according to the Investigator’s 
judgment) for at least 4 weeks prior to the Baseline visit. Non-biologic DMARDs can be 
continued at a stable dose until Week 24 unless there are safety or tolerability issues. 
5.1.2.2 
Methotrexate 
Methotrexate at a stable dose of up to 25 mg/week until Week 24 with folic acid 
supplementation is permitted only for patients who started to receive MTX at least 3 months 
prior to enrollment and were on a stable dose for at least 4 weeks prior to enrollment. The 
dose may be decreased only due to toxicity. The weekly dose of MTX should be taken more 
than 48 hours before any clinical laboratory evaluation.  
After Week 24, the dose and regimen of MTX may be modified as per Investigator’s 
judgment and patient need. 


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Patients on MTX must be taking folic acid supplementation before randomization and during 
the study to minimize the likelihood of MTX-associated toxicity. 
5.1.2.3 
Systemic corticosteroids 
Treatment with systemic corticosteroids is permitted up to a maximum daily dosage of 10 mg 
prednisone equivalent only if the corticosteroid was started 3 months prior to enrollment and 
the dose was stable for at least 4 weeks prior to enrollment. The patient should remain on a 
stable dose until Week 24. After Week 24, the dose and regimen of systemic corticosteroids 
may be modified as per the Investigator’s judgment and patient needs. 
Corticosteroid dose reductions below 10 mg prednisone equivalent are permitted after 
Week 24, although the corticosteroid dose should not be reduced by more than 1 mg 
prednisone equivalent every 4 weeks. Any change in the dose of systemic corticosteroids 
during the study must be recorded on the corresponding electronic CRF (eCRF) page. 
Table 5-1 
Corticosteroids conversion table for the equivalence of 1 mg of 
cortisone 
Corticosteroid 
Equivalence of 1 mg of cortisone 
Cortisone 
1 mg 
Prednisone, prednisolone 
0.2 mg 
Methylprednisone, triamcinolone 
0.16 mg 
Dexamethasone 
0.03 mg 
Fludrocortisone 
0.08 mg 
Deflazacort 
0.24 mg 
Paramethasone 
0.08 mg 
Hydrocortisone, cortisol 
0.8 mg 
Sources:  
Asare 2007, Colburn 2012, Grover et al 2007, Liu et al 2013, Saviola et al 2007, Shaikh et al 2012. 
Intra-articular corticosteroids are not permitted within the 4 weeks preceding randomization. 
No more than 1 joint per 24-week period may be injected.  
No single injection should exceed 40 mg of triamcinolone (or equivalent) and the total dose of 
intra-articular corticosteroid may not exceed 80 mg of triamcinolone (or equivalent) 
during any 24-week period.  
5.1.2.4 
Non-steroidal anti-inflammatory drugs (NSAIDs) (including COX-1 or 
COX-2 inhibitors), low strength opioids and acetaminophen/ 
paracetamol 
Patients on regular use of NSAIDs (including cyclo-oxygenase 1 (COX-1) or 
cyclo-oxygenase 2 (COX-2) inhibitors), low strength opioids, or paracetamol/acetaminophen 
as required should be on stable dose for at least 2 weeks before randomization to allow 
inclusion.  
Changes in NSAID concomitant therapy is permitted for rescue therapy as per the 
Investigator’s clinical judgment and following failure of previously authorized rescue 
medication (i.e. if low strength opioids or paracetamol/acetaminophen are not successful). 


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Any change of the NSAIDs, low strength opioids, or paracetamol/acetaminophen treatment 
during the trial should be recorded on the corresponding eCRF page. 
5.2 
Treatment arms 
At Baseline, patients whose eligibility is confirmed will be randomized in 1:1 ratio in a 
double-blinded fashion to one of 2 treatment groups (secukinumab: placebo).  
Additional 
study 
treatments 
(non-biologic 
DMARDs 
including 
MTX, 
systemic 
corticosteroids, and NSAIDs, low strength opioids, or paracetamol/acetaminophen) permitted 
for use alongside secukinumab in this study are described in Section 5.1.2.  
During the study, the study treatment (secukinumab 150 mg and 300 mg, and placebo) 
provided as PFSs will be self-administered s.c. by the patient at the study center during 
Treatment Period 1 and Treatment Period 2 under supervision of the Investigator/ qualified 
study center staff; and at home at Week 28, 32, 40, 44, and 48 (during the Extension Period) 
as indicated in Table 6-1 and Table 6-2 and described in Section 5.5.4.   
5.2.1 
Group 1: secukinumab double-blind followed by secukinumab 
open-label from Week 12 
Period 1 – Baseline to Week 12 
 secukinumab (150 mg s.c. or 300 mg s.c. depending on severity of skin lesions(1, 2))  
 secukinumab 150 mg (1.0 mL PFS of 150 mg dose) and placebo (1.0 mL PFS) 
administered at Baseline, Weeks 1, 2 and 3, followed by 4-weekly dosing at Week 4 
and Week 8.  
 secukinumab 300 mg (2 × 1.0 mL PFSs of 150 mg dose) administered at Baseline, 
Weeks 1, 2 and 3, followed by 4-weekly dosing at Week 4 and Week 8. 
1. Secukinumab 150 mg will be administered to patients with PsA with BSA ≤ 10% as 
assessed by PASI (Section 6.4.5), corresponding to mild psoriatic skin lesions). 
2. Secukinumab 300 mg s.c. will be administered to patients with PsA (BSA > 10% as 
assessed by PASI (Section 6.4.5), corresponding to moderate-to-severe psoriatic skin 
lesions).  
Period 2 – Week 12 to Week 24 
 secukinumab at the same dose as administered in Period 1 (150 mg s.c. or 300 mg s.c.) 
 secukinumab 150 mg (1.0 mL PFS of 150 mg dose) administered every 4 weeks 
starting from Week 12 (i.e. at Week 12, 16 and 20). 
 secukinumab 300 mg (2 × 1.0 mL PFSs of 150 mg dose) administered every 4 weeks 
starting from Week 12 (i.e. at Week 12, 16 and 20). 
Period 3 – Week 24 to Week 52 
 secukinumab at the same dose as administered in Period 1 and Period 2 (150 mg s.c. or 
300 mg s.c.) 
 secukinumab 150 mg (1.0 mL PFS of 150 mg dose) administered every 4 weeks 
starting from Week 24 (i.e. at Week 24, 28, 32, 36, 40, 44, 48 and 52). 
 secukinumab 300 mg (2 × 1.0 mL PFSs of 150 mg dose) administered every 4 weeks 
starting from Week 24 (i.e. at Week 24, 28, 32, 36, 40, 44, 48 and 52). 


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Note: At Week 24, patients who do not reach at least a 20% improvement in TJC and SJC 
compared to Baseline with secukinumab (150 mg or 300 mg) will be withdrawn from the 
study. 
5.2.2 
Group 2: placebo followed by secukinumab from Week 12 
Period 1 – Baseline to Week 12 
 placebo (2 × 1.0 mL PFSs) administered at Baseline, Week 1, 2 and 3, followed by dosing 
every 4 weeks starting from Week 4 (i.e. at Week 4 and Week 8) 
Period 2 – Week 12 to Week 24 
 secukinumab (150 mg s.c. or 300 mg s.c. depending on severity of skin lesions (1, 2))  
 secukinumab 150 mg (1.0 mL PFS of 150 mg dose) administered open-label every 
4 weeks starting from Week 12 (i.e. at Week 12, 16 and 20).  
 secukinumab 300 mg (2 × 1.0 mL PFSs of 150 mg dose) administered open-label 
every 4 weeks starting from Week 12 (i.e. at Week 12, 16 and 20). 
1. Secukinumab 150 mg will be administered to patients with PsA (BSA ≤ 10% as assessed 
by PASI (Section 6.4.5), corresponding to mild psoriatic skin lesions). 
2. Secukinumab 300 mg s.c. will be administered to patients with PsA (BSA > 10% as 
assessed by PASI (Section 6.4.5), corresponding to moderate-to-severe psoriatic skin 
lesions).  
Period 3 – Week 24 to Week 52 
 secukinumab open-label at the same dose as administered in Period 2 (150 mg s.c. or 
300 mg s.c.) 
 secukinumab 150 mg (1.0 mL PFS of 150 mg dose) continued open-label every 
4 weeks starting from Week 24 (i.e. at Week 24, 28, 32, 36, 40, 44, 48 and 52). 
 secukinumab 300 mg (2 × 1.0 mL PFSs of 150 mg dose) continued open-label every 
4 weeks starting from Week 24 (i.e. at Week 24, 28, 32, 36, 40, 44, 48 and 52). 
Note: At Week 24, patients who do not reach at least a 20% improvement in TJC and SJC 
compared to Baseline with secukinumab (150 mg or 300 mg) will be withdrawn from the 
study. 
5.3 
Treatment assignment, randomization  
At Baseline (Visit 2), all eligible patients will be randomized equally via the IRT system to 
one of the 2 treatment groups (secukinumab or placebo). Within the secukinumab group, 
patients will be assigned 150 mg or 300 mg based in accordance with the severity of their 
lesions as described in Section 3.1 and Section 5.2.  
The Investigator or his/her designated unblinded qualified site staff will contact the IRT after 
confirming that the patient fulfills all the inclusion/exclusion criteria.  
The IRT will assign a randomization number to the patient, which will be used to link the 
patient to a treatment arm and will specify a unique medication number for the first package 
of investigational treatment to be dispensed to the patient. The randomization number will not 
be communicated to the site staff. 


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The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from patients and Investigator staff. A patient 
randomization list will be produced by the IRT provider using a validated system that 
automates the random assignment of patient numbers to randomization numbers. These 
randomization numbers are linked to the different treatment arms, which in turn are linked to 
medication numbers. A separate medication list will be produced by or under the 
responsibility of Novartis Drug Supply Management using a validated system that automates 
the random assignment of medication numbers to packs containing the investigational drug(s).  
The randomization scheme for patients will be reviewed and approved by a member of the 
Integrated Quantitative Sciences Randomization Group. 
5.4 
Treatment blinding 
This study consists of a 12-week double-blind period followed by a 12-week open-label 
period and a 6-month open-label extension period. 
Patients, study center personnel (excluding the unblinded pharmacist/nurse) and data analysts 
will remain blinded to the identity of the study treatment from the time of randomization until 
Week 12 using the following methods: 
1. Randomization data are kept strictly confidential until the time of unblinding and will not 
be accessible by anyone else involved in the study with the exception of the bioanalyst and 
an independent, unblinded pharmacist/nurse or authorized personnel at the investigator’s 
site who will prepare the study treatment (already provided as PFSs) for the patients. 
2. The identity of the secukinumab/placebo treatments will be concealed by the use of study 
treatments in form of PFSs for s.c. injection filled with secukinumab or placebo that are 
identical in appearance. 
The independent, unblinded pharmacist/nurse or authorized personnel will make sure that no 
other person will have access to the study treatment or study drug administration 
documentation. 
The bioanalyst will have access to the randomization list to facilitate analysis of the 
immunogenicity samples (i.e. to avoid the unnecessary analysis of placebo samples). 
The independent, unblinded pharmacist/nurse or authorized personnel will contact the IRT 
after randomization to receive the treatment assignment information. He/she will then prepare 
the study treatment, which will already have been supplied as PFSs. The independent, 
unblinded pharmacist/nurse or authorized personnel will contact the IRT again at each visit 
between Visit 2 (Baseline) and Visit 13 (Week 52) to get the treatment assignment 
information for the patient. 
Starting at Week 12 (end of Treatment Period 1/start of Treatment Period 2) patients will 
receive secukinumab (150 mg or 300 mg) in an open-label fashion. Patients, data analysts, 
and study center personnel will be unblinded to the study treatment patients will receive from 
Week 12. The Clinical Investigator and the site team will be trained during the site initiation 
visit and the Investigator Meeting to avoid discussing the treatment assigned to the patient 
with the Ultrasonography Investigator. This will be done despite opening the blind to ensure 
that the PDUS assessment will be performed without knowledge of current clinical symptoms 
of the patient. 


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A Week 24 analysis will be performed after all patients complete the Week 24 visit (see 
Section 9.6). The data analysts are not blinded after the Week 12 database lock/analyses (as 
unblinding will have occurred at Week 12 as described above). However, site personnel 
including the Ultrasonography Investigator and Clinical Investigator will be blinded to the 
original randomized treatment assignment at randomization (i.e. Baseline to Week 12) until 
the final database lock and statistical analysis have been completed. Summary results will be 
shared internally and externally; however, individual unblinded patient data will not be 
disclosed.  
A final database lock will occur when all patients have completed the study (i.e. after the last 
patient has completed the Week 64/End of Study visit or early withdrawal visit). After the 
final analysis has been conducted, patient level data including treatment group assignment can 
be shared. At that time, the Ultrasonography Investigator and Clinical Investigator will be 
unblinded to the treatment groups. 
5.5 
Treating the patient 
5.5.1 
Patient numbering 
Each patient is uniquely identified in the study by a Patient Number, which is composed of 
center number assigned by Novartis and a sequential number assigned by the Investigator. 
Once assigned to a patient, the Patient Number will not be reused. 
Upon signing the informed consent form, the patient is assigned the next sequential number 
by the Investigator. The Investigator or his/her designated unblinded qualified site staff will 
contact the IRT and provide the requested identifying information for the patient to register 
them into the IRT. The study center should select the eCRF book with a matching Patient 
Number from the electronic data capture system to enter the data.  
If the patient fails to be randomized for any reason, the IRT must be notified within 2 days 
that the patient was not randomized. The reason for not being randomized will be entered on 
the Screening Period Disposition eCRF. 
Patients may be re-screened once and will receive a new Patient Number after they have been 
re-consented. Patients who are mis-randomized cannot be re-screened. 


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5.5.2 
Dispensing the investigational treatment 
Each study site will be supplied by Novartis with investigational treatment in packaging of 
identical appearance. 
The investigational treatment packaging has a 2-part label. A unique medication number is 
printed on each part of the label, which corresponds to the placebo or active (secukinumab 
150 mg or 300 mg) treatment. Investigator staff (i.e. designated unblinded qualified site staff) 
will identify the investigational treatment packages to dispense to the patient by contacting the 
IRT and obtaining the medication numbers. Immediately before dispensing the package to the 
patient, Investigator staff (i.e. designated unblinded qualified site staff) will detach the outer 
part of the label from the packaging and affix it to the respective source document (Drug 
Label Form) for that patient. 
At the study visits preceding home study drug administration (i.e. Week 24 and Week 36) the 
Investigator will dispense, supported by the IRT system, an appropriate number of study drug 
packages for home administration at Week 28, 32, 40, 44 and 48 (Table 6-2). The Investigator 
will detach the outer part of the label from the packaging and affix it to the respective source 
document (Drug Label Form) for that patient. Detailed instructions on the self-administration 
of the study treatment will be described in the Instructions for Use (IFU) provided to each 
patient and made available to the site staff and Investigator. These instructions should be 
reviewed in detail by the patient and the site personnel. 
5.5.3 
Handling of study treatment 
5.5.3.1 
Handling of investigational treatment 
Investigational treatment must be received by a designated person at the study site, handled 
and stored safely and properly, and kept in a secured location to which only the Investigator 
and designees have access. Upon receipt, all investigational treatment should be stored 
according to the instructions specified on the labels. Clinical supplies are to be dispensed only 
in accordance with the protocol. The Investigator should educate the patient on how to 
properly store the study treatment when the patient is self-administering at home. 
Technical complaints are to be reported to the respective Novartis Country Pharma 
Organization (CPO) Quality Assurance.  
Medication labels will be in the local language and comply with the legal requirements of 
each country. They will include storage conditions for the investigational treatment but no 
information about the patient except for the medication number. 
The PFSs (150 mg active/placebo) sealed in their outer box must be stored in an access-
controlled/ locked refrigerator between 2°C and 8°C (36°F and 46°F) (Do Not Freeze) and 
protected from light. They must be carefully controlled in accordance with regulations 
governing investigational medicinal products and local regulations.  
The Investigator or his/her designated unblinded qualified site staff must maintain an accurate 
record of the shipment and dispensing of investigational treatment in a Drug Accountability 
Log. Monitoring of drug accountability will be performed by monitors during site visits or 
remotely and at the completion of the trial.  


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Patients will be asked to return all unused investigational treatment and packaging at the next 
site visit, at the end of the study or at the time of discontinuation of study drug. At the 
conclusion of the study, and as appropriate during the course of the study, the Investigator or 
designee will return all unused study drug, 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 study center.  
Destruction of the unused study drug should be done according to local requirements and after 
approval by the Novartis Clinical Team. 
5.5.3.2 
Handling of other study treatment 
Not applicable. 
5.5.4 
Instructions for prescribing and taking study treatment 
Study treatment (secukinumab (150 mg and 300 mg) and placebo provided as PFSs) will be 
self-administered s.c. by the patient throughout the study. The injections scheduled to occur at 
the study center (as outlined in Table 6-1) will be done by the patient (or caregiver) at the 
study center, under the supervision of the Investigator or study staff. Administration of study 
treatment at the study center must occur after the study assessments for the visit have been 
completed.  
The injections not scheduled to occur during a study center visit (as outlined in Table 6-2) will 
be performed by eligible patients (or caregiver) at their home. Patients will be asked to 
document all doses and dates of self-administration at home in a self-administration log and 
are required to return this log to the study center at the visit following home administration. 
The PFS with the ready-to-use study treatment solution will be provided by the study center 
staff to the patient. Detailed instructions on the self-administration of the study treatment will 
be described in the IFU and provided to each patient.  
At the Baseline visit, patients will be instructed by the study center staff, utilizing the IFU, on 
how to self-inject using a PFS. Patients will be asked to raise questions, if they have any, and 
then to proceed with self-injection. At Visit 3 (Week 1) and for subsequent study visits, 
patients will be asked to refer to the IFU and to proceed directly with self-injection of the 
study drug (i.e. no prior retraining) under the supervision of the Investigator/qualified study 
center staff. However, if the patient is not comfortable self-injecting the study drug, then 
qualified study center staff (such as study nurse) may administer it for the patient.  
At the beginning of the study, the Investigator/qualified study center staff will determine if 
self-administration is appropriate for the patient, e.g. manual dexterity, ability to follow the 
secukinumab PFS-IFU. If a patient requires a caregiver to administer study drug, the caregiver 
should be trained by the Investigator/qualified study center staff. It should be recorded on the 
Dose Administration Record/eCRF(s) whether the patient self-administered the study 
treatment at home or at the site. All patients should be trained sufficiently and be comfortable 
with study drug self-administration before the first home administration visit (i.e. before 
Week 28, Table 6-2). Patients will be instructed to contract the Investigator/study center staff 
in case of any issue during study drug home administration. 
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The first study drug administration will occur at the Baseline/randomization visit only after 
eligibility criteria have been confirmed, all study-scheduled Baseline assessments have been 
performed and the scheduled blood samples have been drawn. 
At each subsequent visit, all study assessments (as per Table 6-1) should be completed prior 
to the self-injection of the study drug. 
The Investigator should 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. The patient should be instructed to contact the Investigator if he/she is 
unable for any reason to attend a study visit as scheduled or if he/she is unable for any reason 
to take the study drug as prescribed.  
All dosages prescribed and dispensed to the patient and all dose changes during the study 
must be recorded on the Dosage Administration Record eCRF. 
Prior to, and following, self-administration at home, patients should be instructed to contact 
the Investigator/ study center staff in case they are experiencing any AEs/SAEs or have any 
concerns. 
5.5.4.1 
Subcutaneous administration with prefilled syringes 
Secukinumab solution for s.c. injection (150 mg in 1.0 mL active/placebo) will be provided in 
PFSs. The study drug solution must be injected into non-affected areas of the skin. 
Patients will be instructed by the study center staff on how to self-inject study drug using a 
PFS, following the IFU. The injections will be self-administered into the appropriate site of 
the body (thighs, arms, abdomen), and each injection should be given at a different injection 
site to reduce the risk of reaction. Each new injection should be given at least one inch from 
the previously used site. If the patient chooses the abdomen, a 2-inch area around the navel 
should be avoided. The study drug should not be injected into areas where the skin is tender, 
bruised, red, or hard, or where the patient has scars or stretch marks. 
Single PFSs will be packaged in individual boxes. The boxes containing the PFSs with study 
drug solution should be kept at 2 to 8°C (36°F and 46°F) (Do Not Freeze) and protected from 
light. Prior to administration the boxes containing the PFSs with study drug solution should be 
allowed to come to room temperature unopened for 15 to 30 minutes prior to injection. Used 
PFSs should be disposed immediately after use in a sharps container OR according to the 
regulatory needs of the respective countries. 
Any PFS for which a defect or malfunction is noticed prior to or during the injection at any of 
the study visits, must be kept at the study center until guidance is received from Novartis on 
whether it should be returned to Novartis for investigation or discarded. Devices identified as 
defective should be stored according to local guidelines, until specific instruction is discussed 
with Novartis personnel. Additionally, from Baseline onwards, any noticed defect, 
malfunction, problem during the injections or product complaints with the PFS should be 
recorded in the source document and the Use of Device eCRF. Study centers should detail the 
issue, the date, the kit number and the visit number. Study centers will be asked to record 
based on their judgment whether the observed issue was primarily related to the device or to 
the user. Device malfunctions should also be immediately reported to Novartis personnel as a 
necessary replacement kit may need to be provided. 


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5.5.5 
Permitted dose adjustments and interruptions of study treatment 
Study drug dose adjustments are not permitted. Study drug interruption should be avoided 
with the following exceptions:  
Study drug interruption is only permitted if, in the opinion of the Investigator, a patient is 
deemed to be placed at a significant safety risk unless dosing is temporarily interrupted. In 
such cases study drug should be interrupted only during the time that this risk is present and 
ongoing. Study drug can be restarted at the next scheduled visit after resolution of the safety 
risk.  
The effect of secukinumab on live vaccines is unknown; therefore live vaccines should not be 
administered during participation in the study. In case a live vaccine has been administered 
due to a medical urgency, the study drug should be interrupted for 12 weeks. 
Any study drug interruption must be recorded on the corresponding eCRF page.  
5.5.6 
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.  
If, despite concomitant medication, the patient presents with worsening of disease or does not 
seem to benefit from study treatment, necessary rescue medication with low strength opioids 
or paracetamol/acetaminophen is permitted for use alongside secukinumab prior to 
completion of Week 24 assessments. In addition, changes in NSAID concomitant therapy are 
permitted prior to Week 24 assessments as per the Investigator’s clinical judgment and 
following failure of previously authorized rescue medication (i.e. if low strength opioids or 
paracetamol/acetaminophen are not successful). 
If there is no patient improvement despite authorized rescue medication and there is a need to 
use prohibited treatments (as described in Table 5-2) prior to completion of Week 24 
assessments, patients will be discontinued from the study and enter into the follow-up period 
after completing Week 24/early withdrawal visit assessments. Efficacy will be assessed in 
detail at every study visit, and patients who are deemed not to be benefiting from the study 
treatment based upon safety and efficacy assessments by the Investigator or for any reason on 
their own accord will be free to discontinue participation in the study at any time. 
Please refer to Section 5.1.2 for details of the additional treatments (non-biologic DMARDs 
including MTX, systemic corticosteroids, and NSAIDs, low strength opioids, or 
paracetamol/acetaminophen) permitted for use alongside secukinumab in this study. Please 
refer to Section 5.5.7 for details of concomitant treatment.  
Use of rescue medication must be recorded on the appropriate page in the eCRF. 
5.5.7 
Concomitant treatment 
The Investigator should instruct the patient to notify the study site about any new medications 
(including over the counter drugs, supplements (such vitamins and calcium), and herbal 
medications) he/she takes after the patient was enrolled into the study. All medications, 


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procedures and significant non-drug therapies (including physical therapy and blood 
transfusions) administered after the patient was enrolled into the study must be recorded.  
Please refer to Section 5.1.2 for details of the additional treatments (non-biologic DMARDs 
including MTX, systemic, intra articular corticosteroids, and NSAIDs, paracetamol/ 
acetaminophen and low strength opioids) permitted for use alongside secukinumab in this 
study.  
Changes in NSAID concomitant therapy are permitted prior to Week 24 assessments as a 
rescue therapy as per the Investigator’s clinical judgment and following failure of previously 
authorized rescue medication (i.e. if low strength opioids or paracetamol/acetaminophen are 
not successful). Changes in NSAID concomitant therapy after Week 24 assessments are 
permitted as per the Investigator’s clinical judgment. After Week 24, the dose and regimen of 
other concomitant medications may also be adjusted slowly at the Investigator’s discretion 
and recorded appropriately on the CRF page. 
5.5.8 
Prohibited Treatment 
Use of the treatments displayed in Table 5-2 is NOT allowed after the start of the washout 
period unless otherwise specified below. Live vaccines should not be given until 12 weeks 
after the last study drug administration. 
Table 5-2 
Prohibited treatment 
Prohibited treatments 
Washout period  
(before randomization) 
Biological immunomodulating agents  
never 
Etanercept1 
never  
Infliximab1 
never 
Adalimumab, golimumab, certolizumab1 
never 
Ustekinumab, apremilast1  
never 
DMARD (except MTX) 
4 weeks 
Leflunomide 
8 weeks 
Leflunomide with cholestyramine washout 
4 weeks 
Unstable dose of NSAIDs† (COX1 or COX2 inhibitors) 
(until Week 24 unless rescue therapy is needed)2 
2 weeks 
Analgesics other than NSAIDs, paracetamol/acetaminophen and low 
strength opioids PRN 
2 weeks 
Systemic corticosteroids > 10 mg prednisone equivalent3 
(until Week 24) 
2 weeks 
Unstable dose of systemic corticosteroids ≤ 10 mg prednisone 
equivalent (until Week 24) 
2 weeks 
Intra-articular injections3 
4 weeks 
Intramuscular or intravenous corticosteroid treatment 
4 weeks 
Any investigational treatment or participation in any interventional 
trial 
4 weeks or 5 half-lives 
(whichever is longer) 
Live vaccinations 
6 weeks 
Oral or topical retinoids 
4 weeks 


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Prohibited treatments 
Washout period  
(before randomization) 
Photochemotherapy (e.g. PUVA) 
4 weeks 
Phototherapy (UVA or UVB) 
2 weeks 
Topical skin treatments (except in face, eyes, scalp and genital area 
during Screening, only corticosteroids with mild to moderate potency) 
2 weeks 
Abbreviations: COX: cyclo-oxygenase, DMARD: disease modifying anti-rheumatic drug, 
MTX: methotrexate, NSAIDs: non-steroidal anti-inflammatory drugs, PRN: pro re nata (as needed); 
PUVA: psoralen and ultraviolet A; TNFα: tumor necrosis factor alpha; UVA: ultraviolet A; 
UVB: ultraviolet B 
† NSAIDs authorized 
1 These agents fall under the category of biologic immunomodulators and are prohibited 
medications. Administration of these agents requires study discontinuation. 
2 Changes in NSAID concomitant therapy are permitted before Week 24 assessments as per 
Investigator’s clinical judgment and following failure of previous authorized rescue medication. 3 
See details about corticosteroid management in Section 5.1.2.3. 
5.5.9 
Discontinuation of study treatment 
Study drug must be discontinued if the Investigator determines that continuation of study drug 
would result in a significant safety risk for a patient.  
The following circumstances require study drug discontinuation: 
 Withdrawal of informed consent. 
 Emergence of the following AEs: 
a. Any severe AE or SAE that is not compatible with administration of study 
medication, including AEs that require treatment with an unacceptable co-medication. 
b. Onset of lymphoproliferative disease or any malignancy except for treated basal cell 
carcinoma, treated actinic keratoses, treated in situ carcinoma of the cervix or 
non-invasive malignant colon polyps, which are being or have been removed. 
c. Life-threatening infection. 
d. Severe hypersensitivity reaction or anaphylactic reaction. 
 Any laboratory abnormalities that in the judgment of the Investigator are clinically 
significant and are deemed to place the patient at a safety risk for continuation in the study 
(general guidance on clinically notable laboratory values is provided in Appendix 1). 
 Pregnancy. 
 Use of any biologic immunomodulating agent except secukinumab. 
 Any protocol deviation that results in a significant risk to the patient’s safety.  
In addition to these requirements for study drug discontinuation, the Investigator should 
discontinue study drug for a given patient if there is a lack of improvement or worsening of 
their symptoms, or if on balance, he/she thinks that continuation would be detrimental to the 
patient’s well-being. The Investigator should discontinue from study drug patients who have 
< 20% improvement from Baseline in either TJC or SJC at Week 24.  
For any patient whose treatment code has been broken inadvertently for any reason the 
appropriate personnel from the site and Novartis will assess whether study drug should be 


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discontinued. The Investigator must also contact the IRT to register the patient’s 
discontinuation from study drug. 
Patients may voluntarily withdraw from the study for any reason at any time. They may be 
considered withdrawn if they state an intention to withdraw, fail to return for visits, or become 
lost to follow-up for any other reason.  
If premature withdrawal occurs for any reason, the Investigator must make every effort to 
determine the primary reason for a patient’s premature withdrawal from the study and record 
this information on the appropriate Study Phase Completion eCRF. 
For patients who prematurely discontinue or withdraw during a specific treatment period, the 
Investigator should ensure that the patient completes an End of Study visit (corresponding to 
the last visit for the current period of treatment, e.g. Week 12, 24 and 52)  and also return for a 
Follow-up visit after 4 weeks of last treatment (i.e. Week 56), and 12 weeks after last study 
treatment  (i.e. at Week 64/F64) as indicated in Table 6-1. Even if the patient is not willing to 
come back for all assessments, every effort should be made to collect the scheduled PDUS 
assessments. The final visit should be performed before any new treatment is initiated. 
For patients who are lost to follow-up (i.e. those patients whose status is unclear because they 
fail to appear for study visits without stating an intention to withdraw), the Investigator should 
show “due diligence” by documenting in the source documents steps taken to contact the 
patient, e.g. dates of telephone calls, registered letters, etc. 
Patients who are prematurely withdrawn from the study will not be replaced. 
5.5.10 
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 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 
assessment table (Table 6-1).  
Novartis will continue to keep and use collected study information (including any data 
resulting from the analysis of a patient’s samples until their time of withdrawal) according to 
applicable law. 


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For US: All biological samples not yet analyzed at the time of withdrawal may still be used 
for further testing/analysis in accordance with the terms of this protocol and of the informed 
consent form.  
For Europe and Rest of World: All biological samples not yet analyzed at the time of 
withdrawal will no longer be used, unless permitted by applicable law. They will be stored 
according to applicable legal requirements. 
5.5.11 
Loss to follow-up 
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to withdraw, the Investigator should show “due diligence” by contacting the 
patient, family or family physician as agreed in the informed consent, and by documenting 
steps taken to contact the patient, e.g. dates of telephone calls, registered letters, etc. in the 
source documents. A patient should not be formally considered lost to follow-up until his/her 
scheduled end of study visit would have occurred. 
5.5.12 
Emergency breaking of assigned treatment code 
Patients, study center personnel (including the Ultrasonography Investigator, and Clinical 
Investigator) and data analysts will be fully blinded to the treatment assigned to patients at 
randomization for the first 12 weeks of the study as described in Section 5.4.  
Emergency treatment code breaks should only be undertaken when it is essential to treat the 
patient safely and efficaciously. Most often, study drug discontinuation and knowledge of the 
possible treatment assignments are sufficient to treat a study patient who presents with an 
emergency condition. Emergency treatment code breaks are performed using the IRT. When 
the Investigator contacts the system to break a treatment code for a patient, he/she must 
provide the requested patient identifying information and confirm the necessity to break the 
treatment code for the patient. The Investigator will then receive details of the investigational 
drug treatment for the specified patient and a fax or email confirming this information. The 
system will automatically inform the Novartis monitor for the site and the Global Trial Lead 
(GTL) that the code has been broken. 
It is the Investigator’s responsibility to ensure that there is a procedure in place to allow 
access to the IRT in case of emergency. The Investigator will inform the patient how to 
contact his/her backup in cases of emergency when he/she is unavailable. The Investigator 
will provide protocol number CAIN457F2354, study drug name if available, patient number, 
and instructions for contacting the local Novartis CPO (or any entity to which it has delegated 
responsibility for emergency code breaks) to the patient in case an emergency treatment code 
break is required at a time when the Investigator and backup are unavailable. 
Study drug must be discontinued after emergency unblinding. 
5.5.13 
Study completion and post-study treatment 
A patient will be considered to have completed the study if he/she received a total of 
52 weeks of study treatment and upon completion of the scheduled study assessments and 
procedures up to and including Visit F64. 


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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 
eCRF page. In any case, the Investigator or designated unblinded qualified site staff must 
contact the IRT as soon as possible to record the patient’s study completion (Visit F64) and/or 
discontinuation. 
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. This treatment may be any non-biologic DMARD. In case of a biologic 
treatment, a waiting period of 3 months before initiating the treatment is recommended. 
5.5.14 
Early study termination 
The study can be terminated at any time for any reason by Novartis. Should this be necessary, 
the patient should be seen as soon as possible and treated as a prematurely withdrawn patient 
as described in Section 6. The Investigator may be informed of additional procedures to be 
followed in order to ensure that adequate consideration is given to the protection of the 
patient’s interests. The Investigator will be responsible for informing the Institutional Review 
Boards (IRBs)/Independent Ethics Committees (IECs) of the early termination of the trial. In 
the Netherlands only, the Investigator will be responsible for informing the METc in case of 
early termination of the trial. 
5.5.15 
End of study 
The end of study will occur when the last patient has completed their last visit (i.e. Week 64 
or early withdrawal visit) in the study.  
In the Netherlands, the end date of the study will be reported to the METc within 90 days of 
study end date.  


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6 
Visit schedule and assessments 
During the period of the study from Screening to Follow-up Week 64 (F64), the assessments 
must be performed as indicated in Table 6-1.  
Patients should be seen for all visits on the designated day or as closely as possible to the 
original planned visit schedule. 
 For visits scheduled through Week 4, the study treatment should not be administered less 
than 4 days from the previous administration.  
 For visits scheduled after Week 4, the study treatment should not be administered less than 
14 days from the previous administration. 
 A visit window of ± 3 days must be observed for visits with PDUS assessments scheduled 
from Baseline through to the end of study. 
Patients who prematurely discontinue during a specific treatment period should return for the 
final visit within that treatment period (4 weeks after the last study treatment), as well as 
return for the follow-up visit (Week F64) 12 weeks after the last study treatment. 
If patients refuse to return for these assessments or are unable to do so, every effort should be 
made to contact them or a knowledgeable informant by telephone to determine the reason. 
Documentation of attempts to contact the patient should be recorded in the source 
documentation. 


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Table 6-1 
Assessment schedule 
 
Screening
Period 
Treatment  
Period 1 
Treatment 
Period 2 
Extension
Period 
Follow-
up 
Week 
-1 to -4
to  
BSL 
BSL 1 
2 
3 
4 
8 124 16 20
24†7 
TD/ 
PSW 
36 
52 
 
56†7
TD/
PSW
F647
TD/
PSW
Visit No. 
11 
2 
3
4
5
6 
7 
8 
9 10
11 
12
13
14
15
Informed consent  
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant medical history/ current medical condition 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Smoking history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiovascular medical history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Psoriasis/PsA medical history and previous therapies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CASPAR criteria  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination1 
X 
X X
X
X
X
X
X
X
X
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
 
 
 
 
 
X
 
 
X 
 
 
X 
X 
Vital signs 
X 
X X
X
X
X
X
X
X
X
X 
X 
X 
X 
X 
PPD skin test2 or QuantiFERON TB-Gold test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray / MRI3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization via IRT 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
IRT contact such as for registration or drug supply 
including home administration. 
X 
X X
X
X
X
X
X X
X
X 
X 
X 
 
 
Administration of s.c. study treatment via PFS at study 
site4 (see Table 6-2 for timing of home 
 
X X
X
X
X
X
X4 X
X
X# 
X 
X 
 
 


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Screening
Period 
Treatment  
Period 1 
Treatment 
Period 2 
Extension
Period 
Follow-
up 
Week 
-1 to -4
to  
BSL 
BSL 1 
2 
3 
4 
8 124 16 20
24†7 
TD/ 
PSW 
36 
52 
 
56†7
TD/ 
PSW 
F647
TD/
PSW
Visit No. 
11 
2 
3
4
5
6 
7 
8 
9 10
11 
12 13
14
15
administrations) 
Check self-administration log for home administration 
 
 
 
 
 
 
 
 
 
 
 
X 
X 
 
 
Prior/concomitant medication/ non-drug therapy 
X 
Update as needed 
AEs/SAEs5  
(incl. injection site reaction & occurrence of infections)
X 
Update as needed 
Hematology, blood chemistry, urinalysis 
X 
X 
 
 
 
X
 
X
 
 
X 
X 
X 
X 
 
Hepatitis B, C or HIV serology** (only in countries 
where required)** 
S 
S 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test6 
 
X 
 
 
 
X
 
X
X
 
X 
X 
X 
X 
 
Immunogenicity 
 
X 
 
 
 
 
 
X
 
 
X 
 
X 
 
X 
Pharmacokinetic assessments 
 
X 
 
 
 
 
 
X
 
 
X 
 
X 
 
X 
Antinuclear antibodies (ANA) 
 
X 
 
 
 
 
 
X
 
 
X 
 
X 
 
X 
Anti-dsDNA 
 
X 
 
 
 
 
 
X
 
 
X 
 
X 
 
X 
Anti-CCP 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Rheumatoid factor (RF) 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
High sensitivity C-reactive protein (hsCRP)  
X 
X X
X
 
X
X
X
X
X
X 
X 
X 
X 
X 
PDUS of affected joints out of 48* 
X 
X X
X
 
X
X
X
X
X
X 
X 
X 
 
 
PDUS of enthesitis sites out of 5 entheses* 
X 
X X
X
 
X
X
X
X
X
X 
X 
X 
 
 


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Screening
Period 
Treatment  
Period 1 
Treatment 
Period 2 
Extension
Period 
Follow-
up 
Week 
-1 to -4
to  
BSL 
BSL 1 
2 
3 
4 
8 124 16 20
24†7 
TD/ 
PSW 
36 
52 
 
56†7
TD/ 
PSW 
F647
TD/
PSW
Visit No. 
11 
2 
3
4
5
6 
7 
8 
9 10
11 
12 13
14
15
Leeds Dactylitis Index  
X 
X X
X 
 
X
X
X
X
X
X 
X 
X 
 
 
Tender and swollen joint counts (TJC 78, SJC 76) 
X 
X X
X
 
X
X
X
X
X
X 
X 
X 
X 
 
Patient’s assessment of PsA pain (VAS) 
 
X X
X
 
X
X
X
X
X
X 
X 
X 
X 
 
Patient’s global assessment of disease activity (VAS) 
 
X X
X
 
X
X
X
X
X
X 
X 
X 
X 
 
SPARCC  
X 
X X
X
 
X
X
X
X
X
X 
X 
X 
X 
 
Physician’s global assessment of disease activity 
(VAS) 
 
X X
X
 
X
X
X
X
X
X 
X 
X 
X 
 
Health assessment questionnaire (HAQ-DI©) 
 
X X
X
 
X
X
X
X
X
X 
X 
X 
X 
 
PASI scoring (only if ≥ 3% of BSA at BSL or after) 
 
X X
X
 
X
X
X
X
X
X 
X 
X 
X 
 
Treatment period 1 completion form 
 
 
 
 
 
 
 
X
 
 
 
 
 
 
 
Treatment period 2 completion form 
 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
Treatment period 3 completion form 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
Follow-up completion form 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Abbreviations:  
AE: adverse event, anti-CCP: anti-cyclic citrullinated peptide, BSA: body surface area, BSL: baseline, CASPAR: Classification of psoriatic arthritis,  
HAQ-DI©: Health assessment questionnaire-disability index, HIV: human immunodeficiency virus, hsCRP: high sensitivity C-reactive protein,  
IRT: interactive response technology, MRI: magnetic resonance imaging, PDUS: power Doppler ultrasound, PFS: prefilled syringe, PPD: purified protein 
derivative, PsA: psoriatic arthritis, PSW: premature subject withdrawal, RF: rheumatoid factor, SAE: serious adverse event, SJC: swollen joint count, 
SPARCC: Spondyloarthritis Research Consortium of Canada, TD: study treatment discontinuation, TJC: tender joint count, VAS: visual analog scale. 
 
 


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** Hepatitis B and/or hepatitis C and/or HIV serology testing to be performed during screening period only if required as per local medical practice or local 
regulations prior to initiation of therapy. These assessments will be documented in source records only and will not be entered into the eCRF.  
* A visit window of ± 3 days must be observed for PDUS assessments scheduled from Baseline to the end of study. 
Note: this study consists of 3 treatment periods: Period 1 (Baseline to Week 12), Period 2 (Week 12 to Week 24) and Period 3 (Week 24 to Week 52) 
1 These assessments are source documentation only and will not be entered into the eCRF. 
2 The PPD skin test can be performed at any time during the Screening period but it has to be read within 72 hours and before randomization.  
3 If patients do not have a chest X-ray available within 3 months of Screening, an X-ray should be performed after it is certain the patient meets 
inclusion/exclusion criteria in order to minimize unnecessary exposure to X-ray radiation. In some sites selected by Novartis, the X-ray assessment may 
be replaced by chest MRI assessment. 
4 All patients will be assigned to open-label secukinumab from Week 12: 
Patients in Group 1 (secukinumab 150 mg or 300 mg) will continue to receive the same dose every 4 weeks but in an open-label fashion (with no 
placebo injections for patients assigned secukinumab 150 mg) starting from Week 12.  
Patients assigned to Group 2 (placebo) at randomization will switch to open-label secukinumab treatment (150 mg or 300 mg s.c.) starting from 
Week 12; secukinumab dosing will be every 4 weeks starting from Week 12 (with no loading dose).  
5 AEs /SAEs that occur after the patient has signed the informed consent (including those that occur during home administration of study drug) must be 
captured on the appropriate eCRF page. Any AEs that are treatment-emergent should be reported until 12 weeks after the last study treatment..  
6 Kits will be provided by the central laboratory and tests will be performed locally.  
7 These assessments are also to be conducted for patients who discontinue.  
† Patients who prematurely discontinue during Treatment Period 1 should return for assessments associated with Week 12 visit (4 weeks after the last 
study treatment in Treatment Period 1) and the final follow-up visit (Week F64) 12 weeks after the last study treatment.  
† Patients who prematurely discontinue during Treatment Period 2 should return and complete assessments associated with Week 24 visit (4 weeks 
after the last study treatment in Treatment Period 2) and the final follow-up visit (Week F64) 12 weeks after the last study treatment. 
† Patients who prematurely discontinue during the Extension Period should return for assessments associated with the Week 56 visit (4 weeks after the 
last study treatment) and the final follow-up visit (Week F64) 12 weeks after the last study treatment. 
# The dose at Week 24 will be administered only if the patient signs the ICF for participating in the Extension Treatment period of the study. 


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Table 6-2 
Overview of study drug administration 
 
Treatment Period 1 
Treatment Period 2
Extension period 
Week 
BSL 
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48 
52 
Study visit 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
 
 
12 
 
 
 
13 
Study drug 
administration 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
All Groups 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
H 
H 
S 
H 
H 
H 
S 
Abbreviations: BSL = baseline, H = home administration; S = administration at study center 


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6.1 
Information to be collected on screening failures 
All patients who have signed informed consent but who are not entered into the treatment 
period will have the study completion page for the Screening period, demographics, 
inclusion/exclusion, and SAE data collected. Adverse events that are not SAEs will be 
followed by the Investigator and collected only in the source data. The reason for screening 
failure will be recorded in the CRF.  
6.2 
Patient demographics/other baseline characteristics 
Patient demographic and Baseline characteristic data to be collected on all patients and 
recorded in the eCRF include: 
 Date of birth, age, sex, race, ethnicity and source of patient referral. 
 Relevant PsA/psoriasis and general medical history/current medical condition data until 
the start of study drug, such as date of diagnosis of PsA/psoriasis, previous PsA/psoriasis 
therapies, BSA, severity of skin lesions, cardiovascular medical history, and smoking 
history. The SPARCC will be assessed at both the Screening and Baseline Visit. 
Whenever possible, diagnoses and not symptoms will be recorded. 
6.3 
Treatment exposure and compliance 
All doses of study drug administered will be recorded on the appropriate Dosage 
Administration Record eCRF page by the designated unblinded qualified site staff. Study 
drug doses and corresponding dates of self-administration at home should be documented by 
the patient in a self-administration log. Patients are required to return the self-administration 
log as well as all dispensed study drug material at every visit back to the study center for a 
compliance check.  
Patient compliance to the study drug should be assessed by qualified site personnel at each 
study visit using the study kits and documentation regarding study drug dispensation and 
administration. Compliance will also be assessed continuously during the conduct of the study 
by Novartis study personnel using medication kits and corresponding documentation. 
6.4 
Efficacy 
The efficacy outcome measures used in this study are as follows: 
 OMERACT/EULAR global synovitis score and its components 
 OMERACT enthesitis score and its morphological components 
 American College of Rheumatology (ACR) 20, 50 and 70 responses 
 Spondyloarthritis Research Consortium of Canada (SPARCC) 
 Swollen joint count (SJC)/Tender joint count (TJC) 
 Patient’s global assessment of disease activity (Visual Analog Scale (VAS)) 
 Physician’s global assessment (PGA) of disease activity (VAS) 
 Patient’s assessment of PsA pain intensity (VAS) 
 Health assessment questionnaire – disability index (HAQ-DI©) 


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 Minimal disease activity (MDA) 
 Psoriasis area and severity index (PASI)  
All efficacy assessments should be performed prior to administration of study drug. 
6.4.1 
Power Doppler Ultrasonography 
PDUS evaluation will be performed at each joint site out of 48 and at each enthesis site out of 
5 entheses by an independent expert in musculoskeletal ultrasound, who will be blinded to the 
patient’s identity, symptoms and clinical evaluations. The processing settings will be kept 
constant during the examination and the temperature of the room will be kept stable at 20°C. 
The PDUS will be performed bilaterally for 24 pairs of joints: 
 Metacarpophalangeal (MCP) joints 1 to 5. 
 Proximal interphalangeal (PIP) joints 1 to 5. 
 Metatarsophalangeal (MTP) joints 1 to 5. 
 Wrist, elbow, shoulder (glenohumeral), knee, and ankle (tibiotalar). 
 Distal interphalangeal (DIP) 2 to 5. 
The PDUS assessment will consist of an evaluation of hypoechoic synovial hyperplasia (SH) 
and joint effusion (JE) using Grayscale and synovial vascularization using Power Doppler. 
The pre-specified set of 24 paired joints will be scanned at each visit from the dorsal aspect 
with the joint in a neutral position, except for the knee, which will also be examined in a 
flexed position (30°). Note: only affected joints will be assessed after Visit 2 (Baseline). 
Standardized joint and probe positions will be used based on a reference atlas, which also 
show examples of synovitis grading for each site examined. The presence of synovitis (i.e. SH 
and Power Doppler, without JE) will be scored according to the OMERACT-EULAR PDUS 
composite semi-quantitative scale (0 to 3) using high resolution PDUS machines as described 
in Appendix 6 and Appendix 9. 
For the enthesis evaluation, ultrasound will be initially performed in B mode to detect 
morphologic abnormalities, and subsequently with power Doppler to detect abnormal 
vascularization at bony insertions. The following entheses will be examined bilaterally: 
1. Common extensor tendon at its insertion at the lateral humeral epicondyle. 
2. Quadriceps tendon at its insertion at the superior pole of the patella. 
3. Patellar tendon at its proximal insertion at the inferior pole of the patella. 
4. Patellar tendon at its distal insertion at the tibia tuberosity. 
5. Calcaneal insertions:  
a. Achilles tendon at its insertion at the calcaneus. 
b. Plantar aponeuroses at its insertion at the calcaneus. 
Each affected enthesis out of 5 targeted entheses will be scored in terms of inflammatory and 
morphological 
components 
according 
to 
the 
OMERACT 
enthesitis 
composite 
semi-quantitative scale (0 to 3) as described in Appendix 7.  
The total time required for each PDUS assessment of joint inflammation and enthesitis in the 
study will be recorded in the eCRF in order to evaluate the variability of time spent by 
ultrasonographers to assess multiple joints and enthesitis across the sites. 


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Quality control assessment of the scoring will be performed for the first patient included from 
each center and once all patients have completed the study (i.e. following the last patient’s last 
visit) when the last patient enrolled in the trial has completed their last visit. Please refer to 
Appendix 6.  
The name and type of PDUS machine used will also be recorded in the eCRF. PDUS 
equipment recommendations are described in Appendix 9.  


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6.4.2 
American College of Rheumatology response 
The ACR response (Appendix 4) will be used to determine efficacy (Felson 1995). A patient 
is defined as e.g. an ACR 20 responder if, and only if, the following 3 conditions hold: 
 Patient has a ≥ 20% improvement in the number of tender joints (based on 78 joints).  
 Patient has a ≥ 20% improvement in the number of swollen joints (based on 76 joints). 
 Patient has a ≥ 20% improvement in 3 of the following 5 domains: 
1. Patient’s global assessment of disease activity (measured on a VAS scale, 0-100).  
2. Physician’s global assessment of disease activity (measured on a VAS scale, 0-100).  
3. Patient’s assessment of PsA pain (measured on a VAS scale, 0-100). 
4. Health Assessment Questionnaire-Disability Index (HAQ-DI©) score. 
5. Acute phase reactant (high-sensitivity C-reactive protein (hsCRP)). 
An ACR 50 response is defined as a 50% improvement in at least 3 of the 5 measures and a 
50% improvement in the SJC and TJC. 
An ACR 70 response is defined as a 70% improvement in at least 3 of the 5 measures and a 
70% improvement in the SJC and TJC. 
The ACR response is to be assessed at the visits/time points shown in Table 6-1.  
6.4.2.1 
Swollen joint count/ tender joint count 
Joint counts will be performed by the independent assessor (i.e. the Clinical Investigator) who 
must be well trained and part of the site personnel. Whenever possible, the same evaluator 
should perform these assessments at all visits. The 78 joints assessed for tenderness include 
the 2 temporomandibular, 2 sternoclavicular, 2 acromioclavicular joints, 2 shoulders, 2 
elbows, 2 wrists, 2 first carpometacarpal, 10 MCP, 10 PIP, 8 DIP joints of the hands, the 2 
hip, 2 knee, 2 talo-tibial, 2 mid-tarsal, 10 MTP, 10 PIP, and 8 DIP joints of the feet. All of 
these except for the hips are assessed for swelling. Joint tenderness and swelling are to be 
graded present (1) or absent (0). Synovial fluid and/or soft tissue swelling but not bony 
overgrowth represents a positive result for SJC.  
Data is recorded for tender and swollen joints (right or left side), i.e. a box (no, yes or not 
applicable) needs to be ticked for all joints. The total number of tender and swollen joints 
(right and left) will be automatically calculated in the eCRF. For more information, please 
refer to Appendix 5. 
6.4.2.2 
Patient’s global assessment of disease activity 
The patient’s global assessment of disease activity will be performed using 100 mm VAS 
ranging from ”very good” to ”very poor”, after the question "Considering all the ways PsA 
affects you, please indicate with a vertical mark ( | ) through the horizontal line how well you 
are doing today”. 
6.4.2.3 
Physician’s global assessment of disease activity 
The PGA of disease activity will be performed using 100 mm VAS ranging from no disease 
activity to maximal disease activity, after the question “Considering all the ways the disease 
affects your patient, draw a line on the scale for how well his or her condition is today.” To 


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enhance objectivity, the physician must not be aware of the specific patient’s global 
assessment of disease activity when performing his own assessment on that patient. 
6.4.2.4 
Patient assessment of psoriatic arthritis pain intensity 
The patient’s assessment of pain will be performed using 100 mm VAS ranging from “no 
pain” to “unbearable pain” after the question “Please indicate with a vertical mark ( | ) through 
the horizontal line the most pain you had from your PsA today”. 
6.4.2.5 
Health assessment questionnaire – disability index 
The HAQ-DI© was developed by Stanford University and is one of the most widely used 
measures to assess the long-term influence of chronic disease on a patient's level of functional 
ability and activity restriction. The disability assessment component of the HAQ, the 
HAQ-DI©, assesses a patient's level of functional ability and includes questions of fine 
movements of the upper extremity, locomotor activities of the lower extremity, and activities 
that involve both upper and lower extremities. There are 20 questions in 8 categories of 
functioning including dressing, rising, eating, walking, hygiene, reach, grip, and usual 
activities. The stem of each item asks over the past week “Are you able to …” perform a 
particular task. Each item is scored on a 4-point scale from 0 to 3, representing normal 
(normal, no difficulty (0)), some difficulty (1), much difficulty (2), and unable to do (3). The 
purpose of the HAQ-DI© in this study is to assess the functional ability of patients with PsA. 
6.4.2.6 
High sensitivity C-reactive protein 
Blood for this assessment will be obtained in order to identify the presence of inflammation, 
to determine its severity, and to monitor response to treatment. Since the results of this test 
may unblind study personnel (such as the Ultrasonography Investigator and Clinical 
Investigator), results from the central laboratory will be provided for Screening and Baseline 
only. The hsCRP results from samples collected during the treatment period will be revealed 
following database lock only. 
6.4.3 
Minimal disease activity 
The proportion of patients achieving MDA (Coates 2010) (5 of the 7 following: ≤ 1 TJC, 
≤ 1 SJC, PASI ≤ 1 or BSA with PsA < 3%, patient pain VAS ≤ 15, patient global VAS ≤ 20, 
HAQ-DI© ≤ 0.5, and tender entheseal points ≤ 1).  
6.4.4 
Spondyloarthritis research consortium of Canada – enthesitis index 
The SPARCC (Maksymowych et al 2009) enthesitis index focuses on the clinical evaluation 
and validation of the 16 sites shown in Table 6-3. SPARCC assessments will be performed as 
indicated in the schedule of assessments (Table 6-1).  


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Table 6-3 
Entheses sites comprising the total spondyloarthritis research 
consortium of Canada enthesitis index 
Greater trochanter  
R/L 
Quadriceps tendon insertion into the patella  
R/L 
Patellar ligament insertion into the patella and tibial tuberosity 
R/L 
Achilles tendon insertion 
R/L 
Plantar fascia insertion 
R/L 
Medial epicondyles 
R/L 
Lateral epicondyles 
R/L 
Supraspinatus insertion 
R/L 
Abbreviations: R = right, L = left 
Note: Tenderness at each site is quantified on a dichotomous basis: 0= non-tender and 1= tender. 
Range of scores: 0 to 16 
6.4.5 
Psoriasis area and severity index 
The percentage BSA affected by psoriatic skin involvement will be performed using PASI for 
patients at Baseline and Week 12 (as applicable) to assess the dose of secukinumab required. 
Patients with a BSA ≤ 10% will be assigned secukinumab 150 mg while those with a BSA 
> 10% will be assigned secukinumab 300 mg as described in Section 5.5.4.  
The PASI assessment will be conducted for patients in whom at least 3% of the BSA was 
affected by psoriatic skin involvement at Baseline. The PASI assesses the extent of psoriasis 
on 4 body surface areas (head, trunk and upper and lower limbs) and the degree of plaque 
erythema, scaling and thickness. A PASI score (Fredriksson and Pettersson 1978, Weisman 
2003, Gottlieb 2005) will be derived as indicated in Table 6-4. PASI scoring will be 
conducted during the study for all patients with a BSA ≥ 3% at Baseline and for patients with 
a BSA ≥ 3% at subsequent visits (i.e. if not ≥ 3% at Baseline). 
The head, trunk, upper limbs and lower limbs are assessed separately for erythema, thickening 
(plaque elevation, induration), and scaling (desquamation). The average degree of severity of 
each sign in each of the 4 body regions is assigned a score of 0-4. The area covered by lesions 
on each body region is estimated as a percentage of the total area of that particular body 
region. Further practical details help the assessment:  
1. The neck is assessed as part of the head. 
2. The axillae and groin are assessed as part of the trunk. 
3. The buttocks are assessed as part of the lower limbs. 
4. When scoring the severity of erythema, scales should not be removed. 
Because the head and neck, upper limbs, trunk and lower limbs correspond to approximately 
10%, 20%, 30% and 40% of the BSA, respectively, the PASI score is calculated using the 
formula: 
PASI =  
0.1 (EH+IH+DH)AH + 0.2(EU+IU+DU)AU + 0.3(ET+IT+DT)AT + 0.4(EL+IL+DL)AL 
The keys for the letters are provided in Table 6-4. 


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PASI scores can range from 0 corresponding to no signs of psoriasis to a theoretic maximum 
of 72.0.  
Table 6-4 
Psoriasis area and severity index 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 
6.4.5.1 
Definitions of efficacy variables based on psoriasis area and severity 
index 
The following definitions will be used in this study based on the Committee for Medicinal 
Products for Human Use (CHMP) guidelines for psoriasis (CHMP/EWP/2454/02 corr): 
 PASI 75 response: patients achieving ≥ 75% improvement (reduction) in PASI score 
compared to Baseline are defined as PASI 75 responders. 
 PASI 90 response: patients achieving ≥ 90% improvement (reduction) in PASI score 
compared to Baseline are defined as PASI 90 responders. 


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6.4.5.2 
Leeds Dactylitis Index (LDI) 
The Leeds Dactylitis Index (LDI) (Helliwell 2005) 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. The ratio of 
circumference is multiplied by a tenderness score, using a modification of LDI which is a 
binary score (1 for tender, 0 for non-tender). If both sides are considered involved, or the 
circumference of the contralateral digit cannot be obtained, the number will be compared to 
data provided in the standard reference tables (see Appendix 11). This modification is referred 
to as LDI basic and will be applied in this study. The LDI requires a finger circumference 
gauge or a tape measure to measure digital circumference. 
6.4.6 
Appropriateness of efficacy assessments 
Power Doppler ultrasound (PDUS), which allows the assessment of both inflammatory 
changes and structural damage, has been shown to be a valid and reliable tool for evaluating 
spondyloarthritis enthesitis (de Miguel et al 2009, D’Agostino et al 2011). The use of PDUS 
for monitoring pathological findings indicative of joint or soft tissue involvement in patients 
with PsA has already been demonstrated for patients treated with anti-TNFα therapy. This 
study will evaluate the use of PDUS for assessing the response to secukinumab (150 mg and 
300 mg s.c.) in terms of the change in the synovium of target joints and peripheral entheses in 
patients with moderate-to-severe PsA who have had an IR to non-biologic DMARD therapy. 
All other efficacy outcome measures used in this study are standard measures used across 
many PsA trials and are consistent with the measures used in the Phase 3 clinical trials in PsA 
with secukinumab.  
6.5 
Safety 
Safety assessments will consist of the evaluation of all AEs and SAEs including injection site 
reactions, physical examination, vital signs and laboratory assessments. An assessment of 
anti-secukinumab antibody development (immunogenicity) will also be performed. 
All blood draws and safety assessments should be done prior to study drug administration. 
Relevant safety assessments (e.g. evaluation of AEs and SAEs including injection site 
reactions) should be repeated after the dose is administered. 
 Incidence and severity of AEs/SAEs. 
 Physical examinations. 
 Vital signs. 
 Height and weight. 
 QuantiFERON TB-Gold test or PPD skin test. 
 Chest X-Ray or MRI  
 Local tolerability (injection site reactions). 
 Laboratory evaluations (hematology, clinical chemistry, urinalysis). 
 Pregnancy and assessment of fertility. 
 Tolerability of secukinumab. 
 Immunogenicity. 


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6.5.1 
Physical examination  
A complete physical examination will include the examination of general appearance, skin, 
neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph 
nodes, extremities, vascular and neurological. If indicated based on medical history and/or 
symptoms, rectal, external genitalia, breast, and pelvic examinations will be performed. 
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 AE eCRF. 
6.5.2 
Vital signs 
Vital signs will include blood pressure and pulse measurements. After the patient has been 
sitting for 5 minutes, with back supported and both feet placed on the floor, systolic and 
diastolic blood pressure will be measured 3 times using an automated validated device, e.g. 
OMRON, with an appropriately sized cuff. The repeat sitting measurements will be made at 
1 to 2 minute intervals and the mean of the 3 measurements will be used. In case the cuff sizes 
available are not large enough for the patient’s arm, a sphygmomanometer with an 
appropriately-sized cuff may be used. 
If possible, vital signs assessments should be performed by the same study site staff member 
using the same validated device throughout the study. 
6.5.3 
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 scale throughout the study. 
6.5.4 
QuantiFERON TB-Gold test or PPD skin test 
Either a QuantiFERON TB-Gold test or a PPD skin test must be performed at Screening. 
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 
tuberculosis, or if presence of latent tuberculosis is established then treatment according to 
local country guidelines must have been initiated. 
QuantiFERON TB-Gold test 
 A QuantiFERON TB-Gold test is to be performed at the Screening visit and the results to 
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. 
 The test will be analyzed by the central laboratory. Details on the collection, processing 
and shipment of samples and reporting of results by the central laboratory are provided in 
the laboratory manual. 


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PPD skin test 
A PPD skin test is to be performed at Screening and read before randomization to determine 
the patient’s eligibility for the study. The test dose is bioequivalent to 5 tuberculin units of 
standard PPD injected intradermally, usually into the volar surface of the forearm. The site is 
cleaned and the PPD extract is then injected into the most superficial layer under the skin. If 
given correctly, the injection should raise a small wheal of about 5 mm, which resolves within 
10-15 minutes. 
Because the reaction (induration) will take 48-72 hours to develop, the patients must return to 
the Investigator’s site within that time for a proper evaluation of the injection site. This will 
determine whether the patient has had a significant reaction to the PPD test. A reaction is 
measured in millimeters of induration (hard swelling) at the site. A PPD skin induration 
≥ 5 mm (or according to local practice/guidelines) is interpreted as a positive result. 
6.5.5 
Laboratory evaluations  
A central laboratory will be used for analysis of all specimens collected as listed below 
(except urinalysis). Details on the collection, shipment of samples and reporting of results by 
the central laboratory are provided in the laboratory manual. For the identification of 
clinically notable values, see Appendix 1. All patients with laboratory tests containing 
clinically significant abnormal values are to be followed until the values return to normal 
ranges or until a valid reason, other than treatment-related AE, is defined. 
6.5.5.1 
Hematology 
Hemoglobin, platelet, red blood cell (RBC), white blood cell (WBC) and differential WBC 
counts will be measured at scheduled visits. 
6.5.5.2 
Clinical chemistry 
Serum chemistries will include glucose, urea, creatinine, total bilirubin, AST/SGOT, 
ALT/SGPT, gamma glutamyl transferase (GGT), alkaline phosphatase, sodium, potassium, 
bicarbonate, calcium, phosphorous, total protein, albumin, and uric acid.  
6.5.5.3 
Urinalysis 
Dipsticks will be provided by the central laboratory to the sites for local urinalysis 
assessments. The urinalysis results for standard parameters such as protein, glucose, blood 
and WBCs will be recorded in the appropriate eCRF page.  
6.5.5.4 
Pregnancy and assessments of fertility  
Secukinumab must not be given to pregnant women; therefore effective methods of birth 
control must be used for women of child-bearing potential (see exclusion criteria definitions, 
Section 4.2). 
A serum β-hCG test will be performed in all women at Visit 1 (Screening). All women of 
child bearing potential at Screening will have local urine pregnancy tests as indicated in 
Table 6-1. A positive urine pregnancy test requires immediate interruption of study treatment 
until serum β-hCG is performed and found to be negative. If positive, the patient must be 
discontinued from the trial. 


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6.5.6 
Tolerability of secukinumab 
Tolerability will be assessed by AEs, laboratory values, injection site reaction, and 
immunogenicity (see Section 6.5.8). 
6.5.7 
Additional parameters 
Blood will be obtained at the Screening visit (Visit 1) for anti-CCP antibodies and the 
Rheumatoid Factor (RF). Antinuclear antibodies (ANA) and anti-dsDNA antibodies will also 
be assessed at the visits/time points indicated in Table 6-1.    
6.5.8 
Immunogenicity 
Blood samples for immunogenicity (anti-AIN457 antibodies) will be taken pre-dose at the 
scheduled time points as indicated in Table 6-1.   
In addition, if a patient discontinues from the study at any time point, he/she will need to 
provide a sample at the last visit. The actual sample collection date and exact time will be 
entered on the Immunogenicity Blood collection eCRF. Sampling problems will be noted in 
the comment section of the eCRF. 
All blood samples will be taken by either direct venipuncture or an indwelling cannula 
inserted in a forearm vein. 
A laboratory manual will be provided to Investigators with detailed information on sample 
collection, handling and shipment. 
Tubes and preprinted labels will be provided by the central laboratory to the study centers. 
Analytical method 
An electrochemiluminescence method will be used for the detection of potential 
anti-secukinumab antibody formation. The detailed method description to assess 
immunogenicity will be described in the bioanalytical raw data of the study and in the 
respective Bioanalytical Data Report. 
Table 6-5 
Immunogenicity sample log 
Week  
Immunogenicity Sample Log* 
0 
301 
12 
302  
24 
303 
52 
304 
64 
305 
* If an IG sample is collected at an unscheduled visit, the sample numbers will follow the 
pattern: 3001, 3002, etc. 


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6.5.9 
Appropriateness of safety measurements  
The safety measures used in this study are reliable and relevant standard measures for a 
biologic in PsA. A chest X-ray 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 tuberculosis. The radiation exposure that results from the chest X-ray safety 
measurements are estimated to be far below 1 mS. For effective radiation doses below 3 mS 
(300 mrem), the risk is considered to be minimal. Therefore, the radiation exposure in this 
study involves minimal risk and is necessary to ensure reliable safety measures before the 
treatment with a biologic. 
6.6 
Other assessments 
No additional tests will be performed on patients entered into this study.  
6.6.1 
Resource utilization 
Not applicable. 
6.6.2 
Pharmacokinetics 
Pharmacokinetic samples will be obtained for all patients and the secukinumab concentrations 
will be assessed in the serum. The PK samples will be collected pre-dose at scheduled visits/ 
time points as indicated in Table 6-1 and Table 6-6. All blood samples will be drawn by direct 
venipuncture in a forearm vein. The actual sample collection date and exact time will be 
entered on the PK blood collection summary eCRF.  
Sampling problems will be noted in the comments section of the eCRF. 
The bioanalyst will receive a copy of the randomization schedule to facilitate analysis of the 
PK samples. The bioanalyst will provide the sample concentration data to the team under 
blinded conditions. The bioanalyst will keep this information confidential until clinical 
database lock.  
Table 6-6 
Pharmacokinetic sample log 
Week  
Timepoint 
PK Sample No.* 
PK Collection No. 
Baseline 
0 (pre-dose) 
1 
1 
Week 12 
2016 h (pre-dose) 
2 
1 
Week 24  
4032 h (pre-dose) 
3 
1 
Week 52 
8736 h (pre-dose) 
4 
1 
Week F64 
10752 h (anytime) 
5 
1 
* If a PK sample is collected at an unscheduled visit, the sample numbers will 
follow the pattern: 1001, 1002 etc.  
Pharmacokinetic sample handling, labeling and shipment instructions 
Laboratory manuals will be provided by the central laboratory with detailed information on 
sample collection, sample handling and shipment. Tubes and labels will be provided by the 
central laboratory with study/sample type information pre-printed on the label. 


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Analytical methods 
An ELISA method will be used for bioanalytical analysis of secukinumab in serum, with an 
anticipated lower limit of quantification (LLOQ) of 80 ng/mL. The detailed method 
description to assess secukinumab concentration will be described in the bioanalytical raw 
data of the study and in the respective Bioanalytical Data Report (BDR). 
6.6.3 
Other biomarkers 
Not applicable. 
7 
Safety monitoring 
7.1 
Adverse events 
An AE is any untoward medical occurrence (i.e. 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 
until the end of study visit. 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 product are also considered an 
AE irrespective if a clinical event has occurred. 
The occurrence of AEs should be sought by non-directive questioning of the patient at each 
visit during the study. Adverse events also may be detected when they are volunteered by the 
patient during or between visits or through physical examination, laboratory test, or other 
assessments. 
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 should be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
Baseline or the previous visit, or values which are considered to be non-typical in patient with 
underlying disease. Investigators have the responsibility for managing the safety of individual 
patient and identifying AEs. Alert ranges for labs and other test abnormalities are included in 
Appendix 1. 
Adverse events should be recorded in the AE eCRF under the signs, symptoms or diagnosis 
associated with them, accompanied by the following information. 
 The severity grade 
 Mild: usually transient in nature and generally not interfering with normal activities. 
 Moderate: sufficiently discomforting to interfere with normal activities. 
 Severe: prevents normal activities. 
 Its relationship to the study drug (no/yes). 


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 Its duration (start and end dates) or if the event is ongoing an outcome of not recovered/ 
not resolved should be reported. 
 Whether it constitutes a SAE (see Section 7.2 for definition of SAE). 
 Action taken regarding study drug. 
All AEs should be treated appropriately. Treatment may include one or more of the following 
and this should be recorded in the CRF:  
 No action taken (i.e. further observation only). 
 Study drug dosage adjusted/temporarily interrupted. 
 Study drug permanently discontinued due to this ae. 
 Concomitant medication given. 
 Non-drug therapy given.  
 Patient hospitalized/patient’s hospitalization prolonged.  
 Its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown). 
Once an AE is detected, it should be followed until its resolution or until it is judged to be 
permanent, and assessment should be made at each visit (or more frequently, if necessary) of 
any changes in severity, the suspected relationship to the study drug, the interventions 
required to treat it, and the outcome. 
Information about common side effects already known about the investigational drug can be 
found in the IB or will be communicated between IB updates in the form of Investigator 
Notifications. This information will be included in the patient informed consent and should be 
discussed with the patient during the study as needed. 
The Investigator should also instruct each patient to report any new AE (beyond the protocol 
observation period) that the patient, or the patient’s personal physician, believes might 
reasonably be related to the study drug. This information should be recorded in the 
Investigator’s source documents; however, if the AE meets the criteria of an SAE, it must be 
reported to Novartis. 
7.2 
Serious adverse events 
7.2.1 
Definition of SAE 
An SAE is defined as any 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: 
 Is fatal or life-threatening. 
 Results in persistent or significant disability/incapacity. 
 Constitutes a congenital anomaly/birth defect. 
 Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
 Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition. 


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 Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent. 
 Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission. 
 Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition. 
 Is medically significant, i.e. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention. 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
Life-threatening in the context of a SAE refers to a reaction in which the patient was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if more severe (see Annex IV, ICH-E2D Guideline). 
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalization but might jeopardize the 
patient or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization or 
development of dependency or abuse (see Annex IV, ICH-E2D Guideline). 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All AEs (serious and non-serious) are captured on the eCRF, SAEs also require individual 
reporting to the Novartis Drug Safety and Epidemiology (DS&E) Department as per 
Section 7.2.2. 
7.2.2 
SAE reporting 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent and until 12 weeks (84 days) after last administered dose of study 
treatment must be reported to Novartis within 24 hours of learning of its occurrence. The 
12-week follow-up period after final study treatment administration also applies to patients 
who have been withdrawn from the study early. 
Any SAEs experienced after this period should only be reported to Novartis if the Investigator 
suspects a causal relationship to study drug.  
Recurrent episodes, complications, or progression of the initial SAE must be reported as 
follow-up to the original episode, regardless of when the event occurs. This report must be 
submitted within 24 hours of the Investigator receiving the follow-up information. An SAE 
that is considered completely unrelated to a previously reported one should be reported 
separately as a new event. 
Information about all SAEs (either initial or follow up information) is collected and recorded 
in English on the paper SAE Report Form or the electronic SAE Form within the Oracle 
Clinical/Remote Data Capture (OC/RDC) system (where available). The Investigator must 


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assess the relationship to each specific component of the study drug (if the study drug consists 
of several components).  
Serious adverse events (initial and follow-up) that are recorded on the paper SAE form should 
be faxed within 24 hours of awareness of the SAE to the local Novartis DS&E Department. 
The telephone and fax number of the contact persons in the local DS&E department, specific 
to the site, are listed in the Investigator folder provided to each site. The original copy of the 
SAE Report Form and the fax confirmation sheet must be kept with the CRF documentation 
at the study center. Follow-up information should be provided using a new paper SAE Report 
Form stating that this is a follow-up to a previously reported SAE.  
Serious adverse events (initial and follow-up) that are recorded electronically in the OC/RDC 
system should be entered, saved and e-signed within 24 hours of awareness of the SAE or 
changes to an existing SAE. These data will automatically be submitted to Novartis DS&E 
Department immediately after Investigator signature or 24 hours after entry, whichever occurs 
first.  
Follow-up information provided should describe whether the event has resolved or continues, 
if and how it was treated, whether the treatment code was broken or not and whether the 
patient continued or withdrew from study participation. Each re-occurrence, complication, or 
progression of the original event should be reported as a follow-up to that event regardless of 
when it occurs. 
If the SAE is not previously documented in the IB or Package Insert (new occurrence) and is 
thought to be related to the study drug a DS&E Department associate may urgently require 
further information from the Investigator for Health Authority reporting. Novartis may need 
to issue an Investigator Notification to inform all Investigators involved in any study with the 
same study drug 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. 
7.2.2.1 
Safety reporting specific to the Netherlands 
For the Netherlands only, the Sponsor will report the SAEs through the web portal 
ToetsingOnline to the accredited METc that approved the protocol, within 7 days of first 
knowledge for SAEs that result in death or are life threatening followed by a period of 
maximum of 8 days to complete the initial preliminary report. All other SAEs will be reported 
within a period of maximum 15 days after the Sponsor has first knowledge of the SAEs. 
Adverse reactions are all untoward and unintended responses to an investigational product 
related to any dose administered. 
Unexpected adverse reactions are SUSARs if the following 3 conditions are met: 
1. The event must be serious (see Section 7.2.1); 
2. There must be a certain degree of probability that the event is a harmful and an 
undesirable reaction to the medicinal product under investigation, regardless of the 
administered dose; 
3. The adverse reaction must be unexpected, that is to say, the nature and severity of the 
adverse reaction are not in agreement with the product information as recorded in: 


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 Summary of Product Characteristics for an authorized medicinal product; 
 Investigator’s Brochure for an unauthorized medicinal product. 
For the Netherlands only, the Sponsor will report expedited the following SUSARs to the 
METc: 
 SUSARs that have arisen in the clinical trial that was assessed by the METc; 
 SUSARs that have arisen in other clinical trials of the same Sponsor and with the same 
medicinal product, and that could have consequences for the safety of the subjects 
involved in the clinical trial that was assessed by the METc. 
The remaining SUSARs are recorded in an overview list (line-listing) that will be submitted 
once every half year to the METc. This line-listing provides an overview of all SUSARs from 
the study medicine, accompanied by a brief report highlighting the main points of concern.  
The expedited reporting of SUSARs through the web portal Eudravigilance or ToetsingOnline 
is sufficient as notification to the Competent Authority. 
The Sponsor will expedite reports of all SUSARs to the Competent Authorities in other 
Member States, according to the requirements of the Member States.  
The expedited reporting will occur not later than 15 days after the Sponsor has first 
knowledge of the adverse reactions. For fatal or life threatening cases the term will be 
maximal 7 days for a preliminary report with another 8 days for completion of the report.  
In addition to the expedited reporting of SUSARs, the Sponsor will submit, once a year 
throughout the clinical trial, a safety report to the accredited METc, Competent Authority, and 
Competent Authorities of the concerned Member States. 
This safety report consists of: 
 A list of all suspected (unexpected or expected) serious adverse reactions, along with an 
aggregated summary table of all reported serious adverse reactions, ordered by organ 
system, per study; 
 A report concerning the safety of the subjects, consisting of a complete safety analysis and 
an evaluation of the balance between the efficacy and the harmfulness of the medicine 
under investigation. 
7.3 
Liver safety monitoring 
To ensure patient safety and enhance reliability in determining the hepatotoxic potential of a 
study drug, a standardized process for identification, monitoring and evaluation of liver events 
has to be followed. 
The following 2 categories of abnormalities/AEs have to be considered during the course of 
the study: 
 Liver laboratory triggers that require repeated assessments of the abnormal laboratory 
parameter. 
 Liver events, which will require close observation, follow-up monitoring and completion 
of the standard base liver CRF pages. 
Please refer to Appendix 2 for complete definitions of liver laboratory triggers and liver 
events. 


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Every liver laboratory trigger or liver event as defined in Appendix 2 should be followed up 
by the Investigator or designated personal at the study center as summarized below: 
Detailed information is outlined in Appendix 2.  
For the liver laboratory trigger: 
 Repeating the liver function test (LFT) within the next week to confirm elevation or 
resolution. 
These LFT repeats should be performed using the central laboratory if possible. If this is not 
possible, then the repeats can be performed at a local laboratory to monitor the safety of the 
patient. Repeat laboratory tests should then be performed at the central laboratory as soon as 
possible. If a liver event is subsequently reported, any local LFTs previously conducted that 
are associated with this event should be reported on the Liver CRF pages. 
For the liver events: 
 Repeating the LFT to confirm elevation as appropriate 
 Discontinuation of the investigational drug if appropriate 
 Hospitalization of the patient if appropriate 
 A causality assessment of the liver event via exclusion of alternative causes (e.g., disease, 
co-medications) 
 An investigation of the liver event which needs to be followed until resolution. 
These investigations can include serology tests, imaging and pathology assessments, 
hepatologist’s consultancy, based on Investigator’s discretion. All follow-up information, and 
the procedures performed should be recorded on appropriate CRF pages, including the liver 
event overview CRF pages. 
7.4 
Renal safety monitoring 
There has been no safety signal for nephrotoxicity with secukinumab to date in approximately 
13000 patients and healthy patients exposed (cut-off date 25-Jun-2018, DSUR No. 008), 
and from a mechanism of action standpoint there is no known effect of blocking IL-17A on 
the kidney. All patients with laboratory tests containing clinically significant abnormal values 
(see Appendix 1 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; however, no special measures for renal safety monitoring are planned. 
7.5 
Reporting of study treatment errors including misuse/abuse  
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, patient or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately 
used not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 


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Study treatment errors and uses outside of what is foreseen in the protocol will be collected in 
the dose administration record eCRF irrespective of whether or not associated with an 
AE/SAE and reported to Safety only if associated with an SAE.  
Misuse or abuse will be collected and reported in the safety database irrespective of it being 
associated with an AE/SAE. 
See Table 7-1 for guidance on capturing the study treatment errors including misuse/abuse. 
Table 7-1 
Treatment error types 
Treatment error 
type 
Document in DAR 
eCRF (Yes/No) 
Document in AE 
eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated with 
an AE 
Only if associated with an 
SAE 
Misuse/Abuse 
Yes 
Yes  
Yes, even if not associated 
with a SAE 
AE=adverse event, eCRF=electronic case report form, DAR=dose administration record, SAE=serious 
adverse event 
7.6 
Pregnancy reporting  
All pre-menopausal women who are not surgically sterile will have a urine pregnancy test. A 
positive urine pregnancy test requires immediate interruption of study drug until serum β-hCG 
is performed and found to be negative. 
To ensure patient safety, each pregnancy occurring while the patient is on study drug must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications. The study drug must be discontinued, though the 
patient may stay in the study, if she wishes to do so. All assessments that are considered as a 
risk during pregnancy must not be performed. The patient may continue all other protocol 
assessments. 
Pregnancy should be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
Investigator to the local Novartis DS&E Department. Pregnancy follow-up should be recorded 
on the same form and should include an assessment of the possible relationship to the study 
drug. Any SAE experienced during the pregnancy and unrelated to the pregnancy must be 
reported on the SAE form. 
8 
Data review and database management 
8.1 
Site monitoring 
Before study initiation, at a site initiation visit or at an Investigator’s meeting, a Novartis 
representative will review the protocol and CRFs with the Investigators and their staff. During 
the study, Novartis employs several methods of ensuring protocol and Good Clinical Practice 
(GCP) compliance and the quality/integrity of the study center data. The field monitor will 
visit the study center to check the completeness of patient records, the accuracy of entries on 
the eCRFs, the adherence to the protocol and to GCP, the progress of enrollment, and to 


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ensure that study drug 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 study center’s data may be performed by a 
centralized Novartis Clinical Research Associate organization. Additionally, a central 
analytics organization may analyze data and identify risks and trends for site operational 
parameters, and provide reports to Novartis Clinical Teams to assist with study 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 informed consent form signed by the patient (a signed copy is 
given to the patient). 
The Investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the CRF entries. Novartis monitoring standards require full verification 
for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the CRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
patients will be disclosed. 
8.2 
Data collection 
Designated Investigator staff will enter the data required by the protocol into the OC/RDC 
system. Designated Investigator center staff will not be given access to the system until they 
have been trained.  
Automatic validation procedures within the system check for data discrepancies during and 
after data entry and, by generating appropriate error messages, allow the data to be confirmed 
or corrected online by the designated Investigator center staff.  
The Investigator must certify that the data entered into the eCRFs are complete and accurate. 
After database lock, the Investigator will receive copies of the patient data for archiving at the 
study center.  
8.3 
Database management and quality control 
Novartis staff review the data entered into the CRFs by investigational staff for completeness 
and accuracy and instruct the study center personnel to make any required corrections or 
additions. Queries are sent to the study center using an electronic data query. Designated 
Investigator center staff is required to respond to the query and confirm or correct the data. If 
the electronic query system is not used, a paper Data Query Form will be faxed to the site. 
Site personnel will complete and sign the faxed copy and fax it back to Novartis staff, who 
will make the correction to the database. The signed copy of the Data Query Form is kept at 
the Investigator study center. 
Concomitant medications entered into the database will be coded using the World Health 
Organization Drug Reference List, which employs the Anatomical Therapeutic Chemical 


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classification system. Concomitant procedures, non-drug therapies and AEs will be coded 
using the Medical dictionary for regulatory activities (MedDRA) terminology. 
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated contract research organization (CRO)). 
Randomization codes and data about all study drug(s) dispensed to the patient and all dosage 
changes will be tracked using the Novartis IRT system. Novartis will also manage the 
database.  
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. 
The code break functionality will remain available until study shut down or upon request of 
Novartis.  
8.4 
Scientific Committee  
A Scientific Committee has been instituted for this study based on member affiliations to the 
OMERACT group and expertise in PDUS and methodology: 
 
, France, Principal Investigator for the study.  
 
, Netherlands  
8.5 
Data Monitoring Committee 
In alignment with the EMA Guideline on Data Monitoring Committees (DMCs) 
(EMEA/CHMP/EWP/5872/03 Corr) no DMC is deemed to be required for this Phase IIIb 
clinical study. A pharmacovigilance review concluded that substantial amount of safety data 
for the study drugs have been collected through all study phases and that a DMC would not be 
beneficial for the study. Furthermore, the study population is not considered to have an 
elevated risk of more severe outcomes during this study, which is also in accordance with US 
Department of Health and Human Services FDA guidelines (Guidance for Clinical Trial 
Sponsors. Establishment and Operation of Clinical Trial Data Monitoring Committees, 2006).  
9 
Data analysis  
Summary statistics for continuous variables include N, mean, standard deviation, minimum, 
lower quartile, median, upper quartile, and maximum. For binary or discrete variables the 
absolute number of patients in each category and relative frequencies will be provided. 
Unless otherwise specified, p-values will be presented as 1-sided p-values and the type I error 
rate (alpha) will be 5%. 
Inferential efficacy comparisons with placebo will generally focus on the first 12 weeks of 
treatment. Efficacy and safety data for the placebo-controlled period (or the entire treatment 
period as appropriate) will be presented by study treatment groups.  
Note that the study treatment groups for a patient may differ depending on the time period of 
the analysis and whether the patient is assessed for efficacy or safety. 
Data may also be presented by a combination of the ‘comparative’ and ‘open-label’ study 
treatment groups. 


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These study treatment groups represent the treatment combinations the patients experience 
over the course of the entire trial. 
9.1 
Analysis sets  
Randomized set: The randomized set will be defined as all patients who were randomized.  
Unless otherwise specified, mis-randomized patients will be excluded from the randomized 
set. Mis-randomized patients are defined as those patients who were mistakenly randomized 
prior to the site confirming all eligibility criteria had been met and to whom no study 
medication was given. Mis-randomized patients are treated as screen failures. 
Full analysis set (FAS): The FAS will comprise all patients from the randomized set to 
whom study treatment has been assigned. Following the intent-to-treat principle, patients will 
be analyzed according to the treatment assigned at randomization. 
Safety set: The Safety set will include all patients who took at least 1 dose of study treatment 
during the treatment period. Patients will be evaluated according to study treatment received. 
9.2 
Patient demographics and other baseline characteristics  
Demographics and baseline characteristics 
Summary statistics will be presented for continuous demographic and baseline characteristic 
variables for each study treatment group and for all patients in the randomized set. The 
number and percentage of patients in each category will be presented for categorical variables 
for each study treatment group and all patients. 
Baseline comparability of the randomized study treatment groups will be assessed through 
descriptive methods for the demographic variables indicated in the schedule of assessments 
(Table 6-1) including: 
 Sex, age, race, ethnicity, weight, height, BMI and smoking history. 
Baseline disease characteristics will also be compared for the variables indicated in the 
schedule of assessments (Table 6-1) including: 
 Time since first diagnosis of PsA, type and dose of DMARDs at randomization, 
Global PDUS, PASI, SPARCC enthesitis index and ACR components. 
The QuantiFERON TB-Gold test or PPD skin test (depending on local guidelines), anti-CCP 
antibodies, chest X-ray or MRI and the RF will be summarized at Screening. 
Medical history 
Any significant prior or active medical condition at the time of signing informed consent will 
be coded using MedDRA. These medical conditions will be summarized by primary system 
organ class and preferred term. Psoriatic arthritis history and psoriasis history will be 
summarized separately by pre-specified categories recorded on the eCRF. 
To establish a baseline level of cardiovascular risk, the number and percentage of patients 
with pre-solicited cardiovascular risk factors will be summarized by treatment group. The 
number of cardiovascular risk factors that each patient has will also be summarized by 
treatment group. If it is unknown whether or not a patient currently or previously experienced 


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a specific cardiovascular risk factor, it will be assumed that cardiovascular risk factor did not 
occur for that patient. 
9.3 
Treatments 
Study treatment 
The analysis of study treatment data will be based on the Safety set. The number of active and 
placebo injections received will be presented by treatment group and by epoch (study period) 
as appropriate. 
The duration of exposure to study treatment will also be summarized by study treatment 
group. In addition, the number and percentage of patients with cumulative exposure levels 
(e.g. any exposure, ≥ 1 week, ≥ 2 weeks, ≥ 3 weeks, ≥ 4 weeks, ≥ 8 weeks, etc.) will be 
presented.  
Prior and concomitant medications 
Prior and concomitant medications will be summarized in separate tables by study treatment 
group. Prior medications are defined as treatments taken and stopped prior to the first dose of 
study treatment. Any medication given at least once between the day of first dose of 
randomized study treatment and the date of the last study visit will be a concomitant 
medication, including those which were started pre-baseline and continued into the period 
where study treatment is administered. 
For DMARDs, those DMARDs taken by patients since at least 3 months prior to Screening 
will be recorded.  
Medications will be presented in alphabetical order, by anatomical therapeutic classification 
(ATC) codes and grouped by anatomical main group. Tables will show the overall number 
and percentage of patients receiving at least one treatment of a particular ATC code and at 
least one treatment in a particular anatomical main group. 
9.4 
Analysis of the primary variable 
9.4.1 
Variable 
The primary analysis variable is the change from baseline in GLOESS over 12 weeks. The 
primary analysis of this study will evaluate: 
 The superiority of secukinumab will be compared to placebo in PsA patients who have an 
IR to non-biologic DMARD with respect to the change from Baseline in GLOESS over 12 
weeks. 
The analysis of all efficacy variables will be based on the FAS. 
9.4.2 
Statistical model, hypothesis, and method of analysis 
The statistical hypothesis for the GLOESS being tested is that there is no difference in the 
mean change from baseline scores over 12 weeks in the secukinumab regimen vs the placebo 
regimen. 


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Between-treatment differences in the change in GLOESS will be evaluated using a 
mixed-effect model repeated measures model (MMRM) with treatment regimen, center, 
machine type and analysis visit as factors and weight and baseline GLOESS as continuous 
covariates. Treatment by analysis visit will be included as an interaction term in the model. 
An unstructured covariance structure will be assumed for this model. If the model does not 
converge, the compound symmetry covariance structure will be used. The data will be 
assumed to be missing at random (MAR).  
9.4.3 
Handling of missing values/censoring/discontinuations 
Missing data for the ACR 20 response and other binary efficacy variables (e.g. ACR 50, 
ACR 70, MDA, PASI 75, PASI 90) for data up to 12 weeks (Week 12) will be handled as 
follows: 
 Patients who drop out of the trial for any reason will be considered non-responders from 
the time they drop out through to Week 12. 
 Patients who do not have the required data to compute ACR response (i.e. TJC and SJC 
and at least 3 of the 5 ACR core set variables) at the specific post-Baseline time points 
will be classified as clinical non-responders. 
The following continuous variables: ACR components, HAQ-DI© score, PDUS score and its 
components will be analyzed using a MMRM, which is valid under the MAR assumption. For 
analyses of these parameters, if all post-baseline values are missing then these missing values 
will not be imputed and the patient will be removed from the analysis of the corresponding 
variable, i.e. it may be that the number of patients providing data to an analysis is smaller than 
the number of patients in the FAS. 
Data collected during the open label period (after Week 12) will generally be presented as 
‘observed case’; i.e. all available data for each time point will be included in the analyses. 
9.4.4 
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. 
For sensitivity analyses, an analysis will be performed with the observed data, and also with 
multiple imputations where patients without any post-baseline values are included. An 
additional sensitivity analysis will be conducted using a non-parametric analysis of covariance 
(ANCOVA) model (Koch et al 1998) with treatment regimen, baseline weight and PDUS 
score as exploratory variables.  
9.5 
Analysis of secondary variables 
9.5.1 
Key secondary efficacy variables  
The key secondary efficacy variables are as follows:  
 ACR 20 response at Week 12. 
 ACR 50 response at Week 12. 
 Change in SPARCC enthesitis index from Baseline to Week 12. 


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Testing strategy 
The following hypotheses will be included in the testing strategy and type-I-errors will be set 
such that a family-wise type-I-error of 5% is kept: 
Primary objective: 
 H1: secukinumab s.c. is not different to placebo regimen with respect to the change in 
GLOESS from Baseline to Week 12. 
See Section 9.4.2 for details.  
Key secondary objectives: 
 H2: secukinumab is not different to placebo regimen with respect to ACR 20 response at 
Week 12. 
 H3: secukinumab s.c. is not different to placebo regimen with respect to ACR 50 response 
at Week 12. 
 H4: secukinumab s.c. is not different to placebo regimen with respect to the change in 
SPARCC enthesitis index from Baseline to Week 12. 
No hypotheses other than H1 to H4 will be considered. The family wise error will be set to 
α=5% (1-sided). The graphical approach of Bretz (Bretz et al 2009) for sequentially rejective 
testing procedures is used to illustrate the hierarchical testing strategy (Figure 9-1). 
Figure 9-1 
Testing strategy 
 
The family-wise error will be set to α = 5% (1-sided). H1 is tested at α (1-sided). The 
following hypotheses will be tested sequentially and are included in the hierarchical testing 
strategy and type-I-errors will be set such that a family-wise type-I-error of 5% is kept: 
The testing sequence will continue to H2 at α (1-sided) only if H1 has been rejected. 
Similarly, the testing sequence will continue to H3 at α (1-sided) only if H2 has been rejected. 
This process will continue as each hypothesis is rejected up to H4. 
Of note, in the description above, rejection of a hypothesis refers to rejection of the 1-sided 
hypothesis; however, the level of a rejected hypothesis is only passed on (according to the 
graphical procedure) for the test of another hypothesis if the treatment effect is in favor of 
secukinumab. 


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ACR 20 at Week 12 
Response at Week 12 in ACR 20 in the FAS will be evaluated using a logistic regression 
model with study treatment as a factor and baseline weight as a covariate. The odds ratios will 
be computed for comparison of secukinumab versus placebo using the logistic regression 
model fitted. Firth’s penalized maximum likelihood estimation method will be used in the 
event of non-convergence of the logistic regression model outlined. 
ACR 50 at Week 12 
Response at Week 12 in ACR 50 in the FAS will be evaluated using a logistic regression 
model with study treatment as a factor and baseline weight as a covariate. The odds ratios will 
be computed for comparison of secukinumab versus placebo using the logistic regression 
model fitted. 
Changes in SPARCC at Week 12 
Between-treatment differences in the change from baseline in SPARCC at Week 12 in the 
FAS will be compared by means of a MMRM with treatment regimen and analysis visit as 
factors and baseline weight and SPARCC score as continuous covariates. Study treatment by 
analysis visit will be included as an interaction term in the model. An unstructured covariance 
structure will be assumed for this model. The significance of the treatment effect for 
secukinumab at different analysis visits will be determined from the comparison to placebo. 
9.5.2 
Other secondary efficacy variables  
The following secondary efficacy variables will be analyzed using the FAS population:  
 Change in GLOESS from Baseline to Week 8. 
 Change in OMERACT enthesitis score from Baseline to Week 8 for each of the 5 targeted 
entheses. 
The between treatment differences will be compared by means of a MMRM with treatment 
regimen, center, machine type and analysis visit as factors and baseline weight and baseline 
score as continuous covariates. Study treatment by analysis visit will be included as an 
interaction term in the model. An unstructured covariance structure will be assumed for this 
model. The significance of the treatment effect for secukinumab at different analysis visits 
will be determined from the comparison to placebo. The OMERACT enthesitis score will be 
analyzed separately for each of the targeted entheses.  
9.5.3 
Exploratory efficacy variables 
All the following exploratory efficacy variables will be analyzed on the FAS for all applicable 
analysis visits unless otherwise specified.  
 Change from Week 12 in GLOESS of the ultrasound active joints out of 48 and its 
components to Week 24 and Week 52 for placebo group who switched to secukinumab at 
Week 12. 
 Change from baseline in GLOESS of the ultrasound active joints out of 48 and its 
components to Week 24 and Week 52 for the secukinumab group. 


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 Change from Week 12 in OMERACT individual enthesitis scores to Week 24 and to 
Week 52 for placebo group who switched to secukinumab at Week 12. 
 Change from baseline in OMERACT individual enthesitis scores to Week 24 and to 
Week 52 for secukinumab group. 
 Correlation between single component of the SPARCC index and semi-quantitative Power 
Doppler in evaluate the improvement of each enthesitis site from baseline to Week 12. 
 Correlation between patients achieving at least 20% improvement in GLOESS from 
baseline to Week 12.and patients achieving ACR 20 response of the same joints involved. 
 Correlation between the PDUS response versus the SPARCC score at Week 12 in each 
enthesis. 
 The response of ACR 20, ACR 50, ACR 70, PASI 75, PASI 90, dactylitis count, 
HAQ-DI© response at Week 24 
 Change from Baseline in ACR components at Week 24: 
 Changes in TJC 78 over time. 
 Change in SJC 76 over time. 
 Change in patient’s global assessment of disease activity. 
 Change in patient’s assessment of PsA pain. 
 Change in Physician’s global assessment of disease activity. 
 Change in HAQ-DI response over time. 
 Change in hsCRP. 
 Proportion of patients achieving MDA at Week 24 and Week 52. 
 Overall time spent on PDUS assessments of joint inflammation and enthesitis for the main 
study and breakdown of time spent on these assessments by visit.  
All results from the exploratory efficacy analyses are to be interpreted descriptively. 
Correlations between variables will be investigated through scatter plots; also Pearson’s 
correlation coefficient will be presented when a linear relationship is assumed otherwise 
Spearman’s rank correlation coefficient will be presented.  
Variables whose distribution are not anticipated to be normal (i.e. hsCRP) will be transformed 
and analyzed on the loge scale. 
All other analysis of the exploratory variables will be outlined in the statistical analysis plan. 
9.5.4 
Substudy 


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9.5.5 
Safety variables  
Adverse events 
Treatment-emergent AEs (i.e. events started after the first dose of study treatment or events 
present prior to the first dose of study treatment but increased in severity based on preferred 
term and on or before last dose + 84 days) will be summarized. 
Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of patients having any AE, having an AE in each primary system organ class and 
having each individual AE (preferred term). Summaries will also be presented for AEs by 
severity and for study treatment related AEs. If a patient reported more than one AE with the 
same preferred term, 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 
AEs will also be summarized. 
These summaries may be presented separately by study periods. 
The incidence of AEs will be presented per 100 patient years of exposure for the most 
frequent AEs (≥ 2% in any group), SAEs and selected SOCs to be outlined in the statistical 
analysis plan. 
Separate summaries will be provided for death, SAEs, other significant AEs leading to 
discontinuation and AEs leading to dose adjustment (including study treatment 
discontinuation). 
A graphical display of relative frequencies within each system organ class and relative risks, 
as appropriate, will be presented. 
Laboratory data 
The summary of laboratory evaluations will be presented for 3 groups of laboratory tests 
(hematology, serum chemistry and urinalysis). Descriptive summary statistics for the change 
from Baseline to each study visit will be presented. These descriptive summaries will be 
presented by test group, laboratory test and study treatment group. Change from Baseline will 
only be summarized for patients with both Baseline and post Baseline data. For each 
parameter, the maximum change from Baseline within each study period will be evaluated 
analogously. 
In addition, shift tables will be provided for all parameters to compare a patient’s Baseline 
laboratory evaluation relative to the visit’s observed value. For the shift tables, the normal 
laboratory ranges will be used to evaluate whether a particular laboratory test value was 
normal, low, or high for each visit value relative to whether or not the Baseline value was 
normal, low, or high.  


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These summaries will be presented by laboratory test and study treatment group. Shifts will 
be presented by visit as well as for most extreme values post-Baseline. 
Immunogenicity 
Summary statistics will be provided for the percentage of patients with blood samples for 
immunogenicity (anti-AIN457 antibodies). If appropriate, shift tables will also be presented. 
Vital signs 
Analysis of the vital sign measurements using summary statistics for the change from 
Baseline for each post-Baseline visit will be performed. These descriptive summaries will be 
presented by vital sign and study treatment group. Change from Baseline will only be 
summarized for patients with both Baseline and post-Baseline values. 
Physical examination 
All physical examination data will be listed by study treatment group, patient and visit and 
summary statistics will be provided by study treatment group and visit. 
Pregnancy tests 
Serum and urine pregnancy tests will be summarized and listed, where applicable. 
9.5.6 
Resource utilization  
Not applicable. 
9.5.7 
Pharmacokinetics  
All patients with concentration data will be included in the pharmacokinetic data analysis. 
Pharmacokinetic variables 
The following pharmacokinetic parameter will be determined: Cmin,ss. Cmin,ss will be 
determined using Phoenix software. Individual serum concentrations in µg/ml will be listed. 
All concentrations below the limit of quantification or missing data will be labeled as such in 
the concentration data listings. Concentrations below the limit of quantification will be treated 
as zero in summary statistics for concentration data only. During modeling of the 
pharmacokinetics of secukinumab, the broad principles outlined in the FDA Guidance for 
Industry: Population Pharmacokinetics will be followed. 
Statistical methods for pharmacokinetic analyses 
Summary statistics by visit/time will be provided for the above mentioned parameter and will 
include arithmetic and geometric means, SD, median, minimum and maximum. Individual 
concentrations will be listed by patient. 
9.5.8 
Pharmacogenetics/pharmacogenomics  
Not applicable. 


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9.5.9 
Biomarkers  
Not applicable. 
9.5.10 
PK/PD  
Not applicable. 
9.6 
Interim analyses  
Prior to the final database lock and end of study reporting there will be 3 interim analyses:  
 Blinded sample size re-estimation (SSR) 
 Week 12 interim analysis  
 Week 24 interim analysis. 
After these 3 interim analyses, there will be one final study database lock i.e. once the last 
patient has completed the Week 64 /EOS visit or early withdrawal visit (in case the last 
patient withdraws early from the study).  
Blinded Sample Size Re-estimation (SSR) 
The blinded SSR will be performed when the first 60 patients have completed the Week 12 
visit. The pooled standard deviation of the change from baseline in GLOESS at Week 12 will 
be calculated for the 60 patients and the pooled change will be transformed based on the 
placebo response observed in the FUTURE 2 study (CAIN457F2312), roughly 50% of 
secukinumab. These estimates will be used to decide whether the study should continue as 
planned. Although the study is originally designed to have at least 90% power, any change  in 
sample size will be based on 80% power due to enrolment feasibility. 
Week 12 analysis 
The analysis of the primary and secondary efficacy variables will be performed after all 
patients complete the Week 12 visit. This analysis will also include exploratory variables 
outlined up to Week 12 and all available safety data. 
Week 24 analysis 
The analysis of the exploratory variables up to Week 24 will be performed after all patients 
complete the Week 24 visit. This analysis will also include all available safety data. 
9.7 
Sample size calculation 
This study was designed using data for abatacept in the APPRAISE study (RA study to assess 
early response to abatacept + MTX (D’Agostino et al, 2016), to test the superiority of 
secukinumab compared to placebo at the 5% significance level using a 2-sided test. Assuming 
a difference in the mean change from Baseline at Week 12 in OMERACT global PDUS score 
of -5.8 with a pooled standard deviation of 13.2, 218 patients in total (109 patients per arm) 
were estimated to achieve a power of 90% (EAST 6). 
A blinded SSR was performed once the first 60 patients completed the Week 12 visit to 
evaluate the assumptions used in the sample size calculations. The statistical test for the 
primary endpoint has been changed from a 2-sided to a 1-sided test. 


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The first 60 patients to reach Week 12 have a pooled mean change from Baseline at Week 12 
in OMERACT global PDUS score of -5.25 with a pooled standard deviation of 9.527. Using 
the estimated placebo effect of roughly 50% of secukinumab based on data from the FUTURE 
2 study (CAIN457F2312) as in the original sample size calculation, the pooled PDUS score 
change of -5.25 translates to an assumed change of -7.000 and -3.500 for the secukinumab and 
placebo group, respectively, providing a difference of 3.500 between the groups. Adapting the 
original sample size calculation to be 1-sided with the power relaxed to 80%, 184 patients in 
total (92 patients per arm) are required (EAST 6). 
At the time of the blinded sample size calculation, 72 patients were available who had reached 
their Week 12 visit, to provide the most accurate estimation, all data available were 
considered i.e. the first 72 patients as opposed to the first 60 patients. Using all available data 
a difference in the mean change from Baseline at Week 12 in OMERACT global PDUS score 
of 4.352 was observed with a pooled standard deviation of 9.822. At the 5% significance level 
using a 1sided test, 126 patients are needed to achieve a power of 80% (EAST 6). 
The 2 calculations produce a sample size range of 127-185 patients; thus, the sample size will 
be adjusted to a new target of 164 patients in total (82 patients per arm). This is mid-way 
point of the range plus a 5% adjustment based on the observed drop-out rate of patients prior 
to Week 12 observed at the time of this calculation. 
For the secondary variables: 
Patients who were naive to TNFα inhibitors where pooled from the 2 confirmatory studies in 
PsA for secukinumab (CAIN457F2306 and CAIN457F2312) and a placebo response rate of 
about 29.6% and 10.7% at Week 12 was observed for ACR 20 and ACR 50 respectively. 
From the same studies pooled, the response rate to secukinumab 150 mg s.c. was around 
63.5% (ACR 20) and 33.3% (ACR 50), and the response rate to secukinumab 300 mg s.c. was 
around 67.2% (ACR 20) and 37.3% (ACR 50). Taking a conservative approach due to the 
pooled groups, the lowest response rate between the secukinumab arms (i.e. ACR 20 = 63.5% 
and ACR 50 = 33.3%) was used to estimate the secukinumab response, which resulted in the 
study having greater than 90% power to detect a difference to placebo using the current 
sample size. 
It is not possible to calculate the power for the SPARCC or early therapeutic effect on 
affected enthesitis variables due to lack of data available.  


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10 
Ethical considerations  
10.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented and reported in accordance with 
International Conference on Harmonization (ICH) Harmonized Tripartite Guidelines for GCP 
with applicable local regulations including the European Directive 2001/20/EC, the Medical 
Research Involving Human Subjects Act in the Netherlands (known as the WMO in Dutch), 
the US Code of Federal Regulations 21, and with the ethical principles laid down in the World 
Medical Association (WMA) Declaration of Helsinki (DOH) 1964 and amendments thereof, 
most recently 2013 (WMA DOH 2013). 
10.2 
Informed consent procedures  
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent, or, if incapable of doing 
so, after such consent has been provided by a legally acceptable representative(s) of the 
patient. In cases where the patient’s representative gives consent, the patient should be 
informed about the study to the extent possible given his/her understanding. If the patient is 
capable of doing so, he/she should indicate assent by personally signing and dating the written 
informed consent document or a separate assent form. Informed consent must be obtained 
before conducting any study-specific procedures (i.e. all of the procedures described in the 
protocol). The process of obtaining informed consent should be documented in the patient 
source documents.  
Novartis will provide to Investigators in a separate document a proposed informed consent 
form that complies with the ICH GCP guideline, and regulatory requirements and is 
considered appropriate for this study. Any changes to the proposed consent form suggested by 
the Investigator must be agreed to by Novartis before submission to the IRB/IEC and a copy 
of the approved version must be provided to the Novartis monitor after IRB/IEC approval. 
Women of child bearing potential should be informed that taking the study drug may involve 
unknown risks to the fetus if pregnancy were to occur during the study and agree that in order 
to participate in the study they must adhere to the contraception requirement for the duration 
of the study. If there is any question that the patient will not reliably comply, they should not 
be entered in the study. 
Two additional informed consent forms will be provided for patient sign-off in this study; one 
to confirm the patient would like to enter into the extension period of the study (see 
Section 3.1); and one to confirm the patient would like to participate in an optional sub-study 
 
 The sub-study will only apply to patients attending study centers 
 
.  
It is required as part of this protocol that the Investigator presents the option to participate in 
the extension period to all patients; and presents the option to participate in the sub-study to 
all applicable patients (i.e. patients attending study centers involved in the sub-study). 
The process for obtaining consent should be exactly the same as described above for the main 
informed consent. 


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Declining to participate in the extension period of the study, or to participate in the sub-study 
(for applicable patients as described above), will in no way affect the patient’s ability to 
participate in the main research study. 
The will be performed at study centers 
 
. 
10.3 
Responsibilities of the investigator and IRB/IEC  
Before initiating a trial, the Investigator/institution should obtain approval/favorable opinion 
from the IRB/IEC for the study protocol, written informed consent form, consent form 
updates, patient recruitment procedures (e.g. advertisements) and any other written 
information to be provided to patients. Prior to study start, the Investigator is required to sign 
a protocol signature page confirming his/her agreement to conduct the study in accordance 
with these documents and all of the instructions and procedures found in this protocol and to 
give access to all relevant data and records to Novartis monitors, auditors, Novartis Quality 
Assurance representatives, designated agents of Novartis, IRBs/IECs, and regulatory 
authorities as required. If an inspection of the clinical site is requested by a regulatory 
authority, the Investigator must inform Novartis immediately that this request has been made. 
10.4 
Publication of study protocol and results  
Novartis assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and 
finalization of the study report the results of this trial will be either submitted for publication 
and/or posted in a publicly accessible database of clinical trial results. 
11 
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected 
on study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances should an 
Investigator collect additional data or conduct any additional procedures for any research 
related purpose involving any investigational drugs. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
Investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be 
implemented. All significant protocol deviations will be recorded and reported in the Clinical 
Study Report. 
11.1 
Protocol Amendments  
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, Health Authorities where required, and the IRB/IEC prior to 
implementation. Only amendments that are intended to eliminate an apparent immediate 
hazard to patients may be implemented immediately provided the Health Authorities are 
subsequently notified by protocol amendment and the reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the Investigator is 


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expected to take any immediate action required for the safety of any patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 7 (Safety Monitoring) should be followed. 
12 
References 
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13 
Appendices 
13.1 
Appendix 1: 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 at the same 
time as sent to the Investigators. Any intervention based on these laboratory values should be 
discussed with Novartis personnel. 
Table 13-1 
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 
13.2 
Appendix 2: Liver event and laboratory trigger definitions 
Table 13-2 
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* 


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Abbreviations: ALP: alkaline phosphatase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, 
INR: international normalized ratio, ULN: upper limit of normal 
* These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver damage-related 
conditions; the non-infectious hepatitis; the benign, malignant and unspecified liver neoplasms.  
Table 13-3 
Follow-up requirements for liver events and laboratory triggers 
Criteria 
Actions required 
Follow-up monitoring 
Potential Hy’s 
Law casea 
 Discontinue the study drug immediately 
 Hospitalize, if clinically appropriate 
 Establish causality 
 Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at Investigator 
discretion) 
 
ALT or AST 
> 8 × ULN 
 Discontinue the study drug immediately 
 Hospitalize if clinically appropriate 
 Establish causality 
 Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at Investigator 
discretion) 
> 3 × ULN and 
INR > 1.5 
 Discontinue the study drug immediately 
 Hospitalize, if clinically appropriate 
 Establish causality 
 Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at Investigator 
discretion) 
> 5 to ≤ 8 × ULN 
 Repeat LFT within 48 hours 
 If elevation persists, continue follow-up 
monitoring 
 If elevation persists for more than 
2 weeks, discontinue the study drug 
 Establish causality 
 Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at Investigator 
discretion) 
> 3 × ULN 
accompanied by 
symptomsb 
 Discontinue the study drug immediately 
 Hospitalize if clinically appropriate 
 Establish causality 
 Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT 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 CRF 
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
TBL (isolated) 
 
 
> 2 × ULN (in the 
absence of 
known Gilbert 
syndrome) 
 Repeat LFT within 48 hours 
 If elevation persists, discontinue the study 
drug immediately 
 Hospitalize if clinically appropriate 
 Establish causality 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at Investigator 
discretion) 
Test for hemolysis (e.g. 
reticulocytes, haptoglobin, 


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Criteria 
Actions required 
Follow-up monitoring 
 Complete liver CRF 
unconjugated (indirect) 
bilirubin) 
 
> 1.5 to 
≤ 2 × ULN 
(patient is 
asymptomatic) 
 Repeat LFT within the next week 
 If elevation is confirmed, initiate close 
observation of the patient  
Investigator discretion 
Monitor LFT within 1 to 4 
weeks or at next visit 
Jaundice 
 Discontinue the study drug immediately 
 Hospitalize the patient 
 Establish causality 
 Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, 
ALP and GGT until resolutionc 
(frequency at Investigator 
discretion) 
Any AE 
potentially 
indicative of a 
liver toxicity* 
 Consider study drug interruption or 
discontinuation  
 Hospitalization if clinically appropriate 
 Establish causality 
 Complete liver CRF 
Investigator discretion 
Abbreviations: Alb: Albumin, ALP: alkaline phosphatase, ALT: alanine aminotransferase, 
AST: aspartate aminotransferase, CRF: case report form, GGT: gamma glutamyl transferase, 
INR: international normalized ratio, LFT: liver function test, PT: prothrombin test, TBL: total bilirubin, 
ULN: upper limit of normal.  
* These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver damage-
related conditions; the non-infectious hepatitis; the benign, malignant and unspecified liver 
neoplasms. 
a Elevated ALT/AST > 3 × ULN and TBL > 2 × ULN but without notable increase  
in ALP to > 2 × ULN 
b (General) malaise, fatigue, abdominal pain, nausea, or vomiting, or rash with eosinophilia  
c Resolution is defined as an outcome of one of the following:  
(1) return to Baseline values,  
(2) stable values at 3 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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13.3 
Appendix 3: The classification criteria for psoriatic arthritis 
(CASPAR) 
To meet the classification criteria for psoriatic arthritis (CASPAR) for diagnosis of psoriatic 
arthritis according to (Taylor 2006) a patient must have inflammatory articular disease (joint, 
spine or entheseal) and at least 3 points from the following 5 categories: 
1. Evidence of current psoriasis, a personal history of psoriasis, or a family history of 
psoriasis 
 Current psoriasis is defined as psoriatic skin or scalp disease present today as judged 
by a rheumatologist or dermatologist* (2 points). 
 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). 
2. Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis 
observed on current physical examination (1 point). 
3. A negative test result for the presence of rheumatoid factor by any method except latex 
(1 point). 
4. Either current dactylitis, defined as swelling of an entire digit, or a history of dactylitis 
recorded by a rheumatologist (1 point). 
5. Radiographic evidence of juxta-articular new bone formation appearing as ill-defined 
ossification near joint margins (but excluding osteophyte formation) on plain radiographs 
of the hand or foot (1 point). 
Total score:  
(The CASPAR criteria eCRF will autopopulate the total number of points of the CASPAR 
criteria met by the patient. If the total score is ≥ 3, the patient meets the CASPAR criteria for 
psoriatic arthritis diagnosis.) 
* Current psoriasis is assigned a score of 2; all other features are assigned a score of 1. 
13.4 
Appendix 4: American College of Rheumatology measures and 
criteria of response 
Number of tender joints: 
Joint counts will be performed by the independent assessor(s) who must be well trained and 
part of the site personnel. Whenever possible, the same evaluator should perform these 
assessments at all visits. 
The 78 joints assessed for tenderness include the 2 temporomandibular, 2 sternoclavicular, 
2 acromioclavicular joints, 2 shoulders, 2 elbows, 2 wrists, 2 first carpometacarpal, 10 MCP, 
10 PIP, 8 distal interphalangeal joints of the hands, the 2 hip, 2 knee, 2 talo-tibial, 2 
mid-tarsal, 10 MTP, 10 PIP, and 8 DIP joints of the feet. 
Joint tenderness and swelling are to be graded present (1) or absent (0). 


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Number of swollen joints: 
Joints are to be scored as either swollen (1) or not swollen (0). The 76 joints to be examined 
for swelling are the same as those examined for tenderness, however excluding both hip 
joints. 
Patient’s assessment of psoriatic arthritis pain 
On a 100 mm non-anchored visual analog scale, from no pain to unbearable pain. 
Patient’s global assessment of disease activity 
On a 100 mm non-anchored visual analog scale, from no arthritis activity to maximal arthritis 
activity, after the question “Considering all the ways your arthritis affects you, draw a line on 
the scale for how well you are doing.” 
Physician’s global assessment of disease activity 
On a 100 mm non-anchored visual analog scale, from no arthritis activity to maximal arthritis 
activity. 
Patient’s assessment of physical function 
Health Assessment Questionnaire – HAQ-DI© 
ACR 20/50/70* 
A patient will be considered as improved according the ACR 20 criteria* if she/he has at least 
20% improvement in the 2 following measures: 
 Tender joint count. 
 Swollen joint count. 
 and at least 3 of the following 5 measures: 
- Patient’s assessment of pain 
- Patient’s global assessment of disease activity 
- Physician’s global assessment of disease activity 
- Health assessment questionnaire (HAQ©) score 
- C-reactive protein (CRP) or erythrocyte sedimentation rate (note: CRP only will be 
assessed in this study) 
ACR 50 = 50% improvement in at least 3 of the 5 measures and 50% improvement in the 
swollen and tender joint count. 
ACR 70 = 70% improvement in at least 3 of the 5 measures and 70% improvement in the 
swollen and tender joint count. 
Reference:  
Felson DT, Anderson JJ, Boers M, et al (1995) American College of Rheumatology. 
Preliminary definition of improvement in rheumatoid arthritis. Arthritis Rheum; 38(6):727-35. 


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13.5 
Appendix 5: Joint assessments 
Joint counts will be performed by a clinical assessor with experience in performing 
examinations in clinical trials. Every effort must be made to ensure that the same clinical 
assessor completes the swollen and tender joint counts for each patient. Visits requiring joint 
assessment should be scheduled according to the availability of the evaluator. If the same 
clinical assessor is unable to complete the joint assessments, then a qualified individual, with 
overlapping experience may perform the evaluation. 
Assessments of clinical efficacy must be performed by the same assessor(s) throughout the 
study. The clinical assessor(s) must be a different person from the one performing the 
ultrasound (US) assessments. Personnel cannot be involved in assessing clinical efficacy in 
one visit and serve as an ultrasound assessor in another visit. Clinical joint assessments should 
be performed at approximately the same time of day during the study. Patients should be 
reminded to avoid taking their weekly dose of MTX during the 48 hours prior to these visits. 
13.6 
Appendix 6 OMERACT-EULAR Global PDUS OMERACT out of 48 
joints  
The Outcome Measures in Rheumatology-Ultrasound (OMERACT-US) Task Force, with 
funding received from the European League Against Rheumatism (EULAR), works to 
standardize the use of ultrasonography in rheumatoid arthritis (RA) and has developed a 
composite scoring system (the OMERACT-EULAR composite PDUS score) to detect and 
score synovitis. This score combines Greyscale-assessed synovial hyperplasia with an 
intra-synovial power Doppler signal for evaluating synovial activity. The score has 
demonstrated validity and intra- and inter-observer reliability in cross-sectional datasets, 
applicability to all joints and consistency between machines 
Medium- to high-level ultrasound machines will be used (Esaote Technos MPX MyLab 70, 
GE Logic [Series 9] or Siemens Acuson Antares), employing high-frequency (12-18 MHz) 
transducers. Doppler parameters will be adjusted according to the device used (range of pulse 
repetition frequency 400–800 Hz; Doppler frequency 7–14.1 MHz). Power Doppler 
ultrasound evaluation will be performed at each site by an independent expert in 
musculoskeletal ultrasound who will be kept blinded from clinical evaluations.  
The PDUS assessment will consist of an evaluation of hypoechoic synovial hyperplasia (SH) 
and joint effusion (JE) using Greyscale and of synovial vascularization using Power Doppler. 
The pre-specified set of 24 paired joints will be scanned at each visit on the dorsal aspect, 
with the joint in a neutral position, except for the knee, which will also be examined in a 
flexed position (30°). Standardized joint and probe positions will be used, based on a 
reference atlas, which also shows examples of synovitis grading for each site examined.  
The presence of synovitis (i.e. SH and Power Doppler, without JE) will be scored according to 
the OMERACT-EULAR PDUS composite semi-quantitative scale (0 to 3; Table 13-4). Each 
single component of joint inflammation (SH, Power Doppler, JE) was also scored separately 
at each visit, using semi-quantitative scales (0 to 3; Table 13-4). The global PDUS scores for 
the 24 paired joints will then be calculated using the sum of the composite PDUS scores for 
all joints examined, giving a potential score and of 0 to 144 for the 24 paired joints.  
In an attempt to ensure homogeneity of synovitis scoring across sites, all PDUS assessors will 
be required to complete a training session and examinations at each center in order to be 


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qualified for PDUS evaluation in this study. Quality control assessment of the scoring will be 
performed for the first patient included from each center and once all patients have completed 
the study (i.e. following the last patient’s last visit) when the last patient enrolled in the trial 
has completed their last visit.  
Table 13-4 
Ultrasound scoring system 
Greyscale ultrasound 
 
Joint effusion 
 
Grade 0 
No effusion 
Grade 1 
Minimal amount of joint effusion 
Grade 2 
Moderate amount of joint effusion (little distension of the joint 
capsule) 
Grade 3 
Extensive amount of joint effusion (with high distension of the 
joint capsule) 
Inflammatory or active synovial 
hyperplasia (hypoechoic) 
 
Grade 0 
No hypoechoic synovial thickening 
Grade 1 
Minimal hypoechoic synovial thickening (filling the angle 
between the periarticular bones, without bulging over the line 
linking tops of the bones) 
Grade 2 
Hypoechoic synovial thickening bulging over the line linking 
tops of the periarticular bones but without extension along 
the bone diaphysis 
Grade 3 
Hypoechoic synovial thickening bulging over the line linking 
tops of the periarticular bones and with extension to at least 
one of the bone diaphysis 
Power Doppler signal 
 
Grade 0 
No flow in the synovium 
Grade 1 
Up to 3 single spots signals or up to 2 confluent spots or 1 
confluent spot plus up to 2 single spots 
Grade 2 
Vessel signals in less than half of the area of the synovium 
(< 50%) 
Grade 3 
Vessel signals in more than half of the area of the synovium 
(> 50%) 
OMERACT-EULAR composite PDUS 
score (for individual joints) 
 
Grade 0 (normal joint) 
No greyscale-detected synovial hyperplasia or Power 
Doppler signal 
Grade 1 (minimal synovitis) 
Minimal synovial hyperplasia and ≤ Grade 1 Power Doppler 
signal 
Grade 2 (moderate synovitis) 
Moderate synovial hyperplasia and ≤ Grade 2 Power Doppler 
signal or minimal synovial hyperplasia and a Grade 2 Power 
Doppler signal 
Grade 3 (severe synovitis) 
Severe synovial hyperplasia and ≤ Grade 3 Power Doppler 
signal or moderate synovial hyperplasia and a Grade 3 
Power Doppler signal 
Global OMERACT-EULAR synovitis 
score (GLOESS) 
Sum of composite PDUS scores for all joints assessed (e.g. 
for MCPs 2–5, Global PDUS score would range from 0 to 24) 


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13.7 
Appendix 7: OMERACT score of enthesitis 
Evaluation of entheses 
For the evaluation of enthesitis, ultrasound will initially be performed in B mode to detect 
morphologic abnormalities and subsequently with power Doppler to detect abnormal 
vascularization at bony insertions.  
This score was developed following an initial Delphi exercise undertaken to define enthesitis 
and its core components. These definitions were subsequently tested on static images taken 
from SpA patients in order to evaluate their reliability (Tersley et al 2014). Excellent 
agreement was obtained for separating signs of active inflammation from signs of structural 
damage. A definition was therefore proposed that included hypoechogenicity, thickening, and 
Doppler signal as signs of inflammation (and therefore of acute/active US enthesitis) and 
included erosions, enthesophytes, calcification, and cortical irregularities as signs of structural 
damage (and therefore of chronic/ inactive US enthesitis). These are as follows: 
 Hypoechogenicity was defined as a lack of the homogeneous fibrillar pattern with loss of 
the tightly packed echogenic lines after correcting for anisotropy.  
 Increased thickness of the enthesis was defined as increased thickness of the 
tendon/ligament/capsule insertion into the bone, as compared to the body of the 
tendon/ligament/ capsule, with or without blurring of the tendon/ligament/ capsule 
margins. 
 Enthesophytes were defined as a step up of bony prominence at the end of the normal 
bone contour, seen in 2 perpendicular planes, with or without acoustic shadow.  
 Calcifications were defined as hyperechoic (bright) foci consistent with calcific deposits, 
with or without acoustic shadow, seen in 2 perpendicular planes, detected at the tendon 
insertion into the bone (i.e. enthesis).  
 Erosion was defined as a cortical breakage with a step down contour defect, seen in 
2 perpendicular planes, at the insertion of the enthesis to the bone, according to the 
OMERACT definition.  
 The Doppler signal at the enthesis was defined as Doppler activity approximately 2 mm 
near the bony cortex. The Doppler signal must be at the enthesis, different from reflecting 
surface artifact or nutrition vessel signal, with or without cortical irregularities, erosions, 
or enthesophytes. 
The following entheses will be examined bilaterally: 
1. Common extensor tendon at its insertion at the lateral humeral epicondyle. 
2. Quadriceps tendon at its insertion at the superior pole of the patella. 
3. Patellar tendon at its proximal insertion at the inferior pole of the patella. 
4. Patellar tendon at its distal insertion at the tibia tuberosity. 
5. Calcaneal insertions: 
a. Achilles tendon at its insertion at the calcaneus. 
b. Plantar aponeuroses at its insertion at the calcaneus. 


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Each affected enthesis out of 5 targeted entheses will be scored on inflammatory and 
morphological 
components 
according 
to 
the 
OMERACT 
enthesitis 
composite 
semi-quantitative scale (0 to 3) as shown in Table 13-5.   
Table 13-5 
Severity grade of enthesitis 
Severity scoring 
Morphological (B mode) 
Inflammation (Doppler) 
0 
No abnormalities 
0 Doppler signal 
1 
Hypoechogenicity alone 
1 or 2 Doppler Spots at cortical 
insertion 
2 
Thickening and hypoechogenicity plus 
calcifications/enthesophytes 
More than 2 Doppler spots at 
cortical insertion and up to 2 mm 
from cortical bone 
3 
Thickening and hypoechogenicity plus 
calcifications/enthesophytes AND 
erosions 
Extensive Doppler signal at cortical 
insertion 


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13.9 
Appendix 9: PDUS equipment 
When performing a sonographic examination, it is important to use a high frequency 
sonographic probe that allows use of the Doppler mode. These high frequency probes have 
excellent resolution and are designed specifically for the exploration of muscular and articular 
superficial structures. 
The following equipment is required for CAIN457F2354: high quality equipment with both a 
high quality Gray-scale setting (linear array transducer with a frequency between 12 MHz 
and16 MHz) and a high quality Doppler device. The presence of a power Doppler system is 
preferred to a color Doppler or an energy Doppler system only. Power Doppler parameters 
will be chosen according to the best setting of each machine, with a pulse repetition frequency 
(PRF) around 500-800 Hz. 
The US equipment of each center will be chosen among a list of equipment featuring both a 
high quality Gray-scale setting and a high quality power Doppler device. This will ensure 
appropriate image quality for the evaluation of progression of psoriatic arthritis. The 
following equipment configurations are appropriate for CAIN457F2354 (Table 13-9): 
Table 13-9 
PDUS equipment recommendations 
Manufacturer 
Model 
Doppler 
Diccom 
HF Probe 
(> 12 MHz) 
 
 
Power 
Doppler 
Color/ 
Energy 
Doppler 
 
 
ESAOTE 
Technos MPX Mylab 70 
Yes 
Yes 
Yes 
Yes 
Acuson 
Antares 
Yes 
Yes 
Yes 
Yes 
GE 
Logic Series 9 
Yes 
Yes 
Yes 
Yes 
Siemens 
 
Yes 
Yes 
Yes 
Yes 
 
 
 
 
 
 
13.10 
Appendix 10: Health assessment questionnaire 
The Health Assessment Questionnaire (HAQ©, Fries JF et al 1980) is a validated measure of 
physical disability and functional status. It has 4 dimensions: disability, pain, drug side effects 
and dollar costs, although, the latter 3 are rarely used in clinical trials. In this trial only the 
disability dimension will be used. The disability dimension consists of 20 multiple choice 
items concerning difficulty in performing eight common activities of daily living; dressing 
and grooming, arising, eating, walking, reaching, personal hygiene, gripping and activities. 
Patients choose from 4 response categories, ranging from “without any difficulty” to “unable 
to do”. The ACR Rheumatology Committee on Outcome Measures in RA recommends the 
use of this questionnaire in clinical trials. 


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Scoring of the HAQ© 
The HAQ© will be scored in accordance with the recommendation from the developers 
outlined in the “HAQ PACK” from Stanford University, California. The following coding is 
to be used for the 8 categories of the disability outcome dimension: 
 
Without ANY difficulty 
0 
With SOME difficulty 
1 
With MUCH difficulty 
2 
UNABLE to do 
3 
Within each of the 8 categories only the item indicating the most severe impairment 
contributes to the category score. If the patient requires the use of aids, devices, or help from 
another to accomplish any of the activities in an associated category, then the score for that 
category will be assigned the value 2, unless the score is already 3 (i.e. scores of 0 or 1 are 
increased to 2). Associated categories are defined in the “HAQ PACK”.  
From the scores for each category a standard disability index (SDI) is computed by summing 
the computed scores for each category and dividing by the number of categories answered. 
The SDI is not computed if the patient does not have scores for at least 6 categories. This SDI 
is the HAQ© score, which will be used in the statistical analyses of this instrument. The range 
for this score is (0, 3). 
HAQ© Data Collection 
The HAQ© is to be completed by the patients in their local languages, using an electronic 
device. The questionnaires should be completed by the patients in a quiet area free from 
disturbance, and before any visit assessments. Patients should receive no help from family 
members; if questions cannot be answered alone (due to problems with reading or 
understanding), then the doctor or nurse should read the questions and record the patient’s 
responses without influencing their answers. The information provided is strictly confidential 
and will be treated as such. If a patient has missed a question or given more than one response 
per question, then this should be brought to patient. Incomplete questions should not be 
accepted without first encouraging the patient to complete unanswered questions.  
The Investigator must complete the patient/visit information on the electronic device and 
ensure that the center number, patient’s number and initials are identical to the Case Record 
Form. As there are no source data for this questionnaire, the data queries will be restricted to 
patient/visit information.  


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13.11 
Appendix 11: Standard reference table for the LDI 
 
Table-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-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 
 

SAP_001.pdf: 
Clinical Development 
Secukinumab (AIN457) 
AIN457F2354 
A 52-week, multicenter study to assess the time course of response to 
secukinumab on joint inflammation using Power Doppler ultrasonography in 
patients with active psoriatic arthritis 
Statistical Analysis Plan (SAP) 
Author: 
Trial statistician, 
; 
Document 
type: 
SAP Documentation 
Document 
status: 
Addendum v1 
Release date: 
20-JUL-2021
Number of 
pages: 
69 
Property of Novartis 
For business use only 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 










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Date / version 
Reason for update 
Section and title impacted 
(Current) 
Section 2.9.1.1 – Adverse events of 
special interest / grouping of AEs 
Section 2.9.5 – Laboratory data 
Section 2.9.7.2 – Vital signs 
Section 
2.10 
– 
Pharmacokinetic 
endpoints 
Section 2.15 – Interim analysis 
Section 3.1 – Determination of sample 
size 
Section 4 – Change to protocol 
specified analyses 
Section 5.2 – AEs coding/grading 
Section 5.4 – Assessment windows 
Section 5.5.1 – Primary analysis 
Section 5.5.2 – Key scondary analysis 
Section 5.6 - Rule of exclusion criteria 
of analysis sets 
  
Section 5.14 - PASI 
 
 


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Table of contents 
Table of contents ......................................................................................................................7 
List of abbreviations ...............................................................................................................10 
1 
Introduction ............................................................................................................................12 
1.1 
Study design ...............................................................................................................12 
1.2 
Study objectives and endpoints ..................................................................................14 
1.2.1 
Primary objective .......................................................................................14 
1.2.2 
Secondary objectives .................................................................................14 
1.2.3 
Exploratory objectives ...............................................................................15 
2 
Statistical methods .................................................................................................................16 
2.1 
Data analysis general information ..............................................................................16 
2.1.1 
General definitions .....................................................................................17 
2.2 
Analysis sets ...............................................................................................................18 
2.2.1 
Subgroup of interest ...................................................................................18 
2.3 
Patient disposition, demographics and other baselinecharacteristics .........................19 
2.3.1 
Patient disposition ......................................................................................19 
2.3.2 
Demographics and other baseline characteristics ......................................19 
2.3.3 
Medical History .........................................................................................21 
2.4 
Treatments (study treatment, concomitant therapies,compliance) .............................21 
2.4.1 
Study treatment / compliance.....................................................................21 
2.4.2 
Prior & concomitant medications ..............................................................23 
2.5 
Analysis of the primary objective...............................................................................23 
2.5.1 
Primary endpoint ........................................................................................23 
2.5.2 
Statistical hypothesis, model, and method of analysis ...............................24 
2.5.3 
Handling of missing values/censoring/discontinuations ............................24 
2.5.4 
Supportive analyses ...................................................................................24 
2.6 
Analysis of the key secondary objective ....................................................................25 
2.6.1 
Key secondary endpoint .............................................................................25 
2.6.2 
Statistical hypothesis, model, and method of analysis ...............................27 
2.6.3 
Handling of missing values/discontinuations .............................................28 
2.6.4 
Supportive analyses ...................................................................................29 
2.7 
Analysis of secondary efficacy objective(s) ...............................................................29 
2.7.1 
Secondary endpoints ..................................................................................29 
2.7.2 
Statistical hypothesis, model, and method of analysis ...............................29 
2.7.3 
Handling of missing values/censoring/discontinuations ............................30 
2.8 
Other efficacy variables/Exploratory analysis ............................................................30 


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2.9 
Safety analyses ...........................................................................................................35 
2.9.1 
Adverse events (AEs) ................................................................................35 
2.9.2 
Deaths ........................................................................................................38 
2.9.3 
Liver Safety ...............................................................................................38 
2.9.4 
Renal Safety ...............................................................................................38 
2.9.5 
Laboratory data ..........................................................................................38 
2.9.6 
Other safety data ........................................................................................39 
2.9.7 
Additional parameters ................................................................................40 
2.10 
Pharmacokinetic endpoints ........................................................................................40 
2.11 
PD and PK/PD analyses .............................................................................................40 
2.12 
Patient-reported outcomes ..........................................................................................41 
2.13 
Biomarkers .................................................................................................................41 
2.14 
Sub study ....................................................................................................................41 
2.15 
Interim analysis ..........................................................................................................41 
3 
Sample size calculation ..........................................................................................................42 
3.1 
Determination of sample size .....................................................................................42 
4 
Change to protocol specified analyses ...................................................................................43 
5 
Appendix ................................................................................................................................44 
5.1 
Imputation rules..........................................................................................................44 
5.1.1 
Study drug ..................................................................................................44 
5.1.2 
AE date imputation ....................................................................................45 
5.1.3 
Concomitant medication date imputation ..................................................46 
5.2 
AEs coding/grading ....................................................................................................48 
5.3 
Laboratory parameters derivations .............................................................................48 
5.4 
Assessment windows, baseline and post baselinedefinitions, missing data handling49 
5.5 
Statistical models ........................................................................................................52 
5.5.1 
Primary analysis .........................................................................................52 
5.5.2 
Key secondary analysis ..............................................................................53 
5.6 
Rule of exclusion criteria of analysis sets ..................................................................53 
5.7 
Power Doppler Ultrasonography ................................................................................54 
5.8 
The classification criteria for psoriatic arthritis (CASPAR) ......................................55 
5.9 
American College of Rheumatology measures and criteriaof response .....................56 
5.10 
OMERACT-EULAR Global PDUS OMERACT out of 48 joints .............................57 
5.11 
OMERACT score of enthesitis...................................................................................59 
 
60 
5.13 
Health assessment questionnaire ................................................................................61 


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5.14 
PASI ...........................................................................................................................62 
 
64 
 
65 
 
66 
 
66 
6 
References ..............................................................................................................................68 


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List of abbreviations 
ACR 
American College of Rheumatology 
AE 
Adverse event 
ANA 
Antinuclear antibodies 
ANCOVA 
Analysis of covariance 
ATC 
Anatomical Therapeutic Chemical Classification 
BMI 
Body Mass Index 
BSA 
Body Surface Area 
CASPAR 
Classification Criteria for Psoriatic Arthritis 
CHMP 
Committee for Medicinal Products for Human Use 
 
 
DBLK 
Database Lock 
DMARD 
Disease Modifying Anti-Rheumatic Drug 
FAS 
Full Analysis Set 
ECG 
Electrocardiography 
eCRF 
Electronic Case Report Form 
EULAR 
European League Against Rheumatism 
GLOESS 
Global OMERACT-EULAR Synovitis Score 
HAQ-DI 
Health Assessment Questionnaire – disability index 
IR 
Inadequate response 
JE 
Joint Effusion 
 
 
 
 
 
 
MAR 
Missing at Random 
MCAR 
Missing Completely at Random 
MCMC 
Markov Chain Mone Carlo 
MCP 
Metacarpophalangeal 
 
 
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
MMRM 
Mixed Model Repeated Measures 
MTP 
Metatarsophalangeal 
MTX 
Methotrexate 
OMERACT 
Outcome Measures in Rheumatology 
PASI 
Psoriasis area and severity index 
PD 
Protocol Deviation 
PDUS 
Power dopper Ultrasound Sonography 
PFS 
Prefilled syringes 
PK 
Pharmacokinetics 
PID 
Distal interphalangeal 
PIP 
Proximal interphalangeal 
PPD 
Purified Protein Derivative 
PsA 
Psoriatic Arthritis 
 
 


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RF 
Rheumatoid Factor 
SAP 
Statistical Analysis Plan 
s.c. 
Subcutaneous 
SDI 
Standard Disability Index 
SH 
Synovial Hyperplasia 
SOC 
System Organ Class 
SpA 
Spondyloarthritis 
SJC 
Swollen Joint Count 
SPARCC 
Spondyloarthritis Research Consortium of Canada 
SRM 
Standarized Response Mean 
SSR 
Sample Size Reestimation 
TEAE 
Treatment Emergent Adverse Events 
TJC 
Tender Joint Count 
VAS 
Visual Analogue Scale 
 
 




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Primary analysis 
The Week 12 analysis will be performed after all patients complete the Week 12 visit 
(see Section 2.15). Only the data analysts will be unblinded to the Treatment Period 1 
randomization data after the Week 12 database lock/analyses. Summary results will be 
shared internally and externally; however, individual unblinded patient data will not be 
disclosed externally. The Ultrasonography Investigator and the Clinical Investigator will 
remain blinded from each other until the final database lock. 
 
 
Treatment Period 2 – open-label treatment period (Week 12 to Week 24) 
From Week 12, secukinumab will be given open-label to all patients irrespective of their 
initial treatment (i.e. only 150 mg or 300 mg secukinumab will be dispensed as 1 or 2 
PFSs, respectively). 
In Group 1, patients will continue to receive the same active dose of secukinumab every 
4 weeks until Week 24 (i.e. at Week 12, 16 and 20); patients will no longer receive the 
placebo PFS, which was administered to maintain blinding. 
In Group 2, patients will commence open-label secukinumab every 4 weeks from Week 
12 until Week 24 (i.e. at Week 12, 16 and 20), based on their clinical characteristics 
(BSA or severity of skin lesions) at Week 12. 
A blinded sample size estimation (SSR) will be performed when the first 60 patients 
have completed the Week 12 visit as described in Section 2.15. 
 
 
 
Treatment Period 3 – extension period (Week 24 to Week 52) 
Treatment Period 3 is an extension period to allow responder patients (if they wish and 
as per clinician’s judgment) the possibility to continue open-label secukinumab 
treatment up to Week 52. 
At Week 24, open-label secukinumab will continue to be assigned to patients in Group 
1 and Group 2 at the same dose every 4 weeks until Week 52 at either the study site (i.e. 
Week 24, 36 and 52) or at home (Week  28, 32, 40, 44, 48). 
At Week 24, patients who do not reach at least a 20% improvement in tender joint count 
(TJC) and swollen joint count (SJC) with secukinumab (150 mg or 300 mg) will be 
withdrawn from the study. 
 
The Week 24 analysis will be performed after all patients complete the Week 24 visit (see 
Section 2.15). 
The final analysis will be performed after the last patient has completed the Week 64/End of 
Study visit or early withdrawal visit (in case of early withdrawal of last patient from the 
study). After the final database lock and analyses have been completed, site personnel 


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(including the Ultrasonography Investigator and Clinical Investigator) will be unblinded to 
the original randomized treatment (sequence) assignment at randomization. 
A follow-up visit is to be done 12 weeks after last study treatment administration for all 
patients, regardless of whether they complete the entire study as planned or discontinue 
prematurely. All AEs that occur during this post-treatment follow-up period will be 
included in the evaluation of treatment-emergent AEs. 
 
The study population will consist of male and female patients aged ≥ 18 years with PsA as 
per the classification criteria for PsA (CASPAR) and with active PsA for at least 6 months 
and must have active disease as assessed by ≥ 3 tender joint count (TJC) out of 78 and ≥3 
swollen joint count (SJC) out of 76 at Baseline and with an IR to non-biologic DMARDs 
and at least one clinical enthesitis at Screening and Baseline. Patients can be re-screened 
only once and ‘no’ re-screening study related procedures should be performed prior to 
written re-consent by the patient. Mis-randomized patients cannot be re-screened. The goal 
is to randomize 164 patients in total (82 patients per arm) at approximately 50 centers 
worldwide. 
 
 
1.2 
Study objectives and endpoints 
 
 
1.2.1 
Primary objective 
To demonstrate that there is a difference between secukinumab and placebo in terms 
of joint synovitis response over 12 weeks as measured by the PDUS Global 
OMERACT-EULAR Synovitis Score (GLOESS) of the affected joints (out of 48 
joints) in PsA patients with an inadequate response (IR) to non-biologic DMARDs. 
 
1.2.2 
Secondary objectives 
 
1.2.2.1 
Key secondary objectives 
• To demonstrate that the efficacy of secukinumab at Week 12 is superior to placebo 
based on the proportion of patients achieving an ACR 20 response. 
• To demonstrate that the efficacy of secukinumab at Week 12 is superior to placebo 
based on the proportion of patients achieving an ACR 50 response. 
• To demonstrate that the clinical response of secukinumab at Week 12 is superior to 
placebo based on the change in SPARCC enthesitis index from Baseline to 
Week 12. 
 
1.2.2.2 
Other secondary objectives 
• To evaluate the therapeutic effect of secukinumab versus placebo on joint 
synovitis from Baseline to Week 8 using the GLOESS score out of 48 joints 






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The statistical analysis planned for the primary and secondary objectives are clearly 
stated, if not otherwise specified 95% confidence intervals may be presented along with 
point estimates and p-values will be presented as 1-sided. 
 
Data analyses and summaries will be performed by treatment group (Secukinumab 150mg 
+ 300 mg and Placebo) for baseline measurements, efficacy and safety data captured 
within the placebo-controlled period and for adverse events throughout the treatment 
periods. 
Analyses of all efficacy and non-AE safety parameters for the treatment periods will be 
performed by treatment sequence and results presented for the following groups: 
secukinumab (150 mg + 300 mg), placebo – secukinumab (150 mg + 300 mg). 
 
All listings will be presented by treatment sequence for efficacy and non-AE safety and 
by treatment for baseline and AE listings. 
 
 
2.1.1 
General definitions 
Treatment periods 
Period 1 = from first dose up to but not including Week 12 dose. 
Period 2 = Week 12 dose up to but not including Week 24 dose. 
Extension = Week 24 dose until Week 52. 
Follow-up = After Week 52 until Week 64 
Study Day 1 and other study days 
The first day of administration of randomized study treatment (first dose) is defined as 
Study Day 1 or Day 1. 
All other study days will be labeled relative to Day 1. For event dates on or after Day 
1, study day for a particular event date is calculated as [Date of event] – [Date of first 
dose]+1, i.e., Day 2, Day 3, etc., will be one day, two days, etc., after Day 1, 
respectively. For the dates before Day 1, study day for an event date is calculated as 
[Date of event] – [Date of first dose], i.e., Day -1, Day -2, etc., will be one day, two 
days, etc., before Day 1, respectively. Duration of an event will be calculated as (Event 
end date – Event start date + 1). 
The descriptor “Day 0” will not be used. 
Screening, baseline and post-baseline definitions 
Screening refers to any procedures (e.g., checking inclusion and exclusion criteria) 
performed prior to the date of first dose of study treatment. Per protocol, subject 
informed consent must be obtained prior to performing any study related activity. The 
date of signing informed consent is the start date of screening period. Any assessment 


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obtained during the screening period will be labeled screening assessment. Assessments 
made on Day 1 may occur before or after the randomization or the first dose. 
For efficacy analyses, baseline is the last assessment (including unscheduled visits) 
obtained before the first dose of study treatment . All assessments obtained after the first 
dose of study treatment are considered as post-baseline unless otherwise specified. 
For safety analyses, baseline is the last assessment (including unscheduled visits) 
obtained before the first dose of study treatment. All assessments obtained after the first 
dose of study treatment are considered as post-baseline unless otherwise specified. 
Of note, re-randomization will not be used for baseline definition and only one baseline 
value will be defined referring to the first randomization. 
Day of last dose of randomized study treatment 
The date of last dose will be collected via the eCRF. The subject’s exposure will be 
calculated considering the end of treatment period visit (e.g., treatment period 3 
completion visit). If a subject discontinued early, then the last visit during the treatment 
period is considered (e.g. last visit in treatment period 2, if subject discontinued from 
treatment period 2). 
 
 
2.2 
Analysis sets 
The following analysis sets will be used for the data analysis. 
All screened patients : The all screened patients set will comprise all patients screened 
regardless of whether they were enrolled. Screen failures will be included. 
Randomized set (RAN): The randomized set will be defined as all patients who were 
randomized. 
Unless otherwise specified, mis-randomized patients will be excluded from the 
randomized set. Mis-randomized patients are defined as those patients who were 
mistakenly randomized prior to the site confirming all eligibility criteria had been met 
and to whom no study medication was given. Mis-randomized patients are treated as 
screen failures. 
Full analysis set (FAS): The FAS will comprise all patients from the randomized set to 
whom study treatment has been assigned. Following the intent-to-treat principle, 
patients will be analyzed according to the treatment assigned at randomization. 
Safety set (SS): The Safety set will include all patients who took at least 1 dose of study 
treatment during the treatment period. Patients will be evaluated according to study 
treatment received. 
 
 
 
 




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Continuous variables: 
o Age (which is derived from date of birth and the screening assessment 
date) 
o Height 
o Weight 
o Body mass index (BMI) 
 
Body Mass Index (BMI) will be calculated using the following formula: 
BMI = (body weight in kilograms) / (height in meters)2 
For BMI, height and body weight used is the last value prior to first dose. If there is no 
weight recorded prior to taking of study treatment, BMI will be missing. 
 
Categorical variables: 
o Age categories (<65 years, 65 years and older, 75 years and older) 
o Sex 
o Race 
o Ethnicity 
o Source of patient referral 
o Child bearing status 
o Smoking status at baseline 
 
Additionally the following psoriasis specific baseline characteristics and history of 
disease will be summarized: 
o Baseline total BSA (≤3%, >3%) 
o Baseline PASI 
o Severity of psoriasis (CHMP guidelines, mild (total BSA <10% or 
PASI < 10), moderate ((PASI ≥10 or total BSA≥10%) and PASI ≤20 
and total BSA ≤20%), severe (total BSA >20% or PASI > 20)) 
o Moderate-to-severe Psoriasis (EMA criteria : total BSA >10% or 
PASI > 10, FDA criteria : total BSA ≥10% and PASI ≥ 12 
o CASPAR 
o Global PDUS (GLOESS) 
o SPARCC enthesitis index 
o ACR components 
o Time since diagnosis of psoriatic arthritis 
o Time since diagnosis of psoriasis 
o Previous exposure psoriasis therapies if applicable /PsA therapies 
o QuantiFERON TV-Gold test or PPD skin test (depending on local 
guidelines) 




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when subjects should receive two identical injections, it will be assumed that they 
received secukinumab or placebo, respectively, as planned. 
The duration of exposure to study treatment will be summarized by the actual treatment 
received or treatment sequence for each treatment period. In addition, the number of 
subjects with cumulative exposure of at least certain time thresholds will be displayed. 
The following categories will be presented: “any exposure”, “<1 week”, “≥1 week” “≥2 
weeks”, “≥3 weeks”, “≥4 weeks”, “≥8 weeks”, “≥12 weeks”, and so on with an increase 
of time threshold by 4 weeks until there are no subjects in the category or the last 
category is presented. 
 
For treatment period 1, the end date for the calculation of duration of exposure will be the 
earlier of: 
a. Date of last injection in treatment period 1 + 84 days, and 
b. Date of first injection in treatment period 2 
 
 
 
For treatment period 2, the end date for the calculation of duration of exposure will be the 
earlier of: 
a. Date of last injection in treatment period 2 + 84 days, and 
b. Date of first injection in treatment period 3 
 
For treatment period 3 (extension period), the end date for the calculation of duration of 
exposure will be the date of last injection in treatment period 3 + 84 days. 
For patients with death as an event, end date for calculation of duration of exposure will 
be the date of death if it is earlier than the date of last injection + 84 days. 
Duration of exposure (years) = duration of exposure (days) / 365.25 
The analyses of duration of exposure described above will be done for the double-blind 
placebo controlled period (Period 1), Treatment Period 2 – open-label treatment period 
(Week 12 to Week 24) and Treatment Period 3 – extension period (Week 24 to Week 
52). 
 
Compliance 
Compliance will be calculated based on documented study drug administrations and 
displayed by treatment group. It is calculated as follows: 
Compliance (%) = 100*(total no. of injections administered) / (no. of injections 
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. Treatment compliance for subjects will be summarized for subjects for each treatment 
period of the study. 
 
2.4.2 
Prior & concomitant medications 
Concomitant medications entered into the database will be coded using the World 
Health Organization Drug Reference List, which employs the Anatomical Therapeutic 
Chemical (ATC) classification system. 
Prior and concomitant medications will be summarized by treatment group in separate 
tables for the safety set unless otherwise specified. Medications will be presented in 
alphabetical order, by ATC codes and grouped by anatomical main group (the 1st level 
of the ATC codes). Tables will also show the overall number and percentage of subjects 
receiving at least one drug of a particular ATC code, at least one drug in a particular 
anatomical main group and any Methotrexate or any Cortcosteroids. 
Prior medications are defined as drugs taken and stopped prior to first dose of study 
treatment. Any medication given at least once between the day of first dose of study 
treatment and the last day of study visit will be a concomitant medication, including 
those which were started pre-baseline and continued into the treatment period. 
Prior or concomitant medication will be identified based on recorded or imputed start 
and end dates of medication taken. 
Prior & concomitant procedures will be coded using the Medical dictionary for 
regulatory activities (MedDRA) terminology. Prior and concomitant procedures will be 
summarized by treatment group for the safety set unless otherwise specified and will be 
displayed by treatment period. 
Prior psoriasis-psoriatic arthritis therapies details will also be listed for each patient and 
summized by therapy type (biologic systemic, non-biological systemic therapy 
{Methotrexate, Corticosteroid, NSAID and DMARDs}, topical, phototherapy and photo 
chemotherapy). 
The number and percentage of subjects receiving prior and concomitant therapies from 
the Prior Psoriasis-Psoriatic Arthritis Therapy eCRF will be presented by randomized 
treatment group as well as the reasons for stopping their therapies (primary lack of 
efficacy, secondary lack of efficacy, lack of tolerability, other). 
 
 
2.5 
Analysis of the primary objective 
The primary objective is to demonstrate that there is a difference between secukinumab 
and placebo in terms of joint synovitis response over 12 weeks as measured by the PDUS 
Global OMERACT-EULAR Synovitis Score (GLOESS) of the affected joints (out of 
48 joints) in PsA patients with an inadequate response (IR) to non-biologic DMARDs 
(reference Appendix 5.7 for further details). 
 
2.5.1 
Primary endpoint 
The primary analysis variable is the change from baseline in GLOESS over 12 weeks. 






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• Proportion of patients with ACR 20 response at Week 12 in each treatment arm. 
• Proportion of patients with ACR 50 response at Week 12 in each treatment arm. 
• Change in SPARCC enthesitis index from Baseline to Week 12 in each treatment 
arm. 
 
2.6.1.1 
American College of Rheumatology response 
The ACR response (reference Appendix 5.9 for details) will be used to determine 
efficacy (Felson 1995). A patient is defined as e.g. an ACR 20 responder if, and only if, 
the following 3 conditions hold: 
• Patient has a ≥ 20% improvement in the number of tender joints (based on 78 
joints). 
• Patient has a ≥ 20% improvement in the number of swollen joints (based on 76 
joints). 
• Patient has a ≥ 20% improvement in 3 of the following 5 domains: 
1. Patient’s global assessment of disease activity (measured on a VAS scale, 0- 
100). 
2. Physician’s global assessment of disease activity (measured on a VAS scale, 
0-100). 
3. Patient’s assessment of PsA pain (measured on a VAS scale, 0-100). 
4. Health Assessment Questionnaire-Disability Index (HAQ-DI©) score. 
5. Acute phase reactant (high-sensitivity C-reactive protein (hsCRP)). 
An ACR 50 response is defined as a 50% improvement in at least 3 of the 5 measures 
and a 50% improvement in the SJC and TJC. 
An ACR 70 response is defined as a 70% improvement in at least 3 of the 5 measures 
and a 70% improvement in the SJC and TJC. 
 
 
2.6.1.2 
Spondyloarthritis research consortium of Canada – enthesitis 
index 
The SPARCC (Maksymowych et al 2009) enthesitis index focuses on the clinical 
evaluation and validation of the 16 sites shown in Table 1. 
 
Table 1: Entheses sites comprising the total spondyloarthritis research consortium 
of Canada enthesitis index 
 
Greater trochanter 
R/L 
Quadriceps tendon insertion into the patella 
R/L 
Patellar ligament insertion into the patella and tibial tuberosity 
R/L 
Achilles tendon insertion 
R/L 
Plantar fascia insertion 
R/L 
Medial epicondyles 
R/L 
Lateral epicondyles 
R/L 


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Supraspinatus insertion 
R/L 
Abbreviations: R = right, L = left 
Tenderness at each site is quantified on a dichotomous basis: 0= non-tender and 1= 
tender. The sum of scores from each site is calculated to give a range of a total score 
for the index from 0 to 16. 
 
2.6.2 
Statistical hypothesis, model, and method of analysis 
The following null hypotheses will be included in the testing strategy and type-I-errors 
will be set such that a family-wise type-I-error of 5% is kept: 
Primary objective: 
• H1: secukinumab s.c. is not different to placebo regimen with respect to the change 
in GLOESS from Baseline to Week 12. 
See section 2.5.2 for details. 
Key secondary objectives: 
• H2: secukinumab is not different to placebo regimen with respect to ACR 20 
response at Week 12. 
• H3: secukinumab s.c. is not different to placebo regimen with respect to ACR 50 
response at Week 12. 
• H4: secukinumab s.c. is not different to placebo regimen with respect to the change 
in SPARCC enthesitis index from Baseline to Week 12. 
No hypotheses other than H1 to H4 will be considered. The family wise error will be set 
to α=5% (1-sided). The graphical approach of Bretz (Bretz et al 2009) for sequentially 
rejective testing procedures is used to illustrate the hierarchical testing strategy (Figure 
1). 
 
Figure 1 
Testing strategy 
 
The family-wise error will be set to α = 5% (1-sided). H1 is tested at α (1-sided). The 
following hypotheses will be tested sequentially and are included in the hierarchical 
testing strategy and type-I-errors will be set such that a family-wise type-I-error of 5% 
is kept: 
The testing sequence will continue to H2 at α (1-sided) only if H1 has been rejected. 
Similarly, the testing sequence will continue to H3 at α (1-sided) only if H2 has been 
rejected. This process will continue as each hypothesis is rejected up to H4. 
Of note, in the description above, rejection of a hypothesis refers to rejection of the 1- 
sided hypothesis; however, the level of a rejected hypothesis is only passed on 


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(according to the graphical procedure) for the test of another hypothesis if the treatment 
effect is in favor of secukinumab. 
 
ACR 20 at Week 12 
Response at Week 12 in ACR 20 in the FAS will be evaluated using a logistic regression 
model with study treatment as a factor and baseline weight as a covariate. The odds 
ratios will be computed for comparison of secukinumab versus placebo using the logistic 
regression model fitted. In cases where separation is a concern for secondary endpoint 
at Week 12 an exact logistic regression model will be applied to all visits. To ensure 
convergence, this model will not include any continuous covariates. When exactlogistic 
regression is unable to be implemented then Fisher’s exact test will be applied.In this 
case no odds ratios or confidence inervals can be estimated but p-values may be 
calculated. 
 
ACR 50 at Week 12 
Response at Week 12 in ACR 50 in the FAS will be evaluated using a logistic regression 
model with study treatment as a factor and baseline weight as a covariate. The odds 
ratios will be computed for comparison of secukinumab versus placebo using the logistic 
regression model fitted. In cases where separation is a concern for secondary endpoint 
at Week 12 an exact logistic regression model will be applied to all visits. To ensure 
convergence, this model will not include any continuous covariates. When exactlogistic 
regression is unable to be implemented then Fisher’s exact test will be applied.In this 
case no odds ratios or confidence inervals can be estimated but p-values may be 
calculated. 
 
Changes in SPARCC at Week 12 
Between-treatment differences in the change from baseline in SPARCC at Week 12 in 
the FAS will be compared by means of a MMRM with treatment regimen and analysis 
visit as factors and baseline weight and SPARCC score as continuous covariates. Study 
treatment by analysis visit will be included as an interaction term in the model. An 
unstructured covariance structure will be assumed for this model. The significance of 
the treatment effect for secukinumab at different analysis visits will be determined from 
the comparison to placebo. 
 
 
2.6.3 
Handling of missing values/discontinuations 
Missing data for the ACR 20 response and other binary efficacy variables (e.g. ACR 50, 
ACR 70,
PASI 75, PASI 90, PASI 100) for data up to 12 weeks (Week 12) will 
be handle
llows: 
• Patients who drop out of the trial for any reason will be considered non-responders 
from the time they drop out through to Week 12. 
• Patients who do not have the required data to compute ACR response (i.e. TJC and 
SJC and at least 3 of the 5 ACR core set variables) at the specific post-baseline 
time points will be classified as clinical non-responders. 
















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A graphical display of the crude rates within system organ classes will be presented. 
The placebo group will be displayed with a bar whereas dots will be used for 
secukinumab treatment groups. 
Non-treatment emergent adverse events will be summarized as well. These adverse 
events occurred before the first dose of the study treatment. The crude incidence rate 
will be provided without treatment information. 
Algorithms for date imputations will be provided in Appendix 5.1.2. 
 
Exposure time-adjusted incidence rates including 95% CIs will be presented for the 
entire treatment period. A graphical display of the crude rates and exposure-adjusted 
incidence rates will be presented for all AEs and SAEs by SOC. 
 
 
In addition, for the legal requirements of clinicaltrials.gov and EudraCT, 2 required tables on 
TEAEs which are not SAEs with an incidence greater than 2% and on treatment emergent AEs 
and SAEs suspected to be related to study treatment will be provided by primary SOC and PT on 
Safety set population. 
If for the same patient, several consecutive AEs (irrespective of study treatment causality, 
seriousness and severity) occurred with the same primary SOC and PT: 
• A single occurrence will be counted if there is ≤ 1 day gap between the end date of the 
preceding AE and the start date of the consecutive AE 
• More than one occurrence will be counted if there is > 1 day gap between the end date of 
the preceding AE and the start date of the consecutive AE 
For occurrence, the presence of at least one SAE/SAE suspected to be related to study 
treatment/non-SAE has to be checked in a block e.g., among AEs in a ≤ 1 day gap block, if at least 
one SAE is occurring, then one occurrence is calculated for that SAE. 
The number of deaths resulting from SAEs suspected to be related to study treatment and SAEs 
irrespective of study treatment relationship will be provided by SOC and PT. 
 
 
2.9.1.1 
Adverse events of special interest / grouping of AEs 
 
Adverse events of special interest (AESI) of the Safety Profiling Plan (SPP) and the Risk 
Management Plan will be identified through an extraction from the electronic Case 
Retrieval Strategy database. The extraction will be performed by selecting those records 
where the drug name is AIN457 and the indication is psoriasis, psoriatic arthritis and 
ankylosing spondylitis. 
To this end, the following events will be considered as adverse events of special interest: 
• Major adverse cardiovascular events (MACE): identified per Novartis MedDra 
Query (NMQ) “MACE (MI, Stroke, Cardiovascular death)” 
• Inflammatory bowel disease: identified per NMQ narrow “Inflammatory bowel 
disease” 
• Infections and infestations: identified per SOC “Infections and infestations” 
o Fungal infectious disorders : identified per HLGT 
o Staphylococcal infections : identified per HLGT 


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o Herpes viral infections : identified per HLGT 
o Mycobacterial infectious disorders : identified per HLGT 
o Central nervous system infections and inflammations : identified per HLGT 
o Oesophageal candidiasis : identified per SMQ narrow 
o Infections of skin structures : identified per NMQ1 
o Infectious pneumonia : identified per NMQ1 
o Opportunistic infections : identified per NMQ1 
• Malignancy: identified per NMQ “Malignant or unspecified tumours (SMQ 
excluding BCC and SCC)” or per SMQ for “Malignant or unspecified tumours 


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(SMQ)”, “Skin tumours malignant and unspecified” or “Non-melanoma skin cancer 
(BCC and SCC) 
• Hypersensitivity: identified per SMQ narrow “Hypersensitivity” 
• Neutropenia : identified per NMQ 
• Suicidal ideation and behaviour : identified per Suicide/self-injury (SMQ) 
• Interactions with live vaccines : identified per HLT “Vaccination related 
complications” 
• Hepatitis B reactivation : identified per HLT “Hepatitis viral infections” 
 
The crude rates for AESIs will be summarized. In addition, listings will be provided 
presenting which subjects experienced which risk. 
Important note: For the evaluation of AESIs risks, primary and secondary system organ 
classes of the MedDRA dictionary will be considered. 
 
 
2.9.2 
Deaths 
A separate summary of adverse events causing death will be presented by treatment 
group. 
 
2.9.3 
Liver Safety 
A summary of liver events will be presented by treatment group. 
 
2.9.4 
Renal Safety 
A summary of renal events will be presented by treatment group. 
 
2.9.5 
Laboratory data 
The summary of laboratory evaluations will be presented for 3 groups of laboratory tests 
(hematology, serum chemistry and urinalysis). For urinalysis, frequency tables will be 
presented. Descriptive summary statistics for the change from baseline to each study 
visit will be presented. These descriptive summaries will be presented by visit, 
laboratory test and study treatment group. Change from baseline will only be 
summarized for patients with both baseline and post baseline data. For each parameter, 
the maximum change (maximum decrease and maximum increase) from baseline within 
each study period will be evaluated analogously. 
In addition, shift tables will be provided for all parameters to compare a patient’s 
baseline laboratory evaluation relative to the visit’s observed value. For the shift tables, 
the normal laboratory ranges will be used to evaluate whether a particular laboratory 
test value was normal, low, or high for each visit value relative to whether or not the 
baseline value was normal, low, or high. 


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These summaries will be presented by laboratory test and study treatment group. Shifts 
will be presented by visit as well as for most extreme values post-baseline. 
Individual subject data listings will be provided for subjects with abnormal laboratory 
data. 
Box plots may be presented for selected laboratory parameters (WBC, neutrophils 
(absolute count), AST, ALT and creatinine). These box plots would show the following 
location parameters: The bottom and top edges of the box will represent the 25th and 
75th percentile, respectively. The center horizontal line of the box will represent the 
median. Lower and upper whiskers will reach to the 10th and 90th percentile, 
respectively. Values below the 10th percentile and above the 90th percentile will be 
presented by circles. Mean values will also be represented in the plot and connected with 
a line. 
 
2.9.6 
Other safety data 
 
2.9.6.1 
ECG and cardiac imaging data 
Not applicable 
 
2.9.6.2 
Immunogenicity 
Summary statistics will be provided for the percentage of patients with blood samples 
for immunogenicity (anti-AIN457 antibodies). 
 
2.9.6.3 
Pregnancy tests 
Serum and urine pregnancy tests will be summarized and listed, where applicable. 
 
2.9.6.4 
QuantiFERON TB-Gold test 
A listing of the QuantiFERON TB-Gold test results will be presented by treatment 
group. 
 
2.9.6.5 
PPD skin test 
A listing of the PPD skin test results will be presented by treatment group. 
 
2.9.6.6 
Local tolerability (injection site reactions) 
A separate summary of injection site reactions will be presented by treatment group. 
 
2.9.6.7 
Antibodies 
A listing of the anti-CCP antibodies, Rheumatoid Factor (RF), Antinuclear antibodies 
(ANA) and anti-dsDNA antibodies will also be listed by visit and treatment group. 
 
2.9.6.8 
Chest X-ray/MRI 
A listing of the chest X-ray/MRI results will be presented by treatment group. 


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2.9.7 
Additional parameters 
 
2.9.7.1 
Physical examination 
Not applicable. 
 
2.9.7.2 
Vital signs 
Analysis of vital sign measurements (systolic blood pressure (mmHg), diastolic blood 
pressure (mmHg) and pulse (bpm)) using descriptive summary statistics for the change 
from baseline for each post-baseline visit will be performed by vital sign and treatment 
group. Change from baseline will only be summarized for subjects with both baseline 
and post-baseline values and will be calculated as: 
change from baseline = post-baseline value – baseline value 
The number and percentage of subjects with newly occurring notable vital signs will be 
presented, by treatment period. Criteria for notable vital sign abnormalities are provided 
in Table 2 below. 
 
Table 3: Criteria for notable vital sign abnormalities 
 
Vital sign (unit) 
Notable abnormalities 
Systolic blood pressure (mmHg) 
>= 140 mmHg or < 90 mmHg 
Diastolic blood pressure (mmHg) 
>=90 mmHg or <60 mmHg 
Pulse (bpm) 
> 100 bpm or <60 bpm 
A blood pressure indicative of prehypertension (systolic 120 to < 140 mmHg and/or 
diastolic 80 to < 90 mmHg) will not be regarded as notable. 
 
2.10 
Pharmacokinetic endpoints 
All patients with concentration data will be included in the pharmacokinetic data 
analysis. 
The following pharmacokinetic parameter will be determined: Cmin,ss. Cmin,ss will be 
determined using Phoenix software. Individual serum concentrations in µg/ml will be listed. 
All concentrations below the limit of quantification or missing data will be labeled as such 
in the concentration data listings. Concentrations below the limit of quantification will be 
treated as zero in summary statistics for concentration data only. During modeling of the 
pharmacokinetics of secukinumab, the broad principles outlined in the FDA Guidance for 
Industry: Population Pharmacokinetics will be followed. 
 
Summary statistics by visit/time will be provided for the above mentioned parameters 
and will include arithmetic and geometric means, SD, median, minimum and maximum. 
Individual concentrations will be listed by patient. 
 
2.11 
PD and PK/PD analyses 
Not applicable 




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Week 12 analysis 
The analysis of the primary and secondary efficacy variables will be performed after all 
patients complete the Week 12 visit. This analysis will also include exploratory variables 
outlined up to Week 12 and all available safety data. 
 
 
Week 24 analysis 
The analysis of the exploratory variables up to Week 24 will be performed after all 
patients complete the Week 24 visit. This analysis will also include all available safety 
data. 
 
 
3 
Sample size calculation 
3.1 
Determination of sample size 
 
This study was designed using data for abatacept in the APPRAISE study (RA study to assess 
early response to abatacept + MTX (D’Agostino et al, 2016), to test the superiority of 
secukinumab compared to placebo at the 5% significance level using a 2-sided test. 
Assuming a difference in the mean change from Baseline at Week 12 in OMERACT global 
PDUS score of -5.8 with a pooled standard deviation of 13.2, 218 patients in total (109 
patients per arm) were estimated to achieve a power of 90% (EAST 6). 
A blinded SSR was performed once the first 60 patients completed the Week 12 visit to 
evaluate the assumptions used in the sample size calculations. The statistical test for the 
primary endpoint has been changed from a 2-sided to a 1-sided test. 
The first 60 patients to reach Week 12 have a pooled mean change from Baseline at Week 12 
in OMERACT global PDUS score of -5.25 with a pooled standard deviation of 9.527. Using 
the estimated placebo effect of roughly 50% of secukinumab based on data from the 
FUTURE 2 study (CAIN457F2312) as in the original sample size calculation, the pooled 
PDUS score change of -5.25 translates to an assumed change of -7.000 and -3.500 for the 
secukinumab and placebo group, respectively, providing a difference of 3.500 between the 
groups. Adapting the original sample size calculation to be 1-sided with the power relaxed 
to 80%, 184 patients in total (92 patients per arm) are required (EAST 6). 
At the time of the blinded sample size calculation, 72 patients were available who had 
reached their Week 12 visit, to provide the most accurate estimation, all data available were 
considered i.e. the first 72 patients as opposed to the first 60 patients. Using all available data 
a difference in the mean change from Baseline at Week 12 in OMERACT global PDUSscore 
of 4.352 was observed with a pooled standard deviation of 9.822. At the 5% significance 
level using a 1sided test, 126 patients are needed to achieve a power of 80% (EAST 6). 
The 2 calculations produce a sample size range of 127-185 patients; thus, the sample size 
will be adjusted to a new target of 164 patients in total (82 patients per arm). This is mid- 






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5.1.2 
AE date imputation 
Incomplete Start Date: 
Missing day and month 
• If the year is the same as the year of the first dosing date, then the day and month of 
the first dosing date will be assigned to the missing fields. 
• If the year is prior to the year of first dosing date, then December 31 will be assigned 
to the missing fields. 
• If the year is after the year of first dosing, then January 1 will be assigned to the 
missing fields. 
Missing day only 
• If the month and year are the same as the year and month of first dosing date, then the 
first doing date will be assigned to the missing day. 
• If either the year of the partial date is before the year of the first dosing date or the 
years of the partial date and the first dosing date are the same but the month of partial 
date is before the month of the first dosing date, then the last day of the month will be 
assigned to the missing day. 
• If either the year of the partial date is after the year of the first dosing date or the years 
of the partial date and the first dose date are the same but the month of partial date is 
after the month of the first dosing date, then the first day of the month will be assigned 
to the missing day. 
• If the stop date is not missing, and the imputed start date is after the stop date, the start 
date will be imputed by the stop date. 
Missing day, month, and year 
• No imputation is needed, the corresponding AE will be included as TEAE. 
Incomplete Stop Date: If the imputed stop date is before the start date, then the imputed 
stop date will be equal to the start date. 
Missing day and month 
• If the year of the incomplete stop date is the same as the year of the last dosing date, 
then the day and month of the last dosing date will be assigned to the missing fields. 
• If the year of the incomplete stop date is prior to the year of the last dosing date or 
prior to the year of the first dosing date, then December 31 will be assigned to the 
missing fields. 
• If the year of the incomplete stop date is prior to the year of the last dosing date but 
is the same as the year of the first dosing date, then the first dosing date will be assigned 
to the missing date. 
• If the year of the incomplete stop date is after the year of the last dosing date, then 
January 1 will be assigned to the missing fields. 
Missing day only 
• If the month and year of the incomplete stop date are the same as the month and year 
of the last dosing date, then the day of the last dosing date will be assigned to the missing 
day. 




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START 
DATE 
STOP 
DATE 
ACTION 
Partial 
Known 
Impute start date as earliest possible date (i.e. first 
day of month if day unknown or 1st January if day 
and month are unknown), then: 
If stop date < study med start date, assign as prior 
If stop date >= study med start date and start date 
<= study med end date, assign as concomitant 
If stop date >= study med start date and start date > 
study med end date, assign as post treatment 
Partial 
Impute start date as earliest possible date (i.e. first 
day of month if day unknown or 1st January if day 
and month are unknown) and impute stop date as 
latest possible date (i.e. last day of month if day 
unknown or 31st December if day and month are 
unknown), then: 
If stop date < study med start date, assign as prior 
If stop date >= study med start date and start date 
<= study med end date, assign as concomitant 
If stop date >= study med start date and start date > 
study med end date, assign as post treatment 
Missing 
Impute start date as earliest possible date (i.e. first 
day of month if day unknown or 1st January if day 
and month are unknown), then: 
If stop date is missing could never be assumed a 
prior medication 
If start date <= study med end date, assign as 
concomitant 
If start date > study med end date, assign as post 
treatment 
Missing 
Known 
If stop date < study med start date, assign as prior 
If stop date >= study med start date, assign as 
concomitant 
Cannot be assigned as ‘post treatment’ 


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START 
DATE 
STOP 
DATE 
ACTION 
Partial 
Impute stop date as latest possible date (i.e. last day 
of month if day unknown or 31st December if day 
and month are unknown), then: 
If stop date < study med start date, assign as prior 
If stop date >= study med start date, assign as 
concomitant 
Cannot be assigned as ‘post treatment’ 
Missing 
Assign as concomitant 
 
 
5.1.3.1 
Prior therapies date imputation 
Refer to Section 5.1.3 above. 
 
5.1.3.2 
Post therapies date imputation 
Refer to Section 5.1.3 above. 
 
5.1.3.3 
Other imputations 
Not applicable. 
 
 
 
5.2 
AEs coding/grading 
 
The verbatim term recorded on CRF will be identified as adverse event and will be coded 
by primary system organ class and preferred term using Medical Dictionary for Regulatory 
Activities (MedDRA) version 21.0 and above. 
 
 
5.3 
Laboratory parameters derivations 
Not applicable. 


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5.4 
Assessment windows, baseline and post baseline 
definitions, missing data handling 
During the period of the study from Screening to Follow-up Week 64 (F64), the 
assessments must be performed as indicated in Table 6.1 of the protocol. 
Patients should be seen for all visits on the designated day or as closely as possible to 
the original planned visit schedule. 
• For visits scheduled through Week 4, the study treatment should not be 
administered less than 4 days from the previous administration. 
• For visits scheduled after Week 4, the study treatment should not be administered 
less than 14 days from the previous administration. 
 
Assessment windows 
No assessment windows have been defined for this study. Visit windows are described 
below. 
Visits windows 
Visit-windows will be used for the data that is summarized by visit; they are based on 
the study evaluation schedule and comprise a set of days around the nominal visit day. 
For any assessment, there are the protocol defined scheduled visits around which visit 
windows were created to cover the complete range of days within the study. The visit 
windows are shown in Table 4. In this table, the days are counted since the first dose of 
study treatment (study days) for safety and efficacy assessments. These visit windows 
apply to measurements taken at every visit. For assessments collected less oftendifferent 
visit windows will be applied as detailed below. 
When visit windows are used, all visits will be re-aligned, i.e., they will be mapped into 
one of the visit windows. E.g., if the Week 4 visit of a subject is delayed and occurs on 
Day 46 instead of on Day 29, say, it will be re-aligned to visit window Week 8. In the 
case of major deviations from the visit schedule, or due to unscheduled visits, several 
assessments of a subject may fall in a particular visit window (either scheduled or 
unscheduled). Statistical approaches to handle multiple assessments in a given visit 
window are specified below. 
Of note, subjects are allowed to have gaps in visits. 


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Table 5-1: Assessment windows for scheduled visits 
Analysis Visit 
Week 
Scheduled 
Day 
Visit Window 
Baseline 
BSL 
1 
-28 days to Day 1* 
Week 1 
1 
8 
Day 2-11 
Week 2 
2 
15 
Day 12-18 
Week 3 
3 
22 
Day 19-25 
Week 4 
4 
29 
Day 26-43 
Week 8 
8 
57 
Day 44-71 
Week 12 
12 
85 
Day 72-99 
Week 16 
16 
113 
Day 100-127 
Week 20 
20 
141 
Day 128-155 
Week 24 
24 
169 
Day 156-211 
Week 36 
36 
253 
Day 212-309 
Week 52 
52 
365 
Day 310-379 
Week 56 
56 
393 
Day 380-421 
Week 64 
64 
449 
Day 422-463 
* Baseline measurement before the first drug administration for safety assessments and 
before the randomization for efficacy assessments. The days are counted since the first 
dose of study treatment for safety assessments, and the days are counted since the date 
of randomization for efficacy assessments. 
For parameters which are not collected at every visit, visit windows defined in Table 4 
will be combined. For example, if a parameter is measured at Week 12 and Week 24 
only, Week 12 visit window will extend from Day 2 to Day 99 (combining Week 1 to 
Week 12 visit windows), Week 24 will extend from Day 89 to Day 211 (combining 
Week 13 to Week 24). If more than one assessment falls into the interval, the rules 
defined below are applied. 
Assessments from one treatment period will not be considered for another treatment 
period. For example, if a Week 13 (scheduled visit) measurement falls into the Week 12 
visit window, this measurement would not be analyzed as treatment period 1 value. 
Of note, for subjects who discontinue in treatment period 1, i.e. not moving into 
treatment period 2, efficacy measurements taken in follow-up period would still be 
considered for the treatment period 1. 
The analysis visit will be used for listing of visit and treatment period for safety data. If 
a visit falls after the last visit window (after Day 463) it is not assigned an analysis visit 
and will be listed under label “After Week 64”. 
 
The administration of study drug at Week 28, 32, 40, 44, and 48 is not in relation to a 
study visit. For exposure data, a specific assessment window for those weeks is used in 
order to account for the home administrations at those weeks. 


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Table 5-2: Drug administration windows for scheduled visits of Exposure Data 
 
Analysis Visit 
Week 
Scheduled 
Day 
Visit Window 
Baseline 
BSL 
1 
-28 days to Day 1* 
Week 1 
1 
8 
Day 2-11 
Week 2 
2 
15 
Day 12-18 
Week 3 
3 
22 
Day 19-25 
Week 4 
4 
29 
Day 26-43 
Week 8 
8 
57 
Day 44-71 
Week 12 
12 
85 
Day 72-99 
Week 16 
16 
113 
Day 100-127 
Week 20 
20 
141 
Day 128-155 
Week 24 
24 
169 
Day 156-183 
Week 28 
28 
197 
Day 184-211 
Week 32 
32 
225 
Day 212-239 
Week 36 
36 
253 
Day 240-267 
Week 40 
40 
281 
Day 268-295 
Week 44 
44 
309 
Day 296-323 
Week 48 
48 
337 
Day 324-351 
Week 52 
52 
365 
>= 352 Days 
 
 
Multiple assessments within visit windows 
When there are multiple assessments in a particular visit window, the following rules 
are applied to select one value “representing” the subject in summary statistics in a visit 
window (See Table 5). 
For baseline assessment definition see Section 2.1.1. For post-baseline visit windows 
the following applies (unless otherwise specified): 
• for quantitative variables, the closest to the actual visit is chosen (if two assessments 
have the same distance, then the earlier one will be chosen) 
• for qualitative variables, the worst record is selected. It is noted that in the analyses 
performed, worst case is always well defined (e.g., for urine protein values “+” and 
“++”, the worst case is defined as “++”) 
• in case qualitative variables are based on quantitative variables, e.g. PASI 75 
response, the visit will be assigned to the quantitative variable, and this visit will be 
used for the derived qualitative variable 


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Table 6: Rules for selecting values for analysis 
 
Timing of 
measurement 
Type of data 
Rule 
Baseline 
All data 
See Section 2.1.1 
Post-baseline efficacy 
Continuous data 
The measurement closest to the 
target day will be used. In the 
event two measurements are 
taken equally apart (e.g., 1 day 
before target date and 1 day 
after), the earlier one will be used 
Post-baseline efficacy 
Categorical data 
The most extreme (the worst) 
measurement in the window will 
be used. For example, among ‘a 
little better’ and ‘moderately 
better’ values ‘a little better’ value 
will be selected. 
Post-baseline safety 
Continuous data 
The (non-missing) measurement 
closest to the target day will be 
used. In the event two 
measurements are taken equally 
apart (e.g., 1 day before target 
date and 1 day after), the earlier 
one will be used. 
If two measurments are taken on 
the same day then select the first 
one (using the time). 
If two measurements are taken on 
the same date/time then use the 
first visit number (assuming this is 
the planned visit). 
Post-baseline safety 
Categorical data 
The most extreme (the worst) 
measurement in the window will 
be used. For example, among ‘a 
little better’ and ‘moderately 
better’ values ‘a little better’ value 
will be selected 
 
 
5.5 
Statistical models 
5.5.1 
Primary analysis 
The statistical hypothesis for the GLOESS being tested is that there is no difference in 
the mean change from baseline scores over 12 weeks in the secukinumab regimen vs the 
placebo regimen. 
The model to be tested is as follows:- 
Change from baseline in GLOESS = Treatment + center + analysis visit + weight + 
baseline GLOESS + Treatment * analysis visit. 


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The procedure PROC MIXED will be used to perform the MMRM analysis. Treatment 
regimen, center and analysis visit will be set as class variables. The model statement 
will be based on the formula outlined above. The repeated statement of PROC MIXED 
will set analysis visit as the repeated variable and the type option will set the 
convergence method. An unstructured covariance structure will be assumed for this 
model (type=UN). If the model does not converge, the compound symmetry covariance 
structure will be used (type=CS). The data will be assumed to be missing at random 
(MAR). The overall method will be set to REML. 
 
From this analysis, the adjusted changes for each treatment group, the difference 
between the adjusted changes (secukinumab group vs placebo), 95% confidence interval 
around the difference and 1-sided p-value will be calculated for each visit. 
 
 
5.5.2 
Key secondary analysis 
The key secondary objectives: 
• H2: secukinumab is not different to placebo regimen with respect to ACR 20 
response at Week 12. 
• H3: secukinumab s.c. is not different to placebo regimen with respect to ACR 50 
response at Week 12. 
• H4: secukinumab s.c. is not different to placebo regimen with respect to the change 
in SPARCC enthesitis index from Baseline to Week 12. 
H2 will be tested as follows:- 
ACR 20 at Week 12 = Treatment + weight. 
The procedure PROC LOGISTIC will be used to perform the logistic regression 
analysis. Treatment regimen will be set as a class variable. The model statement will be 
based on the formula outlined above. Reference coding will be used in the model. The 
odds ratios will be computed for comparison of secukinumab versus placebo using the 
logistic regression model fitted. If the initial model does not converge Firth’s penalized 
maximum likelihood estimation method will be used. 
H3 will be analysed analogous to H2 above. 
H4 will be analysed analogous to the primary efficacy variable. 
 
5.6 
Rule of exclusion criteria of analysis sets 
Table 7 
Subject Classification 
Analysis Set / 
Subgroup of 
interest 
PD ID that 
cause subjects to be excluded 
Non-PD criteria that cause 
subjects to be excluded 
Randomized set 
INCL01 
Not randomized; 
Mistakenly randomized 
FAS 
INCL01 
Not in RAN; 
Study treatment not assigned; 


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Analysis Set / 
Subgroup of 
interest 
PD ID that 
cause subjects to be excluded 
Non-PD criteria that cause 
subjects to be excluded 
Safety set 
INCL01 
No study drug taken 
 
 
 
 
 
 
 
 
 
 
5.7 
Power Doppler Ultrasonography 
Power Doppler and Grayscale ultrasound (PDUS) is a non-invasive imaging method to 
assess peripheral involvement of SpA, including PsA. This technique permits 
visualization of most of the relevant joint pathologies associated with SpA, including 
synovitis, bone erosions, peripheral enthesitis, bursitis, tenosynovitis 
. 
The Outcome Measures in Rheumatology and the European League Against 
Rheumatism (OMERACT-EULAR) Ultrasound Task Force has developed a composite 
scoring system (the OMERACT-EULAR global synovitis score (GLOESS) as measured 
using PDUS) to detect and score synovitis at patient level. This score combines 
Grayscale-assessed synovial hyperplasia with an intra-synovial Power Doppler signal 
for evaluating synovial activity at joint level. 
PDUS evaluation will be performed at each joint site out of 48 The PDUS will be 
performed bilaterally for 24 pairs of joints: 
• Metacarpophalangeal (MCP) joints 1 to 5. 
• Proximal interphalangeal (PIP) joints 1 to 5. 
• Metatarsophalangeal (MTP) joints 1 to 5. 
• Wrist, elbow, shoulder (glenohumeral), knee, and ankle (tibiotalar). 
• Distal interphalangeal (PID) 2 to 5. 
The PDUS assessment will consist of an evaluation of hypoechoic synovial hyperplasia 
(SH) and joint effusion (JE) using Grayscale and synovial vascularization using Power 
Doppler. The pre-specified set of 24 paired joints will be scanned at each visit from the 
dorsal aspect with the joint in a neutral position, except for the knee, which will also be 
examined in a flexed position (30°). Note: only affected joints will be assessed after 
Visit 2 (Baseline). Standardized joint and probe positions will be used based on a 
reference atlas, which also show examples of synovitis grading for each site examined. 
The presence of synovitis (i.e. SH and Power Doppler, without JE) will be scored 
according to the OMERACT-EULAR PDUS composite semi-quantitative scale (0 to 3). 
For the enthesis evaluation, ultrasound will be initially performed in B mode to detect 
morphologic abnormalities, and subsequently with power Doppler to detect abnormal 
vascularization at bony insertions. The following entheses will be examined bilaterally: 
1. Common extensor tendon at its insertion at the lateral humeral epicondyle. 
2. Quadriceps tendon at its insertion at the superior pole of the patella. 


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3. Patellar tendon at its proximal insertion at the inferior pole of the patella. 
4. Patellar tendon at its distal insertion at the tibia tuberosity. 
5. Calcaneal insertions: 
a. Achilles tendon at its insertion at the calcaneus. 
b. Plantar aponeuroses at its insertion at the calcaneus. 
Each affected enthesis out of 6 targeted entheses will be scored in terms of inflammatory 
and morphological components according to the OMERACT enthesitis composite semi- 
quantitative scale (0 to 3). 
 
5.8 
The classification criteria for psoriatic arthritis (CASPAR) 
To meet the classification criteria for psoriatic arthritis (CASPAR) for diagnosis of 
psoriatic arthritis according to (Taylor 2006) a patient must have inflammatory articular 
disease (joint, spine or entheseal) and at least 3 points from the following 5 categories: 
1. Evidence of current psoriasis, a personal history of psoriasis, or a family history of 
psoriasis 
• Current psoriasis is defined as psoriatic skin or scalp disease present today as 
judged by a rheumatologist or dermatologist* (2 points). 
• 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). 
2. Typical psoriatic nail dystrophy including onycholysis, pitting, and hyperkeratosis 
observed on current physical examination (1 point). 
3. A negative test result for the presence of rheumatoid factor by any method except 
latex (1 point). 
4. Either current dactylitis, defined as swelling of an entire digit, or a history of 
dactylitis recorded by a rheumatologist (1 point). 
5. Radiographic evidence of juxta-articular new bone formation appearing as ill- 
defined ossification near joint margins (but excluding osteophyte formation) on 
plain radiographs of the hand or foot (1 point). 
Total score: If the total score is ≥ 3, the patient meets the CASPAR criteria for psoriatic 
arthritis diagnosis. 
* Current psoriasis is assigned a score of 2; all other features are assigned a score of 1. 


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5.9 
American College of Rheumatology measures and criteria 
of response 
The ACR has seven criteria:- 
Number of tender joints: 
The 78 joints assessed for tenderness include the 2 temporomandibular, 2 
sternoclavicular, 2 acromioclavicular joints, 2 shoulders, 2 elbows, 2 wrists, 2 first 
carpometacarpal, 10 MCP, 10 PIP, 8 distal interphalangeal joints of the hands, the 2 hip, 
2 knee, 2 talo-tibial, 2 mid-tarsal, 10 MTP, 10 PIP, and 8 DIP joints of the feet. 
Joint tenderness and swelling are to be graded present (1) or absent (0). 
Number of swollen joints: 
Joints are to be scored as either swollen (1) or not swollen (0). The 76 joints to be 
examined for swelling are the same as those examined for tenderness, however 
excluding both hip joints. 
Patient’s assessment of psoriatic arthritis pain 
The patient’s assessment of pain will be performed using 100 mm VAS ranging from 
“no pain” to “unbearable pain” after the question “Please indicate with a vertical mark 
( | ) through the horizontal line the most pain you had from your PsA today”. 
Patient’s global assessment of disease activity 
The patient’s global assessment of disease activity will be performed using 100 mm 
VAS ranging from ”very good” to ”very poor”, after the question "Considering all the 
ways PsA affects you, please indicate with a vertical mark ( | ) through the horizontal 
line how well you are doing today”. 
Physician’s global assessment of disease activity 
The PGA of disease activity will be performed using 100 mm VAS ranging from no 
disease activity to maximal disease activity, after the question “Considering all the ways 
the disease affects your patient, draw a line on the scale for how well his or her condition 
is today.” To enhance objectivity, the physician must not be aware of the specific 
patient’s global assessment of disease activity when performing his own assessment on 
that patient. 
High sensitivity C-reactive protein 
The purpose of this assessment is to identify the presence of inflammation, to determine 
its severity, and to monitor response to treatment. As the results of this test may unblind 
study personnel (such as the Ultrasonography Investigator and Clinical Investigator), 
results from the central laboratory will be provided for Screening and Baseline only. 
The hsCRP results from samples collected during the treatment period will be revealed 
following database lock only. 
Patient’s assessment of physical function 
Health Assessment Questionnaire – HAQ-DI© (reference Appendix 5.13) 


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5.10 
OMERACT-EULAR Global PDUS OMERACT out of 48 joints 
The Outcome Measures in Rheumatology-Ultrasound (OMERACT-US) Task Force, 
with funding received from the European League Against Rheumatism (EULAR), 
works to standardize the use of ultrasonography in rheumatoid arthritis (RA) and has 
developed a composite scoring system (the OMERACT-EULAR composite PDUS 
score) to detect and score synovitis. This score combines Greyscale-assessed synovial 
hyperplasia with an intra-synovial power Doppler signal for evaluating synovial 
activity. The score has demonstrated validity and intra- and inter-observer reliability in 
cross-sectional datasets, applicability to all joints and consistency between machines 
The PDUS assessment will consist of an evaluation of hypoechoic synovial hyperplasia 
(SH) and joint effusion (JE) using Greyscale and of synovial vascularization using 
Power Doppler. The pre-specified set of 24 paired joints will be scanned at each visit on 
the dorsal aspect, with the joint in a neutral position, except for the knee, which will also 
be examined in a flexed position (30°). Standardized joint and probe positions will be 
used, based on a reference atlas, which also shows examples of synovitis grading for 
each site examined. 
The presence of synovitis (i.e. SH and Power Doppler, without JE) will be scored 
according to the OMERACT-EULAR PDUS composite semi-quantitative scale (0 to 
3;Table 8). 
Each single component of joint inflammation (SH, Power Doppler, JE) was also scored 
separately at each visit, using semi-quantitative scales (0 to 3; Table 8). The global 
PDUS scores for the 24 paired joints will then be calculated using the sum of the 
composite PDUS scores for all joints examined, giving a potential score and of 0 to 144 
for the 24 paired joints. 
Table 8: Ultrasound scoring system 
Greyscale ultrasound 
Joint effusion 
Grade 0 
No effusion 
Grade 1 
Minimal amount of joint effusion 
Grade 2 
Moderate amount of joint effusion (little distension of 
the joint capsule) 
Grade 3 
Extensive amount of joint effusion (with high 
distension of the joint capsule) 
Inflammatory or active synovial 
hyperplasia (hypoechoic) 
Grade 0 
No hypoechoic synovial thickening 
Grade 1 
Minimal hypoechoic synovial thickening (filling the 
angle between the periarticular bones, without 
bulging over the line linking tops of the bones) 
Grade 2 
Hypoechoic synovial thickening bulging over the line 
linking tops of the periarticular bones but without 
extension along the bone diaphysis 
Grade 3 
Hypoechoic synovial thickening bulging over the line 
linking tops of the periarticular bones and with 
extension to at least one of the bone diaphysis 


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Power Doppler signal 
Grade 0 
No flow in the synovium 
Grade 1 
Up to 3 single spots signals or up to 2 confluent 
spots or 1 confluent spot plus up to 2 single spots 
Grade 2 
Vessel signals in less than half of the area of the 
synovium (< 50%) 
Grade 3 
Vessel signals in more than half of the area of the 
synovium (> 50%) 
OMERACT-EULAR composite 
PDUS score (for individual 
joints) 
Grade 0 (normal joint) 
No greyscale-detected synovial hyperplasia or 
Power Doppler signal i.e. B MODE=0 and 
Doppler=0 
Grade 1 (minimal synovitis) 
Minimal synovial hyperplasia and ≤ Grade 1 Power 
Doppler signal i.e. B MODE=1 and Doppler ≤1 OR B 
MODE=0 and Doppler=1 
For revised GLOESS : Minimal synovial hyperplasia 
and ≤ Grade 1 Power Doppler signal i.e. B MODE=1 
and Doppler ≤1 
Grade 2 (moderate synovitis) 
Moderate synovial hyperplasia and ≤ Grade 2 
Power Doppler signal or minimal synovial 
hyperplasia and a Grade 2 Power Doppler signal i.e. 
B MODE=2 and Doppler ≤2 or B MODE≤2 and 
Doppler=2 
Grade 3 (severe synovitis) 
Severe synovial hyperplasia and ≤ Grade 3 Power 
Doppler signal or moderate synovial hyperplasia 
and a Grade 3 Power Doppler signal i.e. B MODE=3 
and Doppler ≤3 or B MODE≤3 and Doppler=3 
Global OMERACT-EULAR 
synovitis score (GLOESS) 
Sum of composite PDUS scores for all joints 
assessed (e.g. for MCPs 2–5, Global PDUS score 
would range from 0 to 24) 
Note: B MODE is hypoechoic synovial hypertrophy independently of the presence of 
effusion. 
The revised GLOESS definition will also be known as GLOESS definition 2 with the 
original GLOESS derivation known as GLOESS definition 1. 
 
Proportion of patients with a presence of PDUS synovitis (Composite PDUS, SH and PD) 
will be summarised over time. 


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5.11 
OMERACT score of enthesitis 
Evaluation of entheses 
For the evaluation of enthesitis, ultrasound will initially be performed in B mode to 
detect morphologic abnormalities and subsequently with power Doppler to detect 
abnormal vascularization at bony insertions. 
The following entheses will be examined bilaterally: 
1. Common extensor tendon at its insertion at the lateral humeral epicondyle. 
2. Quadriceps tendon at its insertion at the superior pole of the patella. 
3. Patellar tendon at its proximal insertion at the inferior pole of the patella. 
4. Patellar tendon at its distal insertion at the tibia tuberosity. 
5. Calcaneal insertions: 
a. Achilles tendon at its insertion at the calcaneus. 
b. Plantar aponeuroses at its insertion at the calcaneus. 
 
 
Table 9: Severity grade of enthesitis 
Severity scoring 
Morphological (B mode) 
Inflammation (Doppler) 
0 
No abnormalities 
0 Doppler signal 
1 
Hypoechogenicity alone 
1 or 2 Doppler Spots at 
cortical insertion 
2 
Thickening and hypoechogenicity 
plus calcifications/enthesophytes 
More than 2 Doppler spots at 
cortical insertion and up to 2 
mm from cortical bone 
3 
Thickening and hypoechogenicity 
plus calcifications/enthesophytes 
AND erosions 
Extensive Doppler signal at 
cortical insertion 
 
 
 
Each affected enthesis out of 6 targeted entheses will be scored on inflammatory and 
morphological components according to  the following formulae; 
 
Total OMERACT (PDUS) enthesitis score Definition 1 : The sum of inflammation (Power 
Doppler: ranging from 0-3) and morphological (B mode: 0=absence, 1=presence) 
components 
Total OMERACT (PDUS) enthesitis score Definition 2 : The inflammation component 
(Power Doppler: ranging from 0-3), independently of the B Mode. 
 
 
The Global score at each assessment visit (i.e. the sum of the total score of each enthesis 
site involved) will be derived using the following formulae; 






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Within each of the 8 categories only the item indicating the most severe impairment 
contributes to the category score. If the patient requires the use of aids, devices, or help 
from another to accomplish any of the activities in an associated category, then the score 
for that category will be assigned the value 2, unless the score is already 3 (i.e. scores 
of 0 or 1 are increased to 2). Associated categories are defined in the “HAQ PACK”. 
From the scores for each category a standard disability index (SDI) is computed by 
summing the computed scores for each category and dividing by the number of 
categories answered. The SDI is not computed if the patient does not have scores for at 
least 6 categories. This SDI is the HAQ© score, which will be used in the statistical 
analyses of this instrument. The range for this score is (0, 3). 
 
HAQ-DI response is defined as an improvement of at least 0.35 score points compared 
to baseline (change ≤ -0.35). 
 
 
5.14 
PASI 
PASI scoring will be conducted during the study for all patients with a BSA >= 3% at 
baseline and for patients with a BSA >=3% at subsequent visits (i.e. if not >=3% at 
baseline). The PASI assesses the extent of psoriasis on 4 body surface areas (head, trunk 
and upper and lower limbs) and the degree of plaque erythema, scaling and thickness. 
A PASI score (Fredriksson and Pettersson 1978, Weisman 2003, Gottlieb 2005) will be 
derived. 
The head, trunk, upper limbs and lower limbs are assessed separately for erythema, 
thickening (plaque elevation, induration), and scaling (desquamation). The average 
degree of severity of each sign in each of the 4 body regions is assigned a score of 0-4. 
The area covered by lesions on each body region is estimated as a percentage of the total 
area of that particular body region. Further practical details help the assessment: 
1. The neck is assessed as part of the head. 
2. The axillae and groin are assessed as part of the trunk. 
3. The buttocks are assessed as part of the lower limbs. 
4. When scoring the severity of erythema, scales should not be removed. 
Because the head and neck, upper limbs, trunk and lower limbs correspond to 
approximately 10%, 20%, 30% and 40% of the BSA, respectively, the PASI score is 
calculated using the formula: 
PASI = 0.1 (EH+IH+DH)AH + 0.2(EU+IU+DU)AU + 0.3(ET+IT+DT)AT + 
0.4(EL+IL+DL)AL 
The keys for the letters are provided in Table 12 below. 
PASI scores can range from 0 corresponding to no signs of psoriasis to a theoretic 
maximum of 72.0. 


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T 
Psoriasis area and severity index scori ng system 
Body 
Erythema (E) 
Thickening 
Scaling 
Area score 
regio 
(plaque 
(desquamatio 
(based on 
n 
elevation, 
n, D) 
true area %, 
induration, I) 
A)* 
Head 
0 = none 
0 = none 
0 = none 
0 = no 
(H)† 
1 = slight 
1 = slight 
1 = slight 
involvement 
2 = moderate 
2 = moderate 
2 = moderate 
1 = >0-<10% 
3 = severe 
3 = severe 
3 = severe 
2 = 10-<30% 
4 = very 
4 = very severe 
4 = very 
3 = 30-<50% 
severe 
severe 
4 = 50-<70% 
5 = 70-<90% 
6 = 90-100% 
Trunk 
0 = none 
0 = none 
0 = none 
0 = no 
(T)‡ 
1 = slight 
1 = slight 
1 = slight 
involvement 
2 = moderate 
2 = moderate 
2 = moderate 
1 = >0-<10% 
3 = severe 
3 = severe 
3 = severe 
2 = 10-<30% 
4 = very 
4 = very severe 
4 = very 
3 = 30-<50% 
severe 
severe 
4 = 50-<70% 
5 = 70-<90% 
6 = 90-100% 
Uppe 
0 = none 
0 = none 
0 = none 
0 = no 
r 
1 = slight 
1 = slight 
1 = slight 
involvement 
limbs 
2 = moderate 
2 = moderate 
2 = moderate 
1 = >0-<10% 
(U) 
3 = severe 
3 = severe 
3 = severe 
2 = 10-<30% 
4 = very 
4 = very severe 
4 = very 
3 = 30-<50% 
severe 
severe 
4 = 50-<70% 
5 = 70-<90% 
6 = 90-100% 
Lowe 
0 = none 
0 = none 
0 = none 
0 = no 
r 
1 = slight 
1 = slight 
1 = slight 
involvement 
limbs 
2 = moderate 
2 = moderate 
2 = moderate 
1 = >0-<10% 
(L)§ 
3 = severe 
3 = severe 
3 = severe 
2 = 10-<30% 
4 = very 
4 = very severe 
4 = very 
3 = 30-<50% 
severe 
severe 
4 = 50-<70% 
5 = 70-<90% 
6 = 90-100% 
* Percentage (not score) of body region (not whole body) affected will be entered in the eCRF 
† Neck is assessed as part of the Head (H) body region 
‡ Axillae and groin are assessed as part of the Trunk (T) body region 
§ Buttocks are assessed as part of the Lower limbs (L) body region 
 
Definitions of efficacy variables based on psoriasis area and severity index 
• PASI 75 response: patients achieving ≥ 75% improvement (reduction) in 
PASI score compared to Baseline are defined as PASI 75 responders. 
• PASI 90 response: patients achieving ≥ 90% improvement (reduction) in 
PASI score compared to Baseline are defined as PASI 90 responders. 
• PASI 100 response: patients achieving ≥ 100% improvement (reduction) in 
PASI score compared to Baseline are defined as PASI 100 responders.