A Randomized, Open Label Multicenter Trial to Investigate the Efficacy of a Treat-to-target (T2T) Treatment Strategy With Secukinumab (AIN457) as a First-line Biologic Compared to a Standard-of-care (SOC) Treatment Over 36 Weeks in Patients With Active Axial Spondyloarthritis (axSpA)
Phase: PHASE3
Conditions: Axial Spondyloarthritis
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development
AIN457/Secukinumab 
Clinical Trial Protocol CAIN457HDE01 / NCT03906136
A randomized, open label multicenter trial to investigate 
the efficacy of a treat-to-target treatment strategy with 
secukinumab (AIN457) as a first-line biologic compared to 
a standard-of-care treatment over 36 weeks in patients with 
active axial spondyloarthritis (axSpA) - AScalate 
Document type:
Clinical Trial Protocol Amendment 
EUDRACT number:
2018‐003882‐32
Version number:
02
Clinical Trial Phase:
IIIb
Release date:
19-May-2021
Property of Novartis
Confidential
May not be used, divulged, published, or otherwise disclosed
without the consent of Novartis
Clinical Trial Protocol Template Version 2.0 (01-Aug-2018)

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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 6 
List of abbreviations ............................................................................................................ 7 
Glossary of terms ................................................................................................................. 9 
Amendment rationale ........................................................................................................ 11 
Amendment rationale ........................................................................................................ 12 
Protocol summary .............................................................................................................. 14 
1 
Introduction ....................................................................................................................... 25 
1.1 
Background ............................................................................................................ 25 
1.2 
Purpose .................................................................................................................. 26 
2 
Objectives and endpoints ................................................................................................... 26 
3 
Study design ...................................................................................................................... 29 
4 
Rationale ............................................................................................................................ 31 
4.1 
Rationale for study design ..................................................................................... 31 
4.1.1 
Bias-reducing measures ........................................................................ 32 
4.2 
Rationale for dose/regimen and duration of treatment .......................................... 32 
4.3 
Rationale for choice of second biological treatment in the treat-to-target 
group, and for reference treatment ......................................................................... 35 
4.4 
Risks and benefits .................................................................................................. 35 
5 
Population .......................................................................................................................... 37 
5.1 
Inclusion criteria .................................................................................................... 37 
5.2 
Exclusion criteria ................................................................................................... 38 
6 
Treatment ........................................................................................................................... 40 
6.1 
Study treatment ...................................................................................................... 40 
6.1.1 
Additional study treatments .................................................................. 43 
6.1.2 
Treatment arms/group ........................................................................... 43 
6.1.3 
Treatment duration ................................................................................ 43 
6.2 
Other treatment ...................................................................................................... 44 
6.2.1 
Concomitant therapy ............................................................................. 44 
6.2.2 
Prohibited medication ........................................................................... 45 
6.2.3 
Rescue medication ................................................................................ 46 
6.3 
Patient numbering, treatment assignment, randomization ..................................... 47 
6.3.1 
Patient numbering ................................................................................. 47 
6.4 
Treatment blinding ................................................................................................. 47 

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6.5 
Permitted dose adjustments and interruptions of study treatment ......................... 47 
6.6 
Additional treatment guidance ............................................................................... 48 
6.6.1 
Treatment compliance ........................................................................... 48 
6.6.2 
Emergency breaking of assigned treatment code .................................. 48 
6.7 
Preparation and dispensation ................................................................................. 49 
6.7.1 
Handling of study treatment and additional treatment .......................... 49 
6.7.2 
Instruction for prescribing and taking study treatment and reference 
treatment ................................................................................................ 49 
7 
Informed consent procedures ............................................................................................ 50 
8 
Visit schedule and assessments ......................................................................................... 51 
8.1 
Screening ............................................................................................................... 59 
8.1.1 
Information to be collected on screening failures ................................. 59 
8.2 
Patient demographics/other baseline characteristics ............................................. 59 
8.2.1 
Demographic characteristics ................................................................. 59 
8.2.2 
Other baseline characteristics ................................................................ 60 
8.3 
Efficacy .................................................................................................................. 62 
8.3.1 
Assessment of SpondyloArthritis International Society response 
criteria (ASAS) ...................................................................................... 62 
8.3.2 
Ankylosing spondylitis disease activity score....................................... 65 
8.3.3 
Physician’s global assessment of disease activity ................................. 65 
 
 65 
 
 
 66 
8.3.6 
Appropriateness of efficacy assessments .............................................. 66 
8.4 
Safety ..................................................................................................................... 67 
8.4.1 
Physical examination ............................................................................ 67 
8.4.2 
Body weight .......................................................................................... 67 
8.4.3 
Vital signs.............................................................................................. 67 
8.4.4 
Laboratory evaluations .......................................................................... 67 
8.4.5 
Pregnancy and assessments of fertility ................................................. 68 
8.4.6 
Appropriateness of safety measurements .............................................. 68 
8.5 
Additional assessments .......................................................................................... 68 
8.5.1 
Health-related quality of life outcomes ................................................. 68 
 
 71 
 
 72 
 
 72 
9 
Study discontinuation and completion .............................................................................. 73 

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9.1 
Discontinuation ...................................................................................................... 73 
9.1.1 
Discontinuation of study treatment / reference treatment ..................... 73 
9.1.2 
Withdrawal of informed consent ........................................................... 74 
9.1.3 
Lost to follow-up ................................................................................... 75 
9.1.4 
Early study termination by the sponsor ................................................. 75 
9.2 
Study completion and post-study treatment .......................................................... 75 
10 Safety monitoring and reporting ........................................................................................ 76 
10.1 
Definition of adverse events and reporting requirements ...................................... 76 
10.1.1 
Adverse events ...................................................................................... 76 
10.1.2 
Serious adverse events .......................................................................... 77 
10.1.3 
SAE reporting........................................................................................ 78 
10.1.4 
Pregnancy reporting .............................................................................. 79 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................ 80 
10.2 
Additional safety monitoring ................................................................................. 80 
10.2.1 
Liver safety monitoring ......................................................................... 80 
10.2.2 
Renal safety monitoring ........................................................................ 80 
11 Data collection and database management ........................................................................ 81 
11.1 
Data collection ....................................................................................................... 81 
11.2 
Database management and quality control ............................................................ 81 
11.3 
Site monitoring ...................................................................................................... 82 
12 Data analysis and statistical methods ................................................................................ 82 
12.1 
Analysis sets .......................................................................................................... 82 
12.2 
Patient demographics and other baseline characteristics ....................................... 83 
12.3 
Treatments ............................................................................................................. 83 
12.4 
Analysis of the primary efficacy endpoint ............................................................. 83 
12.4.1 
Definition of primary endpoint ............................................................. 83 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 84 
12.4.3 
Handling of missing values/censoring/discontinuations ....................... 84 
12.4.4 
Sensitivity and supportive analyses ...................................................... 85 
12.5 
Analysis of secondary 
 endpoints ................................................. 85 
12.5.1 
Analysis of secondary 
 efficacy endpoints ................... 85 
12.5.2 
Analysis of secondary safety endpoints ................................................ 87 
12.5.3 
Analysis of secondary 
 health-related quality of life 
endpoints ............................................................................................... 88 
 
 90 
12.7 
Sample size calculation .......................................................................................... 90 
12.7.1 
Primary endpoint ................................................................................... 90 

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13 Ethical considerations and administrative procedures ...................................................... 91 
13.1 
Regulatory and ethical compliance ........................................................................ 91 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 91 
13.3 
Publication of study protocol and results............................................................... 91 
13.4 
Quality control and quality assurance .................................................................... 92 
14 Protocol adherence ............................................................................................................ 92 
14.1 
Protocol Amendments ........................................................................................... 92 
15 References ......................................................................................................................... 93 
16 Appendices ........................................................................................................................ 96 
16.1 
Appendix 1: Clinically notable laboratory values ................................................. 96 
16.2 
Appendix 2: Assessment of spondyloarthritis international society criteria for 
axial spondyloarthritis ........................................................................................... 97 
16.3 
Appendix 3: Modified New York diagnostic criteria for ankylosing 
spondylitis .............................................................................................................. 98 
16.4 
Appendix 4: Definition of sacroiliitis on imaging ................................................. 99 
16.5 
Appendix 5: Bath Ankylosing Spondylitis Disease Activity Index .................... 100 
16.6 
Appendix 6: Bath Ankylosing Spondylitis Metrology Index .............................. 101 
16.7 
Appendix 7: Guidelines for administering the questionnaires for patient 
reported outcomes ................................................................................................ 103 
 
 106 
16.9 
Appendix 10: Environmental factors related to ASAS Health Index .................. 107 
 
List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 26 
Table 4-1 
Summary of efficacy results at Week 16 and Week 104 – 
MEASURE-3 by overall population ..................................................... 34 
Table 6-1 
Prohibited prior treatments (both arms) ................................................ 45 
Table 6-2 
Concomitant treatment in T2T arm ....................................................... 46 
Table 8-1 
Assessment schedule ............................................................................. 53 
Table 8-2 
Drug administration schedule for treat-to-target group ........................ 57 
Table 8-3 
Items of the ASAS health index ............................................................ 70 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 80 
Table 16-1 
Safety analyses: expanded limits and notable criteria ........................... 96 
 

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List of figures 
Figure 3-1 
Study design .......................................................................................... 30 
Figure 3-2 
The 2016 updated Ankylosing SpondyloArthritis International 
Society (ASAS)/European League Against Rheumatism (van der 
Heijde et al 2017) .................................................................................. 42 
 

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List of abbreviations 
AE 
Adverse Event 
ALT (SGPT) 
Alanine Aminotransferase (Serum Glutamate-Pyruvate Transaminase) 
AS 
Ankylosing Spondylitis 
ASAS 
Ankylosing Spondyloarthritis International Society 
ASAS-HI 
Ankylosing Spondyloarthritis International Societ Health Index 
ASDAS 
Ankylosing Spondylitis Disease Activity Score 
ASQoL 
Ankylosing Spondylitis Quality of Life  
AST (SGOT) 
Aspartate Aminotransferase (Serum Glutamic Oxaloacetic Transaminase) 
ATC 
Anatomical Therapeutic Chemical 
axSpA 
Axial Spondyloarthritis 
bDMARD 
Biological DMARD 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
BASFI 
Bath Ankylosing Spondylitis Functional Index 
BASMI 
Bath Ankylosing Spondylitis Metrology Index 
BL 
Baseline 
CI 
Confidence Interval 
COX-1 
Cyclooxygenase-1 
COX-2 
Cyclooxygenase-2 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CRO 
Contract Research Organization 
csDMARD(s) 
Conventional Systemic DMARD(s) 
CV 
Cardiovascular 
DGRh 
German Society of Rheumatology (Detusche Gesellschaft für Rheumatologie e.V.) 
DMARD(s) 
Disease-Modifying Anti-Rheumatic Drug(s) 
eCRF 
Electronic Case Report Form 
EAM 
Extraarticular manifestations 
EDC 
Electronic Data Capture 
EF 
Environmental Factor 
EMA 
European Medicines Agency 
ESR 
Erythrocyte Sedimentation Rate 
FACIT-Fatigue 
Functional Assessment of Chronic Illness Therapy - Fatigue 
FAS 
Full Analysis Set 
GCP 
Good Clinical Practice 
GGT 
Gamma-Glutamyl Transferase 
hCG 
Human Chorionic Gonadotropin 
HLA-B27 
Human Leukocyte Antigen-B27 
hsCRP 
High sensitive C-Reactive Protein 
IA 
Interim Analysis 
IB 
Investigator's Brochure 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation of Technical Requirements for 

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Pharmaceuticals for Human Use 
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
IL-17 
Interleukin-17 
IL-17A 
Interleukin-17A 
IN 
Investigator Notification  
IRB 
Institutional Review Board 
i.v. 
Intravenous 
 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
Mixed-Effect Model Repeated Measures 
MRI 
Magnetic Resonance Imaging 
nr-axSpA 
Non-Radiographic Axial Spondyloarthritis 
NRS 
Numeric rating scale 
NSAID 
Non-Steroidal Anti-Inflammatory Drug 
OR 
Odds Ratio 
PFS 
Prefilled Syringe 
PR 
Partial Remission 
PRO(s) 
Patient Reported Outcome(s) 
PsA 
Psoriatic Arthritis 
PT 
Preferred Term 
RA 
Rheumatoid Arthritis 
RAS 
Randomized Analysis Set 
r-axSpA 
Radiographic Axial Spondyloarthritis 
RMP 
Risk Management Plan 
SAE 
Serious Adverse Event 
s.c. 
Subcutaneous 
SF-36 
Short Form Health Survey 
SIB 
Suicidal Ideation and Behavior 
 
 
SOC 
Standard-of-Care 
SpA 
Spondyloarthritis 
TB 
Tuberculosis 
T2T 
Treat-to-Target 
 
 
TNFα 
Tumor Necrosis Factor Alpha 
ULN 
Upper Limit of Normal 
VAS 
Visual Analog Scale 
WBC 
White Blood Cell 

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Glossary of terms 
Additional treatment 
Medicinal products that may be used during the clinical trial as described in 
the protocol, but not as an investigational medicinal product (e.g. any 
background therapy). 
Assessment 
A procedure used to generate data required by the study. 
Biologic samples 
A biological specimen including, for example, blood (plasma, serum), 
saliva, tissue, urine, stool, etc. taken from a study patient. 
DMARDs 
Disease modifying anti-rheumatic drugs. This drug class includes biological 
DMARDs (bDMARDs) and conventional systemic DMARDs (csDMARDs). 
Dosage 
Dose of the study treatment given to the patient in a time unit (e.g. 300 mg 
every 4 weeks). 
Electronic data capture 
(EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical study 
data using data collection systems, such as Web-based applications, 
interactive voice response systems and clinical laboratory interfaces. EDC 
includes the use of Electronic Case Report Forms (eCRFs) which are used 
to capture data transcribed from paper source forms used at the point of 
care. 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last patient or at 
a later point in time as defined by the protocol.  
Enrollment 
Point/time of patient entry into the study at which informed consent must be 
obtained. 
Investigational 
drug/treatment 
The drug whose properties are being tested in the study. 
Medication number 
A unique identifier on the label of medication kits. 
Mis-randomized patients 
Mis-randomized patients are those who were not qualified for 
randomization and who did not take study treatment, but have been 
inadvertently randomized into the study. 
Other treatment 
Treatment that may be needed/allowed during the conduct of the study 
(concomitant or rescue therapy). 
Patient 
An individual with the condition of interest for the study. 
Period 
The subdivisions of the trial design (e.g. Screening, Treatment, Follow-up) 
which are described in the Protocol. Periods define the study phases and 
will be used in clinical trial database setup and eventually in analysis. 
Personal data 
Patient information collected by the Investigator that is transferred to 
Novartis for the purpose of the clinical trial. This data includes patient 
identifier information, study information and biological samples. 
Premature patient 
withdrawal 
Point/time when the patient exits from the study prior to the planned 
completion of all study drug administration and/or assessments; at this time 
all study drug administration is discontinued and no further assessments 
are planned. 
Randomization number 
A unique identifier assigned to each randomized patient. 
Screen failure 
A patient who did not meet one or more criteria that were required for 
participation in the study. 
Source data/document 
Source data refers to the initial record, document, or primary location from 
where data comes. The data source can be a database, a dataset, a 
spreadsheet or even hard-coded data, such as paper or eSource. 
Start of the clinical trial 
The start of the clinical trial is defined as the signature of the informed 
consent by the first patient. 

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Study treatment 
Any single drug or combination of drugs or intervention administered to the 
patient as part of the required study procedures. 
Study treatment 
discontinuation 
When the patient permanently stops taking any of the study drugs prior to 
the defined study treatment completion date (if any) for any reason; may or 
may not also be the point/time of study discontinuation. 
Patient number 
A unique number assigned to each patient upon signing the informed 
consent. This number is the definitive, unique identifier for the patient and 
should be used to identify the patient throughout the study for all data 
collected, sample labels, etc. 
Treatment arm/group  
A treatment arm/group defines the dose and regimen or the combination, 
and may consist of 1 or more cohorts. 
Variable 
A measured value or assessed response that is determined from specific 
assessments and used in data analysis to evaluate the drug being tested in 
the study. 
Withdrawal of study 
consent  
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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Amendment rationale 
 
The protocol including amendment 1 is being amended to delete the planned IA that became 
obsolete due to availability of secukinumab data that fully supports the assumptions for initial 
sample size calculation.    
 
The sample size was calculated based on the primary efficacy variable ASAS40 response at 
Week 24. At the time point of the conception of the AScalate study, no data on effect of 
secukinumab in patients with non-radiographic spondyloarthritis, or data on direct 
secukinumab escalation from 150 mg to 300 mg was available. Therefore data on 
secukinumab efficacy (150 and/or 300 mg treatment) from trials with ankylosing spondylitis 
patients (MEASURE 2/MEASURE 3 trials (Sieper et al 2017, Pavelka et al 2017) was taken as a 
basis for estimation of the effect size of treatment in treat-to-target arm.  In order to confirm 
the assumption for the sample size calculation an interim analysis for the study has been 
planned.  
Recently, new data on secukinumab dose escalation in AS patients became available (Novartis 
data on file), furthermore PREVENT study1 showed secukinumab efficacy in nr-axSpA patients 
be comparable to its efficacy in AS patients.    
This novel data confirms assumptions used as a basis for initial sample size calculation, making 
the planned interim analysis obsolete.     
 
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 font for insertions. 
 
• Cover page information has been updated as well as document version number in 
headers on each page of the protocol 
• Protocol summary:  
o IA details have been deleted in ‘data analysis’ section 
• Section 4.4: information regarding the interim analysis have been deleted 
• Section 12.7: information regarding the interim analysis have been deleted 
• Section 15: reference regarding the interim analysis has been deleted 
 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. The changes described in 
this amended protocol require IRB/IEC approval prior to implementation. 
 

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Amendment rationale 
The main purpose of this amendment is to incorporate two novel components into the protocol 
for the following reasons: 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
  
 
None of the changes made are due to evidence-based safety concerns.  
 
Changes to the protocol: 
Changes to specific sections of this protocol are shown in the track changes version of the 
document using strike through red font for deletions and red underlined font for insertions. 
 
• Cover page information has been updated as well as document version number in 
headers on each page of the protocol 
• List of abbreviations: addition of baseline (BL) and numeric rating scale (NRS) 
• Protocol summary:  
 
 
 
o refinement of inclusion criteria 5 
• Introduction – Background: 
 
 
• Section 2: 
 
  
• Section 4.1: 
 
 
• Section 5.1: refinement of inclusion criteria 5 
• Section 5.2: ‘Laboratory results at screening visit’ was added for clarification 

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• Section 6.2.2 – Table 6-1: addition of medical cannabis to prohibited prior medication 
table and clarification of amount of corticosteroids as per day 
• Section 6.2.2.2 – Table 6-2: addition of medical cannabis use and correction of 
algebraic sign and additional information added to corticosteroids criteria 
• Section 6.3.1: removal incomplete sentence 
• Section 6.6.1: added defined tolerance levels regarding allowed visit/treatment 
windows 
• Section 6.7.2: updated handling instructions because packaging label cannot be 
attached to the drug label form  
• Section 8 – Table 8-1: 
o 
 
o updated footnote number 6 to reflect refined inclusion criteria 5  
• Section 8.2.2.9: corrected BL to SV2 to ensure consistency throughout the protocol 
• Section 8.5.2: 
 
 
• Section 8.5.3: section was added to provide detailed information regarding the 
companion app implementation 
• Section 8.5.4: 
 
 
• Section 12.4.1: removed unnecessary word to clarify 
• Section 12.5.1: corrected spelling error 
• Section 12.6: 
 
 
• Section 15: additional reference inserted 
• Section 16.8: corrected spelling error 
 

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Protocol summary 
 
Protocol number 
CAIN457HDE01 
Full title 
A randomized, open label multicenter trial to investigate the efficacy of a 
treat-to-target treatment strategy with secukinumab (AIN457) as a 
first-line biologic compared to a standard-of-care treatment over 
36 weeks in patients with active axial spondyloarthritis (axSpA) – 
AScalate 
Brief title 
Efficacy of a treat-to-target strategy with first-line secukinumab 
compared to standard-of-care in patients with active axSpA 
Sponsor and clinical 
phase 
Novartis Pharma GmbH, Phase IIIb 
Investigation type 
Biological 
Study type 
Interventional 
Purpose and rationale 
The standard treatment approach in axSpA is to start with one 
non-steroidal anti-inflammatory drug (NSAID), switch to another one if 
the first one is not effective enough, and, if the second one also fails, 
start a biological disease modifying anti-rheumatic drug (bDMARD). 
According 
to 
the 
2016 
updated 
Ankylosing 
SpondyloArthritis 
International Society (ASAS)/European League Against Rheumatism 
recommendations, current practice is to start biological therapy with a 
tumor necrosis factor alpha (TNFα) blocker; however, based on indirect 
comparisons the efficacy of TNFα and interleukin-17A (IL-17A) blockade 
seems to be similar. 
In case of failure of the first bDMARD, a switch within the class or 
between classes of biological drugs is possible, but there is not enough 
evidence to support either strategy.  
The purpose of the study is to demonstrate superiority of the intensive 
treat-to-target (T2T) strategy with secukinumab as first-line biologic vs. 
standard-of-care (SOC) therapy in order to achieve strong clinical 
efficacy in patients with active axSpA inadequately responding to NSAID 
therapy. AxSpA includes radiographic axSpA (r-axSpA), also known as 
ankylosing spondylitis (AS), and non-radiographic-axSpA (nr-axSpA).  
Primary objective  
To demonstrate that the efficacy of a T2T approach (with secukinumab 
as first-line biologic) is superior to the SOC approach as measured by 
percentage of patients achieving an ASAS 40% response (ASAS40) at 
Week 24. 
Secondary objectives 
• 
To demonstrate that the efficacy of the T2T approach (with 
secukinumab as first-line biologic) is superior to the SOC approach 
based on the percentage of patients achieving an ASAS40 
response at Week 12. 
• 
To demonstrate that the efficacy of the T2T (with secukinumab as 
first-line biologic) is superior to the SOC approach based on the 
percentage of patients achieving an AS Disease Activity Score 
(ASDAS) clinically important improvement (defined as change from 
Baseline of ≥ 1.1) at Week 12 and Week 24. 

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• 
To demonstrate that the efficacy of the T2T (with secukinumab as 
first-line biologic) is superior to the SOC approach based on the 
percentage of patients achieving an ASDAS major improvement 
(defined as change from BL of ≥ 2.0) at Week 12 and Week 24. 
• 
To demonstrate that the efficacy of the T2T approach (with 
secukinumab as first-line biologic) is superior to the SOC approach 
based on the percentage of patients achieving ASDAS < 1.3 at 
Week 12 and Week 24. 
• 
To demonstrate that the efficacy of the T2T approach (with 
secukinumab as first-line biologic) is superior to the SOC approach 
based on the percentage of patients achieving ASDAS < 2.1 (low 
disease activity) at Week 12 and Week 24. 
• 
To demonstrate that the efficacy of the T2T approach (with 
secukinumab as first-line biologic) is superior to the SOC approach 
based on the percentage of patients achieving ASAS 20% 
response (ASAS20), ASAS partial remission (PR), and Bath 
Ankylosing Spondylitis Disease Activity Index 50% response 
(BASDAI50) at Week 12 and Week 24. 
• 
To demonstrate that the T2T approach (with secukinumab as 
first-line biologic) is superior to the SOC approach in terms of 
improvement of disease activity, function, axial mobility, and quality 
of life measures at Week 12 and Week 24 as compared to Baseline 
according to: 
• 
BASDAI 
• 
ASDAS 
• 
C-reactive protein (CRP) and erythrocyte sedimentation rate 
(ESR) 
• 
Bath ankylosing spondylitis functional index (BASFI) 
• 
Bath ankylosing spondylitis metrology index (BASMI) and chest 
expansion 
• 
Global assessment of disease activity (patient/physician) and 
general pain on visual analog scale (VAS) 
• 
ASAS health index (ASAS-HI) 
• 
Short form health survey (SF-36) 
• 
Ankylosing spondylitis quality of life (ASQoL) 
• 
Functional Assessment of Chronic Illness Therapy - Fatigue 
(FACIT-Fatigue) 
• 
To demonstrate overall safety and tolerability of secukinumab. 

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Study design 
This is a randomized, parallel-group, open-label, multicenter study of 
patients with active axSpA. The aim is to demonstrate that the efficacy of 
a T2T approach (with secukinumab as first-line biologic) is superior to a 
SOC approach in terms of achieving strong clinical efficacy in patients 
with active axSpA who are naïve to biological therapy and who have had 
an inadequate response to NSAID treatment. The study will include an 
8-week Screening period, a 36-week treatment period according to 
previous randomization, and a safety follow-up period of 20 weeks. 
Neither investigators nor patients will be blinded. The primary endpoint is 
the percentage of patients achieving an ASAS40 response at Week 24. 
Population 
The study population will consist of approximately 300 patients fulfilling 
the ASAS classification criteria for axSpA with active disease (measured 
by ASDAS ≥ 2.1 and elevated CRP and/or active inflammation on MRI of 
the sacroiliac joints and/ or spine) inadequately responding to or with 
intolerance/contraindications for NSAIDs, and with no previous treatment 
with a biological drug. 
Inclusion criteria 
Patients eligible for inclusion in this study must 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 non-pregnant, non-lactating female patients at least 
18 years of age. 
3. Diagnosis of axSpA (either r-axSpA (AS) or nr-axSpA) fulfilling the 
ASAS classification criteria for axSpA (see Appendix 2 of main 
protocol).  
4. Active disease as defined by having an ASDAS ≥ 2.1 at Screening 
and Baseline despite concurrent NSAID therapy, or 
intolerance/contraindication to NSAIDs. 
5. Objective signs of inflammation at Screening as defined by:  
• MRI of sacroiliac joints performed up to 3 months prior to 
screening showing acute inflammatory lesion(s), 
OR 
• elevated quick CRP (> 5 mg/L), 
OR 
• MRI showing acute inflammatory lesion(s) in the sacroiliac joints  
performed during screening period. 
6. Patients should have been on at least 2 different NSAIDs at the 
highest recommended dose for at least 4 weeks (in total) in the past, 
with an inadequate response or failure to respond, or less if therapy 
had to be reduced due to intolerance, toxicity or contraindications. 
7. Patients who are regularly taking NSAIDs (including 
cyclooxygenase-1 [COX-1] or cyclooxygenase-2 [COX-2] inhibitors) 
as part of their axSpA therapy are required to be on a stable dose for 
at least 1 week before randomization. 

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8. Patients taking methotrexate (MTX) 7.5 mg/week to 25 mg/week or 
sulfasalazine (≤ 3 g/day) are allowed to continue their medication but 
are required to be on a stable dose for at least 4 weeks before 
randomization.  
9. Patients who are on a disease modifying anti-rheumatic drug 
(DMARD) other than MTX or sulfasalazine must discontinue the 
DMARD 4 weeks prior to randomization.  
10. Patients taking corticosteroids must be on a stable dose of 
≤ 10 mg/day prednisone or equivalent for at least 2 weeks before 
randomization.  
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 who have previously been treated with TNFα inhibitors 
(investigational or approved). 
4. Patients taking high potency opioid analgesics (e.g. methadone, 
hydromorphone, morphine). 
5. Previous treatment with any cell-depleting therapies including 
but not limited to anti-CD20 or investigational agents 
(e.g. CAMPATH, anti-CD3, anti-CD4, anti-CD5, anti-CD19). 
6. History of hypersensitivity to secukinumab or adalimumab or 
their excipients or to drugs of similar chemical classes. 
7. Contraindications for secukinumab or adalimumab. 
8. Inability or unwillingness to undergo MRI (e.g. patients with 
pacemakers, aneurysm clips or metal fragments / foreign 
objects in the eyes, skin or body that are not MRI compatible) in 
case MRI is not already available (maximum 3 months old). 
9. Use of any investigational agents within 4 weeks or within 
5 half-lives of the drug (whichever is longer) prior to the 
Baseline Visit. 
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 dosing of study 
treatment and minimum 16 weeks or longer if local label 
requires it after the last dose (e.g. 20 weeks for secukinumab, 
5 months for adalimumab in the European Union). 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. 

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• 
Female sterilization (have had surgical bilateral 
oophorectomy with or without hysterectomy), total 
hysterectomy or tubal ligation at least 6 weeks before 
taking investigational drug. In case of oophorectomy alone, 
only when the reproductive status of the woman has been 
confirmed by follow-up hormone level assessment. 
• 
Male sterilization (at least 6 months prior to Screening). 
For female patients on the study, the vasectomized male 
partner should be the sole partner for that patient. 
• 
Barrier methods of contraception: condom or occlusive cap 
(diaphragm or cervical/vault caps). 
• 
Use of oral (estrogen and progesterone), injected, or 
implanted hormonal methods of contraception or other 
forms of hormonal contraception that have comparable 
efficacy (failure rate < 1%), for example hormone vaginal 
ring or transdermal hormone contraception or placement of 
an intrauterine device or intrauterine system. 
*Periodic abstinence (e.g. calendar, ovulation, symptothermal, 
post-ovulation methods) and withdrawal are not acceptable 
methods of contraception. 
In case of use of oral contraception women should have been 
stable on the same pill for a minimum of 3 months before taking 
investigational drug. 
In case local regulations deviate from the contraception 
methods listed above, local regulations apply and will be 
described in the informed consent form (ICF). 
Women are considered post-menopausal and not of child 
bearing potential if they have had 12 months of natural 
(spontaneous) amenorrhea with an appropriate clinical profile 
(e.g. age appropriate, history of vasomotor symptoms) or have 
had surgical bilateral oophorectomy (with or without 
hysterectomy), total hysterectomy or tubal ligation at least 
6 weeks ago. In the case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by 
follow-up hormone level assessment is she considered not of 
child-bearing potential.  
12. Active ongoing inflammatory diseases other than axSpA that 
might confound the evaluation of the benefit of secukinumab 
therapy, including inflammatory bowel disease or uveitis. 
13. Underlying metabolic, hematologic, renal, hepatic, pulmonary, 
neurologic, endocrine, cardiac, infectious or gastrointestinal 
conditions, which in the opinion of the investigator 
immunocompromises the patient and/or places the patient at 
unacceptable risk for participation in an immunomodulatory 
therapy. 
14. Significant medical problems or diseases, including but not 
limited to the following: uncontrolled hypertension (≥ 160/95 
mmHg), congestive heart failure (New York Heart Association 
status of class III or IV) and uncontrolled diabetes.  
15. History of clinically significant liver disease or liver injury as 
indicated by abnormal liver function tests such as aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), 
alkaline phosphatase or serum bilirubin. The investigator should 

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be guided by the following criteria:  
a. 
Any single parameter may not exceed 2 x upper limit of 
normal (ULN). A single parameter elevated up to and 
including 2 x ULN should be re-checked once more as 
soon as possible and in all cases, at least prior to 
enrollment/randomization, to rule out any possible 
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.  
16. History of renal trauma, glomerulonephritis, or patients with one 
kidney only, or a serum creatinine level exceeding 1.8 mg/dL 
(159.12 μmol/L).  
17. Screening total white blood cell (WBC) count < 3000/μL, or 
platelets < 100 000/μL or neutrophils < 1500/μL or hemoglobin 
< 8.3 g/dL (83 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 (TB) infection as defined by 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 TB. If presence of latent TB is 
established, then treatment according to local country 
guidelines must have been initiated prior to randomization.  
20. Patients positive for human immunodeficiency virus, hepatitis B 
or hepatitis C at 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. Live vaccinations within 6 weeks prior to Baseline or planned 
vaccination during study participation until 12 weeks after last 
study treatment administration.  
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. 
Study treatment 
Investigational treatment – treat-to-target regimen 
• 
Secukinumab 150 mg, liquid formulation in 1 mL prefilled syringe 
(PFS) for subcutaneous (s.c.) injection – all patients will receive 150 

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mg dose at Baseline, Week 1, 2, 3, 4 and 8. From Week 12, only 
responders (i.e. patients with ASDAS clinically important 
improvement, defined as change from Baseline ≥ 1.1) will continue 
to receive 4-weekly doses until Week 32 if they maintain the 
response. 
• 
Secukinumab 300 mg, liquid formulation in 2 × 1 mL PFS for s.c. 
injection – patients who are non-responders at Week 12 will receive 
4-weekly doses until Week 24. From Week 24, only responders will 
continue to receive 4-weekly doses until Week 32.  
• 
Adalimumab biosimilar (Hyrimoz®) 40 mg, liquid formulation in 
0.8 mL PFS for s.c. injection – patients who are non-responders to 
secukinumab 300 mg only at Week 24 will receive biweekly doses of 
adalimumab biosimilar (Hyrimoz®) until Week 34.  
• 
Escape treatment: Secukinumab 300 mg liquid formulation in 
2 × 1 mL PFS for s.c. injection. Patients who are receiving 
secukinumab 150 mg (i.e. were responders at Week 12) can be 
escalated to secukinumab 300 mg at Week 24 every 4 weeks until 
Week 32 if they experienced a loss of response (defined as ASDAS 
change from Baseline < 1.1).  
Reference treatment – standard-of-care regimen 
• 
SOC treatment up to the maximum recommended dose at the 
discretion of the investigator as according to current 
recommendation for treatment of axSpA. 
Efficacy assessments 
Primary endpoint 
• 
Percentage of patients achieving an ASAS40 response at Week 24. 
Secondary endpoints 
• 
Percentage of patients achieving an ASAS40 response at Week 12. 
• 
Percentage of patients achieving an ASDAS clinically important 
improvement (defined as change from BL of ≥ 1.1) at Week 12 and 
Week 24. 
• 
Percentage of patients achieving an ASDAS major improvement 
(defined as change from BL of ≥ 2.0) at Week 12 and Week 24. 
• 
Percentage of patients achieving ASDAS < 1.3 at Week 12 and 
Week 24. 
• 
Percentage of patients achieving ASDAS < 2.1 (low disease activity) 
at Week 12 and Week 24. 
• 
Percentage of patients achieving ASAS20, ASAS PR, BASDAI50 
responses at Week 12 and Week 24. 
• 
Improvement of disease activity, function, axial mobility, and quality 
of life measures at Week 12 and Week 24 as compared to Baseline 
according to: 
o 
BASDAI 
o 
ASDAS 
o 
CRP and ESR 
o 
BASFI 
o 
BASMI and chest expansion 
o 
Global assessment of disease activity (patient/physician) 
and general pain on the VAS 

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o 
ASAS-HI 
o 
SF-36 
o 
ASQoL 
o 
FACIT-Fatigue 

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Safety assessments 
• 
The number (and percentage) of patients with treatment-emergent 
AEs. 
Data analysis 
The primary analysis will be performed comparing treatments with 

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respect to the primary efficacy variable (i.e. the proportion of patients 
achieving treatment response as defined by the ASAS40 criteria at 
Week 24) in a logistic regression model with treatment and center as 
factors and weight as well as Baseline CRP level as covariates.  
The odds ratio (OR), the corresponding 95% confidence interval (CI) and 
the p-value will be given. The null hypothesis of equal odds will be 
rejected if the 2-sided p-value from the logistic regression model for the 
factor “treatment” is < 0.05.  
Sensitivity analyses as well as supportive analyses will be conducted in 
order to provide evidence that the results seen from the primary model 
results are robust. These analyses will center on the deviations in model 
assumptions and the treatment of missing data. 
 
Key words 
Secukinumab, axSpA, ASAS, ASDAS, treat-to-target 

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1 
Introduction 
1.1 
Background 
Axial Spondyloarthritis (axSpA) is a group of rheumatic disorders with spinal inflammation 
and inflammatory back pain as common denominator. Based on the presence or absence of 
sacroiliitis 
on 
conventional 
radiographs, 
axSpA 
patients 
are 
sub-grouped 
into 
non-radiographic axSpA (nr-axSpA) and ankylosing spondylitis (AS) also termed 
radiographic axSpA (r-axSpA). Although nr-axSpA is often regarded as a milder disease 
compared to AS/r-axSpA, it has been demonstrated that the burden of the 2 diseases is similar 
in terms of symptom levels (Poddubnyy and Sieper 2014, Sieper et al 2013). 
For patients with active r-axSpA (AS), effective therapeutic options are currently limited to 
3 drug classes. These are non-steroidal anti-inflammatory drugs (NSAIDs), tumor necrosis 
factor alpha (TNFα) blockers, and interleukin-17A (IL-17A) inhibitors. In the IL-17A 
inhibitor class, only 1 substance, secukinumab, the investigational product in this study, is 
approved for the treatment of patients with active r-axSpA (AS). Secukinumab, a human 
monoclonal antibody that inhibits the effector function of IL-17A, has been shown to be better 
than placebo in improving the signs and symptoms of AS. In the Phase III MEASURE 1 
(Braun et al 2017) and MEASURE 2 studies (Sieper et al 2017) involving a total of 590 
patients with AS, secukinumab significantly improved key clinical domains of disease vs. 
placebo, including signs and symptoms, physical functioning, and quality of life (Baeten et al 
2015). Interim results of the ongoing MEASURE-3 study (involving 226 patients) assessing 
the efficacy and safety of s.c. maintenance therapy with secukinumab 150 mg and 300 mg 
following intravenous (i.v.) loading have demonstrated rapid and significant improvements in 
the signs and symptoms of active AS with responses sustained through 104 weeks (Pavelka et 
al 2017) (see Section 4.2 for further details). Secukinumab has been implicated to mediate 
early pain relief in patients suffering from AS. In this present study, patient’s pain diaries will 
be used to gather detailed insights into the alteration of pain status, especially during the early 
stages of treatment. Additionally, a digital option (companion app) will be offered to patients 
to track their health status over time on their mobile phone. 
For patients with active axSpA the main treatment aim according to the recently updated treat-
to-target (T2T) recommendation is remission (Smolen et al 2018). The initial treatment 
approach in axSpA is straightforward: start with one NSAID, switch to another one if the first 
one is not effective enough, and, if the second one also fails, start a biological disease 
modifying anti-rheumatic drug (bDMARD). According to the 2016 updated Ankylosing 
SpondyloArthritis International Society (ASAS)/European League Against Rheumatism 
recommendations, current practice is to start biological therapy with a TNFα blocker (van der 
Heijde et al 2017); however, based on indirect comparisons, the efficacy of TNFα and IL-17A 
blockade seems to be similar (Maksymowych et al 2017). In case of the failure of the first 
bDMARD, a switch within the class or between classes is possible, but again, there is not 
enough evidence to support either strategy.  
Indeed, many questions related to the optimal treatment strategy remain: What is the optimal 
first biologic drug in axSpA? Could the introduction of a biologic therapy combined with tight 
disease control rapidly lead to beneficial effects? Could dosage escalation of an IL-17A 

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blocker in patients that did not reach Ankylosing Spondylitis Disease Activity Score 
(ASDAS) clinically important improvement criterion lead to the achievement of that goal? 
Would a TNFα inhibition after IL-17A inhibitor treatment be beneficial to patients? In order 
to answer these questions a randomized controlled study is proposed.  
1.2 
Purpose 
The purpose of this study is to provide 36-week efficacy data on a T2T approach with 
secukinumab as first line biologic compared with the standard-of-care (SOC) approach in 
patients with active axSpA who have an inadequate response to NSAID therapy in order to 
confirm that such a T2T approach results in superior efficacy compared to the SOC approach, 
thereby providing an optimal treatment strategy for this patient population.  
2 
Objectives and endpoints 
Table 2-1 
Objectives and related endpoints 
Objectives 
Endpoints 
Primary objective 
Endpoint for primary objective 
• 
To demonstrate that the efficacy of a T2T 
approach (with secukinumab as first-line 
biologic) is superior to the SOC approach as 
measured by percentage of patients 
achieving an ASAS40 response at Week 24. 
• 
Percentage of patients achieving an 
ASAS40 response at Week 24. 
Secondary objectives 
Endpoints for secondary objectives 
• 
To demonstrate that the efficacy of the T2T 
approach (with secukinumab as first-line 
biologic) is superior to the SOC approach 
based on the percentage of patients 
achieving an ASAS40 response at Week 12. 
• 
Percentage of patients achieving an 
ASAS40 response at Week 12. 
 
• 
To demonstrate that the efficacy of the T2T 
(with secukinumab as first-line biologic) is 
superior to the SOC approach based on the 
percentage of patients achieving an ASDAS 
clinically important improvement (defined as 
change from BL of ≥ 1.1) at Week 12 and 
Week 24. 
• 
Percentage of patients achieving an ASDAS 
clinically important improvement (defined as 
change from BL of ≥ 1.1) at Week 12 and 
Week 24. 
• 
To demonstrate that the efficacy of the T2T 
(with secukinumab as first-line biologic) is 
superior to the SOC approach based on the 
percentage of patients achieving an ASDAS 
major improvement (defined as change from 
BL of ≥ 2.0) at Week 12 and Week 24. 
• 
Percentage of patients achieving an ASDAS 
major improvement (defined as change from 
BL of ≥ 2.0) at Week 12 and Week 24. 
• 
To demonstrate that the efficacy of the T2T 
approach (with secukinumab as first-line 
biologic) is superior to the SOC approach 
based on the percentage of patients 
achieving ASDAS < 1.3 at Week 12 and 
Week 24. 
• 
Percentage of patients achieving ASDAS 
< 1.3 at Week 12 and Week 24. 
 

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Objectives 
Endpoints 
• 
To demonstrate that the efficacy of the T2T 
approach (with secukinumab as first-line 
biologic) is superior to the SOC approach 
based on the percentage of patients 
achieving ASDAS < 2.1 (low disease activity) 
at Week 12 and Week 24. 
• 
Percentage of patients achieving ASDAS 
< 2.1 (low disease activity) at Week 12 and 
Week 24. 
 
• 
To demonstrate that the efficacy of the T2T 
approach (with secukinumab as first-line 
biologic) is superior to the SOC approach 
based on the percentage of patients 
achieving ASAS20, ASAS PR, and 
BASDAI50 responses at Week 12 and Week 
24. 
• 
Percentage of patients achieving ASAS20, 
ASAS PR, BASDAI 50 responses at Week 
12 and Week 24. 
 
• 
To demonstrate that the T2T approach (with 
secukinumab as first-line biologic) is superior 
to the SOC approach in terms of 
improvement of disease activity, function, 
axial mobility, and quality of life measures at 
Week 12 and Week 24 as compared to 
Baseline according to: 
o 
BASDAI 
o 
ASDAS 
o 
CRP and ESR 
o 
BASFI 
o 
BASMI and chest expansion 
o 
Global assessment of disease 
activity (patient/physician) and 
general pain on VAS 
o 
ASAS-HI 
o 
SF-36 
o 
ASQoL 
o 
FACIT-Fatigue 
• 
Improvement of disease activity, function, 
axial mobility, and quality of life measures at 
Week 12 and Week 24 as compared to 
Baseline according to: 
o 
BASDAI 
o 
ASDAS 
o 
CRP and ESR 
o 
BASFI 
o 
BASMI and chest expansion 
o 
Global assessment of disease 
activity (patient/physician) and 
general pain on the VAS 
o 
ASAS-HI 
o 
SF-36 
o 
ASQoL 
o 
FACIT-Fatigue 
 
• 
To demonstrate overall safety and tolerability 
of secukinumab. 
• 
The number (and percentage) of patients 
with treatment-emergent AEs. 

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Objectives 
Endpoints 

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Objectives 
Endpoints 
ASAS=Ankylosing SpondyloArthritis International Society, ASDAS=AS disease activity score, 
ASQoL=ankylosing spondylitis quality of life, BASDAI=Bath ankylosing spondylitis disease activity 
index, BASFI=Bath ankylosing spondylitis functional index, BASMI=Bath ankylosing spondylitis 
Metrology 
Index, 
CRP=C-reactive 
protein, 
ESR=erythrocyte 
sedimentation 
rate, 
FACIT-Fatigue=functional assessment of chronic illness therapy – fatigue, 
 
 MRI=magnetic resonance imaging, PR= partial remission, 
SF-36=Short form health survey, SOC=standard-of-care, VAS=visual analog scale 
3 
Study design 
This is a randomized, parallel-group, open-label, multicenter study in patients with active 
axSpA. The aim of the study is to demonstrate that the efficacy of a T2T approach (with 
secukinumab as a first-line biologic) is superior to a SOC approach in terms of achieving 
strong clinical efficacy in patients with active axSpA who are naïve to biological therapy and 
who have an inadequate response to prior NSAID treatment. The study will include an 8-week 
Screening period, a 36-week treatment period, and a 20-week safety follow-up period. Neither 
investigators nor patients will be blinded. The primary endpoint is the percentage of patients 
achieving an ASAS40 response at Week 24. At Baseline, patients will be randomized equally 
to one of 2 treatment groups (T2T or SOC) as shown in Figure 3-1: 

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Figure 3-1
Study design
Patients will be evaluated every 12 weeks from Baseline up to Week 36. Safety evaluations
will be included in the regular visits; in addition, a safety follow-up visit will be performed 
20 weeks after the last study visit (i.e. Week 36) and will take place at Week 56 for patients
completing the study according to the protocol. In addition, patients in the T2T arm will be 
seen for safety monitoring at Visit 4 (Week 4) and Visit 5 (Week 8). Patients who prematurely 
discontinue completely from the study for any reason should return for the final visit to 
conduct the Week 36 assessments (4 weeks after the last study treatment administration), then 
also return after an additional 20 weeks for a final follow-up visit, corresponding to Week 56 
assessments.
T2T group (n = 150)
Starting from Baseline, patients will be treated with secukinumab 150 mg subcutaneous (s.c.)
weekly until Week 4 and then at Week 8.
At Week 12:
•
If ASDAS clinically important improvement is achieved (i.e. patient is a responder) and 
maintained, patient will continue the treatment with secukinumab 150 mg s.c. every 
4 weeks up to Week 32.
•
If ASDAS clinically important improvement is not achieved (i.e. patient is 
non-responder), patient will receive an escalated dose of secukinumab 300 mg s.c. every 
4 weeks until Week 20. 

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At Week 24:  
Patients who are receiving secukinumab 300 mg, and  
• Achieved ASDAS clinically important improvement (i.e. are responders), will continue 
treatment with secukinumab 300 mg s.c. every 4 weeks up to Week 32.  
• Did not achieve ASDAS clinically important improvement (i.e. are non-responders), will 
be switched to adalimumab biosimilar (Hyrimoz®) 40 mg s.c. every 2 weeks until Week 
34. 
Escape arm 
• Patients who are receiving 150 mg secukinumab (i.e. were responders at Week 12) can be 
escalated at Week 24 to 300 mg secukinumab every 4 weeks until Week 32 if they 
experience a loss of response, where loss of response is defined as ASDAS change from 
Baseline < 1.1. 
SOC group (n = 150) 
Patients will receive treatment according to local practice standards by their treating physician 
following the current treatment recommendations with NSAIDs as the first-choice drug 
treatment and disease modifying anti-rheumatic drugs (DMARDs) for patients with active 
disease despite the use (or intolerance/contraindication) of NSAIDs (van der Heijde et al 
2017). Patients will be seen every 12 weeks or more often, if clinically indicated up to 
Week 36; assessment of the outcome parameters will be performed at Week 12, Week 24 
. 
4 
Rationale  
4.1 
Rationale for study design 
A randomized, parallel-group, open-label, multicenter study design is considered appropriate 
for assessing whether a T2T approach with secukinumab as a first-line biologic confers 
superior efficacy to a SOC approach for patients with active axSpA as measured primarily 
based on the percentage of patients with an ASAS40 response at Week 24. All patients 
included in this study must have active disease despite concurrent NSAID therapy or 
intolerance/contraindication to NSAIDs. 
 
 
 
 
Patients assigned to the SOC treatment group will receive SOC treatment at the discretion of 
the Investigator in accordance with current clinical practice.  
Patients assigned to the T2T treatment group will receive first line biological treatment with 
secukinumab 150 mg. Responders are defined as those patients with an ASDAS clinically 
important improvement of ≥ 1.1. At Week 12, responders will continue secukinumab 150 mg 
through to Week 32 if they maintain the response, and non-responders will be switched to 
secukinumab 300 mg through to Week 20. At Week 24, responders will continue 
secukinumab 300 mg through to Week 32 and non-responders will be switched to 

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adalimumab biosimilar (Hyrimoz®) 40 mg through to Week 34. In addition, patients who 
were responders at Week 12 but experienced a loss of response (defined as ASDAS change 
from Baseline < 1.1) at Week 24 will be switched to an escape arm and treated with 
secukinumab 300 mg through to Week 32. This T2T approach will ensure patients have 
maximal opportunity to achieve remission. 
 
4.1.1 
Bias-reducing measures 
In order to avoid selection bias in this study, patients will be randomized to the two treatment 
groups. All study sites will be provided with a set of sealed allocation cards. At the 
Randomization Visit, the investigator will assign each patient who meets the study eligibility 
criteria to the lowest available randomization number, open the corresponding treatment 
allocation card and treat the patient with the treatment noted on the card (i.e. T2T treatment or 
SOC treatment).  
As blinding of site personnel and patients is not possible in practice for the chosen study 
design, there is a risk of performance bias. Performance bias refers to systematic differences 
between groups in the care that is provided. To ensure the control of performance bias, the 
assessments (timing of study visits, patient and physician disease activity checks and 
outcomes, etc.) in both treatment groups are identical, with the exception of additional blood 
samples at Week 4 and Week 8, which are required for secukinumab as per German Society 
of Rheumatology (Deutsche Gesellschaft für Rheumatologie e.V.  - DGRh) recommendations 
(Table 8-1).  
The treatment in T2T arm and in SOC arm is described in detail in Section 6.1. The treatment 
in the SOC arm will follow the clinical routine of the investigator and should be in accordance 
with current guidelines for treatment of axSpA (van der Heijde et al 2017). All investigators 
will be trained on the specifics of treating patients that receive the standard-of-care regimen. 
In addition, current EULAR guidelines for treatment of axSpA will be provided to all study 
sites. The clinical monitoring team, who are educated in current treatment guidelines, will 
check site adherence to these guidelines during the regular monitoring visits. Reasons for non-
adherence will be investigated and documented properly. Furthermore, the necessity of 
adherence to guidelines will be emphasized to investigators.  
4.2 
Rationale for dose/regimen and duration of treatment 
The secukinumab dosing regimens in this study are based upon the currently approved dose 
for r-axSpA (AS) by the European Medicines Agency (EMA), which is 150 mg s.c. every 4 
weeks (with a loading dosage of 150 mg at Week 0, 1, 2, 3, and 4), as well as the 300 mg s.c. 
dose every 4 weeks (with a loading dosage of 300 mg at Week 0, 1, 2, 3, and 4), which is 
approved by the EMA for plaque-psoriasis and psoriatic arthritis (PsA). The higher dose (300 
mg) has also been reported to be safe and effective when used up to 104 weeks in patients 
with ax-SpA in the interim analysis (IA) of the ongoing MEASURE-3 study (Pavelka et al 
2017).  
The approval of secukinumab in AS was based on evaluation of 590 patients with AS in 
2 randomized, double-blind, placebo-controlled phase III studies (MEASURE-1: Braun et al 
2017, and MEASURE-2: Sieper et al 2017), in which 75 mg and 150 mg were evaluated vs. 
placebo with either an i.v. or s.c. loading regimen. In MEASURE-1 and MEASURE-2, 27.0% 

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and 38.8% of patients, respectively, were previously treated with an anti-TNFα agent and 
discontinued the anti-TNF-α agent due to either lack of efficacy or intolerance (anti-TNFα-
inadequate responder [IR] patients). 
In MEASURE-2, treatment with secukinumab150 mg resulted in greater improvement in 
ASAS20 (61.1% vs. 28.4%), ASAS40 (36.1% vs. 10.8%), as well as in high-sensitivity 
C-reactive protein (hsCRP), ASAS 5/6 and bath ankylosing spondylitis disease activity index 
(BASDAI) score compared with placebo at Week 16. The onset of action of secukinumab 
150 mg occurred as early as Week 1 for ASAS20 (superior to placebo) in MEASURE-2. 
ASAS20 responses were improved at Week 16 in both anti-TNFα-naïve patients (68.2% vs. 
31.1%; p < 0.05) and anti-TNFα-IR patients (50.0% vs. 24.1%; p < 0.05) for secukinumab 
150 mg compared with placebo, respectively. The magnitude of response (treatment 
difference vs. placebo) with regards to signs and symptoms at Week 16 was similar in anti-
TNFα-naïve and anti-TNFα-IR patients in both studies. 
In MEASURE-2, secukinumab-treated patients reported improvements compared to 
placebo-treated patients in tiredness (fatigue) as reported at Week 16 by scores on the 
functional assessment of chronic illness therapy - fatigue (FACIT-Fatigue) scale and in 
health-related quality of life as measured by short form health survey (SF-36) physical 
component summary (PCS) (LS mean change: 6.06 vs. 1.92, p < 0.001). These improvements 
were sustained up to Week 52. In MEASURE-1, secukinumab-treated patients reported 
improvement in physical function compared to placebo-treated patients at Week 16, as 
assessed by the FACIT-Fatigue, EQ-5D and SF-36 PCS. These improvements in physical 
function were all sustained up to Week 52.  
Interim results of the ongoing MEASURE-3 study (involving 226 patients) (Pavelka et al 
2017) assessing the efficacy and safety of s.c. maintenance therapy with secukinumab 150 mg 
and 300 mg following i.v. loading have shown that secukinumab provided rapid and 
significant improvements in the signs and symptoms of active AS, with responses sustained 
through 104 weeks. Secukinumab was well-tolerated with a safety profile consistent with 
previous reports. The primary endpoint was ASAS20 response rate at Week 16. Secondary 
endpoints included ASAS40, high sensitivity CRP, ASAS 5/6, BASDAI and ASAS partial 
remission (PR). Analyses by prior anti-TNF therapy use (anti-TNF-naïve and -inadequate 
response or intolerance) were pre-specified and reported as observed at Week 104. 
A total of 84.2% (64/76; secukinumab i.v.→300 mg) and 77.0% (57/74; secukinumab i.v. 
→150 mg) of patients completed 104 weeks of treatment at the time of the IA. The ASAS20 
response rate was significantly greater at Week 16 (primary endpoint) in secukinumab 
i.v.→300 mg and i.v.→150 mg groups compared to placebo. All secondary endpoints were 
met at Week 16, except ASAS PR in the i.v.→150 mg group. Improvements achieved with 
secukinumab in all clinical endpoints at Week 16 were sustained through Week 104. 
ASAS20/40 and ASAS PR responses by anti–TNF status are shown in Table 4-1. At 
Week 104, response rates on more stringent clinical endpoints (e.g. ASAS PR) were higher 
with the 300 mg dose, particularly in the smaller group of anti–TNF-IR pts. Safety profiles of 
both secukinumab doses were similar through Week 104 (mean ± SD exposure: 633.8 ± 165.4 
days [300 mg] and 644.5 ± 135.4 days [150 mg]). 

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Table 4-1 
Summary of efficacy results at Week 16 and Week 104 – MEASURE-3 
by overall population 
Variable 
Week 
Secukinumab 
10 mg/kg 
IV→ 300 mg 
SC (N = 76) 
Secukinumab 
10 mg/kg 
IV → 150 mg 
SC (N = 74) 
Placebo 
(N = 76) 
ASAS20a, n (%)  
16 
46 (60.5)§ 
43 (58.1)‡ 
28 (36.8) 
104 
55 (72.1) 
54 (73.6) 
- 
ASAS40a, n (%) 
16 
32 (42.1)‡ 
30 (40.5)‡ 
16 (21.1) 
104 
42 (55.7) 
36 (49.2) 
- 
hsCRPb (post-baseline/baseline 
ratio), mean change from 
baseline ± SE 
16 
0.48 ± 1.1‡ 
0.55 ± 1.1‡ 
1.09 ± 1.1 
104 
0.50 ± 1.1 
0.59 ± 1.1 
- 
ASAS5/6a, n (%) 
16 
30 (39.5)‡ 
31 (41.9)‡ 
11 (14.5) 
104 
42 (54.9) 
37 (50.0) 
- 
BASDAIb, mean change from 
baseline ± SE 
16 
-2.7 ± 0.3‡ 
-2.3 ± 0.3‡ 
-1.5 ± 0.3 
104 
-3.3 ± 0.3 
-3.0 ± 0.3 
- 
ASASa PR, n (%) 
16 
16 (21.1)‡ 
7 (9.5) 
1 (1.3) 
104 
20 (25.7) 
13 (18.2) 
- 
By anti–TNFα statusc 
 
Anti–TNF-naïve 
Anti–TNF-IR 
Variable,  
% responders 
Week 
IV→ 
300 mg 
(N = 57) 
IV→ 
150 mg 
(N = 57) 
Placebo 
(N = 59) 
IV→ 
300 mg 
(N = 19) 
IV→ 
150 mg 
(N = 17) 
Placebo (N 
= 17) 
ASAS20 
16 
64.9§ 
63.2‡ 
39.0 
47.4 
41.2 
29.4 
104* 
78.4 
80.4 
- 
84.6 
54.5 
- 
ASAS40 
16 
43.9‡ 
43.9‡ 
23.7 
36.8 
29.4 
11.8 
104* 
64.7 
56.5 
- 
61.5 
27.3 
- 
ASAS PR 
16 
21.1§ 
10.5 
1.7 
21.1 
5.9 
0 
104* 
31.4 
26.1 
- 
23.1 
0 
- 
§P < 0.01; ‡P < 0.05 vs. placebo (P-values at Week 16 adjusted for multiplicity of testing in overall population) 
aNRI at Week 16 and multiple imputation at Week 104 
bMean changes from MMRM 
cNRI at Week 16 and observed data at Week 104.  
*Total number of evaluable pts in anti–TNF-naïve: IV→ 300 mg= 51, IV→ 150 mg = 46, and in anti–TNF-IR: 
IV→ 300 mg= 13, IV→ 150 mg = 11  
ASAS, Assessment of Spondyloarthritis International Society; BASDAI, Bath Ankylosing Spondylitis Disease 
Activity Index;  
hsCRP, high sensitivity C-reactive protein; n, number of pts meeting criteria; N, number of randomized pts; PR, 
partial remission; SE, standard error 
Source: Pavelka et al 2017 

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4.3 
Rationale for choice of second biological treatment in the 
treat-to-target group, and for reference treatment 
Adalimumab has been selected as the second bDMARD for the T2T approach (in case of 
insufficient response to secukinumab treatment at Week 24) as this is a commonly used 
anti-TNFα agent, approved for the treatment of patients with AS /axSpA, and which confers 
similar efficacy to secukinumab in terms of signs and symptoms (van der Heijde et al 2006). 
The reference treatment in this study will be SOC treatment for axSpA. Patients assigned to 
the SOC treatment arm will receive treatment according to local practice standards by their 
treating rheumatologist following the current treatment recommendations with NSAIDs as the 
first-choice drug treatment and DMARDs for patients with active disease despite the use (or 
intolerance/contraindication) of NSAIDs. 
4.4 
Risks and benefits 
As of 25-Jun-2018, approximately 24279 subjects (which included patients and a small 
number of healthy volunteers) were enrolled in the secukinumab clinical development 
program (including trials where secukinumab had been used as a protocol specified 
treatment), of whom approximately 20000 subjects (comprised of patients and healthy 
volunteers) had received at least 1 dose of secukinumab. Overall, healthy subjects and patients 
suffering from psoriasis, PsA, rheumatoid arthritis (RA), AS (r-axSpA), nr-axSpA, multiple 
sclerosis, uveitis, dry eye, Crohn’s disease, asthma and polymyalgia rheumatica have received 
secukinumab at doses ranging from single and multiple i.v. 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 (r-axSpA) and psoriasis completed studies show that 
secukinumab generally is safe and well tolerated. 
The safety profile observed in the latest drug safety update report (Issue 008: 26-Jun-2017 to 
25-Jun-2018) is in line with the current known safety profile of secukinumab in moderate to 
severe psoriasis, PsA and AS.  
For all 3 indications, secukinumab has shown an imbalance vs. placebo in total adverse events 
(AEs), which was driven by infections, mainly non-serious upper respiratory tract infections 
during the placebo-controlled epoch of the trials (12 to 16 weeks depending on the protocol). 
This imbalance was not translated into infection serious adverse events (SAEs) and there was 
also no difference between secukinumab 300 mg and 150 mg in the overall rate of infections 
or in upper respiratory tract infections. In all indications, Candida infections were more 
frequent with secukinumab when compared to placebo and, in psoriasis trials, Candida 
infections were more common with the 300 mg dose compared to the 150 mg secukinumab 
regimen. The imbalance between the doses was limited to non-serious, localized mucosal or 
cutaneous candidiasis, with no reports of chronic or systemic disease in any treatment group. 
Across indications, Candida infections were responsive to standard treatment and did not 
necessitate discontinuation. No serious opportunistic infections were reported. No 
tuberculosis (TB) reactivation or viral hepatitis reactivation were observed in clinical trials, 
regardless of indication (psoriasis, PsA or AS).  

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Neutropenia was more frequently observed with secukinumab than with placebo, but most 
cases were mild, transient, and spontaneously reversible. 
The incidence of hypersensitivity AEs was slightly higher with secukinumab compared with 
placebo, with the difference mostly due to mild to moderate urticaria and eczema not 
associated with systemic symptoms. 
The incidence of selected rare events of interest (major adverse cardiovascular events and 
malignancies) adjusted for exposure over 52 weeks was comparable to placebo in clinical 
trials across multiple indications. 
There was no clear association between treatment with secukinumab and new onset of 
inflammatory bowel disease but due to the potential involvement of the interleukin-17 (IL-17) 
pathway in the pathogenesis of the disease, it is not possible to rule out a potential increased 
risk of exacerbation. 
Secukinumab 300 mg was comparable to 150 mg and both doses showed comparable safety to 
placebo and etanercept over 52 weeks of treatment.  
Infections, neutropenia, and hypersensitivity are important identified risks, while 
malignancies, major adverse cardiovascular events, immunogenicity, Crohn’s disease, and 
hepatitis B reactivation are important potential risks. Interaction with live vaccines is an 
important potential interaction (and also included as an important potential risk).  
No new identified risks were reported. During the reporting interval, 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. 
No new safety signal was identified and no actions were taken for safety reasons during the 
reporting period of the latest drug safety update report. 
The risk to patients in this trial will be minimized by compliance with the eligibility criteria, 
close clinical monitoring, and extensive guidance to the investigators, provided in the current 
version of the Investigator’s Brochure (IB). 
Taking into account the individual risks, the expected risk profile of secukinumab from a 
mechanism of action perspective in axSpA is anticipated to be similar to that of the 
approved indications. 
From the standpoint of the overall risk benefit assessment, the current trial with secukinumab 
is justified. 
Women of child-bearing potential must be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study, and agree that 
in order to participate in the study they must adhere to the contraception requirements outlined 
in Section 5.2 (Exclusion criteria). If there is any question that the patient will not reliably 
comply, they should not be entered or continue in the study. 

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5 
Population 
The study population will consist of 300 randomized patients fulfilling the ASAS 
classification criteria for axSpA with active disease (measured by ASDAS ≥ 2.1 and elevated 
CRP and/or active inflammation on MRI of the sacroiliac joints and/ or spine) inadequately 
responding to or with intolerance/contraindications for NSAIDs, and with no previous 
treatment with a biological drug.  
5.1 
Inclusion criteria 
Patients eligible for inclusion in this study must 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 non-pregnant, non-lactating female patients at least 18 years of age. 
3. Diagnosis of axSpA (either r-axSpA (AS) or nr-axSpA) fulfilling the ASAS classification 
criteria for axSpA (Appendix 2).  
4. Active disease as defined by having an ASDAS ≥ 2.1 at Screening and Baseline despite 
concurrent NSAID therapy, or intolerance/contraindication to NSAIDs. 
5. Objective signs of inflammation at Screening as defined by:  
MRI of sacroiliac joints performed up to 3 months prior to screening showing acute 
inflammatory lesion(s), 
OR 
elevated quick CRP (> 5 mg/L), 
OR 
MRI showing acute inflammatory lesion(s) in the sacroiliac joints  performed during 
screening period. 
6. Patients should have been on at least 2 different NSAIDs at the highest recommended 
dose for at least 4 weeks (in total) in the past, with an inadequate response or failure to 
respond, or less if therapy had to be reduced due to intolerance, toxicity or 
contraindications. 
7. Patients who are regularly taking NSAIDs (including cyclooxygenase-1 [COX-1] or 
cyclooxygenase-2 [COX-2] inhibitors) as part of their axSpA therapy are required to be on 
a stable dose for at least 1 week before randomization. 
8. Patients taking MTX (7.5 mg/week to 25 mg/week) or sulfasalazine (≤ 3 g/day) are 
allowed to continue their medication but are required to be on a stable dose for at least 
4 weeks before randomization.  
9. Patients who are on a DMARD other than methotrexate (MTX) or sulfasalazine must 
discontinue the DMARD 4 weeks prior to randomization.  
10. Patients taking corticosteroids must be on a stable dose of ≤ 10 mg/day prednisone or 
equivalent for at least 2 weeks before randomization and should remain on a stable dose 
up to Week 24. 

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5.2 
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 who have previously been treated with TNFα inhibitors (investigational or 
approved). 
4. Patients taking high potency opioid analgesics (e.g. methadone, hydromorphone, 
morphine). 
5. Previous treatment with any cell-depleting therapies including but not limited to 
anti-CD20 or investigational agents (e.g. CAMPATH, anti-CD3, anti-CD4, anti-CD5, 
anti-CD19). 
6. History of hypersensitivity to secukinumab or adalimumab or their excipients or to drugs 
of similar chemical classes. 
7. Contraindications for secukinumab or adalimumab. 
8. Inability or unwillingness to undergo MRI (e.g. patients with pacemakers, aneurysm clips 
or metal fragments / foreign objects in the eyes, skin or body that are not MRI compatible) 
in case MRI is not already available (maximum 3 months old). 
9. Use of any investigational agents within 4 weeks or within 5 half-lives of the drug 
(whichever is longer) prior to the Baseline Visit. 
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 
dosing of study treatment and minimum 16 weeks or longer if local label requires it after 
the last dose (e.g. 20 weeks for secukinumab, 5 months for adalimumab in the European 
Union). Effective contraception methods include: 
• Total abstinence* (when this is in line with the preferred and usual lifestyle of the 
patient. Female sterilization (have had surgical bilateral oophorectomy with or 
without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before 
taking investigational drug. In case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by follow-up hormone level 
assessment. 
• Male sterilization (at least 6 months prior to Screening). For female patients on the 
study, the vasectomized male partner should be the sole partner for that patient. 
• Barrier methods of contraception: condom or occlusive cap (diaphragm or 
cervical/vault caps). 
• Use of oral (estrogen and progesterone), injected, or implanted hormonal methods of 
contraception or other forms of hormonal contraception that have comparable efficacy 

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(failure rate < 1%), for example hormone vaginal ring or transdermal hormone 
contraception or placement of an intrauterine device or intrauterine system. 
* Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) 
and withdrawal are not acceptable methods of contraception. 
 
In case of use of oral contraception women should have been stable on the same pill for a 
minimum of 3 months before taking investigational drug. 
In case local regulations deviate from the contraception methods listed above, local 
regulations apply and will be described in the informed consent form (ICF). 
Women are considered post-menopausal and not of child bearing potential if they have 
had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile 
(e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral 
oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at 
least 6 weeks ago. In the case of oophorectomy alone, only when the reproductive status 
of the woman has been confirmed by follow up hormone level assessment is she 
considered not of child-bearing potential.  
12. Active ongoing inflammatory diseases other than axSpA that might confound the 
evaluation of the benefit of secukinumab therapy, including inflammatory bowel disease 
or uveitis. 
13. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator 
immunocompromises the patient and/or places the patient at unacceptable risk for 
participation in an immunomodulatory therapy. 
14. Significant medical problems or diseases, including but not limited to the following: 
uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure (New York Heart 
Association status of class III or IV) and uncontrolled diabetes.  
15. History of clinically significant liver disease or liver injury as indicated by abnormal liver 
function tests 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 any possible 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.  
16. History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum 
creatinine level exceeding 1.8 mg/dL (159.12 μmol/L).  
17. Laboratory results at screening visit: total white blood cell (WBC) count < 3000/μL, or 
platelets < 100 000/μL or neutrophils < 1500/μL or hemoglobin < 8.3 g/dL (83 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 TB infection as 
defined by a positive result is defined as an induration of ≥ 5 mm or according to local 

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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 TB. If presence of latent 
TB is established, then treatment according to local country guidelines must have been 
initiated prior to randomization.  
20. Patients positive for human immunodeficiency virus, hepatitis B or hepatitis C at 
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. Live vaccinations within 6 weeks prior to Baseline or planned vaccination during study 
participation until 12 weeks after last study treatment administration.  
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.  
6 
Treatment 
6.1 
Study treatment 
Investigational treatment – treat-to-target regimen 
• Secukinumab 150 mg, liquid formulation in 1 mL prefilled syringe (PFS) for s.c. 
injection – all patients will receive 150 mg dose at Baseline, Week 1, 2, 3, 4 and 8. From 
Week 12, only responders (i.e. patients with ASDAS clinically important improvement, 
defined as change from Baseline ≥ 1.1) will continue to receive 4-weekly doses until 
Week 32 if they maintain the response. 
• Secukinumab 300 mg, liquid formulation in 2 × 1 mL PFS for s.c. injection – patients 
who are non-responders at Week 12 will receive 4-weekly doses until Week 20. From 
Week 24, only responders will continue to receive 4-weekly doses until Week 32.  
• Secukinumab 300 mg as escape treatment, liquid formulation in 2 × 1 mL PFS for s.c. 
injection - patients who were responders at Week 12, but experienced a loss of response 
(defined as ASDAS change from Baseline < 1.1) at Week 24 will receive 4-weekly 
300 mg doses until Week 32.  
• Adalimumab biosimilar (Hyrimoz®) 40 mg, liquid formulation in 0.8 mL PFS for s.c. 
injection – patients who are non-responders to secukinumab 300 mg at Week 24 will 

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receive from this time point biweekly doses of adalimumab biosimilar (Hyrimoz®) until 
Week 34.  
Reference treatment – standard-of-care regimen 
• Patients will receive treatment according to local practice standards by their treating 
physician following the current treatment recommendations. Current guideline 
recommends to start a biological disease modifying anti-rheumatic drug (bDMARD) after 
the failure of the NSAIDs therapy. According to the 2016 updated Ankylosing 
SpondyloArthritis International Society (ASAS)/European League Against Rheumatism 
recommendations, current practice is to start biological therapy with a TNFα blocker.  
After the failure of the first biologic therapy and in case of positive opinion of the 
rheumatologist, a switch to another TNFα-inhibitor or to IL-17-inhibitor should be 
considered (van der Heijde et al 2017). In accordance with these recommendation the 
treatment initiation, adjustment and switch will be conducted based on the disease activity 
and the positive opinion of the investigator. These therapy re-arrangement can be decided 
and performed at the time of regular study visit (e.g. Visit week 12 or Visit Week 24) or 
during unscheduled visits as per clinical routine of the investigator.    
  

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Figure 6-2 
The 2016 updated Ankylosing SpondyloArthritis International Society 
(ASAS)/European League Against Rheumatism (van der Heijde et al 
2017) 
 
 
ASDAS, Ankylosing Spondylitis Disease Activity Score; BASDAI, Bath Ankylosing Spondylitis Disease Activity Index; bDMARD, biological 
disease-modifying antirheumatic drug; TNFi, tumor necrosis factor inhibitor; IL17-inhibitor, interleukin-17 inhibitor. *Either BASDAI or 
ASDAS, but the same outcome per patient. 
Novartis will supply the investigational treatment in an open-label manner. Patients or 
caregivers will be instructed by site staff on how to self-administer the s.c. injection using the 
PFS containing the liquid formulation of secukinumab and/or adalimumab biosimilar 
(Hyrimoz®). Study treatment administrations at mandatory site visits (i.e. at Baseline, Week 
12 and Week 24) will be performed by the patient under the supervision of site staff. Study 
treatment administrations outside of these site visits can either be performed at the patient’s 
home or at optional study visits under the supervision of site staff as described in 
Section 6.7.2. Patients receiving secukinumab will follow the secukinumab Instructions for 
Use (IFU) document, and patients receiving adalimumab biosimilar (Hyrimoz®) will follow 
the adalimumab biosimilar (Hyrimoz®) IFU document. The IFUs for the medication in the 
SOC arm will be provided by the investigator in accordance with her/his clinical routine. Site 
staff will administer the injection to patients who are not able or feel insecure to self-
administer the PFS injection. 

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6.1.1 
Additional study treatments 
No additional treatment beyond investigational and reference treatment are included in this 
trial. 
6.1.2 
Treatment arms/group 
Patients will be randomly assigned at the Baseline Visit to either the T2T group or the SOC 
group.  
T2T group (n = 150) 
Starting from the Baseline Visit, patients will be treated with secukinumab 150 mg s.c. 
weekly until Week 4 and then at Week 8. 
At Week 12: 
• If ASDAS clinically important improvement is achieved and maintained, patients will 
continue the treatment up to Week 32 if they maintain the response. 
• If ASDAS clinically important improvement is not achieved, patients will receive 
escalated dose of secukinumab 300 mg s.c. every 4 weeks until Week 20.  
At Week 24:  
Patients who are receiving secukinumab 300 mg, and  
• Achieved ASDAS clinically important improvement, will continue the treatment up to 
Week 32.  
• Did not achieve ASDAS clinically important improvement, will be switched to 
adalimumab biosimilar (Hyrimoz®) 40 mg s.c. every 2 weeks until Week 34. 
Escape arm 
• Patients who are receiving 150 mg secukinumab (i.e. were responders at Week 12) can be 
escalated at Week 24 to 300 mg secukinumab every 4 weeks until Week 32, if they 
experienced a loss of response, where loss of response is defined as ASDAS change from 
Baseline < 1.1.  
SOC group (n = 150) 
Patients will receive treatment according to local practice standards by their treating 
rheumatologist following the current treatment recommendations with NSAIDs as the 
first-choice drug treatment and DMARDs for patients with active disease despite the use (or 
intolerance/contraindication) of NSAIDs.  
6.1.3 
Treatment duration 
Each patient will be treated for a maximum of 36 weeks (last dose of secukinumab at 
Week 32, last dose of adalimumab biosimilar (Hyrimoz®) at Week 34).  

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6.2 
Other treatment 
6.2.1 
Concomitant therapy 
The investigator must instruct the patient to notify the study site about any new medications 
he/she takes after the patient is enrolled into the study. All medications, procedures, and 
significant non-drug therapies (including physical therapy and blood transfusions) 
administered after the patient was enrolled into the study must be recorded on the appropriate 
case report form (CRF). 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt, the investigator should contact the Novartis medical monitor before 
randomizing a patient or allowing a new medication to be started. If the patient is already 
enrolled, contact Novartis to determine if the patient should continue participation in the 
study. 
6.2.1.1 
Permitted concomitant therapy requiring caution and/or action 
Methotrexate  
Patients taking MTX (up to 25 mg/week) must be on a stable dose for at least 4 weeks before 
randomization. 
Sulfasalazine 
Patients taking sulfasalazine (≤ 3 g/day) must be on a stable dose for at least 4 weeks before 
randomization. 
Systemic corticosteroids 
Treatment with systemic corticosteroids is permitted if the dose was stable within the 2 weeks 
preceding randomization, up to a maximum daily dosage of 10 mg prednisone equivalent. 
Higher-dose, time-limited corticosteroid courses (bursts) may be permitted for exacerbations 
of medical conditions unrelated to axSpA (e.g. asthma, chronic obstructive pulmonary 
disease, contact dermatitis) after randomization.  
Nonsteroidal anti-inflammatory drugs (including COX-1 or COX-2 inhibitors) 
and acetaminophen/paracetamol 
Patients should have been on at least 2 different NSAIDs at the highest recommended dose for 
at least 4 weeks (in total) prior to randomization with an inadequate response or failure to 
respond, or less if therapy had to be withdrawn due to intolerance, toxicity or 
contraindications. 
Patients regularly using NSAIDs, low strength opioids, or paracetamol/acetaminophen should 
be on a stable dose for at least 1 week before randomization to allow inclusion in the study. 

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6.2.2 
Prohibited medication  
6.2.2.1 
Prohibited prior medication (washout periods) 
Previous use of medication listed in Table 6-1 is either not allowed at all or the given 
medication must be washed out as indicated. Table 6-1 refers to both treatment arms.  
Table 6-1 
Prohibited prior treatments (both arms) 
axSpA=ankylosing spondyloarthritis, COX-1=cyclooxygenase 1, COX-2=cyclooxygenase 2, 
DMARD=disease modifying anti-rheumatic drug, IL-17=interleukin-17, MTX=methotrexate, 
NSAIDs=non-steroidal anti-inflammatory drugs 
6.2.2.2 
Prohibited concomitant medication (T2T arm only) 
Use of the treatments displayed in Table 6-2 is NOT allowed after the start of the washout 
period (see Table 6-1) and refers to T2T arm only.  
There is no prohibited concomitant treatment in SOC arm, all SOC patients should be 
treated at the discretion of the investigator and in accordance with current therapy 
recommendation. 
Live vaccines should not be given until 12 weeks after the last study drug administration. 
Prohibited prior treatments 
Washout period before randomization 
Biologic drugs directly targeting IL-17 or IL-17 receptor 
Previous exposure at any time: exclusion 
criterion 
TNFα inhibitors (e.g. adalimumab, infliximab, 
certolizumab, golimumab).  
Previous exposure at any time: exclusion 
criterion  
Any cell-depleting therapies including but not limited to 
anti-CD20 or investigational agents [e.g. alemtuzumab 
(Campath), anti-CD4, anti-CD] 
Previous exposure at any time: exclusion 
criterion 
Unstable dose of MTX or sulfasalazine 
4 weeks 
Other DMARD (incl. apremilast, except MTX and – in 
case of axSpA – sulfasalazine) 
4 weeks 
Leflunomide with cholestyramine washout 
4 weeks 
Unstable doses of NSAIDs (COX1 or COX2 inhibitors), 
low strength opioids, paracetamol/acetaminophen.  
2 weeks 
Analgesics, other than NSAIDs or 
paracetamol/acetaminophen or low strength opioids as 
described above 
2 weeks 
Systemic corticosteroids > 10 mg prednisone per day 
equivalent 
2 weeks 
Unstable dose of systemic corticosteroids ≤ 10 mg 
prednisone equivalent per day 
2 weeks 
Any investigational treatment other than study 
medication or participation in any interventional trial 
4 weeks or 5 half-lives (whichever is longer) 
Live vaccinations 
6 weeks 
Medical cannabis 
2 weeks 

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Table 6-2 
Concomitant treatment in T2T arm 
COX-1=cyclooxygenase 1, COX-2=cyclooxygenase 2, DMARD=disease modifying anti-rheumatic 
drug, IL-17=interleukin-17, MTX=methotrexate, NSAIDs=non-steroidal anti-inflammatory drugs, 
TNFα=tumor necrosis factor alpha 
6.2.3 
Rescue medication 
Rescue medication is defined as any new therapeutic intervention or a significant change to 
ongoing therapy made because a patient is experiencing either no benefit from participation in 
the study or worsening/exacerbation of his/her disease. Since patients in the SOC arm will 
receive treatment according to local practice standards by their treating rheumatologist the 
study protocol cannot dictate any rescue treatment. The Investigator decides if and which 
rescue treatment should be applied.  
Although no T2T-arm-patient will be restricted from receiving necessary rescue medications 
for lack of benefit or worsening of disease, if treatment with prohibited biologics (as 
described in Section 6.2.2) is started, patients may remain in the study but must discontinue 
study treatment. Efficacy and safety will be assessed at each on-site study visit, and patients 
who are deemed by the investigator not to be benefiting from study treatment, or for any 
reason of the patient’s own accord, will be free to discontinue study participation at any time. 
Prohibited treatments 
Action to be taken 
Biologic drugs directly targeting IL-17 or IL-17 receptor other than 
investigational drug 
Discontinue study treatment 
TNFα inhibitors (e.g. adalimumab, infliximab, certolizumab, 
golimumab) other than investigational drug  
Discontinue study treatment 
Any cell-depleting therapies including but not limited to anti- 
CD20 or investigational agents [e.g. alemtuzumab (Campath), 
anti-CD4, anti-CD 
Discontinue study treatment 
csDMARDs other than MTX or sulfasalazine 
Protocol deviation 
Leflunomide 
Protocol deviation 
High potency opioid analgesics (e.g. methadone, hydromorphone, 
morphine) 
Protocol deviation 
Analgesics (other than NSAIDs, paracetamol/acetaminophen or 
low strength opioids) 
Protocol deviation 
Any investigational treatment other than study medication or 
participation in any interventional trial 
Discontinue study treatment 
Systemic corticosteroids ≥ 10 mg prednisone equivalent per day 
Local (injectable) steroids: > 2 injections or >80 mg triamcinolone 
equivalent in total. 
Dose increase should be 
avoided; dose reduction at the 
investigator’s discretion 
NSAIDs  
(including COX-1 and COX-2 inhibitors) 
Dose increase should be 
avoided; dose reduction at the 
investigator’s discretion  
MTX or sulfasalazine  
Dose increase should be 
avoided; dose reduction at the 
investigator’s discretion  
Live vaccinations 
Discontinue study treatment 
Medical cannabis 
Protocol deviation 

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Changes in NSAIDs, non-biologic DMARDs and corticosteroid concomitant therapy are 
permitted as per investigator’s discretion. Use of rescue medication must be recorded on the 
corresponding CRF.  
6.3 
Patient numbering, treatment assignment, randomization  
6.3.1 
Patient numbering 
Each patient is identified in the study by a Patient ID that is assigned when the patient is first 
enrolled for Screening and is retained as the primary identifier for the patient throughout 
his/her entire participation in the trial. The Patient ID consists of the Center Number 
(Center No. as assigned by Novartis to the investigative site) with a sequential Patient No. 
suffixed to it, so that each patient is numbered uniquely across the entire database. Upon 
signing the ICF, the patient is assigned to the next sequential Patient No. available. 
Patients can be re-screened (only once) - no study-related re-screening procedure should be 
performed prior to written re-consent by the patient. Once re-screened, the patient will be 
assigned with a new identifier. For these patients, the previous primary identifier will be 
collected in the eCRF.  
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 
randomization list will be produced by or under the responsibility of Novartis Biometrics 
Department using a validated system that automates the random assignment of treatment 
groups to randomization numbers in the specified 1:1 ratio (T2T group, SOC group). The 
randomization scheme will be reviewed and locked after approval. According to the 
recommendations given in the International Council for Harmonisation of Technical 
Requirements for Pharmaceuticals for Human Use (ICH) E9 Guideline “Statistical Principles 
for Clinical Trials”, the used block length is specified in a separate document which will be 
with-held from the study centers. The randomization list will be kept sealed in a secure 
location.  
All study sites will be provided with a given set of sealed allocation cards.  
At the Randomization Visit, the investigator will assign each patient who meets all the 
inclusion criteria and does not fulfill any of the exclusion criteria to the lowest available 
randomization number, open the corresponding treatment allocation card and treat the patient 
with the treatment noted on this card (i.e. T2T treatment or SOC treatment). 
6.4 
Treatment blinding 
Not applicable. 
6.5 
Permitted dose adjustments and interruptions of study treatment 
In the T2T arm study treatment dose adjustments are not permitted. Study treatment 
interruption is also not permitted with the following exception: 
• Study treatment interruption is only permitted if, in the opinion of the investigator, a 
patient is deemed to be at a significant safety risk unless administration of investigational 
treatment is temporarily interrupted. In such cases study treatment should be interrupted 

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only during the time that this risk is present and ongoing. Study treatment can be restarted 
at the next scheduled visit after resolution of the safety risk. 
The effect of secukinumab or adalimumab biosimilar (Hyrimoz®) on live vaccines is 
unknown; therefore live vaccines should not be administered during participation in the study. 
The elimination of adalimumab may take up to 4 months (Humira® SmPC); in case a live 
vaccine has been administered due to a medical urgency, study treatment should be 
discontinued  
Treatment and thus any dose adjustments and/or treatment interruption and/or 
permanent discontinuations in the SOC arm are at the discretion of the investigator.  
Study treatment/reference treatment interruption or permanent discontinuation of study 
treatment/reference treatment will not affect the ability of the patient to remain in the study. 
Any study treatment interruption must be recorded on the corresponding CRF. 
6.6 
Additional treatment guidance 
6.6.1 
Treatment compliance 
All dates of study treatment and reference treatment administration will be recorded on the 
appropriate CRF. 
Drugs administered prior to start of treatment and other drugs/procedures continued or started 
during the study treatment/reference treatment period will be entered in the appropriate CRF. 
Compliance to study treatment and reference treatment is expected to be 100% if possible, 
unless temporary interruption is needed for safety reasons as described in Section 6.5. In case 
full compliance with the visit schedule for the T2T arm cannot be reached, visits and/or 
treatments that fall into the following tolerance levels do not constitute a PD: 
V1 up to and including V4: +/- 2 days 
V5: +/- 3 days 
V6 up to and including V9: +/- 7 days 
V10 up to and including V15 for patients treated with secukinumab: +/- 7 days 
V10 up to and including V15 for patients treated with adalimumab: +/- 3 days 
Compliance will be assessed continuously during the conduct of the study by Novartis study 
personnel using medication kits and corresponding documentation.  
Study drug doses and corresponding dates of self-administration at home should be 
documented in a self-administration log. Patients are required to return the self-administration 
log as well as all dispensed study drug for a compliance check at their subsequent visit back to 
the study center. Compliance will be assessed by a field monitor using information provided 
by the patient and the authorized site personnel. All study treatment dispensed and returned 
must be recorded in the Drug Accountability Log. 
6.6.2 
Emergency breaking of assigned treatment code 
Not applicable.  

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6.7 
Preparation and dispensation 
For the T2T arm, each study site will be supplied with study drug in packaging as described 
under the investigational and reference treatment section (Section 6.1).  
The investigator or site staff will allocate the treatment arm at the randomization visit as 
described in Section 6.3.2.  
Treatment in the SOC arm is at discretion of the investigator – the medication will be 
prepared and dispensed as per the routine daily clinical practice of the investigator.  
In the T2T arm, the investigator will follow the treatment scheme provided in Table 8-2 and 
dispense either one secukinumab 150 mg PFS, or 2 secukinumab 150 mg PFS or one 
adalimumab biosimilar (Hyrimoz®) 40 mg PFS per scheduled visit, depending on the time 
point and the patient’s response at Week 12 and/or Week 24. 
6.7.1 
Handling of study treatment and additional treatment 
6.7.1.1 
Handling of study treatment  
Study treatment for the T2T arm (secukinumab 150 mg, adalimumab biosimilar (Hyrimoz®) 
40 mg) must be received by a designated person at the study site, handled and stored safely 
and properly and kept in a secure location to which only the investigator and designated site 
personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified on the labels and in the IB. Clinical supplies are to be dispensed only in 
accordance with the protocol. Technical complaints are to be reported to the respective 
Novartis Country Organization Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of 
each country. They will include storage conditions for the study treatment but no information 
about the patient. 
The investigator must maintain an accurate record of the shipment and dispensing of study 
treatment in a drug accountability log. Monitoring of drug accountability will be performed by 
monitors during site visits or remotely and at the completion of the trial. Patients will be asked 
to return all unused study treatment and packaging at the end of the study or at the time of 
discontinuation of study treatment. 
At the conclusion of the study, and as appropriate during the course of the study, the 
investigator will return all unused study treatment, packaging, drug labels, and a copy of the 
completed drug accountability log to the Novartis monitor or to the Novartis address provided 
in the investigator folder at each site. 
6.7.1.2 
Handling of additional treatment  
Not applicable.  
6.7.2 
Instruction for prescribing and taking study treatment and reference 
treatment 
The T2T treatments (secukinumab 150 mg, and adalimumab biosimilar (Hyrimoz®) 40 mg) 
will be provided in PFSs for s.c. use. SOC treatments will be provided in accordance with 

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routine practice. Administration of the study treatments must occur after the study 
assessments for the visit have been completed. The PFS with the ready-to-use study treatment 
solution will be provided by the site staff to the patient. Detailed instructions on the self-
administration of the T2T study treatment will be described in the IFUs for secukinumab and 
adalimumab biosimilar (Hyrimoz®) and provided to each patient.  
The IFUs for the medication in the SOC arm will be provided by the investigator in 
accordance with her/his clinical routine. 
During the scheduled study visits (Baseline, Week 12 and Week 24), T2T and SOC treatments 
will either be administered by the investigator/site staff or by the patient but under the 
supervision of the investigator/site staff.  
At the Baseline Visit, patients or caregivers will be instructed by the site staff, utilizing the 
IFU, on how to self-inject using a PFS. Patients will be asked to raise any questions and then 
to proceed with self-injection. However, if the patient is not comfortable self-injecting the 
study treatment, then the site staff or caregiver may administer it to the patient. 
Study treatment administration outside mandatory study visits 
At the Baseline Visit, patients will also decide if they would like to perform study treatment 
administrations that occur outside the mandatory study visits either at home or at optional 
study visits as included in the schedule of assessments (Table 8-1) and study treatment 
administration schedule (Table 8-2). 
If the patient decides to attend the optional study visits, the patient will be required to 
self-administer the study treatment (via PFS) at the study site under the supervision of the site 
staff. If the patient opts for home administration, the patient will be required to self-administer 
the study treatment (via PFS) at home. If the patient is unable or unwilling to self-administer 
the treatment via PFS, a caregiver may administer the study treatment for him/her. Caregivers 
should be trained on the IFU prior to administering the study treatment to the patient.  
Prior to self-administration at home, patients should contact the investigator/site staff in case 
they are experiencing any AE/SAEs, or have any concerns.  
All dates of self-administrations by the patient during the study must be recorded on the 
appropriate CRF. Immediately before dispensing the package to the patient, site staff will note 
medication specifications on the source document (Drug Label Form) for that patient’s unique 
Patient No. 
The investigator must promote compliance by instructing the patient to take the treatment 
exactly as prescribed and by stating that compliance is necessary for the patient’s safety and 
the validity of the study. The patient must also be instructed to contact the investigator if 
he/she is unable for any reason to take the study treatment/reference treatment as prescribed. 
7 
Informed consent procedures 
Eligible patients may only be included in the study after providing (witnessed, where required 
by law or regulation), institutional review board/independent ethics committee (IRB/IEC) 
approved informed consent. 

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If applicable, in cases where the patient’s representative(s) gives consent (if allowed 
according to local requirements), the patient must be informed about the study to the extent 
possible given his/her understanding. If the patient is capable of doing so, he/she must 
indicate agreement by personally signing and dating the written informed consent document. 
Informed consent must be obtained before conducting any study-specific procedures (e.g. all 
of the procedures described in the protocol). The process of obtaining informed consent must 
be documented in the patient source documents. 
Novartis will provide to investigators in a separate document an ICF that complies with the 
ICH Good Clinical Practice (GCP) guidelines and regulatory requirements and is considered 
appropriate for this study.  
Information about common side effects already known about the investigational drug can be 
found in the IB. This information will be included in the patient informed consent and should 
be discussed with the patient during the study as needed. Any new information regarding the 
safety profile of the investigational drug that is identified between IB updates will be 
communicated as appropriate, for example, via an investigator notification (IN) or an 
aggregate safety finding. New information might require an update to the informed consent 
and then must be discussed with the patient. 
Women of child-bearing potential must be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirements. 
A copy of the approved version of all consent forms must be provided to Novartis/sponsor 
after IRB/IEC approval. 
8 
Visit schedule and assessments 
The assessment schedule (Table 8-1) lists all of the assessments and indicates with an ‘X’, 
‘S’, or ‘C’ the visits when they are performed. An ‘X’ designates assessments which need to 
be recorded in the source data and CRF by the investigator or site staff. ‘S’ designates 
assessments which are recorded in source documentation only. ‘C’ designates centrally 
analyzed laboratory or questionnaire results, which are entered into the database by a central 
laboratory or by data management; for these assessments, only the date of the assessment 
needs to be entered into the electronic case report form (eCRF) by the site staff. All data 
obtained from these assessments must be supported in the patient’s source documentation. 
 
Patients should be seen for all visits/assessments as outlined in the assessment schedule or as 
close to the designated day/time as possible. Missed or rescheduled visits should not lead to 
automatic discontinuation. Patients who prematurely discontinue the study for any reason 
should return for the final visit to conduct the Week 36 assessments (4 weeks after the last 
study treatment administration), then also return after an additional 20 weeks for a final 
follow-up visit, corresponding to Week 56 assessments. 

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At this final visit, all dispensed investigational product should be reconciled, and the AEs and 
concomitant medications recorded on the CRF. 
The timing of study treatment administration at home and at the study site for patients 
assigned to the T2T treatment group is additionally presented in Table 8-2.  
 

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Table 8-1 
Assessment schedule 
Visit Name/ Visit Number 
SV1 
SV2 
Baseline 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Visit 12 
Visit 13 
Visit 14 
Visit 15 
FUP 
Week 
 
-8 to-4 
-4 to BSL 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
26 
28 
30 
32 
34 
36 
56 
Home administration visit,  
can be performed optionally at the 
site 
 
 
 
yes 
yes 
yes 
yes* 
yes* 
 
yes 
yes 
 
yes 
yes 
yes 
yes 
yes 
 
 
Safety monitoring visit for patients 
in T2T arm1 
 
 
 
 
 
 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
Information and informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria2 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
axSpA classification and diagnosis 
(incl. peripheral involvement)  
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upload of X-ray and/or MRI of 
sacroiliac joints3 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant medical history/ current 
medical condition (incl. CV and 
EAM history)2 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Washout evaluation/ 
instruction 
S 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Smoking history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medication/non-
drug therapy (incl. axSpA prior and 
concomitant medication) 
X 
X 
X 
Xa 
Xa 
Xa 
Xa 
Xa 
X 
Xa 
Xa 
X 
Xa 
Xa 
Xa 
Xa 
Xa 
X 
X 

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Visit Name/ Visit Number 
SV1 
SV2 
Baseline 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Visit 12 
Visit 13 
Visit 14 
Visit 15 
FUP 
Week 
 
-8 to-4 
-4 to BSL 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
26 
28 
30 
32 
34 
36 
56 
Physical examination 
 
S 
S 
 
 
 
 
 
S 
 
 
S 
 
 
 
 
 
S 
S 
Vital signs 
 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
X 
X 
Height 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
X 
 
QuantiFERON TB-Gold test 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray/MRI4 
 
S 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
MRI sacroiliac joints and spine5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Upload of MRI sacroiliac joints and 
spine6 
 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
HLA-B277 
 
C/X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
 
 
S 
 
 
 
 
 
S 
 
 
S 
 
 
 
 
 
S 
S 
AEs/SAEs (including injection site 
reactions) 
X 
X 
X 
Xa 
Xa 
Xa 
Xa 
Xa 
X 
Xa 
Xa 
X 
Xa 
Xa 
Xa 
Xa 
Xa 
X 
X 
Clinical laboratory standard 
variables (central laboratory) 
 
C 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
C 
C 
HIV-, Hepatitis B- and Hepatitis C 
Screening 
C 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Additional laboratory assessments 
for patients in T2T arm (ESR, 
hsCRP, full blood count, ALT, 
Creatinine) 
 
 
 
 
 
 
C 
C 
 
 
 
 
 
 
 
 
 
 
 

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Visit Name/ Visit Number 
SV1 
SV2 
Baseline 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Visit 12 
Visit 13 
Visit 14 
Visit 15 
FUP 
Week 
 
-8 to-4 
-4 to BSL 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
26 
28 
30 
32 
34 
36 
56 
Urinalysis (dipstick) 
 
S 
S 
 
 
 
 
 
S 
 
 
S 
 
 
 
 
 
S 
Quick hsCRP (locally) 
X 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
hsCRP (central laboratory) 
 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
ESR (locally) 
 
X 
X 
 
 
 
 
 
X 
 
 
X 
 
 
 
 
 
 
BASDAI9 
 
C 
C 
 
 
 
 
 
 C 
 
 
C 
 
 
 
 
 
 
Patient’s global assessment of 
disease activity9 
 
C 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
BASFI9 
 
 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
BASMI 
 
 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
Back pain (VAS)9 
 
 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
ASAS health index9 
 
 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
SF-369 
 
 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
ASQoL9 
 
 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
FACIT-Fatigue9 
 
 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
Physician’s global assessment of 
disease activity  
 
 
C 
 
 
 
 
 
C 
 
 
C 
 
 
 
 
 
 
ASDAS  
 
X 
X 
 
 
 
 
 
X10 
 
 
X10 
 
 
 
 
 
 

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Visit Name/ Visit Number 
SV1 
SV2 
Baseline 
Visit 1 
Visit 2 
Visit 3 
Visit 4 
Visit 5 
Visit 6 
Visit 7 
Visit 8 
Visit 9 
Visit 10 
Visit 11 
Visit 12 
Visit 13 
Visit 14 
Visit 15 
FUP 
Week 
 
-8 to-4 
-4 to BSL 
0 
1 
2 
3 
4 
8 
12 
16 
20 
24 
26 
28 
30 
32 
34 
36 
56 
Administration of T2T s.c. study 
treatment (see also Table 8-2) 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X11 
X 
X11 
X 
X11 
 
 
SOC treatment at investigator’s 
discretion 
 
 
Documentation of SOC treatment in the eCRF 
 
AE=adverse event, ALT=Alanine Aminotransferase, ASAS= Ankylosing SpondyloArthritis International Society, ASDAS=ankylosing spondylitis disease activity score, 
ASQoL= ankylosing spondylitis quality of life, axSpA=axial spondyloarthritis, BASDAI= Bath ankylosing spondylitis disease activity index, BASFI=Bath ankylosing 
spondylitis functional index, BASMI=Bath ankylosing spondylitis metrology index, BSL=baseline, CV=cardiovascular, hsCRP=high sensitive C-reactive protein, 
EAM=extra-articular manifestations, eCRF=electronic case report form, ESR=erythrocyte sedimentation rate, FACIT-Fatigue=functional assessment of chronic illness 
therapy- fatigue, FUP=follow-up, HIV=human immunodeficiency virus, 
 MRI=magnetic resonance imaging, 
SAE=serious adverse event, SF-36=short form health survey, SOC=standard-of-care, SV1=screening visit 1, SV2=screening visit 2, TB=tuberculosis, T2T=treat-to-target, 
VAS=visual analog scale, CV=cardiovascular  
 
Note: visits highlighted in grey are for patients who opt for administration of study treatment outside of mandatory visits at the study site instead of at home.* 
*All patients in the T2T arm must visit the site at the obligatory safety monitoring visits (Visit 4 and Visit 5); however, secukinumab can be administered at home by the 
patient or a caregiver. 
‘X’ designates assessments which need to be recorded in the source data and CRF by the investigator or site staff.  
‘S’ designates assessments which are recorded in source documentation only.  
‘C’ designates centrally analyzed laboratory or questionnaire results which are entered into the database by a central laboratory or by data management; for these 
assessments, only the date of the assessment needs to be entered into the eCRF by the site staff. 
a only in case the patient has been seen for the optional visit at site, else, the information will be obtained at the next obligatory site visit. 
1 As according to the DGRh recommendation, for patients treated with secukinumab following laboratory parameters should be evaluated at the therapy week 4 and 8:m 
ESR, hsCRP, full blood count, ALT, Creatinine. 
2 Eligibility and relevant medical history assessments are conducted at SV1, SV2 and Baseline but recorded only once in the eCRF. 
3 The last available X-ray and/or MRI of the sacroiliac joints done in order to confirm/revise the axSpA diagnosis should be uploaded into the central reading platform. 

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4 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.  
5 MRIs performed up to 3 months prior to Screening will be accepted; MRI should be performed during Screening only if patient’s quick CRP test is negative (i.e. ≤ 5 
mg/L). 
6 In case an actual (not older than 3 months) MRI image of sacroiliac joints (and spine) is available, it should be uploaded into the central reading platform. If a patient has 
a negative quick CRP (i.e. ≤5 mg/L) at Screening, a MRI of the sacroiliac joints and spine must be performed during the Screening to ensure the presence of objective 
signs of inflammation of the sacroiliac joint and the MRI should be uploaded into the central reading platform. 
7 In case the patient has been already tested for HLA-B27 antigen, the result of the test will be entered in the eCRF and no central re-test will be performed. 
  
9 All questionnaires will be completed at the scheduled study visit prior to the patient seeing the investigator for any clinical assessment or evaluation. 
10 This will be recorded in the CRF for patients in T2T arm only; in case an objective estimation of ASDAS is not possible due to e.g. an increase of CRP caused by 
reasons other than axSpA-related inflammation (e.g. common cold), the escalation/switch of the T2T-treatment must be done at the discretion of the investigator, the 
re-estimation of the ASDAS must be performed at the unscheduled visit 2 weeks later.  
11 Adalimumab biosimilar (Hyrimoz®) only. 
 
 
 
Table 8-2 
Drug administration schedule for treat-to-target group 
Visit 
Base
line 
Visit 
1 
Visit 
2 
Visit 
3 
Visit 
4 
Visit 
5 
Visit 
6 
Visit 
7 
Visit 
8 
Visit 
9 
Visit 
10 
Visit 
11 
Visit 
12 
Visit 
13 
Visit 
14 
Week 
W0 
W1 
W2 
W3 
W4 
W8 
W12 
W16 
W20 
W24 
W26 
W28 
W30 
W32 
W34 
All patients* 
S150 
S150 
S150 
S150 
S150 
S150 
 
 
 
 
 
 
 
 
 
Responder at Week 12 
 
 
 
 
 
 
S150 
S150 
S150 
S150 
n/a 
S150 
n/a 
S150 
n/a 
Non-responder at Week 12** 
 
 
 
 
 
 
S300 
S300 
S300 
 
 
 
 
 
 
Escape Treatment*** 
 
 
 
 
 
 
 
 
 
S300 
n/a 
S300 
n/a 
S300 
n/a 
Responder at Week 24 
 
 
 
 
 
 
 
 
 
S300 
n/a 
S300 
n/a 
S300 
n/a 
Non-responder at Week 24 
 
 
 
 
 
 
 
 
 
A40 
A40 
A40 
A40 
A40 
A40 

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Visits highlighted in grey are home administration visits, which can also be performed optionally at the study site.  
A40 = adalimumab biosimilar (Hyrimoz®) 40 mg s.c.; S150 = secukinumab 150 mg s.c.; S300 = secukinumab 300 mg s.c.; W = week, n/a = not applicable 
* After evaluation of response at Week 12, the patient will either continue to be treated with secukinumab 150 mg until the end of study (see row responder at Week 12) or 
be escalated to secukinumab 300 mg s.c.; the response will be re-assessed at Week 24 prior to study drug administration (see row non-responder at Week 12). 
** After evaluation of response at Week 24, the patient will either continue to be treated with secukinumab 300 mg until the end of study (see row responder at Week 24) 
or switched to adalimumab biosimilar (Hyrimoz®) 40 mg s.c. (see row non-responder at Week 24). 
*** In case a Week 12 responder loses his/her response at Week 24, he/she should be treated with 300 mg secukinumab at Week 24, Week 28 and Week 32.  
 
 

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8.1 
Screening 
Screening will be flexible (up to 8 weeks in duration) in order to allow sufficient time for 
MRI of sacroiliac joints and spine. During Screening, the patient will be evaluated for 
eligibility in addition to all other assessments indicated in Table 8-1. Screening will consist of 
2 consecutive visits. During Screening Visit 1, initial assessments will be performed as 
outlined in Table 8-1. At that visit, it will be determined whether MRI of sacroiliac joints and 
spine are required. Screening Visit 2 will be performed as follows: 
 
• If the MRI assessment is ≤ 4 weeks prior to baseline, the investigator should proceed 
directly to Screening Visit 2 (SV2) on the same day and complete all assessments in 
the next 4 weeks prior to randomization. 
• If the MRI assessment is more than 4 weeks prior to baseline, the patient should return 
for Screening Visit 2 at up to 4 weeks prior to baseline. 
The rationale is that in all cases Screening Visit 2 must occur within the 4 weeks prior to 
randomization to ensure that the results of laboratory evaluations performed during the 
screening are still actual at baseline.  
Screening Visit 1 and Visit 2 may be performed on the same day if possible.  
 
8.1.1 
Information to be collected on screening failures 
Patients who sign an ICF and subsequently found to be ineligible prior to randomization will 
be considered a Screen failure. The reason for Screen failure should be recorded on the 
appropriate CRF. The demographic information, informed consent, and Inclusion/Exclusion 
pages must also be completed for Screen failure patients. No other data will be entered into 
the clinical database for patients who are Screen failures, unless the patient experienced a 
SAE during the Screening phase (see Section 10.1.3 for reporting details).  
Patients who are randomized and fail to start treatment, e.g. patients randomized in error, will 
be considered early terminators. The reason for early termination should be recorded on the 
appropriate CRF.  
8.2 
Patient demographics/other baseline characteristics 
All Baseline assessments should be performed prior to first study drug administration. These 
may occur during the Screening period or at the Baseline Visit depending on the assessment 
(Table 8-1).  
8.2.1 
Demographic characteristics 
Patient demographic data to be collected for all patients include: year of birth, sex, race, 
child-bearing potential (for females only), and source of patient referral. 

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8.2.2 
Other baseline characteristics 
8.2.2.1 
AxSpA classification and diagnosis 
Patient’s disease history will be collected. The information to be collected and entered as 
“axSpA history” includes the following: 
• Date of first signs and symptoms of axSpA including date of onset of inflammatory back 
pain 
• r-axSpA (AS) diagnosis including X-ray with presence/absence of sacroiliitis or 
• nr-axSpA diagnosis by MRI or by presence of human leukocyte antigen-B27 (HLA-B27) 
• Positive spondyloarthritis (SpA) features (Appendix 2) 
Diagnosis of axSpA (either r-axSpA (AS) or nr-axSpA) should have been in accordance with 
ASAS axSpA criteria (Appendix 2 and Appendix 3, Appendix 4) as defined in the inclusion 
criteria (Section 5.1). In addition, peripheral involvement will be recorded in the eCRF. 
Central reading of images 
The X-ray and/or MRI images with presence/absence of sacroiliitis performed for axSpA 
diagnosis confirmation or revision will be uploaded onto the platform of the central reading 
center by the site personnel. Only the last available image (X-ray and/or MRI) should be 
uploaded. 
8.2.2.2 
Relevant medical history/current medical conditions 
Relevant medical history and current medical conditions (other than axSpA) present prior to 
signing the ICF (including cardiovascular and extra-articular manifestations (EAM) history) 
will be recorded in the medical history CRF. Whenever possible, diagnoses and not symptoms 
will be recorded. 
Significant findings that are observed after the patient has signed the ICF and that meet the 
definition of an AE must be recorded in the AE summary pages. 
Cardiovascular comorbidities and extra-articular manifestations – medical history 
Any information pertaining to cardiovascular medical history or EAMs, such as uveitis or 
inflammatory bowel disease, assessed prior to Screening should be reported as cardiovascular 
history/EAM in the eCRF. Cardiovascular risk factors should also be recorded. 
8.2.2.3 
Smoking history 
The current and/or previous use of tobacco products will be recorded. Non-smokers will be 
advised not to start smoking during the study. 
8.2.2.4 
Prior medication/concomitant medication 
All previous and current axSpA treatment other than study drugs will be captured as 
documented in the patient’s medical history or reported by the patient or determined by the 
investigator at the Screening Visit and documented in the eCRF.  

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All other prior medications taken within the 6 months preceding the study Screening Visit 
(Visit 1), any other relevant medication taken before these 6 months at the discretion of the 
investigator, and any concomitant medication irrespective of the start date will be captured in 
the eCRF. 
8.2.2.5 
Height 
Height in centimeters (cm) will be measured without shoes. 
8.2.2.6 
Tuberculosis screening 
A central laboratory test (QuantiFERON TB-Plus test) be performed at the Screening Visit to 
screen the patient population for latent TB infection. The results must be known prior to 
randomization to determine the patient’s eligibility for the study.  
Patients with a positive test may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that  
• The patient has no evidence of active TB 
• If presence of latent TB is established then treatment according to local country guidelines 
must have been initiated. 
Central laboratory test for tuberculosis screening 
The test (e.g. QuantiFERON TB-Plus test) will be analyzed by the central laboratory. Details 
on the collection, processing, and shipment of samples and reporting of results by the central 
laboratory are provided in the laboratory manual. 
 
8.2.2.7 
X-ray or MRI of the chest 
A chest X-ray (posteroanterior view) or MRI at Screening (or within 3 months prior to 
Screening) will be performed to rule out the presence of a pulmonary malignancy or 
infectious process, in particular, TB. The results must be known prior to randomization to 
determine the patient’s eligibility for the study. These assessments will be documented in 
source records only and will not be entered into the CRF. 
8.2.2.8 
MRI of the sacroiliac joints and spine 
An actual MRI image (not older than 3 months) of the sacroiliac joints and spine will be 
accepted. In case patient’s quick CRP is negative at Screening, a MRI of the sacroiliac joints 
and spine will be performed during Screening. The MRI will include T1 and short TI 
inversion recovery sequences of the sagittal spine (cervical, thoracic, and lumbar) and oblique 
coronal of the pelvis including both sacroiliac joints.  
 
8.2.2.9 
HLA-B27 
A blood sample to analyze HLA-B27 will be obtained at SV2 from all patients for whom the 
antigen has not been determined in the past. 

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Details on the collection, handling and shipment of the sample to the central laboratory will be 
provided to investigators in the laboratory manual. 
8.2.2.10 Other baseline assessments 
Other Baseline characteristic data to be collected for all patients at either the Screening or 
Baseline Visit (see also Table 8-1) include the following: 
• Physical examination, body weight, vital signs, clinical laboratory assessments as 
described in Section 8.4 and AEs/SAEs (including injection site reactions) as described in 
Section 10. 
• For women of childbearing potential, a serum pregnancy test will be performed at 
Screening and a urine pregnancy test will be performed at Baseline as described in 
Section 8.4.5.  
• Baseline assessments of ASDAS, BASDAI, erythrocyte sedimentation rate (ESR), hsCRP 
/quick hsCRP, 
 
 as described in 
Section 8.3.  
• Documentation of SOC treatment in the eCRF.  
Whenever possible, diagnoses and not symptoms will be recorded.  
8.3 
Efficacy 
• Ankylosing spondylitis disease activity score (ASDAS) 
• Bath ankylosing spondylitis disease activity index (BASDAI) 
• Patient’s global assessment of disease activity (visual analog scale [VAS]) 
• Physician’s global assessment of disease activity (VAS) 
• Bath ankylosing spondylitis functional index (BASFI) 
• Bath ankylosing spondylitis metrology index (BASMI)  
• Patient’s assessment of back pain intensity (VAS) 
 
  
 
 
All efficacy assessments should be performed prior to administration of study 
treatment/reference treatment.  
8.3.1 
Assessment of SpondyloArthritis International Society response 
criteria (ASAS) 
The ASAS response measures consist of the following assessment domains (Sieper et al 
2009). 
ASAS domains: 
1. Patient’s global assessment of disease activity measured on a VAS scale. 
2. Patient’s assessment of back pain, represented by either total or nocturnal pain scores, 
both measured on a VAS scale. 

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3. Function represented by BASFI average of 10 questions regarding ability to perform 
specific tasks as measured by VAS scale. 
4. Inflammation represented by mean duration and severity of morning stiffness, represented 
by the average of the last 2 questions on the 6-question BASDAI as measured by VAS 
scale. 
Additional assessment domains: 
5. Spinal mobility represented by the BASMI lateral spinal flexion assessment 
6. CRP (acute phase reactant) 
ASAS assessment will be performed only during the analysis, will not be collected on the 
eCRF during the study, only ASAS compounds as listed above will be collected in the eCRF 
as indicated in the table 8-1.  
ASAS response criteria 20% (ASAS 20) 
ASAS20 response is defined as an improvement of ≥ 20% and ≥ 1 unit on a scale of 0 to 10 in 
at least 3 of the 4 domains, and no worsening at all in the remaining domain. 
ASAS response criteria 40% (ASAS 40) 
ASAS40 response is defined as an improvement of ≥ 40% and ≥ 2 units on a scale of 10 in at 
least 3 of the 4 domains and no worsening at all in the remaining domain. 
8.3.1.1 
Patient’s global assessment of disease activity (VAS) 
The patient’s global assessment of disease activity will be performed using a 100 mm VAS 
ranging from not severe to very severe, after the question "How active was your disease on 
average during the last week?”. 
8.3.1.2 
Patient’s assessment of back pain intensity (VAS) 
The patient’s assessment of back pain will be performed using a 100 mm VAS ranging from 
no pain to unbearable pain, after the question “Based on your assessment, please indicate 
what is the amount of back pain at any time that you experienced during the last week?” and 
“Based on your assessment, please indicate what is the amount of back pain at night that you 
experienced during the last week?”. 
8.3.1.3 
Bath ankylosing spondylitis functional index 
The BASFI is a set of 10 questions designed to determine the degree of functional limitation 
in those patients with AS. The 10 questions were chosen with major input from patients with 
AS. The first 8 questions consider activities related to functional anatomy. The final 
2 questions assess the patients’ ability to cope with everyday life. A 0 through 10 scale 
(captured as a continuous VAS) is used to answer the questions. The mean of the 10 scales 
gives the BASFI score – a value between 0 and 10. 

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8.3.1.4 
Bath ankylosing spondylitis disease activity index 
The BASDAI consists of a 0 through 10 scale (0 being no problem and 10 being the worst 
problem, captured as a continuous VAS), which is used to answer 6 questions pertaining to 
the 5 major symptoms of AS: 
1. Fatigue 
2. Spinal pain 
3. Joint pain/swelling 
4. Areas of localized tenderness (called enthesitis, or inflammation of tendons and ligaments) 
5. Morning stiffness severity 
6. Morning stiffness duration 
To give each symptom equal weighting, the mean (average) of the 2 scores relating to 
morning stiffness is taken. The mean of questions 5 and 6 is added to the scores from 
questions 1 to 4. The resulting 0 to 50 score is divided by 5 to give a final 0 – 10 BASDAI 
score. Scores of 4 or greater suggest suboptimal control of disease, and patients with scores of 
4 or greater are usually good candidates for either a change in their medical therapy or for 
enrollment in clinical studies evaluating new drug therapies directed at AS. The BASDAI is a 
quick and simple index taking between 30 seconds and 2 minutes to complete. 
See Appendix 5 for further details.  
8.3.1.5 
Bath ankylosing spondylitis metrology index  
The BASMI is a validated instrument that uses the minimum number of clinically appropriate 
measurements that accurately assess axial status, with the goal to define clinically significant 
changes in spinal movement. Parameters include: 
1. Lateral spinal flexion 
2. Tragus-to-wall distance 
3. Lumbar flexion (modified Schoeber) 
4. Maximal intermalleolar distance 
5. Cervical rotation angle 
Additionally, the following assessments should be taken: 
6. Chest expansion 
7. Occiput-to-wall distance 
See Appendix 6 for further details. 
8.3.1.6 
Erythrocyte sedimentation rate 
Blood for ESR, which is helpful in diagnosing inflammatory diseases, will be used to monitor 
disease activity and response to therapy. ESR assessments will be performed locally at the 
study centers, using a centrally provided assessment kit. 

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8.3.1.7 
High sensitive Quick C-reactive protein test/ high sensitive C-reactive 
protein test 
This assessment will be performed in order to identify the presence of inflammation, to 
determine its severity, and to monitor response to treatment. The quick hsCRP assessments 
will be performed locally at the study centers using a centrally provided assessment kit. The 
result of the quick hsCRP will be used to confirm eligibility of the patient (ASDAS ≥ 2.1 or 
CRP > 5 mg/L) at Screening and Baseline or to estimate further treatment of patients in the 
T2T arm at the Week 12 or Week 24 visit. In addition, the hsCRP assessment will be 
performed centrally as indicated in Table 8-1 and used in final data analyses only. 
8.3.2 
Ankylosing spondylitis disease activity score 
The ASDAS is a composite index to assess disease activity in AS (Lukas et al 2009, Sieper et 
al 2009, Machado et al 2011, Machado et al 2018). The ASDAS-ESR and ASDAS-CRP will 
be utilized to assess the disease activity status. Parameters used for the ASDAS include spinal 
pain (BASDAI question 2), the patient’s global assessment of disease activity, peripheral 
pain/swelling (BASDAI question 3), duration of morning stiffness (BASDAI question 6) and 
CRP in mg/L (or ESR). 
Disease activity states are inactive disease, low disease activity, high disease activity, and 
very high disease activity. The 3 values selected to separate these states were < 1.3 between 
inactive disease and low disease activity, < 2.1 between low disease activity and high disease 
activity, and > 3.5 between high disease activity and very high disease activity. Selected 
cutoffs for improvement scores were a change of ≥ 1.1 unit for “minimal clinically important 
improvement” and a change of ≥ 2.0 units for “major improvement” (Machado et al 2011, 
Machado et al 2018). 
ASDAS will be assessed by the investigator via eCRF at Screening and Baseline for all 
patients in order to estimate the eligibility of the patient. Only patients with ASDAS ≥ 2.1 can 
be considered to be enrolled into the study.  
In addition, for patients in T2T arm the ASDAS will be calculated via eCRF at week 12 and 
week 24 in order to estimate the response and to decide further treatment.  
8.3.3 
Physician’s global assessment of disease activity 
The physician’s global assessment of disease activity will be performed using 100 mm VAS 
ranging from no disease activity to maximal disease activity, after the question “Considering 
all the ways the disease affects your patient, draw a line on the scale for how well his or her 
condition is today.” To enhance objectivity, the physician must not be aware of the specific 
patient’s global assessment of disease activity when performing his own assessment on that 
patient. 
 
 
 
 
 
 

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8.3.6 
Appropriateness of efficacy assessments 
The efficacy outcome measures used in this study are the standard measures used across all 
r-axSpA (AS) and nr-axSpA trials studies. 

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8.4 
Safety 
Safety assessments are specified below with the assessment schedule detailing when each 
assessment is to be performed. 
For details on AE collection and reporting, refer to the AE section (Section 10). 
8.4.1 
Physical examination 
The physical examination will include the examination of general appearance, skin, neck 
(including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, 
extremities, and vascular and neurological system.  
Information for all physical examinations must be included in the source documentation at the 
study site. Clinically relevant findings that are present prior to the ICF must be included in the 
relevant medical history CRF. Significant findings made during a physical exam after signing 
the ICF which meet the definition of an AE must be recorded on the appropriate CRF, 
capturing AEs and if SAE criteria are met, also as a SAE. 
8.4.2 
Body weight 
Body weight (to the nearest 0.1 kilogram (kg) in indoor clothing) will be measured without 
shoes. 
8.4.3 
Vital signs 
Vital signs will include blood pressure and pulse rate measurements after 5 minutes rest in a 
sitting position. 
If possible, vital sign assessments should be performed by the same study site staff member 
using the same validated device throughout the study. 
8.4.4 
Laboratory evaluations 
A central laboratory will be used for analysis of all specimens collected listed below. Details 
on the collection, shipment of samples and reporting of results by the central laboratory are 
provided in the laboratory manual. Clinically notable laboratory findings are defined in 
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.  
8.4.4.1 
Hematology 
Hemoglobin, hematocrit, platelet count, red blood cell, WBC and differential WBC counts 
will be measured at scheduled visits.  
8.4.4.2 
Clinical chemistry 
Serum chemistries will include glucose, urea, creatinine, total bilirubin, AST, ALT, gamma-
glutamyltransferase (GGT), alkaline phosphatase, sodium, potassium, bicarbonate, calcium, 
phosphorous, total protein, albumin, and uric acid. 

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8.4.4.3 
Lipid panel  
A lipid profile including high density lipoprotein, low density lipoprotein, cholesterol and 
triglycerides.. 
8.4.4.4 
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. In case any abnormality are 
observed in the result of the dipstick, a urine sample will be send to central laboratory for 
further examination. 
8.4.5 
Pregnancy and assessments of fertility 
All pre-menopausal women who are not surgically sterile will have a serum β-hCG test 
(serum pregnancy test) performed at the Screening Visit, and local urine pregnancy tests as 
indicated in Table 8-1. A positive urine pregnancy test requires immediate interruption of 
study drug until serum β-hCG is performed and found to be negative. Additional pregnancy 
testing may be performed if requested by local requirements. 
Secukinumab and adalimumab biosimilar (Hyrimoz®) should 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). 
Assessments of fertility 
Medical documentation of oophorectomy, hysterectomy, or tubal ligation must be retained as 
source documents. Subsequent hormone level assessment to confirm the woman is not of 
child-bearing potential must also be available as source documentation in the following cases: 
1. Surgical bilateral oophorectomy without a hysterectomy. 
2. Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile. 
In the absence of the above medical documentation, follicle-stimulating hormone testing is 
required of any female patient, regardless of reported reproductive/menopausal status at 
Screening/Baseline. 
8.4.6 
Appropriateness of safety measurements 
The safety assessments selected are standard for this indication/patient population. 
8.5 
Additional assessments 
8.5.1 
Health-related quality of life outcomes 
The impact of axSpA on various aspects of patient’s health-related quality of life (QoL) will 
be assessed by the following instruments: 
• SF-36 version 2 (acute form) 
• Ankylosing spondylitis quality of life (ASQoL) 

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• ASAS health index (ASAS-HI)  
• FACIT-Fatigue 
All questionnaires will be available in the local languages of the participating countries. 
All questionnaires will be completed at the scheduled study visit prior to the patient seeing the 
investigator for any clinical assessment or evaluation.  
All patients will complete the patient reported outcome (PRO) questions on paper. Patients 
should be given sufficient instruction, space, time and privacy to complete all study PROs. 
The study coordinator should check the responses to the questionnaire for completeness and 
encourage the patient to complete any missing responses. Attempts should be made to collect 
responses to all PROs for all patients, including from those who prematurely discontinue prior 
to the study evaluation completion visit, however, if patients refuse to complete PROs, this 
should be documented in study source records. Patient’s refusal to complete study PROs are 
not protocol deviations.  
Guidelines for administering the PRO questionnaires can be found in Appendix 7. A detailed 
training manual relating to the administrative procedures of the questionnaires will be 
provided to the sites. 
Completed questionnaires will be reviewed and examined by the investigator, before the 
clinical examination, for responses that may indicate potential AEs or SAEs. The investigator 
should review not only the responses to the questions in the questionnaires but also for any 
unsolicited comments written by the patient. If AEs or SAEs are confirmed, then the 
physician must record the events as per instructions given in Section 10.1 of the protocol. 
Investigators should not encourage the patients to change the responses reported in the 
completed questionnaires. 
8.5.1.1 
Medical outcome short form health survey (SF-36) version 2 acute 
form 
The SF-36 is a widely used and extensively studied instrument to measure health-related QoL 
among healthy patients and patients with acute and chronic conditions. It consists of eight 
subscales that can be scored individually: Physical Functioning, Role- Physical, Bodily Pain, 
General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health (Ware and 
Sherbourne 1992). Two overall summary scores, the Physical Component Summary and the 
Mental Component Summary also can be computed (McHorney et al 1993). The SF-36 has 
proven useful in monitoring general and specific populations, comparing the relative burden 
of different disease, differentiating the health benefits produced by different treatments, and in 
screening individual patients. 
The purpose of the SF-36 in this study is to assess the health-related QoL of patients. Given 
the acute nature of this disease, version 2, with a 1-week recall period, will be used in this 
study. 

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8.5.1.2 
Ankylosing spondylitis quality of life  
The ASQoL is a self-administered questionnaire designed to assess health-related quality of 
life in adult patients with AS. The ASQoL contains 18 items with a dichotomous yes/no 
response option. A single point is assigned for each “yes” response and no points for each 
“no” response resulting in overall scores that range from 0 (least severity) to 18 (highest 
severity). As such, lower scores indicate better quality of life. Items include an assessment of 
mobility/energy, self-care and mood/emotion. The recall period is “at the moment,” and the 
questionnaire requires approximately 6 minutes to complete. The purpose of the ASQoL is to 
assess the disease specific QoL of patients in this study. 
8.5.1.3 
ASAS health index 
The ASAS-HI is a disease-specific questionnaire that was developed based on the 
comprehensive International Classification of Functioning, Disability and Health Core Set 
(also known as the ICF Core Set) for AS (Kiltz et al 2014). The ASAS HI is a linear 
composite measure and contains 17 items (dichotomous response option: “I agree” and “I do 
not agree”), which cover most of the ICF Core Set, as presented in Table 8-3. The ASAS HI 
contains items addressing categories of pain, emotional functions, sleep, sexual function, 
mobility, self-care, and community life. The total sum of the ASAS HI ranges from 0 to 17, 
with a lower score indicating a better health status. In addition, the Environmental Factor (EF) 
Item Set (Appendix 10) contains items addressing categories of support/relationships, 
attitudes and health services. The EF Item Set contains 9 dichotomous items with an identical 
response option but without a sum score because of its multidimensional nature (Kiltz et al 
2016). 
Table 8-3 
Items of the ASAS health index 
Item 
Categories 
ICF number 
Pain sometimes disrupts my normal activities.  
Pain 
b280  
I find it hard to stand for long. 
Maintaining a body position 
d415  
I have problems running. 
Moving around 
d455  
I have problems using toilet facilities.  
Toileting 
d530  
I am often exhausted. 
Energy and drive 
b130  
I am less motivated to do anything that requires 
physical effort. 
Motivation 
b1301 
I have lost interest in sex. 
Sexual functions  
b640  
I have difficulty operating the pedals in my car. 
Driving  
d475  
I am finding it hard to make contact with people. 
Community life  
d910  
I am not able to walk outdoors on flat ground. 
Moving around 
d455  
I find it hard to concentrate. 
Handling stress 
d240  
I am restricted in traveling because of my mobility.  
Recreation and leisure 
d920  
I often get frustrated. 
Emotional functions  
b152  
I find it difficult to wash my hair. 
Washing oneself  
d510  
I have experienced financial changes because of 
my rheumatic disease. 
Economic self-sufficiency 
d870 
I sleep badly at night 
Sleep 
b134 
I cannot overcome my difficulties. 
Handling stress 
d240 

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Item 
Categories 
ICF number 
ICF = International Classification of Functioning, Disability and Health  
Source: Kiltz et al 2014 
8.5.1.4 
Functional assessment of chronic illness therapy – Fatigue  
The Functional Assessment of Chronic Illness Therapy - Fatigue (FACIT-Fatigue©) is a 
13-item questionnaire (Cella et al 1993, Yellen et al 1997) that assesses self-reported fatigue 
and its impact upon daily activities and function. The purpose of FACIT-Fatigue in this study 
is to assess the impact of fatigue on patients with AS. 

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9 
Study discontinuation and completion 
9.1 
Discontinuation 
9.1.1 
Discontinuation of study treatment / reference treatment 
Discontinuation of study treatment/reference treatment for a patient occurs when study 
treatment is stopped earlier than the protocol planned duration, and can be initiated by either 
the patient or the investigator. 
Study treatment must be discontinued if the investigator determines that continuation of study 
treatment would result in a significant safety risk for a patient. The following circumstances 
require study treatment discontinuation: 
• Withdrawal of informed consent 
• Emergence of the following adverse events: 
a. Any severe or serious adverse event that is not compatible with administration of study 
medication, including adverse events that require treatment with prohibited comedication  
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 noninvasive 
malignant colon polyps which are being or have been removed 
c. Life-threatening infection 
d. 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 (A 
general guidance on clinically notable laboratory values is provided in Appendix 1.) 
e. Pregnancy 

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g. Any protocol deviation that results in a significant risk to the patient’s safety 
 
• Use of prohibited treatment as per recommendations in the prohibited treatment section 
• Unsatisfactory therapeutic effect 
If discontinuation of study treatment/reference treatment occurs, the investigator should make 
a reasonable effort to understand the primary reason for the patient’s premature 
discontinuation of study treatment and record this information. 
Patients who discontinue study treatment/reference treatment or who decide they do not wish 
to participate in the study further should NOT be considered withdrawn from the study 
UNLESS they withdraw their consent (see withdraw of informed consent section). Where 
possible, they should return for the assessments indicated in the assessment schedule. If 
they fail to return for these assessments for unknown reasons, every effort (e.g. telephone, e-
mail, letter) should be made to contact the patient/pre-designated contact as specified in the 
lost to follow-up section. This contact should preferably be done according to the study visit 
schedule. 
If the patient cannot or is unwilling to attend any visit(s), the site staff should maintain regular 
telephone contact with the patient, or with a person pre-designated by the patient. This 
telephone contact should preferably be done according to the study visit schedule. 
After study treatment/reference treatment discontinuation, at a minimum, in abbreviated 
visits, the following data should be collected at clinic visits or via telephone/email contact: 
• New/concomitant treatments 
• AEs/SAEs 
9.1.2 
Withdrawal of informed consent 
Patients may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent occurs only when a patient: 
• Does not want to participate in the study anymore, and 
• Does not allow further collection of personal data 
In this situation, the investigator should make a reasonable effort (e.g. telephone, e-mail, 
letter) to understand the primary reason for the patient’s decision to withdraw his/her consent 
and record this information.  
Study treatment/reference treatment must be discontinued and no further assessments 
conducted, and the data that would have been collected at subsequent visits will be considered 
missing.  
Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the patient’s study withdrawal should be made as detailed in the 
assessment table.  

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Novartis will continue to keep and use collected study information (including any data 
resulting from the analysis of a patient’s samples until their time of withdrawal) according to 
applicable law. 
All biological samples not yet analyzed at the time of withdrawal will no longer be used, 
unless permitted by applicable law. They will be stored according to applicable legal 
requirements. 
9.1.3 
Lost to follow-up 
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the investigator must show “due diligence” by 
documenting in the source documents steps taken to contact the patient, e.g. dates of 
telephone calls, registered letters, etc. A patient should not be considered as lost to follow-up 
until due diligence has been completed or until the end of the study. 
9.1.4 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit/risk assessment of participating in the study, practical reasons (including 
slow enrollment), or for regulatory or medical reasons. In taking the decision to terminate, 
Novartis will always consider the patient welfare and safety. Should early termination be 
necessary, patients must be seen as soon as possible (provide instruction for contacting the 
patient, when the patient should stop taking drug, when the patient should come for a final 
visit) and treated as a prematurely withdrawn patient. The investigator may be informed of 
additional procedures to be followed in order to ensure that adequate consideration is given to 
the protection of the patient’s interests. The investigator or sponsor depending on the local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial. 
9.2 
Study completion and post-study treatment 
A patient will be considered to have completed the study when the patient has completed the 
last visit planned in the protocol i.e. Follow-up Visit /Week 56 (see Table 8-1). Information 
on the patient’s completion or discontinuation from the study and the reason for 
discontinuation from the study will be recorded on the appropriate Study Phase Completion 
page in the eCRF.  
The investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study or must refer them for appropriate ongoing care. This care may 
include initiating another treatment outside of the study as deemed appropriate by the 
investigator. Based on the individual risk/benefit profile of a patient, treatment options may 
include DMARDs.  
In case of follow-up medical care with a biologic treatment the waiting period before 
initiating treatment will be at the discretion of the investigator or a minimum of 5-half-lives of 
the selected biologic treatment, whichever is longer.  

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10 
Safety monitoring and reporting 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An AE is any untoward medical occurrence (e.g. any unfavorable and unintended sign 
[including abnormal laboratory findings], symptom or disease) in a patient or clinical 
investigation patient after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. In addition, all reports of intentional misuse and abuse of 
the study treatment are also considered an AE irrespective if a clinical event has occurred. See 
Section 10.1.5 for an overview of the reporting requirements.  
The investigator has the responsibility for managing the safety of individual patient and 
identifying AEs. 
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
The occurrence of AEs must be sought by non-directive questioning of the patient at each 
visit during the study. Adverse events also may be detected when they are volunteered by the 
patient during or between visits or through physical examination finding, laboratory test 
finding, or other assessments. 
Adverse events must be recorded under the signs, symptoms or diagnosis associated with 
them, accompanied by the following information (as far as possible) (if the event is serious 
refer to Section 10.1.3): 
1. The severity grade: 
• Mild: Usually transient in nature and generally not interfering with normal activities 
• Moderate: Sufficiently discomforting to interfere with normal activities 
• Severe: Prevents normal activities 
2. Its relationship to the investigational treatment and other treatment. If the event is due to 
lack of efficacy or progression of underlying illness (i.e. progression of the study 
indication) the assessment of causality will usually be ‘not suspected.’ The rationale for 
this guidance is that the symptoms of a lack of efficacy or progression of underlying 
illness are not caused by the trial drug, they happen in spite of its administration and/or 
both lack of efficacy and progression of underlying disease can only be evaluated 
meaningfully by an analysis of cohorts, not on a single patient. 
3. Its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved must be reported. 
4. Whether it constitutes a SAE (see Section 10.1.3 for definition of SAE) and which 
seriousness criteria have been met. 
5. Action taken regarding investigational treatment and other treatment.  
All AEs must be treated appropriately. Treatment may include one or more of the 
following: 
• Dose not changed 

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• Dose reduced/increased 
• Drug interrupted/withdrawn. 
6. Its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown). 
Conditions that were already present at the time of informed consent should be recorded in the 
patient’s medical history. 
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Adverse event monitoring should be continued for at least 20 weeks (or 5 half-lives or end of 
study visit, whichever is longer) following the last dose of study treatment. 
Once an AE is detected, it must be followed until its resolution or until it is judged to be 
permanent (e.g. continuing at the end of the study), and assessment should be made at each 
visit (or more frequently, if necessary) of any changes in severity, the suspected relationship 
to the investigational 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. This information will be included in the patient informed consent and should 
be discussed with the patient during the study as needed. Any new information regarding the 
safety profile of the medicinal product that is identified between IB updates will be 
communicated as appropriate, for example, via an IN or an aggregate safety finding. New 
information might require an update to the informed consent and has then to be discussed with 
the patient. 
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria: 
• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
Baseline or the previous visit, or values which are considered to be non-typical in patients with 
the underlying disease. Clinically notable laboratory values are presented in Appendix 1.  
10.1.2 
Serious adverse events 
An SAE is defined as any AE [appearance of (or worsening of any pre-existing)] 
undesirable sign(s), symptom(s) or medical conditions(s)) which meets any one of the 
following criteria: 
• Fatal 
• Life-threatening. 
Life-threatening in the context of a SAE refers to a reaction in which the patient was at risk of 
death at the time of the reaction, it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to Annex IV, ICH-E2D Guideline) 
• Results in persistent or significant disability/incapacity. 

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• Constitutes a congenital anomaly/birth defect. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
• Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition. 
• Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent. 
• 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, e.g. defined as an event that jeopardizes the patient or may 
require medical or surgical intervention to prevent one of the outcomes above. 
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalization but might jeopardize the 
patient or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization or 
development of dependency or abuse (please refer to Annex IV, ICH-E2D Guideline). 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All reports of intentional misuse and abuse of the products are also considered SAEs 
irrespective if a clinical event has occurred. 
10.1.3 
SAE reporting 
Randomized patients 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent until 20 weeks after the patient has discontinued or stopped study 
treatment must be reported to Novartis safety within 24 hours of learning of its occurrence. 
Detailed instructions regarding the submission process and requirements are to be found in the 
investigator folder provided to each site. 
Screen failures 
SAEs occurring after the patient has provided informed consent until the time the patient 
is deemed a Screen Failure must be reported to Novartis. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at 

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a different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event. 
Information about all SAEs is collected and recorded on the SAE Report Form (this may be a 
paper or electronic SAE CRF); all applicable sections of the form must be completed in order 
to provide a clinically thorough report. The investigator must assess the relationship of each 
SAE to each specific component of study treatment, (if study treatment consists of several 
components) complete the SAE Report Form in English, and submit the completed form 
within 24 hours to Novartis. Detailed instructions regarding the submission process and 
requirements for signature are to be found in the investigator folder provided to each site.  
Follow-up information is submitted as instructed in the investigator folder. Each 
re-occurrence, complication, or progression of the original event must be reported as a 
follow-up to that event regardless of when it occurs. The follow-up information should 
describe whether the event has resolved or continues, if and how it was treated, whether the 
patient continued or withdrew from study participation. 
If the SAE is not previously documented in the IB or Package Insert (new occurrence) and is 
thought to be related to the study treatment, a Chief Medical Office and Patient Safety 
Department associate may urgently require further information from the investigator for 
health authority reporting. Novartis may need to issue an IN to inform all investigators 
involved in any study with the same study treatment that this SAE has been reported.  
Suspected unexpected serious adverse reactions will be collected and reported to the 
competent authorities and relevant ethics committees in accordance with EU Guidance 
2011/C 172/01 or as per national regulatory requirements in participating countries. 
Any SAEs experienced after the period of 20 weeks after last administration of study drug 
should only be reported to Novartis Safety if the investigator suspects a causal relationship to 
study treatment.  
10.1.4 
Pregnancy reporting 
To ensure patient safety, each pregnancy occurring after signing the informed consent must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications. 
Pregnancy should be recorded and reported by the investigator to the Novartis Chief Medical 
Office and Patient Safety. Pregnancy follow-up (Birth, 1, 3 and 12 months after the expected 
delivery) should be recorded on the same form and should include an assessment of the 
possible relationship to the study treatment. 
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form. 
Additionally, pregnancy outcomes (Birth, 1, 3 and 12 months after the expected delivery) 
should be collected for the female partners of any males who took study treatment in this 
study. Consent to report information regarding these pregnancy outcomes should be obtained 
from the mother. 

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10.1.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, patient or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately 
used not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be collected in 
the appropriate eCRF, irrespective of whether or not associated with an AE/SAE and reported 
to Safety only if associated with an SAE. Misuse or abuse will be collected and reported in the 
safety database irrespective of it being associated with an AE/SAE within 24 hours of 
investigator’s awareness. 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error type 
Document in dosing 
CRF (Yes/No) 
Document in AE 
eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated 
with an AE 
Only if associated with an 
SAE 
Misuse/Abuse 
Yes 
Yes 
Yes, even if not associated 
with a SAE 
For more information on AE and SAE definition and reporting requirements, please see the 
respective sections. 
10.2 
Additional safety monitoring 
10.2.1 
Liver safety monitoring 
There has been no safety signal for liver toxicity with secukinumab to date in 
approximately 13000 patients and healthy patients exposed, and from a mechanism of 
action standpoint there is no known effect of blocking IL-17a on the liver. Standard liver 
function tests will be obtained at regular intervals, but special measures for liver safety 
monitoring are not planned. For further information on standard liver function tests, see 
Appendix 1. 
10.2.2 
Renal safety monitoring 
There has been no safety signal for nephrotoxicity with secukinumab to date in 
approximately 13000 patients and healthy patients exposed, and from a mechanism of 
action standpoint there is no known effect of blocking IL-17a on the 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 

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tests (blood urea nitrogen, serum creatinine) will be obtained at regular intervals, but 
special measures for renal safety monitoring are not planned. 
11 
Data collection and database management 
11.1 
Data collection 
Data not requiring a separate written record will be defined in the protocol and the assessment 
schedule and can be recorded directly on the CRFs. All other data captured for this study will 
have an external originating source (either written or electronic) with the CRF not being 
considered as source. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation and verification. 
Designated investigator staff will enter the data required by the protocol into the eCRF. The 
eCRFs have been built using fully validated secure web-enabled software that conforms to 21 
CFR Part 11 requirements, Investigator site staff will not be given access to the electronic data 
capture (EDC) system until they have been trained. Automatic validation programs check for 
data discrepancies in the eCRFs allow modification and/or verification of the entered data by 
the investigator staff. 
The investigator/designee is responsible for assuring that the data (recorded on CRFs) 
(entered into eCRF) is complete, accurate, and that entry and updates are performed in a 
timely manner. The Investigator must certify that the data entered are complete and accurate. 
After final database lock, the investigator will receive copies of the patient data for archiving 
at the investigational site. 
11.2 
Database management and quality control 
Novartis personnel (or designated contract research organization (CRO)) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated 
investigator site staff are required to respond promptly to queries and to make any necessary 
changes to the data. 
Concomitant treatments and prior medications entered into the database will be coded using 
the WHO Drug Reference List, which employs the Anatomical Therapeutic Chemical (ATC) 
classification system. Medical history/current medical conditions and AEs will be coded using 
the Medical dictionary for regulatory activities (MedDRA) terminology. 
Randomization codes and data about all study treatment(s) and reference treatment dispensed 
to the patient and all dosage changes will be entered into the eCRF.  
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked. Any changes to the database after that time can only 
be made after written agreement by Novartis development management. 

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11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a 
Novartis/delegated CRO representative will review the protocol and data capture requirements 
(i.e. eCRFs) with the investigators and their staff. During the study, Novartis/sponsor employs 
several methods of ensuring protocol and GCP compliance and the quality/integrity of the 
sites’ data. The field monitor will visit the site to check the completeness of patient records, 
the accuracy of data capture / data entry, the adherence to the protocol and to GCP, the 
progress of enrollment, and to ensure that study treatment is being stored, dispensed, and 
accounted for according to specifications. Key study personnel must be available to assist the 
field monitor during these visits. Continuous remote monitoring of each site’s data may be 
performed by a centralized Novartis/delegated CRO organization. Additionally, a central 
analytics organization may analyze data & identify risks & trends for site operational 
parameters, and provide reports to Novartis/sponsor clinical teams to assist with trial 
oversight. 
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data and the results of any other tests or assessments. All information 
on CRFs must be traceable to these source documents in the patient’s file. The investigator 
must also keep the original ICF signed by the patient (a signed copy is given to the patient). 
The investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the data capture and/or data entry. Novartis/sponsor monitoring 
standards require full verification for the presence of informed consent, adherence to the 
inclusion/exclusion criteria, documentation of SAEs, and of data that will be used for all 
primary variables. Additional checks of the consistency of the source data with the CRFs are 
performed according to the study-specific monitoring plan. No information in source 
documents about the identity of the patients will be disclosed. 
12 
Data analysis and statistical methods 
The data will be analyzed by Novartis and/or a designated CRO. 
The analyses will be conducted on all patient data after data base lock for the trial. Any data 
analysis carried out independently by the investigator should be submitted to Novartis before 
publication or presentation. 
The primary analyses for all efficacy and safety endpoints will be carried out after the last 
patient completed Week 24 assessment. 
 
  
12.1 
Analysis sets 
The following analysis sets will be used in this trial: 
Randomized Analysis Set (RAS): The RAS is defined as all patients who were randomized. 
Unless otherwise specified, miss-randomized patients will be excluded from the RAS. 
Full Analysis Set (FAS): The FAS comprises all patients to whom study treatment/reference 
treatment has been assigned by randomization. According to the intent to treat principle, 

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patients will be analyzed according to the treatment they have been assigned to during the 
randomization procedure. 
Safety Set: The Safety Set includes all patients who received at least one dose of study 
treatment/reference treatment. Patients will be analyzed according to the study treatment 
received, where treatment received is defined as the randomized treatment if the patient took 
at least one dose of that treatment or the first treatment received if the randomized treatment 
was never received.  
12.2 
Patient demographics and other baseline characteristics 
Demographic and other Baseline data including disease characteristics will be listed and 
summarized descriptively by treatment group and in total for the FAS and Safety Set. 
Categorical data will be presented as frequencies and percentages. For continuous data, mean, 
standard deviation, median, minimum, and maximum will be presented.  
Relevant medical histories and current medical conditions at Baseline will be summarized by 
system organ class and preferred term (PT), and by treatment group. 
12.3 
Treatments 
The Safety Set will be used for the analyses below. Categorical data will be summarized as 
frequencies and percentages. For continuous data, mean, standard deviation, median, 25th and 
75th percentiles, minimum, and maximum will be presented. 
The duration of exposure to study treatment by treatment group will be summarized by means 
of descriptive statistics using the Safety Set. In addition, the number of patients with exposure 
of certain thresholds will be displayed. Compliance will be calculated based on documented 
study drug administrations and syringe counts and displayed by treatment group and study 
phase. 
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be listed and summarized according to the ATC classification system, by 
treatment group. Prior treatments are defined as treatments taken and stopped prior to first 
dose of study treatment. Any treatment given at least once between the day of first dose of 
randomized study treatment and the last day of study visit will be a concomitant treatment, 
including those which were started pre-Baseline and continued into the treatment period. 
Treatments will be presented in alphabetical order, by ATC codes and grouped by anatomical 
main group. Tables will also show the overall number and percentage of patients receiving at 
least one treatment of a particular ATC. 
12.4 
Analysis of the primary efficacy endpoint 
12.4.1 
Definition of primary endpoint 
The primary aim of the study is to demonstrate an advantage of an intensified secukinumab 
T2T approach, as measured by the proportion of patients achieving ASAS40 response, when 
compared to a SOC treatment regimen in patients with active axSpA inadequately responding 
to NSAID therapy. 

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The primary endpoint variable is the proportion of patients achieving treatment response as 
defined by the ASAS40 criteria at Week 24. 
The analysis of the primary variable will be based on the following: 
• Analysis set: FAS 
• Variable of interest: proportion of patients achieving treatment response as defined by the 
ASAS40 criteria at Week 24. 
• Intervention effect: effect between a secukinumab T2T dose escalation regime vs. a SOC 
treatment approach based upon investigator’s discretion regardless of adherence to 
randomized treatment. 
• Summary measure: Odds ratio (OR) 
12.4.2 
Statistical model, hypothesis, and method of analysis  
The null hypothesis to be rejected is that the odds of ASAS40 response at Week 24 are equal 
in both treatment groups. The corresponding alternative hypothesis is that the odds of 
response at Week 24 are higher under the secukinumab T2T approach compared to a SOC 
regimen. 
Let pj denote the proportion of ASAS40 responders at 24 weeks for treatment group j, j=0,1 
where 
• 0 corresponds to the SOC regimen 
• 1 corresponds to the secukinumab T2T regimen 
The following hypotheses will be tested: 
H0: (p1 / 1-p1)) / (p0 / 1-p0)) = 1 vs. HA: (p1 / 1-p1)) / (p0 / 1-p0)) ≠ 1 
In other words: 
HA: The OR of achieving an ASAS40 response at Week 24 for the comparison of 
secukinumab T2T vs. SOC is different from 1. 
The primary analysis will be performed comparing treatments with respect to the primary 
efficacy variable in a multiple logistic regression model with treatment and center as factors 
and weight as well as Baseline CRP level as covariates. The OR, the corresponding 95% 
confidence interval (CI) and the p-value will be given. The H0 of equal odds will be rejected 
if the 2-sided p-value from the logistic regression model for the factor “treatment” is < 0.05. 
The primary efficacy analysis will be based on the FAS. The primary analysis will be 
performed when all patients have completed the Week 24 assessment. 
12.4.3 
Handling of missing values/censoring/discontinuations  
Patients will be analyzed irrespective of adherence to assigned treatment regimen. Patients 
without a valid ASAS40 assessment at Week 24 will be regarded as non-responders for the 
primary analysis. Non-responder imputation will also be applied to all secondary response 
variables.  

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12.4.4 
Sensitivity and supportive analyses 
Sensitivity analyses 
Sensitivity analyses as well as supportive analyses will be conducted in order to provide 
evidence that the results seen from the primary model results are robust. These analyses will 
center on the deviations in model assumptions and the treatment of missing data. 
In case of substantial missing data in the primary analysis, alternative approaches will be 
assessed by repeating the logistic regression model using ways to handle missing values. 
These may include, but are not limited to: 
• Multiple imputation 
• Observed data analysis 
Supportive analyses 
Possible effect modification due to patient characteristics will be explored by subgroup 
analyses for sex, age class, disease severity and CRP blood level at Baseline. The primary 
model may also be recalculated with these factors included as well as with the respective 
terms for a subgroup*treatment interaction. 
12.5 
Analysis of secondary 
 endpoints 
The primary analysis will be performed when all patients have completed the Week 24 
assessment.  
12.5.1 
Analysis of secondary 
 efficacy endpoints 
ASAS20/40 response 
ASAS20/ ASAS40 response at Week 12, Week 24 
 will be evaluated using the 
multiple logistic regression model utilized for the primary efficacy variable.  
ASAS partial remission 
The proportion of patients meeting the ASAS definition for PR at Week 12, Week 24 
 
 will be analyzed by means of a multiple logistic regression model including 
treatment and center as factors and weight as covariate.  
AS disease activity score 
The proportion of patients meeting the ASDAS definition of inactive disease (< 1.3), ASDAS 
clinically important improvement (change in ASDAS ≥ 1.1) and ASDAS major improvement 
(change in ASDAS ≥ 2.0) as well as ASDAS low disease activity (< 2.1) at Week 12, Week 
24 
 will be evaluated using a multiple logistic regression model with treatment 
group and center as factors and weight and Baseline ASDAS as covariates. 
Furthermore, the between-treatment difference in change from Baseline in ASDAS will be 
evaluated using a mixed-effect model repeated measures (MMRM). Treatment group and 
analysis visit as factors and Baseline ASDAS index score and weight as continuous covariates 

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will be included in the model. Treatment group by analysis visit and Baseline ASDAS index 
score by analysis visit will be included as interaction terms in the model. An unstructured 
covariance matrix will be assumed. The treatment effect for the secukinumab T2T regimen at 
different analysis visits will be determined from the pairwise comparison performed between 
the 2 treatment groups. 
Bath ankylosing spondylitis disease activity index 
The proportion of patients achieving the BASDAI50 response criteria at Week 12, Week 24 
 will be analyzed by means of a multiple logistic regression model with 
treatment and center as factors and weight and Baseline BASDAI as covariates. 
Furthermore, the between-treatment difference in change from Baseline in BASDAI will be 
evaluated using a MMRM. Treatment group and analysis visit as factors and Baseline 
BASDAI score and weight as continuous covariates will be included in the model. Treatment 
group by analysis visit and Baseline BASDAI score by analysis visit will be included as 
interaction terms in the model. An unstructured covariance matrix will be assumed. The 
treatment effect for the secukinumab T2T regimen at different analysis visits will be 
determined from the pairwise comparison performed between the 2 treatment groups. 
Bath ankylosing spondylitis functional index 
The between-treatment difference in change from Baseline in BASFI will be evaluated using 
a MMRM. Treatment group and analysis visit as factors and Baseline BASFI score and 
weight as continuous covariates will be included in the model. Treatment group by analysis 
visit and Baseline BASFI score by analysis visit will be included as interaction terms in the 
model. An unstructured covariance matrix will be assumed. The treatment effect for the 
secukinumab T2T regimen at different analysis visits will be determined from the pairwise 
comparison performed between the 2 treatment groups. 
Bath ankylosing spondylitis metrology index and chest expansion 
The between-treatment difference in change from Baseline in BASMI will be evaluated using 
a MMRM. Treatment group and analysis visit as factors and Baseline BASMI score and 
weight as continuous covariates will be included in the model. Treatment group by analysis 
visit and Baseline BASMI score by analysis visit will be included as interaction terms in the 
model. An unstructured covariance matrix will be assumed. The treatment effect for the 
secukinumab T2T regimen at different analysis visits will be determined from the pairwise 
comparison performed between the 2 treatment groups. 
Change in patient’s global assessment of disease activity 
The between-treatment difference in change from Baseline in patient’s global disease 
assessment will be evaluated using a MMRM. Treatment group and analysis visit as factors 
and Baseline patient’s global disease assessment VAS score and weight as continuous 
covariates will be included in the model. Treatment group by analysis visit and Baseline 
patient’s global disease assessment VAS score by analysis visit will be included as interaction 
terms in the model. An unstructured covariance matrix will be assumed. The treatment effect 

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for the secukinumab T2T regimen at different analysis visits will be determined from the 
pairwise comparison performed between the 2 treatment groups. 
Change in ASDAS-CRP and ESR 
The between-treatment difference in change from Baseline in ASDAS-CRP and ASDAS-ESR 
will be evaluated using a MMRM. Treatment group and analysis visit as factors and Baseline 
ASDAS and weight as continuous covariates will be included in the model. Treatment group 
by analysis visit and Baseline ASDAS by analysis visit will be included as interaction terms 
in the model. An unstructured covariance matrix will be assumed. The treatment effect for the 
secukinumab T2T regimen at different analysis visits will be determined from the pairwise 
comparison performed between the 2 treatment groups. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12.5.2 
Analysis of secondary safety endpoints  
For all safety analyses, the Safety Set will be used. All listings and tables will be presented by 
treatment group. 
Safety summaries (tables, figures) will include only data from the on-treatment period with 
the exception of Baseline data, which will also be summarized where appropriate (e.g. change 
from Baseline summaries). In addition, a separate summary for death including on-treatment 
and post-treatment deaths will be provided. In particular, summary tables for AEs will 
summarize only on-treatment events, with a start date during the on-treatment period (i.e. 
treatment-emergent AEs as defined below).  
The on-treatment period lasts from the date of first administration of study treatment to 
30 days after the date of the last actual administration of any study treatment. 

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Adverse events 
All information obtained on AEs will be displayed by treatment group and patient. 
The number (and percentage) of patients with treatment-emergent AEs (defined as events 
started after the first dose of study medication or events present prior to start of study 
treatment but increased in severity based on PT) will be summarized in the following ways: 
• By treatment, primary system organ class and PT. 
• By treatment, primary system organ class, PT and maximum severity. 
• By treatment, standardized MedDRA query and PT. 
Separate summaries will be provided for study medication related AEs, death, SAEs, other 
significant AEs leading to discontinuation, AEs leading to dose adjustment and AE of special 
interest. 
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 (PT). Summaries will also be presented for AEs by severity and 
for study treatment related AEs. If a patient reported more than one AE with the same PT, the 
AE with the greatest severity will be presented. If a patient reported more than one AE within 
the same primary system organ class, the patient will be counted only once with the greatest 
severity at the system organ class level, where applicable. Serious adverse events will also be 
summarized. 
Vital signs 
All vital signs data will be listed by treatment group, patient, and visit/time, and if ranges are 
available, abnormalities will be flagged. 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 treatment group. 
Change from Baseline will only be summarized for patients with both Baseline and 
post-Baseline values. 
12.5.3 
Analysis of secondary 
 health-related quality of life 
endpoints 
Health-related quality of life assessments will be evaluated based on the FAS unless otherwise 
specified.  

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Short form-36 version 2 (acute form)  
The following variables will be evaluated: 
SF-36 domain scores, 
SF-36 PCS and MCS, 
SF-36 responder analyses 
For the change in SF-36 summary scores (PCS and MCS), between-treatment differences will 
be evaluated utilizing a MMRM. Treatment group and analysis visit will be included as 
categorical factors in the model and Baseline SF-36 score (PCS or MCS) and weight as 
continuous covariates. Treatment group by analysis visit and Baseline SF-36 score (PCS or 
MCS respectively) by analysis visit will be included as interaction terms in the model. An 
unstructured covariance matrix will be assumed. The treatment effect for the secukinumab 
T2T regimen at different analysis visits will be determined from the pairwise comparison 
performed between the 2 treatment groups. 
For the responder analyses the proportion of patients achieving a clinically meaningful 
difference in SF-36 summary score, PCS and MCS at week 24 will be analyzed by means of a 
multiple logistic regression model with treatment and center as factors and weight and 
Baseline ´score value as continuous covariates. 
Ankylosing spondylitis quality of life 
Between-treatment differences in the change from Baseline in the ASQoL will be evaluated 
using a MMRM with treatment group and analysis visit as factors as well as Baseline ASQoL 
score and weight as continuous covariates. Treatment group by analysis visit and Baseline 
ASQoL by analysis visit will be included as interaction terms in the model. An unstructured 
covariance matrix will be assumed. The treatment effect for the secukinumab T2T regimen at 
different analysis visits will be determined from the pairwise comparison performed between 
the 2 treatment groups. 
Functional assessment of chronic illness therapy – fatigue  
Between-treatment differences in the change from Baseline in the FACIT-Fatigue total score 
will be evaluated using a MMRM with treatment group and analysis visit as factors as well as 
Baseline FACIT-Fatigue score and weight as continuous covariates. Treatment group by 
analysis visit and Baseline FACIT-Fatigue score by analysis visit will be included as 
interaction terms in the model. An unstructured covariance matrix will be assumed. The 
treatment effect for the secukinumab T2T regimen at different analysis visits will be 
determined from the pairwise comparison performed between the 2 treatment groups. 
ASAS health index 
The between-treatment difference in change from baseline in ASAS-HI will be evaluated 
using a MMRM. Treatment group and analysis visit as factors and baseline ASAS-HI score 
and weight as continuous covariates will be included in the model. Treatment group by 
analysis visit and baseline ASAS-HI score by analysis visit will be included as interaction 
terms in the model. An unstructured covariance matrix will be assumed. The treatment effect 
for the secukinumab T2T regimen at different analysis visits will be determined from the 
pairwise comparison performed between the 2 treatment groups. 

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12.7 
Sample size calculation 
12.7.1 
Primary endpoint 
The sample size was calculated based on the primary efficacy variable ASAS40 response at 
Week 24 for the Full Analysis Set. Available data from the DESIR cohort (Molto et al 2014) 
and the DANBIO registry (Glintborg et al 2017) showed an ASAS40 response of 30% in 
TNFα inhibitor naïve axSpA patients, that were treated with common biological DMARDs.  
Data from MEASURE 2/MEASURE 3 trials (Sieper et al 2017, Pavelka et al 2017) showed 
an ASAS40 response of 43.2% and 43.9% at Week 16, while approximately 50% of patients 
did not achieve an ASDAS clinically important improvement (defined as change from BL of 
≥ 1.1) criterion at Week 12. Taking into account the longer duration of active treatment with 
secukinumab 150 mg and the substantial proportion of patients that will be escalated to 
300 mg, it is justifiable to conservatively assume an ASAS40 response of 50% at Week 24. 
With an ASAS40 response of 50% for the secukinumab 150 mg/300 mg arm and a 30% 
response in the SOC arm at Week 24 (corresponding to an OR of 2.3), 134 patients per 
treatment arm are required to achieve a power of 90% to demonstrate superiority at a 
significance level of 0.05 using the 2-group continuity corrected χ² test of equal proportions. 

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In order to account for some uncertainties in the underlying assumptions and to compensate 
for some expected dropout and protocol violations, a total of 300 patients (150 patients in the 
T2T and 150 patients in the SOC arm) should be randomized into this study.  
An IA will be conducted to evaluate and possibly adapt the sample size calculated in order to 
show superiority in the primary efficacy endpoint. 
Through an IA sample size adaption would be possible in case the assumed number of 
patients is not enough or is too high. Results from a sample size simulation using the above 
mentioned response values as well as the parameters for the two-stage adaptive design 
resulted in the assumption of a maximum of 400 patients spanning over the two study stages.  
13 
Ethical considerations and administrative procedures  
13.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in 
accordance with the ICH Harmonized Tripartite Guidelines for GCP, with applicable local 
regulations (including European Directive 2001/20/EC), and with the ethical principles laid 
down in the Declaration of Helsinki. 
13.2 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion 
from the IRB/IEC for the trial protocol, written ICF, consent form updates, patient recruitment 
procedures (e.g. advertisements) and any other written information to be provided to patients. 
Prior to study start, the investigator is required to sign a protocol signature page confirming 
his/her agreement to conduct the study in accordance with these documents and all of the 
instructions and procedures found in this protocol and to give access to all relevant data and 
records to Novartis monitors, auditors, Novartis Quality Assurance representatives, designated 
agents of Novartis, IRBs/IECs, and regulatory authorities as required. If an inspection of the 
clinical site is requested by a regulatory authority, the investigator must inform Novartis 
immediately that this request has been made. 
13.3 
Publication of study protocol and results 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required in EudraCT. In addition, after study completion and finalization of the study report 
the results of this trial will be submitted for publication and posted in a publicly accessible 
database of clinical trial results, such as the Novartis clinical trial results website and all 
required Health Authority websites (e.g. Clinicaltrials.gov, EudraCT etc.). 
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the trial 
investigator meetings. 

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13.4 
Quality control and quality assurance 
Novartis maintains a robust Quality Management System that includes all activities involved 
in quality assurance and quality control, to ensure compliance with written Standard 
Operating Procedures as well as applicable global/local GCP regulations and ICH Guidelines. 
Audits of investigator sites, vendors, and Novartis/sponsor systems are performed by auditors, 
independent from those involved in conducting, monitoring or performing quality control of 
the clinical trial. The clinical audit process uses a knowledge/risk based approach. 
Audits are conducted to assess GCP compliance with global and local regulatory 
requirements, protocols and internal standard operating procedures, and are performed 
according to written Novartis/sponsor processes. 
14 
Protocol adherence 
This protocol defines the study objectives, the study procedures, and the data to be collected 
on study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case-by-case basis. Under no circumstances including 
incidental collection is an investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the investigator shall immediately disclose it to 
Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be 
implemented. 
14.1 
Protocol Amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. 
Only amendments that are required for patient safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis 
should be notified of this action and the IRB/IEC at the study site should be informed 
according to local regulations. 

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15 
References 
References are available upon request 
Baeten D, Sieper J, Braun J, et al (2015) Secukinumab, an Interleukin-17A Inhibitor, in 
Ankylosing Spondylitis. N Engl J Med; 373(26):2534-48 
Bennett and Burch (1968) The epidemiological diagnosis of ankylosing spondylitis. Book: 
Population studies of rheumatic diseases; pp:305-313. 
Braun J, Baraliakos X, Deodhar A, et al (2017) Effect of secukinumab on clinical and 
radiographic outcomes in ankylosing spondylitis: 2-year results from the randomised phase III 
MEASURE 1 study. Ann Rheum Dis;76(6):1070-1077.  
Cella DF, Tulsky DS, Gray G, et al (1993) The Functional Assessment of Cancer Therapy 
scale: Development and validation of the general measure. Journal of Clinical Oncology; 
11(3):570-9 
Deodhar A, Conaghan PG, Kvien TK, et al (2018) Secukinumab provides rapid and persistent 
relief in pain and fatigue symptoms in patients with ankylosing spondylitis irrespective of 
baseline C-reactive protein levels or prior tumour necrosis factor inhibitor therapy: 2-year data 
from the MEASURE 2 study. Clin Exp Rheumatol; 37(2):260-269. 
Gladman DD, Mease PJ, Strand V, et al (2007) Consensus on a core set of domains for 
Psoriatic Arthritis. J Rheumatol; 34:1167-70. 
Glintborg B, Sørensen I, Ostergaard M, et al (2017) Ankylosing Spondylitis versus 
Nonradiographic Axial Spondyloarthritis: Comparison of Tumor Necrosis Factor Inhibitor 
Effectiveness and Effect of HLA-B27 Status. An Observational Cohort Study from the 
Nationwide DANBIO Registry. J Rheumatol;44 (1);59-69 
Heuft-Dorenbosch L, Spoorenberg A, van Tubergen A, et al (2003) Assessment of enthesitis 
in ankylosing spondylitis. Ann Rheum Dis; 62:127-132. 
Humira SmPC (2016) London: EMA. 
Kiltz U, van der Heijde D, Boonen A, et al (2014) The ASAS Health Index (ASAS HI) - a 
new tool to assess the health status of patients with spondyloarthritis. Clin Exp Rheumatol; 
32(5 Suppl 85):S-105-8 
Kiltz U, van der Heijde D, Boonen A, et al (2016) Measuring impairments of functioning and 
health in patients with axial spondyloarthritis by using the ASAS Health Index and the 
Environmental Item Set: translation and cross-cultural adaptation into 15 languages. RMD 
Open 2016;2:e000311. doi:10.1136/rmdopen-2016-000311. 
Lukas C, Landewé R, Sieper J (2009) Development of an ASAS-endorsed disease activity 
score (ASDAS) in patients with ankylosing spondylitis. Ann Rheum Dis; 68(1):18-24. 
Machado PM, Landewé RB, van der Heijde DM (2011) Endorsement of definitions of disease 
activity states and improvement scores for the Ankylosing Spondylitis Disease Activity Score: 
results from OMERACT 10. J Rheum; 38(7):1502-06 

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Machado PM, Landewé RB, van der Heijde DM (2018) Ankylosing Spondylitis Disease 
Activity Score (ASDAS): 2018 update of the nomenclature for disease activity states. Ann 
Rheum Dis;77(10):1539-1540 
Maksymowych W, Strand V, Nash P, et al (2017) Comparative Effectiveness of Secukinumab 
and Adalimumab in Ankylosing Spondylitis as Assessed by Matching-Adjusted Indirect 
Comparison: An Analysis Based on All Pivotal Phase 3 Clinical Trial Data. Value in Health; 
20(9):A935 
McHorney CA, Ware JE, Raczek AE (1993) The MOS 36-Item Short-Form Health Survey 
(SF-36). Medical Care; 31: 247-63 
Moltó A, Paternotte S, Claudepierre P, et al (2014) Effectiveness of tumor necrosis factor α 
blockers in early axial spondyloarthritis: data from the DESIR cohort. Arthritis & 
Rheumatology;66(7):1734-44 
Pavelka K, Kivitz AJ, Blanco R, et al (2017) Secukinumab Provides Sustained Improvements 
in the Signs and Symptoms of Active Ankylosing Spondylitis: 2-Year Results from a Phase 3 
Study. Abstract ID: 1828, ACR congress 2017 
Poddubnyy D and Sieper J (2014) Similarities and differences between nonradiographic and 
radiographic axial spondyloarthritis: a clinical epidemiological and therapeutic assessment. 
Curr Opin Rheumatol;26(4):377-83 
Sieper J, Rudwaleit M, Baraliakos X, et al (2009) The Assessment of SpondyloArthritis 
international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis.; 
68 Suppl 2:ii1-44 
Sieper J, van der Heijde D, Dougados M, et al (2013) Efficacy and safety of adalimumab in 
patients with non-radiographic axial spondyloarthritis: results of a randomised placebo 
controlled trial (ABILITY-1). Ann Rheum Dis;72(6):815-22 
Sieper J, Deodhar A, Marzo-Ortega H, et al (2017) Secukinumab efficacy in anti-TNF-naïve 
and anti-TNF-experienced subjects with active ankylosing spondylitis: results from the 
MEASURE 2 study. Ann Rhen Dis; 76(3):571-592 
Smolen J, Schols M, Braun J, et al (2018) Treating axial spondyloarthritis and peripheral 
spondyloarthritis, especially psoriatic arthritis, to target: 2017 update of recommendations by 
an international task force. Ann Rheum Dis;77(1):3-17 
van der Heijde D, Kivitz A, Schiff MH, et al (2006) Efficacy and safety of adalimumab in 
patients with ankylosing spondylitis: results of a multicenter, randomized, double-blind, 
placebo-controlled trial. Arthritis Rheum; 54(7):2136-46 
van der Heijde D, Ramiro S, Landewe R, et al (2017) 2016 update of the ASAS-EULAR 
management recommendations for axial spondyloarthritis. Ann Rheum Dis;76(6):978-991 
 
van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of the diagnostic criteria for 
ankylosing spondylitis - A proposal for modification of the New York criteria. Arthritis 
Rheum; 27:361-8. 

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Ware JE and Sherbourne CD (1992) The MOS 36-Item Short-Form Health Survey (SF- 36). 
Medical Care; 30:473-83 
Yellen SB, Cella DF, Webster K, et al (1997) Measuring fatigue and other anemia-related 
symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system. J 
Pain Symptom Manage; 13:63-74 

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16 
Appendices 
16.1 
Appendix 1: Clinically notable laboratory values 
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. 
Clinically notable values will be forwarded to Novartis/CRO at the same time that they are 
sent to investigators. Any action based on these laboratory values should be discussed with 
Novartis/CRO personnel. 
Table 16-1 
Safety analyses: expanded limits and notable criteria 
 
Final Harmonization 
Laboratory Variable 
Notable Criteria 
Standard Units 
SI Units 
LIVER FUNCTION AND RELATED VARIABLES 
SGOT (AST) 
> 3 x ULN 
> 3 x ULN 
SGPT (ALT) 
> 3 x ULN 
> 3 x ULN 
GGT 
 
 
Bilirubin 
> 2 x ULN 
> 2 x ULN 
Alkaline phosphatase 
> 2.5 x ULN 
> 2.5 x ULN 
RENAL FUNCTION, METABOLIC AND ELECTROLYTE VARIABLES 
Creatinine (serum) 
> 2 x ULN 
> 2 x ULN 

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16.2 
Appendix 2: Assessment of spondyloarthritis international 
society criteria for axial spondyloarthritis 
ASAS criteria for classification of axSpA will be applied as defined by Sieper et al (2009). 
Diagnosis of axial spondyloarthritis according to the assessment of 
spondyloarthritis international society classification criteria 
Diagnosis of axSpA (either AS or nr-axSpA) according to ASAS axSpA classification criteria 
to be applied in patients with back pain for at least 3 months and age of onset < 45 years: 
• Sacroiliitis on imaging with ≥ 1 SpA feature or 
• HLA-B27 positive with ≥ 2 SpA features 
Sacroiliitis on imaging 
• Active (acute) inflammation on MRI highly suggestive of sacroiliitis associated with SpA 
(see Appendix 6) 
• Definite radiographic sacroiliitis according to the modified New York diagnostic criteria 
(van der Linden et al 1984) (see Appendix 5) 
Spondyloarthritis features 
• Inflammatory back pain 
• Arthritis 
• Enthesitis (heel) 
• Uveitis 
• Dactylitis 
• Psoriasis 
• Crohn’s disease or colitis 
• Good response to NSAIDs 
• Family history for SpA 
• HLA-B27 
• Elevated CRP 
 
Source: Sieper J, Rudwaleit M, Baraliakos X, et al (2009) The Assessment of 
SpondyloArthritis international Society (ASAS) handbook: a guide to assess 
spondyloarthritis. Ann Rheum Dis.; 68 Suppl 2:ii1-44 
 

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16.3 
Appendix 3: Modified New York diagnostic criteria for ankylosing 
spondylitis 
Patients with axSpA are classified as having AS, based on the fulfillment of the 1984 
modified New York diagnostic criteria (van der Linden et al 1984). 
Clinical criteria for ankylosing spondylitis 
• Low back pain and stiffness for more than 3 months that improves with exercise, but is not 
relieved by rest 
• Limitation of motion of the lumbar spine in the sagittal and frontal planes 
• Limitation of chest expansion relative to normal values correlated for age and sex 
Radiological criterion for ankylosing spondylitis 
• Sacroiliitis grade ≥ 2 bilaterally or grade 3–4 unilaterally 
Definite AS if the radiological criterion is associated with at least one clinical criterion. 
 
Source: van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of the diagnostic criteria 
for ankylosing spondylitis - A proposal for modification of the New York criteria. Arthritis 
Rheum; 27:361-8. 
 

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16.4 
Appendix 4: Definition of sacroiliitis on imaging 
Sacroiliitis on magnetic resonance imaging 
An MRI will be considered positive for sacroiliitis (active inflammatory lesions, “positive 
MRI”, MRI+) if the following characteristics are evident (Sieper et al 2009): 
• The presence of definite subchondral bone marrow edema/osteitis highly suggestive of 
sacroiliitis is mandatory 
• The presence of synovitis, capsulitis, or enthesitis only without concomitant subchondral 
bone marrow edema/osteitis is compatible with sacroiliitis but not sufficient for making a 
diagnosis of active sacroiliitis 
• Amount of signal required: if there is one signal (lesion) only, this should be present on at 
least two slices. If there is more than one signal on a single slice, one slice may be enough 
Sacroiliitis on X-ray 
Grading of radiographic sacroiliitis according to the New York diagnostic criteria 
(Bennett and Burch 1968): 
• Grade 0: normal 
• Grade 1: suspicious changes 
• Grade 2: minimal abnormality (small localized areas with erosion or sclerosis, without 
alteration in the joint width) 
• Grade 3: unequivocal abnormality - (moderate or advanced sacroiliitis with erosions, 
evidence of sclerosis, widening, narrowing, or partial ankylosis 
• Grade 4: severe abnormality (total ankylosis) 
 
Sources:  
Bennett and Burch (1968) The epidemiological diagnosis of ankylosing spondylitis. Book: 
Population studies of rheumatic diseaseas, pp. 305-313 
Sieper J, Rudwaleit M, Baraliakos X, et al (2009) The Assessment of SpondyloArthritis 
international Society (ASAS) handbook: a guide to assess spondyloarthritis. Ann Rheum Dis.; 
68 Suppl 2:ii1-44 

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16.5 
Appendix 5: Bath Ankylosing Spondylitis Disease Activity Index  
The BASDAI consists of a 0 through 10 scale (0 being no problem and 10 being the worst 
problem, captured as a continuous VAS), which is used to answer 6 questions pertaining to 
the 5 major symptoms of AS: 
1. How would you describe the overall level of fatigue/tiredness you have experienced? 
2. How would you describe the overall level of AS neck, back or hip pain you have had? 
3. How would you describe the overall level of pain/swelling in joints other than neck, back, 
hips you have had? 
4. How would you describe the overall level of discomfort you have had from any areas 
tender to touch or pressure? 
5. How would you describe the overall level of morning stiffness you have had from the 
time you wake up? 
6. How long does your morning stiffness last from the time you wake up? 
To give each symptom equal weighting, the mean (average) of the two scores relating to 
morning stiffness (questions 5 and 6) is taken. The mean of questions 5 and 6 is added to the 
scores from questions 1-4. The resulting 0 to 50 score is divided by 5 to give a final 0 – 10 
BASDAI score. Scores of 4 or greater suggest suboptimal control of disease, and subjects 
with scores of 4 or greater are usually good candidates for either a change in their medical 
therapy or for enrollment in clinical trials evaluating new drug therapies directed at 
Ankylosing Spondylitis. BASDAI is a quick and simple index (taking between 30 seconds 
and 2 minutes to complete). 

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16.6 
Appendix 6: Bath Ankylosing Spondylitis Metrology Index  
Cervical rotation 
Cervical rotation is measured twice with the subject supine on plinth, head in neutral position, 
forehead horizontal (if necessary, with the head on a pillow or foam block, which must be 
documented for future reassessments). A goniometer (preferably a gravity goniometer) is 
placed centrally on the forehead. Subject rotates head as far as possible to the right, keeping 
shoulders still; ensure no neck flexion or side flexion occurs. The angle between the sagittal 
plane and the new plane after rotation is recorded. The higher reading of two assessments is 
recorded in degrees. The same procedure is repeated twice for the left side. Record the mean 
of the higher reading from the right side and the higher reading from the left side. 
Tragus to wall distance 
Tragus to wall distance is measured twice with the subject’s heels and back rested against the 
wall. The chin should be at usual carrying level and the subject takes maximal effort to touch 
the head against the wall. The distance between the tragus and the wall is assessed on each 
side, and an average of the two distances from each side is calculated. The procedure is 
repeated, and the shorter of the two average assessments is reported. 
Spinal lateral flexion (lumbar lateral flexion) 
Subject stands with heels and buttocks touching the wall, knees straight, shoulders back, and 
hands by the side. The subject bends to the right side as far as possible, without lifting the left 
foot/heel or flexing the right knee and maintaining a straight posture with heels, buttocks, and 
shoulders against the wall. The distance from the third fingertip to the floor when subject 
bends to the side is subtracted from the distance when subject stands upright. The higher of 
two tries is recorded. The maneuver is repeated on the left side. Record the mean of the larger 
difference from the right side and the larger difference from the left side.  
Lumbar flexion (modified Schoeber index) 
Subject is standing erect. Set marks in upright position 5 cm below and 10 cm above 
lumbosacral junction (spinal section of a line joining the dimples of Venus). Measure the 
difference between the distance between marks in a standing position (15 cm) vs. a forward 
flexed position when the subject bends forward as far as possible, keeping the knees straight. 
The procedure is repeated, and the higher difference of the two tries is reported. 
Maximal intermalleolar distance 
Subject is lying down with the legs separated as far as possible with knees straight and toes 
pointing upwards. Alternatively, the subject stands and separates the legs as far as possible. 
Distance between medial malleoli is measured, and the higher of the two readings is recorded. 

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Chest expansion 
Chest expansion is measured with the subject’s hands resting on or behind the head. The 
measurement is taken at the fourth intercostal level anteriorly. The difference between 
maximal inspiration and expiration in cm (to the nearest 0.1 cm) is recorded twice, and the 
higher difference of the two tries is reported. 
Occiput-to-wall distance 
Occiput to wall distance is measured twice with the subject’s heels and back rested against the 
wall. The chin should be at usual carrying level, and the subject takes maximal effort to touch 
the head against the wall. The distance between the occiput and the wall is assessed, and the 
shorter of the two readings is reported. 

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16.7 
Appendix 7: Guidelines for administering the questionnaires for 
patient reported outcomes 
Before study start 
Study coordinators should familiarize themselves with the PRO questionnaire(s) in the study 
and identify any items where a patient’s response might highlight issues of potential concern. 
For example, one question in the SF-36 asks ‘How much of the time in the past 4 weeks- have 
you felt downhearted and blue?’ If a patient responds ‘most or all of the time’, then the study 
coordinator should inform the study investigator. 
Before completion 
1. Subjects should be provided with the correct questionnaire at the appropriate visits and in 
the appropriate language 
2. Subjects should have adequate space and time to complete the forms 
3. Questionnaire should be administered before the clinical examination 
During completion 
1. Administrator may clarify the questions but should not influence the response 
2. Only one response for each question 
3. Also see “Addressing Problems and Concerns” 
After completion 
1. Check for completeness and not for content* 
2. Check for multiple responses that were made in error 
*However, any response which may directly impact or reflect the patient’s medical condition 
(e.g. noting of depression) should be communicated by the study coordinator to the 
investigator). 
Addressing problems and concerns 
Occasionally a patient may have concerns or questions about the questionnaires administered. 
Guidance related to some of the most common concerns and questions are given below. 
The patient does not want to complete the questionnaire(s) 
Tell the patient that completion of the questionnaire(s) is voluntary. The goal is to better 
understand the physical, mental and social health problems of patients. Emphasize that such 
information is as important as any other medical information and that the questionnaire(s) is 
simple to complete. Suggest that the questionnaire(s) may be different from anything the 
respondent has filled in the past. If the patient still declines, retrieve the questionnaires. 
Record the reason for the decline and thank the patient. 

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The patient is too ill or weak to complete the questionnaire(s) 
In these instances, the coordinator may obtain patient responses by reading out loud each 
question, followed by the corresponding response categories, and entering the patient’s 
response. No help should be provided to the patient by any person other than the designated 
study coordinator. The coordinator should not influence patient responses. The study 
coordinator cannot translate the question into simpler language and has to be read verbatim. 
The patient wants someone else to complete the questionnaire(s) 
In no case should the coordinator or anyone other than the patient provide responses to the 
questions. Unless specified in the study protocol, proxy data are not an acceptable substitute 
for patient self-report. Patients should be discouraged from asking a family member or friend 
for help in completing a questionnaire. 
The patient does not want to finish completing the questionnaire(s) 
If non-completion is a result of the patient having trouble understanding particular items, ask 
the patient to explain the difficulty. Re-read the question for them verbatim but do not 
rephrase the question. If the respondent is still unable to complete the questionnaire, accept it 
as incomplete. Thank the patient. 
The patient is concerned that someone will look at his/her responses 
Emphasize that all responses are to be kept confidential. Point out that their names do not 
appear anywhere on the questionnaire, so that their results will be linked with an ID number 
and not their name. Tell the patient that his/her answers will be pooled with other patients’ 
answers and that they will be analyzed as a group rather than as individuals. Tell the patient 
that completed forms are not routinely shared with treating staff and that their responses will 
only be seen by you (to check for completeness) and by the investigator. Any response which 
may directly impact on or reflect their medical condition (e.g. noting of severe depression) 
will be communicated by the coordinator to the physician. 
The patient asks the meaning of a question/item 
While completing the questionnaire, some patients might ask the meaning of specific items so 
that they can better understand and respond. If this happens, assist the patient by rereading the 
question for them verbatim. If the patient asks to interpret the meaning of an item, do not try 
to explain it, but suggest that he/she use his/her own interpretation of the question. Patients 
should answer the questions based on what they think the questions mean. 
General information about all questionnaire(s): 
All questionnaires have to be completed by the patients in their local languages. 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 

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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 PRO 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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16.9 
Appendix 10: Environmental factors related to ASAS Health 
Index