A Randomized, Double-blind, Placebo Controlled, Multicenter, Phase III Study of Subcutaneous Secukinumab to Compare Efficacy at 16 Weeks With Placebo and to Assess Safety and Tolerability up to 52 Weeks in Chinese Participants With Active Non-radiographic Axial Spondyloarthritis
Phase: PHASE3
Conditions: Non-radiographic Axial Spondyloarthritis
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development 
AIN457 
Clinical Trial Protocol CAIN457I2301 / NCT04732117
A randomized, double-blind, placebo controlled, 
multicenter，phase III study of subcutaneous secukinumab 
to compare efficacy at 16 weeks with placebo and to 
assess safety and tolerability up to 52 weeks in Chinese 
participants with active non-radiographic axial 
spondyloarthritis. 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
Not Applicable 
Version number: 
00 (Original Protocol) 
Clinical Trial Phase: 
III 
Release date: 
16-Nov-2020 (content final)
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 3.0 dated 31-Jan-2020 

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Table of contents 
Table of contents .................................................................................................................. 2 
List of tables ......................................................................................................................... 6 
List of figures ....................................................................................................................... 6 
List of abbreviations ............................................................................................................. 7 
Glossary of terms ............................................................................................................... 10 
Protocol summary .............................................................................................................. 12 
1 
Introduction ........................................................................................................................ 16 
1.1 
Background ............................................................................................................ 16 
1.2 
Purpose ................................................................................................................... 17 
2 
Objectives and endpoints ................................................................................................... 18 
2.1 
Primary estimands .................................................................................................. 20 
2.2 
Secondary estimands .............................................................................................. 21 
3 
Study design ....................................................................................................................... 22 
4 
Rationale ............................................................................................................................ 23 
4.1 
Rationale for study design ...................................................................................... 23 
4.1.1 
Rationale for choice of background therapy .......................................... 24 
4.2 
Rationale for dose/regimen and duration of treatment ........................................... 24 
4.3 
Rationale for choice of control drugs (comparator/placebo) or combination 
drugs ....................................................................................................................... 25 
4.4 
Purpose and timing of primary analyses/design adaptations .................................. 25 
4.5 
Risks and benefits .................................................................................................. 25 
5 
Study Population ................................................................................................................ 26 
5.1 
Inclusion criteria ..................................................................................................... 27 
5.2 
Exclusion criteria ................................................................................................... 28 
6 
Treatment ........................................................................................................................... 31 
6.1 
Study treatment ...................................................................................................... 31 
6.1.1 
Investigational and control drugs ........................................................... 31 
6.1.2 
Additional study treatments ................................................................... 32 
6.1.3 
Treatment arms/group ............................................................................ 32 
6.1.4 
Treatment duration ................................................................................ 32 
6.2 
Other treatments ..................................................................................................... 33 
6.2.1 
Concomitant therapy.............................................................................. 33 
6.2.2 
Prohibited medication ............................................................................ 34 
6.2.3 
Escape Medication ................................................................................. 35 
6.3 
Participant numbering, treatment assignment, randomization ............................... 36 
6.3.1 
Participant numbering ........................................................................... 36 

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8.4.5 
QuantiFERON TB-Gold test or PPD skin test ...................................... 56 
 
 57 
8.4.7 
Local tolerability (Injection site reactions) ............................................ 57 
8.4.8 
Tolerability of secukinumab .................................................................. 57 
8.4.9 
Appropriateness of safety measurements .............................................. 57 
8.5 
Additional assessments .......................................................................................... 57 
8.5.1 
Clinical Outcome Assessments (COAs) ................................................ 58 
 
 59 
 
 60 
 
 61 
8.5.5 
HLA-B27 ............................................................................................... 61 
8.5.6 
X-ray of the sacroiliac joints ................................................................. 61 
9 
Study discontinuation and completion ............................................................................... 61 
9.1 
Discontinuation and completion ............................................................................ 61 
9.1.1 
Study treatment discontinuation and study discontinuation .................. 61 
9.1.2 
Withdrawal of informed consent ........................................................... 63 
9.1.3 
Lost to follow-up ................................................................................... 63 
9.1.4 
Early study termination by the sponsor ................................................. 64 
9.2 
Study completion and post-study treatment ........................................................... 64 
10 Safety monitoring and reporting ........................................................................................ 65 
10.1 
Definition of adverse events and reporting requirements ...................................... 65 
10.1.1 
Adverse events ....................................................................................... 65 
10.1.2 
Serious adverse events ........................................................................... 66 
10.1.3 
SAE reporting ........................................................................................ 67 
10.1.4 
Pregnancy reporting ............................................................................... 68 
10.1.5 
Reporting of study treatment errors including misuse/abuse ................. 69 
10.2 
Additional Safety Monitoring ................................................................................ 69 
10.2.1 
Liver safety monitoring ......................................................................... 69 
10.2.2 
Renal safety monitoring......................................................................... 69 
11 Data Collection and Database management ....................................................................... 70 
11.1 
Data collection ....................................................................................................... 70 
11.2 
Database management and quality control ............................................................ 70 
11.3 
Site monitoring ....................................................................................................... 71 
12 Data analysis and statistical methods ................................................................................. 71 
12.1 
Analysis sets ........................................................................................................... 72 
12.2 
Participant demographics and other baseline characteristics ................................. 72 
12.3 
Treatments .............................................................................................................. 73 

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12.4 
Analysis of the primary endpoints/estimands ......................................................... 74 
12.4.1 
Definition of primary endpoints/estimands ........................................... 74 
12.4.2 
Statistical model, hypothesis, and method of analysis .......................... 74 
12.4.3 
Handling of missing values/censoring/discontinuations ........................ 74 
12.4.4 
Sensitivity analyses for primary endpoint/estimand .............................. 75 
12.4.5 
Supplementary analysis ......................................................................... 75 
12.5 
Analysis of secondary endpoints/estimands ........................................................... 76 
12.5.1 
Efficacy and/or Pharmacodynamic endpoints ....................................... 76 
12.5.2 
Safety endpoints .................................................................................... 77 
 
 79 
 
 79 
12.5.5 
Patient reported outcomes ..................................................................... 79 
 
 80 
12.7 
Interim analyses ..................................................................................................... 82 
12.8 
Sample size calculation .......................................................................................... 82 
12.8.1 
Primary endpoints .................................................................................. 82 
12.9 
Primary endpoint analysis ...................................................................................... 83 
13 Ethical considerations and administrative procedures ....................................................... 83 
13.1 
Regulatory and ethical compliance ........................................................................ 83 
13.2 
Responsibilities of the investigator and IRB/IEC .................................................. 83 
13.3 
Publication of study protocol and results ............................................................... 84 
13.4 
Quality Control and Quality Assurance ................................................................. 84 
14 Protocol adherence ............................................................................................................. 84 
14.1 
Protocol amendments ............................................................................................. 85 
15 References .......................................................................................................................... 86 
16 Appendices ......................................................................................................................... 90 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs ......................... 90 
16.2 
Blood collection log ............................................................................................... 91 
16.3 
Modified New York criteria ................................................................................... 91 
16.4 
ASAS Classification Criteria for Axial Spondyloarthritis (axSpA) ...................... 92 
16.5 
Assessment of SpondyloArthritis International Society criteria (ASAS) .............. 92 
16.5.1 
Bath Ankylosing Spondylitis Functional Index (BASFI) ...................... 92 
16.5.2 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ......... 92 
 
 93 
16.6 
Definition of Sacroiliitis on MRI ........................................................................... 94 
 
 94 
16.8 
Guidelines for administering the questionnaires for patient reported outcomes .... 95 

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16.9 
Guidance of Study management during potential future pandemic/epidemic ....... 97 
 
List of tables 
Table 2-1 
Objectives and related endpoints ........................................................... 18 
Table 6-1 
Investigational and control drug ............................................................ 31 
Table 6-2 
Prohibited medication ............................................................................ 34 
Table 6-3 
Blinding Level ....................................................................................... 38 
Table 8-1 
Assessment Schedule............................................................................. 44 
Table 8-2 
Safety and tolerabilityassessments ......................................................... 54 
Table 8-3 
Clinical Laboratory Assessments .......................................................... 55 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse .......................................................................................... 69 
Table 12-1 
Probability of Success with Different Observed Response Rates of 
ASAS40 in TNF-α naïve participants .................................................... 83 
Table 16-1 
Safety Analyses: Expanded Limits and Notable Criteria ...................... 90 
 91 
 
91 
 91 
List of figures 
Figure 3-1 
Study Design ......................................................................................... 23 

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List of abbreviations 
 
ACR 
American College of Rheumatology 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
ANCOVA 
Analysis of covariance 
AS 
Ankylosing Spondylitis 
ASAS 
Ankylosing SpondyloArthritis International Society 
ASDAS 
Ankylosing Spondylitis Disease Activity Score 
ASDAS-MI 
Ankylosing Spondylitis Disease Activity Score-Major Improvement 
ASQoL 
Ankylosing Spondylitis Quality of Life 
AST 
Aspartate Aminotransferase 
ATC 
Anatomical Therapeutic Classification 
axSpA 
Axial Spondyloarthritis 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
BASFI 
Bath Ankylosing Spondylitis Functional Index 
 
 
bDMARDs 
biologic disease-modifying anti-rheumatic drugs 
BMI 
Body Mass Index 
BSL 
Baseline 
BUN 
Blood Urea Nitrogen 
CFR 
Code of Federal Regulation 
CI 
Confidence Interval 
CMO&PS 
Chief Medical Office and Patient Safety 
COA 
Clinical Outcome Assessment 
COVID-19 
Coronaviruses 2019 
COX 
Cyclooxygenase 
CRA 
Clinical Research Associate 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CRP (hsCRP) 
(high sensitivity) C-reactive protein 
CRP+ 
Patient with a CRP value above the ULN at screening 
csDMARDs 
(conventional synthetic) Disease Modifying Anti-Rheumatic Drugs 
CSR 
Clinical Study Report 
CT 
Computed Tomography 
CXCL 
Chemokine (C–X–C motif) ligand 
DDE 
Detailed Design Enhancement 
DMARD 
Disease modifying anti-rheumatic drug 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
EDD 
Expected Delivery Date 
ELISA 
Enzyme-linked immuno sorbent assay 
EMA/EMEA 
European Medical Agency 
EOS 
End of Study 
EOT 
End of Treatment 
eSource 
Electronic Source 

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EU 
European Union 
EULAR 
European League Against Rheumatism 
FAS 
Full analysis set 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
h 
Hour 
hCG 
Human Chorionic Gonadotropin 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
hsCRP 
(high sensitivity) C-Reactive Protein 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
IEC 
Independent Ethics Committee 
IFU 
Instructions for Use 
IgG 
Immunoglobulin G 
IL 
Interleukin 
IN 
Investigator Notification 
IRB 
Institutional Review Board 
IRT 
Interactive Response Technology 
IUD 
Intrauterine Device 
IUS 
Intrauterine System 
LDH 
lactate dehydrogenase 
LLN 
Lower limit of normal 
LLOQ 
Lower limit of quantification 
LOCF 
Last observation carried forward 
MAR 
Missing at Random 
 
 
MCH 
Mean Corpuscular Hemoglobin 
MCHC 
Mean Corpuscular Hemoglobin Concentration 
MCV 
Mean Corpuscular Volume 
MedDRA 
Medical dictionary for regulatory activities 
MMRM 
Mixed-effects model repeated measures 
MRI 
Magnetic resonance imaging 
MRI+ 
Patient with a MRI considered positive for sacroiliitis at screening 
MTX 
Methotrexate 
NDA 
New Drug Application 
NMPA 
National Medical Products Administration 
nr-axSpA 
Non-radiographic axial spondyloarthritis 
NSAID 
Non-steroidal anti-inflammatory drug 
PCS 
Physical Component Summary 
PDD 
Purified Protein Derivative 
PFS 
Pre-filled syringe 
PK 
Pharmacokinetic(s) 
PRN 
Pro re nata 
PRO 
Patient Reported Outcomes 
PsA 
Psoriatic arthritis 

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QMS 
Quality Management System 
QoL 
Quality of life 
RA 
Rheumatoid Arthritis 
RBC 
red blood cell(s) 
s.c. 
Subcutaneous 
SAA 
Spondylitis Association of America 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SD 
Standard deviation 
SF-36 
Short Form-36 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamic Pyruvic Transaminase 
SIJ/SI Joint 
Sacroiliac Joint 
SpA 
Spondyloarthritis 
SPARTAN 
Spondyloarthritis Research and Treatment Network 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
t.i.d 
ter in die, three times a day 
TB 
Tuberculosis 
TNFα-IR 
TNFα inhibitor inadequate responder 
TNF/TNFα 
Tumor Necrosis Factor 
ULN 
upper limit of normal 
VAS 
Visual analog scale 
WBC 
White blood cell(s) 
WHO 
World Health Organization 

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Glossary of terms 
Additional 
treatment 
Medicinal products that may be used during the clinical trial as described in the protocol, 
but not as an investigational medicinal product (e.g. any background therapy) 
Assessment 
A procedure used to generate data required by the study 
Biologic Samples 
A biological specimen including, for example, blood (plasma, serum), saliva, tissue, 
urine, stool, etc. taken from a study participant 
Control drug 
A study drug (active or placebo) used as a comparator to reduce assessment bias, 
preserve blinding of investigational drug, assess internal study validity, and/or evaluate 
comparative effects of the investigational drug 
Dosage 
Dose of the study treatment given to the participant in a time unit (e.g. 150 mg once in 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 participant or at a later 
point in time as defined by the protocol 
Enrollment 
Point/time of participant entry into the study at which informed consent must be obtained 
Epoch 
A portion of the study which serves a specific purpose. Typical Epochs are: screening / 
wash-out, treatment, and follow-up. 
Estimand 
A precise description of the treatment effect reflecting the clinical question posed by the 
trial objective. It summarizes at a population-level what the outcomes would be in the 
same patients under different treatment conditions being compared. Attributes of an 
estimand include the population, variable (or endpoint) and treatment of interest, as well 
as the specification of how the remaining intercurrent events are addressed and a 
population-level summary for the variable. 
Investigational 
drug/ treatment 
The drug whose properties are being tested in the study 
Investigational 
treatment 
All investigational drug(s) whose properties are being tested in the study as well as their 
associated treatment controls. 
This includes any placebos, any active controls, as well as approved drugs used outside 
of their indication/approved dosage or tested in a fixed combination. 
Investigational treatment generally does not include protocol-specified concomitant 
background therapies when these are standard treatments in that indication 
Medication number 
A unique identifier on the label of medication kits 
Mis-randomized 
participants 
Mis-randomized participants are those who were not qualified for randomization and who 
did not take study treatment, but have been inadvertently randomized into the study 
Other treatment 
Treatment that may be needed/allowed during the conduct of the study (i.e. concomitant 
or rescue therapy) 
Participant 
A trial participant (can be a healthy volunteer or a patient) 
Participant number 
A unique number assigned to each participant upon signing the informed consent. This 
number is the definitive, unique identifier for the participant and should be used to 
identify the participant throughout the study for all data collected, sample labels, etc. 
Period 
The subdivisions of the trial design (e.g. Screening, Treatment, Follow-up) which are 
described in the Protocol. Periods define the study phases and will be used in clinical 
trial database setup and eventually in analysis 
Personal data 
Participant information collected by the Investigator that is coded and transferred to 
Novartis for the purpose of the clinical trial. This data includes participant identifier 
information, study information and biological samples. 
Premature 
participant 
withdrawal 
Point/time when the participant exits from the study prior to the planned completion of all 
study drug administration and/or assessments; at this time all study drug administration 
is discontinued and no further assessments are planned 

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Protocol 
A written account of all the procedures to be followed in a trial, which describes all the 
administrative, documentation, analytical and clinical processes used in the trial. 
Randomization 
number 
A unique identifier assigned to each randomized participant 
Screen Failure 
A participant who did not meet one or more criteria that were required for participation in 
the study 
Source 
Data/Document 
Source data refers to the initial record, document, or primary location from where data 
comes. The data source can be a database, a dataset, a spreadsheet or even hard-
coded data, such as paper or Electronic Source (eSource) 
Study treatment 
Any drug or combination of drugs or intervention administered to the study participants 
as part of the required study procedures; includes investigational drug(s), control(s) or 
background therapy 
Study treatment 
discontinuation 
When the participant permanently stops taking any of the study drug(s) prior to the 
defined study treatment completion date (if any) for any reason; may or may not also be 
the point/time of study discontinuation 
Treatment 
arm/group 
A treatment arm/group defines the dose and regimen or the combination, and may 
consist of 1 or more cohorts. 
Treatment of 
interest 
The treatment of interest and, as appropriate, the alternative treatment to which 
comparison will be made. These might be individual interventions, combinations of 
interventions administered concurrently, e.g. as add-on to standard of care, or might 
consist of an overall regimen involving a complex sequence of interventions. This is the 
treatment of interest used in describing the related clinical question of interest, which 
might or might not be the same as the study treatment. 
Variable (or 
endpoint) 
The variable (or endpoint) to be obtained for each participant that is required to address 
the clinical question. The specification of the variable might include whether the 
participant experiences an intercurrent event. 
Withdrawal of 
study consent 
(WoC) 
Withdrawal of consent from the study occurs only when a participant does not want to 
participate in the study any longer and does not allow any further collection of personal 
data 

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Protocol summary 
Protocol 
number 
CAIN457I2301 
Full Title 
A randomized, double-blind, placebo controlled, multicenter study of subcutaneous 
secukinumab, to compare efficacy at 16 weeks with placebo and to assess safety and 
tolerability up to 52 weeks in Chinese participants with active non-radiographic axial 
spondyloarthritis 
Brief title 
Efficacy and safety study of secukinumab in Chinese participants with non-radiographic 
axial spondyloarthritis 
Sponsor and 
Clinical Phase 
Novartis, Phase III 
Investigation 
type 
Drug: Biologic 
Study type 
Interventional 
Purpose and 
rationale 
To demonstrate the clinical efficacy, safety and tolerability of secukinumab. compared to 
placebo in Chinese participants with active non-radiographic axial spondyloarthritis 
Primary 
Objective(s) 
To assess the efficacy of secukinumab 150 mg s.c. relative to placebo at Week 16 based 
on the proportion of TNF-α naive participants achieving an ASAS40 response (Assessment 
of SpondyloArthritis International Society criteria). 
Secondary 
Objectives 
• 
To assess the efficacy of secukinumab 150 mg s.c. relative to placebo at Week 16 
based on the proportion of overall participants achieving an ASAS40 response. 
• 
To assess the efficacy of secukinumab 150 mg s.c. relative to placebo at Week 16 
based on the proportion of participants meeting the ASAS 5/6 response criteria. 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on the change from baseline in total Bath Ankylosing Spondylitis Disease 
Activity Index (BASDAI). 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on the proportion of participants achieving BASDAI 50. 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on the change from baseline of high sensitivity C-Reactive Protein (hsCRP). 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on the change from baseline in total Bath Ankylosing Spondylitis Functional 
Index (BASFI). 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on the change from baseline in sacroiliac (SI) joint edema on Magnetic 
resonance imaging (MRI). 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on the proportion of participants achieving an ASAS20 response. 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on proportion of participants achieving Ankylosing Spondylitis Disease Activity 
Score (ASDAS) inactive disease as defined by ASDAS < 1.3. 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on the change from baseline in Short Form-36 Physical Component Summary 
(SF-36 PCS). 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on the change from baseline in Ankylosing Spondylitis Quality of Life (ASQoL) 
scores. 
• 
To assess the efficacy of secukinumab 150 mg s.c. compared to placebo at Week 16 
based on the proportion of participants achieving ASAS partial remission. 
• 
To evaluate overall safety and tolerability of secukinumab. 
Study design 
This is a randomized, double-blind, placebo-controlled study. 

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Study 
population 
The study population will consist of male and female participants (≥ 18 years old at the time 
of consent) fulfilling the ASAS classification criteria for Axial Spondyloarthritis (axSpA) plus 
an abnormal CRP and/or MRI, with no radiographic evidence of changes in the sacroiliac 
joints that would meet the modified New York criteria for Ankylosing Spondylitis (AS). 
Key Inclusion 
criteria 
• 
Signed informed consent must be obtained prior to participation in the study. 
• 
Male or non-pregnant, non-lactating female participant at least 18 years of age. 
• 
Diagnosis of axSpA according to ASAS axSpA criteria: 
1. Inflammatory back pain for at least 6 months 
2. Onset before 45 years of age 
3. Sacroiliitis on MRI (as assessed by central reader) with ≥ 1 Spondyloarthritis 
(SpA) feature OR HLA-B27 positive with ≥2 SpA features 
• 
Objective signs of inflammation at screening, evident by either 
1. MRI with Sacroiliac Joint inflammation (as assessed by central reader AND / OR 
2. hsCRP > upper limit of normal (ULN) (as defined by the central lab) 
• 
Active axSpA as assessed by total BASDAI ≥ 4 cm (0-10 cm) at baseline. 
• 
Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at baseline. 
• 
Total back pain as measured by Visual analog scale (VAS) ≥ 40 mm (0-100 mm) at 
baseline. 
• 
Participants should have been on at least 2 different Non-steroidal anti-inflammatory 
drug (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. 
• 
Participants who are regularly taking NSAIDs [including cyclooxygenase-1 (COX-1) or 
COX-2 inhibitors] as part of their axSpA therapy are required to be on a stable dose for 
at least 2 weeks before randomization. 
• 
Participants who have been on a TNFα inhibitor (not more than one) must have 
experienced an inadequate response to previous or current treatment given at an 
approved dose for at least 3 months prior to randomization or have been intolerant to 
at least one administration of an anti-TNFα agent. 
• 
Participants who have previously been on a TNFα inhibitor will be allowed entry into 
study after an appropriate wash-out period prior to randomization: 
1. 4 weeks for Enbrel® (etanercept) or "Yi Sai Pu", “An Bai Nuo” or “Qiang Ke” – 
with a terminal half-life of 102 ± 30 hours (s.c. route) 
2. 8 weeks for Remicade® (infliximab) – with a terminal half-life of 8.0-9.5 days 
(i.v. infusion) 
3. 10 weeks for Humira® (adalimumab) – with a terminal half-life of 10-20 days 
(average 2 weeks) (s.c. route) 
4. 10 weeks for Simponi® (golimumab) – with a terminal half-life of 11-14 days 
5. 10 weeks for Cimzia® (certolizumab) – with a terminal half-life of 14 days 
• 
Participants taking Methotrexate(MTX) (≤ 25 mg/week) or sulfasalazine (≤ 3 g/day) are 
allowed to continue their medication and must have taken it for at least 3 months and 
have to be on a stable dose for at least 4 weeks prior to randomization 
• 
Participants on MTX must be on stable folic acid supplementation before 
randomization 
• 
Participants who are on a DMARD other than MTX or sulfasalazine must discontinue 
the DMARD 4 weeks prior to randomization, except for leflunomide, which has to be 
discontinued for 8 weeks prior to randomization unless a cholestyramine washout has 
been performed 
• 
Participants taking systemic corticosteroids have to be on a stable dose of ≤ 10 
mg/day prednisone or equivalent for at least 2 weeks before randomization 
Key Exclusion 
criteria 
• 
Participants with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 
unilaterally (radiological criterion according to the modified New York diagnostic criteria 
for AS) as assessed by central reader 

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Key safety 
assessments 
● QuantiFERON TB-Gold test or PPD skin test 
● Chest X-ray or CT 
● Physical examination 
● Vital signs 
● Height and weight 
● Laboratory evaluations 
 
● Electrocardiogram 
● Pregnancy and assessment of fertility 
● Local tolerability (Injection site reactions) 
● Tolerability of secukinumab 
Other 
assessments 
● Health-related Quality of Life 
● SF-36 
● ASQoL 
 
● HLA-B27 
 
● X-Ray of the sacroiliac joints 
 
Data analysis 
The primary analysis will be conducted via logistic regression with treatment and 
stratification factor (CRP+/MRI+, CRP+/MRI-, CRP-/MRI+) as factors and weight as a 
covariate. Difference in response proportions between secukinumab regimen and placebo 
regimen and the corresponding 95% confidence interval (CI) will be computed utilizing the 
logistic regression model fitted. 
Key words 
Non-radiographic spondyloarthritis, chronic inflammatory disease, inflammatory back pain, 
secukinumab, AIN457 

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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 a common denominator. Patients with axSpA experience a 
substantial burden of disease, including pain in the sacrum, lower back, peripheral joints and 
tendon insertions, stiffness, decreased spinal mobility, decreased physical function, difficulty 
sleeping, fatigue, difficulty working, and decreased quality of life. 
Patients with chronic back pain (onset before 45 years of age) are classified according to the 
Assessment of Spondyloarthritis international Society (ASAS) classification criteria 
(Rudwaleit et al 2009) for axSpA if they fulfill either the clinical arm or the imaging arm of the 
criteria. Based on the presence or absence of sacroiliitis on conventional X-ray radiographs, 
axSpA patients are sub-grouped into ankylosing spondylitis (AS) and non-radiographic axSpA 
(nr-axSpA). Patients with evidence for sacroiliitis on X-ray fulfilling the 1984 modified New 
York diagnostic criteria (van der Linden et al 1984) are classified as AS whereas patients who 
do not show sacroiliitis on X-ray but may show evidence of sacroiliitis on magnetic resonance 
imaging (MRI) are classified as having nr-axSpA. The prevalence of AS and nr-axSpA is 
comparable,  with  each  occurring  in  0.3%  to  0.6%  of  the  population 
(Reveille and Weisman 2013), (Strand et al 2013) There is no exact epidemiology data for nr-
axSpA in China, the prevalence of AS in China is around 0.3% (Chinese Rheumatology 
Association 2010), nr-axSpA prevalence in China could be estimated to be 0.3% as comparable 
to AS. 
AS and nr-axSpA share many common epidemiologic, genetic, and clinical characteristics 
(Kiltz et al 2012), (Ciurea et al 2013), (Reveille and Weisman 2013), (Song et al 2013), 
(Strand et al 2013), 
(Landewé et al 2014), 
(Poddubnyy and Sieper 2014), 
(Poddubnyy et al 2015). Progression from nr-axSpA to AS was observed in about 12% of nr-
axSpA patients over the course of 2 years (Poddubnyy et al 2011). However, it is estimated that 
10-15%  of  nr-axSpA  patients  do  not  develop  radiographic  sacroiliitis 
(Sieper and van der Heijde 2013). 
Disease parameters and response rates to treatment with tumor necrosis factor (TNFα) 
antagonists are similar in patients with AS and nr-axSpA, further supporting the concept that 
axSpA is a disease with distinct stages (Song et al 2013). Moreover, results from the C-
axSpAnd trial (a 52-week, randomized, multicenter, double-blind, placebo controlled study of 
certolizumab pegol in nr-axSpA) showed that at Week 52, the placebo group was associated 
with a poor outcome (with only 7.0% of patients attaining an Ankylosing Spondylitis Disease 
Activity Score-Major Improvement (ASDAS-MI) vs. 47.2% in the biological disease 
modifying anti-rheumatic drugs (bDMARDs) treatment group (Deodhar et al 2019). This 
shows that nr-axSpA is a true disease that does not resolve spontaneously or improve without 
adequate treatment. 
Non-steroidal anti-inflammatory drugs (NSAIDs) are considered first-line therapy for all 
patients with axSpA. International management guidelines developed by experts in the field 
((ACR/SAA/SPARTAN: (Ward et al 2016) ASAS/EULAR: (van der Heijde et al 2017)) 
recognize nr-axSpA and AS as viable disease entities within the spectrum of axSpA and support 
the use of bDMARDs for the full spectrum of axSpA. 

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Anti-TNFα agents are approved therapies for patients with AS who continue to have active 
disease despite NSAIDs. In Europe, several anti-TNFα agents are approved for nr-axSpA with 
objective signs of inflammation, whereas only one anti-TNFα agent is approved in the United 
States. It's worth noting that no anti-TNFα agents are approved for the treatment of nr-axSpA 
in China. 
More than 60% of nr-axSpA patients treated with adalimumab or etanercept did not achieve an 
ASAS40 response in randomized clinical trials (Sieper et al 2013), (Dougados et al 2014). 
Moreover, TNFα blockade does not result in long-term remission in AS and responders usually 
relapse within a few weeks after interruption of treatment (Baraliakos et al 2005). While 
effective in treating the inflammatory symptoms, TNFα antagonists have also not been shown 
to impact structural damage of the joints in AS beyond the level of NSAIDs in blinded cohort 
comparisons over 2 years of treatment (van der Heijde et al 2008). Thus, there remains an 
unmet medical need for new therapies. 
Secukinumab (AIN457) is a high-affinity recombinant, fully human monoclonal anti-human 
Interleukin-17A antibody of the Immunoglobulin G (IgG1)/κ-class. Secukinumab binds to 
human IL-17A and neutralizes the bioactivity of this cytokine. Interleukin (IL)-17A is the 
central lymphokine of a newly defined subset of inflammatory T cells (Th17) which appear to 
be pivotal in several autoimmune and inflammatory processes in some animal models. IL-17A 
is mainly produced by memory CD4+ and CD8+ T lymphocytes and is being recognized as one 
of the principal pro-inflammatory cytokines in immune mediated inflammatory diseases. 
Assuming a potential role of Th17 cells in the inflammatory infiltrate in spondyloarthritides, it 
can be speculated that the activity of inflammation in early disease stages, such as nr-axSpA 
and the ensuing structural changes in axial joints over the longer term, characteristic of axSpA 
may be amenable to modulation via IL-17 antagonism. 
Secukinumab 150 mg showed very good efficacy in the two AS Phase III global pivotal studies 
CAIN457F2305 (MEASURE 1) and CAIN457F2310 (MEASURE 2), as well as a China- 
centric Phase III study CAIN457F2308 (MEASURE 5) which enrolled 327 out of 458 (71.4%) 
Chinese patients with active AS. Recently, secukinumab 150 mg has been approved in Europe 
and United States for nr-axSpA patients based on data from a global pivotal study 
CAIN475H2315 (PREVENT) conducted to evaluate the efficacy and safety of secukinumab 
150 mg vs. placebo in patients with nr-axSpA. 
Secukinumab is approved for the treatment of psoriasis and AS in China. Full safety results 
from completed studies show that secukinumab is generally safe and well tolerated in Chinese 
patients. Please refer to the AIN457 Investigator's Brochure edition 20 for a more detailed 
review of the risk: benefit profile of secukinumab which supports its clinical development for 
the treatment of nr-axSpA patients with secukinumab in China. 
1.2 
Purpose 
The purpose of this bridging study is to evaluate efficacy, safety and tolerability of secukinumab 
150 mg s.c. compared to placebo in Chinese participants with active nr-axSpA at Week 16 to 
support registration in China. Meanwhile, this study will also observe the long-term efficacy, 
safety and tolerability of secukinumab including spinal and SI-joint inflammation as evidenced 
by magnetic resonance imaging (MRI) at Week 52. 

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Additionally, efficacy, safety and tolerability of secukinumab 300 mg s.c. will be assessed in 
non-responders, defined as participants who have not achieved ASAS20 at Week 24. 
 
2 
Objectives and endpoints 
Table 2-1 
Objectives and related endpoints 
 
Objectives 
Endpoints 
 
Primary objective 
Endpoints for primary objective 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the 
proportion of TNF-α naive participants achieving an 
ASAS40 response (Assessment of SpondyloArthritis 
International Society criteria). 
● ASAS40 response rate at Week 16 
ASAS40 response is defined as an improvement of 
≥40% and an absolute improvement from baseline of 
≥2 units on a 10-point scale in at least three of the four 
main domains and no worsening assessed at all in the 
remaining domain. 
Main 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 
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 
 
Secondary objectives 
Endpoints for secondary objectives 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the 
proportion of overall participants achieving an 
ASAS40 response. 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the 
proportion of participants meeting the ASAS 5/6 
response criteria. 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the change 
from baseline in total Bath Ankylosing Spondylitis 
Disease Activity Index (BASDAI). 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the 
proportion of participants achieving BASDAI 50. 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the change 
from baseline of high sensitivity C-Reactive Protein 
(hsCRP). 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the change 
from baseline in total Bath Ankylosing Spondylitis 
Functional Index (BASFI). 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the change 
from baseline in sacroiliac joint (SIJ) edema on MRI. 
● ASAS40 response rate in overall participants at 
Week 16 
 
 
● ASAS 5/6 response rate at Week 16 
ASAS 5/6 response is defined as an improvement of 
≥20% in at least five of all six domains. 
 
● Change from baseline in total BASDAI at Week 16 
 
 
 
● BASDAI 50 proportion at Week 16 
BASDAI 50 is defined as an improvement of at least 
50% in the BASDAI total score compared to baseline. 
● Change from baseline in hsCRP at Week 16 
 
 
 
● Change from baseline in BASFI at Week 16 
 
 
 
● Change from baseline in SIJ edema score on MRI at 
Week 16 
 

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Objectives 
Endpoints 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the 
proportion of participants achieving an ASAS20 
response. 
 
 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the change 
from baseline in Short Form-36 Physical Component 
Summary (SF-36 PCS). 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the change 
from baseline in Ankylosing Spondylitis Quality of Life 
(ASQoL) scores. 
● To assess the efficacy of secukinumab 150 mg s.c. 
relative to placebo at Week 16 based on the 
proportion of participants achieving ASAS partial 
remission. 
● To evaluate overall safety and tolerability of 
secukinumab. 
● ASAS20 response rate at Week 16 
ASAS20 response is defined as an improvement of 
≥20% and an absolute improvement from baseline 
of ≥1 unit on a 10-point scale in at least three of the 
four main domains and no worsening of ≥20% 
and ≥1 unit at all in the remaining domain. 
● Change from baseline in SF-36 PCS at Week 16 
 
 
 
● Change from baseline in ASQoL score at Week 16 
 
 
 
● ASAS partial remission rate at Week 16 
ASAS partial remission is defined as a value not 
above 2 units in each of the four main ASAS domains 
on a 10-point scale. 
● Number of participants with adverse events (AE) 
serious adverse events (SAE), clinically significant 
changes in laboratory value and vital signs. 
 

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2.1 
Primary estimands 
The clinical question of interest is: What is the effect of secukinumab 150 mg s.c. versus placebo 
on the composite endpoint ASAS40 response at Week 16 and the completion of 16 week-
treatment in Chinese participants with active nr-axSpA who are TNF-α naïve? 
The justification for targeting this treatment effect is that we wish to estimate the effect of the 
study drug for the full duration when administered without dose changes. 
The primary estimand is described by the following attributes: 
A. Population: defined through appropriate inclusion/exclusion criteria to reflect the targeted 
nr-axSpA population 
B. Variable: composite of remaining in the study and on randomized treatment through 16 
weeks and achieving ASAS40 response at Week 16 

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C. Intercurrent event: the intercurrent event of discontinuation from treatment or study prior to 
Week 16 has been addressed via the variable definition 
D. Population-level summary: difference in proportions of responders between secukinumab 
and placebo groups 
2.2 
Secondary estimands 
The clinical questions of interest are: 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the composite endpoint 
ASAS 40 response at Week 16 and the completion of 16 weeks-treatment in Chinese 
participants with active nr-axSpA? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the composite endpoint 
ASAS 5/6 response at Week 16 and the completion of 16 weeks-treatment in Chinese 
participants with active nr-axSpA? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the change from baseline 
in BASDAI at Week 16 in Chinese participants with active nr-axSpA had patients 
completed 16 weeks-treatment? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the composite endpoint 
BASDAI 50 response at Week 16 and the completion of 16 weeks-treatment in Chinese 
participants with active nr-axSpA? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the change from baseline 
in hsCRP at Week 16 in Chinese participants with active nr-axSpA had participants 
completed 16 weeks-treatment 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the change from baseline 
in BASFI at Week 16 in Chinese participants with active nr-axSpA had patients completed 
16 weeks-treatment 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the change from baseline 
in SI joint edema on MRI at Week 16 in Chinese participants with active nr-axSpA had 
participants completed 16 week-treatment 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the composite endpoint 
ASAS20 response at Week 16 and the completion of 16 weeks-treatment in Chinese 
participants with active nr-axSpA? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the change from baseline 
in SF-36 PCS at Week 16 in Chinese participants with active nr-axSpA had participants 
completed 16 weeks-treatment? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the change from baseline 
in ASQoL at Week 16 in Chinese participants with active nr-axSpA had participants 
completed 16 weeks-treatment? 
• What is the effect of secukinumab 150 mg s.c. versus placebo on the composite endpoint 
ASAS partial remission response at Week 16 and the completion of 16 weeks-treatment in 
Chinese participants with active nr-axSpA? 
The justification for targeting this treatment effect is that we wish to estimate the effect of the 
study drug for the full duration when administered without dose changes. 

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The estimand definition of all secondary objectives related to response (e.g., ASAS 5/6, etc.) 
will have the same attributes as that for the primary estimand, except for the variable of interest. 
Estimand definition for the secondary continuous variables (e.g., BASDAI, etc.) is the 
following: 
a. Population: defined through appropriate inclusion/exclusion criteria to reflect the targeted 
nr-axSpA population 
b. Variable: change from baseline in the variable of interest 
c. Intercurrent event: discontinuation Population-level summary: difference in variable 
means between secukinumab and from treatment or study prior to Week 16 
d. Placebo groups 
 
3 
Study design 
This is a randomized, double-blind, placebo-controlled study of secukinumab 150 mg s.c. to 
evaluate the safety, tolerability and efficacy in Chinese participants with active non-
radiographic axial spondyloarthritis (nr-axSpA). 
A screening period of up to 10 weeks before randomization will assess participant eligibility, 
followed by 16 weeks of double blind treatment period and 44 weeks open label period. 
Approximately 134 participants will be randomized in a ratio of 1:1 to receive secukinumab 
150 mg s.c. or placebo: 
• Group 1: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. pre-filled syringe (PFS) at 
baseline (BSL), Weeks 1, 2, and 3, followed by administration every four weeks starting 
at Week 4 
• Group 2: placebo (1 mL) s.c. PFS at BSL, Weeks 1, 2 and 3, followed by administration 
every four weeks starting at Week 4 
Participants will be stratified at randomization according to the subgroup of objective signs of 
inflammation they belong to (based on their CRP and MRI status at screening: CRP+ and MRI+, 
CRP+ and MRI-, CRP- and MRI+). 
Additionally, it is planned to enroll no more than approximately 10% Tumor Necrosis Factor - 
Inadequate Response (TNFα-IR) participants in the study. 
The primary analysis will be performed after all participants complete Week 16 visit to support 
registration in China. 
From Week 16, all participants will switch to open label secukinumab 150 mg s.c., including 
all placebo participants. The first dose of open label secukinumab 150 mg s.c. should start at 
the Week 16 visit, only after performing all assessments for that visit. However, all participants 
and investigators/site staff will remain blinded to the original randomized treatment group 
assignment (150 mg vs placebo). 
At week 24, non-responders (defined as not achieving ASAS20) will be escalated to 
secukinumab 300 mg s.c. Responders will continue secukinumab 150 mg s.c. treatment. 
Study treatment will continue up to Week 48. 

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An end of treatment visit will be performed 4 weeks after last study treatment administration 
i.e. at Week 52 and a post treatment follow-up visit is to be done 12 weeks after last study 
treatment administration for all participants (regardless of whether they complete the entire 
study as planned or exit the study early). 
Figure 3-1 
Study Design 
 
SV1: Screening Visit 1, SV2: Screening Visit 2, BSL: Baseline, EOT: End of Treatment, EOS: End of Study, R: Randomization, q4wk: every 4 weeks, 
s.c.: subcutaneously, ASAS: Assessment of SpondyloArthritis international Society, NDA: New Drug Application 
 
 
4 
Rationale 
4.1 
Rationale for study design 
The randomized, double-blind, placebo controlled design used in this study is aligned with 
global phase III pivotal study (PREVENT) to show similar efficacy trend in Chinese population 
with active nr-axSpA. The study design is in compliance with the EMA/EMEA (European 
Medicines Agency) guidelines for AS (EMA 2009) and The National Medical Products 
Administration (NMPA) requirement in use of biologics drug, considered relevant for trials in 
nr-axSpA and available precedent. The treatment duration of placebo group in this study was 
kept for 16 weeks and participants in the two groups will receive 150 mg secukinumab s.c. open 
label treatment at Week 16 (cut-off point for primary analysis). The blinding to original 
treatment assignment is maintained to ensure reliable efficacy and safety measures over time. 
Participants who do not achieve ASAS 20 response at Week 24 visit will be escalated to 300 
mg secukinuimab s.c. through Week 48 to assess if secukinumab 300 mg will provide further 
benefit to participants. The 300 mg dose is an approved dose for secukinumab in psoriasis, 
psoriatic arthritis, as well as in AS in regions globally. The regular assessments of disease 
activity ensure that participants who experience worsening of the disease in any of the treatment 
groups can exit the study upon their own wish or based on the advice of the investigator at any 
time. 

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4.1.1 
Rationale for choice of background therapy 
According to the guideline from international associations for treating axial spondyloarthritis, 
NSAIDs are considered as first-line therapy up to the maximum dose, taking risks and benefits 
into account, in both AS and nr-axSpA. Although sulfasalazine may be considered in patients 
with peripheral arthritis, conventional synthetic (cs) DMARDs including methotrexate (MTX) 
do not demonstrate credible evidence on efficacy in axSpA. Despite not being recommended by 
the international guidelines, csDMARDs are still regularly prescribed in China to treat nr-
axSpA patients, given there are no biologic treatment approved. Short-term glucocorticoids 
treatment is also an option for cases refractory to NSAIDs. 
In this study, participants are permitted to concomitantly use NSAIDs, csDMARDs and 
systemic glucocorticoids with specific restrictions detailed in Section 6.2.1. Starting from Week 
24, the modification of the background therapy will be allowed for all participants as per the 
investigator's judgement or participant's need. 
4.2 
Rationale for dose/regimen and duration of treatment 
In the previous AS pivotal studies CAIN457F2305 with intravenous loading, CAIN457F2310 
with s.c. loading, CAIN457F2308 with s.c. loading and nr-axSpA pivotal study 
(CAIN457H2315 with or without s.c. loading), secukinumab 150 mg s.c. is a sufficient dose to 
provide consistent efficacy across multiple endpoints, with clinically meaningful improvements 
in axSpA measures of signs and symptoms, objective measures of inflammation, physical 
function, and patient-reported quality of life. 
In contrast, the 75 mg s.c. loading and maintenance regimen tested in CAIN457F2310 did not 
achieve statistically significant improvements in any of the efficacy endpoints tested in a pre-
defined testing hierarchy, including ASAS20, ASAS 40, hsCRP, ASAS5/6, BASDAI, SF-36 
PCS and ASQoL. Therefore, there are currently no plans to further pursue the 75 mg dose in 
future studies. Furthermore, a meta-analysis of trials examining TNF-α inhibitors, demonstrated 
that nr-axSpA patients respond similarly well to biologic anti-TNFα treatments as AS patients 
(Callhoff et al 2015). There was no evidence that different axSpA populations (e.g. AS and nr-
axSpA) could require different dose regimens (Callhoff et al 2015), (Landewé et al 2014). As 
other phase III trials of TNF-α inhibitors in nr-axSpA also evaluated dosages that already 
proved to be efficacious in AS, this trial will use the secukinumab dose of 150 mg s.c which is 
consistent with the dose regimen used in AS registration study CAIN457F2308 in China. 
Notably, 300 mg s.c. administered monthly is an approved dose for secukinumab in psoriasis 
in China, and in Psoriatic arthritis (PsA) and AS globally. The safety profile for 300 mg s.c. 
every 4 weeks is comparable to 150 mg s.c. every 4 weeks (Langley et al 2014), 
(Mease et al 2015). The higher dose of secukinumab confers an additional benefit in other 
disease conditions (e.g., psoriasis, PsA and AS). This study will explore whether a higher dose 
of secukinumab will have an effect on participants with nr-axSpA with respect to increase in 
treatment response. The dose escalation will be starting at Week 24 in participants who do not 
achieve an ASAS20 response. 

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4.3 
Rationale for choice of control drugs (comparator/placebo) or 
combination drugs 
A placebo group up to the primary endpoint Week 16 is included in this study. Due to the nature 
of the disease and the outcome measures used (e.g., ASAS response criteria, MRI for 
inflammation), a placebo group is necessary to obtain reliable efficacy measurements and can 
be supported from an ethical standpoint, as participants can continue on a range of concomitant 
treatments. Moreover, the inclusion of a placebo group is in accordance with previously 
implemented methodology including placebo setting in China centric AS study CAIN457F2308 
(MEASURE 5) and in compliance with the EMA/EMEA guidelines for AS (EMA 2009), 
considered relevant for trials in nr-axSpA. 
4.4 
Purpose and timing of primary analyses/design adaptations 
The primary analysis will be performed after all participants complete the Week 16 visit 
assessments to support regulatory submission in China. The final analysis will be conducted 
after all participants complete the study at Week 60 or end of study (EOS) visit. 
Additional analyses may be performed to support interactions with health authorities, as 
necessary. 
Although unblinding will occur after the Week 16 database lock, the original randomization to 
active treatment vs. placebo will remain blinded to all investigators, site personnel, participants 
and sponsor's monitors until all participants have completed the study and the Week 60 database 
lock has occurred. 
4.5 
Risks and benefits 
The risk to participants in this trial will be minimized by compliance with the eligibility criteria, 
close clinical monitoring, and extensive guidance for the investigators provided in the 
Investigator’s Brochure. 
As of 25-June-2020, over 26,000 participants have been enrolled in both completed and ongoing 
studies with secukinumab, with over 22,000 having received active drug at doses ranging from 
single and/or multiple doses of 0.1 mg/kg to 30 mg/kg i.v. and 25 mg to 300 mg s.c. across 
various indications (including psoriasis, rheumatoid arthritis, AS, PsA, multiple sclerosis and 
uveitis). 
The risk profile of secukinumab in nr-axSpA is informed by the safety experience from trials 
performed in psoriasis, psoriatic arthritis, rheumatoid arthritis, ankylosing spondylitis, and non-
radiographic axial spondyloarthritis. 
Observed risks in global studies at doses up to 300 mg s.c. every 4 weeks from included 
infections, of which the most frequently reported were upper respiratory tract infections. Oral 
herpes, oral candidiasis and tinea pedis were also more frequently reported. Most of the 
infections were non-serious, mild to moderate in severity, clinically manageable and did not 
lead to treatment discontinuation. Neutropenia and hypersensitivity reactions are also risks 
observed with secukinumab. Cases of neutropenia were uncommon, generally mild to moderate, 
transient, did not lead to treatment discontinuation, and very few cases were temporally 
associated with non-serious infections. 

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In global phase III AS studies CAIN457F2305 and CAIN457F2310, secukinumab i.v. 10mg/kg, 
75mg s.c. and 150mg s.c. were assessed in the study, data observed from 590 participants 
including participants enrolled from Taiwan demonstrated secukinumab provided significant 
improvement of signs and symptoms as well as quality of life for patients with active AS, the 
most common side effects in the 52-week dataset were upper respiratory tract infection, 
nasopharyngitis, pharyngitis and oral herpes as secukinumab treatment-related adverse events 
which generally were mild to moderate in severity and did not lead to study drug discontinuation. 
A China centric pivotal study CAIN457F2308 also demonstrated good efficacy of secukinumab 
150mg s.c. in Chinese population with active AS, and the safety results studied in 
CAIN457F2308 in Chinese population wassimilar to overall population and comparable to 
global AS studies. 
In a global phase III nr-axSpA pivotal study CAIN457H2315, secukinumab 150mg s.c. 
demonstrated efficacy versus placebo in terms of improvement of signs and symptoms of their 
disease was proved to be effcacious and significantly improved patient's outcome regarding of 
both patient reported outcomes (PROs) and objective measurements compared to placebo. The 
safety profile of secukinumab at both doses showed no new or unexpected safety signals and 
was consistent with the overall safety profile of secukinumab, based on the extensive safety 
data across multiple indications. 
Immunogenicity was low with secukinumab and did not correlate with hypersensitivity-related 
adverse events or loss of efficacy across indications studied up to date. 
From the standpoint of the overall risk benefit assessment, the current trial with secukinumab 
in Chinese active nr-axSpA population is justified. 
 
5 
Study Population 
The study population will consist of male and female participants (≥ 18 years old at the time of 
consent) fulfilling the ASAS classification criteria for axSpA plus an abnormal CRP and/or 
MRI, with no radiographic evidence of changes in the sacroiliac joints that would meet the 
modified New York criteria for AS. 
Participants must have active disease despite current or previous NSAID, non-biologic 
DMARD, and/or anti-TNFα therapy. Participants should have been on 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 than 4 weeks if therapy had to be withdrawn due to 
intolerance, toxicity or contraindications. Participants who have been on a TNFα inhibitor (not 
more than one) must have experienced an inadequate response to treatment given at an approved 
dose for at least 3 months prior to randomization or have been intolerant to at least one 
administration of an anti-TNFα agent. It is planned to limit the inclusion of participants that are 
TNFα-IR to no more than 10% of the overall randomized population. Due to the long wash out 
required for some TNFα-IR participants, enrolment of TNFα-IR participants will end two 
months prior to the projected end of screening period. 
The study aims to randomize approximately 134 analyzable participants in total. Enrollment 
will stop as soon as the target number of randomized analyzable participants is reached. 

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Participants can be re-screened only once, and no study-related re-screening procedure should 
be performed prior to written re-consent by the participant. Mis-randomization occurs when a 
participant who does not meet all eligibility criteria receives a randomization number 
nevertheless; mis-randomized participants will not be re-screened. 
5.1 
Inclusion criteria 
Participants eligible for inclusion in this study must meet all of the following criteria: 
1. Signed informed consent must be obtained prior to participation in the study. 
2. Male or non-pregnant, non-lactating female participant at least 18 years of age. 
3. Diagnosis of axSpA according to ASAS axSpA criteria: 
a. Inflammatory back pain for at least 6 months 
b. Onset before 45 years of age 
c. Sacroiliitis on MRI (as assessed by central reader) with ≥ 1 SpA feature OR Human 
Leukocyte Antigen-B27 (HLA-B27) positive with ≥2 SpA features 
4. Objective signs of inflammation at screening, evident by either 
• MRI with Sacroiliac Joint inflammation (as assessed by central reader) 
AND / OR 
• hsCRP > ULN (as defined by the central lab) 
5. Active axSpA as assessed by total BASDAI ≥ 4 cm (0-10 cm) at baseline. 
6. Spinal pain as measured by BASDAI question #2 ≥ 4 cm (0-10 cm) at baseline. 
7. Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at baseline. 
8. Participants 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. 
9. Participants who are regularly taking NSAIDs [including COX-1 or COX-2 inhibitors] as 
part of their axSpA therapy are required to be on a stable dose for at least 2 weeks before 
randomization. 
10. Participants who have been on a TNFα inhibitor (not more than one) must have 
experienced an inadequate response to previous or current treatment given at an approved 
dose for at least 3 months prior to randomization or have been intolerant to at least one 
administration of an anti-TNFα agent (detailed in Section 6.2.1 and Section 6.2.2) 
11. Participants who have previously been on a TNFα inhibitor will be allowed entry into 
study after an appropriate wash-out period prior to randomization: (detailed in 
Section 6.2.1 and Section 6.2.2) 
• 4 weeks for Enbrel® (etanercept) or "Yi Sai Pu", "An Bai Nuo" and "Qiang Ke" – with 
a terminal half-life of 102 ± 30 hours (s.c. route) 
• 8 weeks for Remicade® (infliximab) – with a terminal half-life of 8.0-9.5 days (i.v. 
infusion) 
• 10 weeks for Humira® (adalimumab) – with a terminal half-life of 10-20 days (average 
2 weeks) (s.c. route) 
• 10 weeks for Simponi® (golimumab) – with a terminal half-life of 11-14 days 

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• 10 weeks for Cimzia® (certolizumab) – with a terminal half-life of 14 days 
12. Participants taking MTX (≤ 25 mg/week) or sulfasalazine (≤ 3 g/day) are allowed to 
continue their medication and must have taken it for at least 3 months and have to be on a 
stable dose for at least 4 weeks prior to randomization (detailed in Section 6.2.1 and 
Section 6.2.2) 
13. Participants on MTX must be on stable folic acid supplementation before randomization 
(detailed in Section 6.2.1 and Section 6.2.2) 
14. Participants who are on a DMARD other than MTX or sulfasalazine must discontinue the 
DMARD 4 weeks prior to randomization, except for leflunomide, which has to be 
discontinued for 8 weeks prior to randomization unless a cholestyramine washout has 
been performed (detailed in Section 6.2.1 and Section 6.2.2) 
15. Participants taking systemic corticosteroids have to be on a stable dose of ≤ 10 mg/day 
prednisone or equivalent for at least 2 weeks before randomization (detailed in 
Section 6.2.1 and Section 6.2.2). 
5.2 
Exclusion criteria 
Participants meeting 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 participants. 
1. Participants with radiographic evidence for sacroiliitis, grade ≥ 2 bilaterally or grade ≥ 3 
unilaterally (radiological criterion according to the modified New York diagnostic criteria 
for AS) as assessed by central reader 
2. Inability or unwillingness to undergo MRI scan (e.g., participants with pacemakers, 
aneurysm clips or metal fragments / foreign objects in the eyes, skin or body that are not 
MRI compatible) 
3. Chest X-ray or computed tomography (CT) scan with evidence of ongoing infectious or 
malignant process, obtained within 3 months of screening and evaluated by a qualified 
physician 
4. Participants taking high potency opioid analgesics (e.g., methadone, hydromorphone, 
morphine) 
5. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or 
IL-17 receptor 
6. Use of any investigational drug and/or devices within 4 weeks of randomization, or a 
period of 5 half-lives of the investigational drug, whichever is longer 
7. History of hypersensitivity to the study drug or its excipients or to drugs of similar 
chemical classes 
8. Any therapy by intra-articular injections (e.g., corticosteroid) within 4 weeks before 
randomization 
9. Any intramuscular corticosteroid injection within 2 weeks before randomization 
10. Participants previously treated with any biological immunomodulating agents, except 
those targeting TNFα 
11. Participants who have taken more than one anti-TNFα agent 

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12. Previous treatment with any cell-depleting therapies including but not limited to anti-
CD20 or investigational agents (e.g., anti-CD52, anti-CD4, anti-CD5, anti-CD3, anti-
CD19) 
13. 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 
14. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during entire 
study or longer if required by locally approved prescribing information Effective 
contraception methods include: 
• Total abstinence, when this is in line with the preferred and usual lifestyle of the 
participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception 
• Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy), total hysterectomy, or tubal ligation at least six weeks before taking 
study treatment. In case of oophorectomy alone, only when the reproductive status of 
the woman has been confirmed by follow up hormone level assessment 
• Male sterilization (at least 6 months prior to screening). For female participants on the 
study, the vasectomized male partner should be the sole partner for that participant 
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository 
• Use of oral, injected or implanted hormonal methods of contraception or other forms 
of hormonal contraception that have comparable efficacy (failure rate <1%), for 
example hormone vaginal ring or transdermal hormone contraception or placement of 
an intrauterine device (IUD) or intrauterine system (IUS) 
In case of use of oral contraception, women should have been stable on the same pill for a 
minimum of 3 months before taking study treatment. 
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 
six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the 
woman has been confirmed by follow up hormone level assessment is she considered not 
of childbearing potential. 
If local regulations deviate from the contraception methods listed above to prevent 
pregnancy, local regulations apply and will be described in the inform consent form (ICF). 
15. Active ongoing inflammatory diseases other than nr-axSpA that might confound the 
evaluation of the benefit of secukinumab therapy, including inflammatory bowel disease 
or uveitis 
16. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal conditions, which in the opinion of the investigator 
immunocompromises the participant and/or places the participant at unacceptable risk for 
participation in an immunomodulatory therapy 

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17. Significant medical problems or diseases, including but not limited to the following: 
uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure (New York Heart 
Association status of class III or IV), uncontrolled diabetes, or very poor functional status 
unable to perform self-care 
18. History of clinically significant liver disease or liver injury as indicated by abnormal liver 
function tests such as Serum Glutamic Oxaloacetic Transaminase (SGOT) (Aspartate 
Aminotransferase (AST)), SGPT (Alanine Aminotransferase (ALT)), alkaline 
phosphatase, or serum bilirubin. The Investigator should be guided by the following 
criteria: 
• Any single parameter may not exceed 2 x 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 lab error. 
• If the total bilirubin concentration is increased above 2 x ULN, total bilirubin should 
be differentiated into the direct and indirect reacting bilirubin. 
19. History of renal trauma, glomerulonephritis, or participants with one kidney only, or a 
serum creatinine level exceeding 1.5 mg/dL (132.6 µmol/L) 
20. Screening total White blood cell(s) (WBC) count <3,000/µL, or platelets <100,000/µL or 
neutrophils <1,500/µL or hemoglobin <8.5 g/dL (85 g/L) 
21. Active systemic infections during the last two weeks prior to randomization (exception: 
common cold) 
22. History of ongoing, chronic or recurrent infectious disease or evidence of tuberculosis 
infection as defined by either a positive purified protein derivative (PPD) skin test (the 
size of induration will be measured after 48-72 hours, and a positive result is defined as an 
induration of ≥ 5 mm or according to local practice/guidelines) or a positive 
QuantiFERON TB-Gold test as indicated in the assessment schedule in Table 8-1. 
Participants with a positive test may participate in the study if further work up (according 
to local practice/guidelines) establishes conclusively that the participant has no evidence 
of active tuberculosis. If presence of latent tuberculosis is established, then treatment 
according to local country guidelines must have been initiated 
23. Known infection with HIV, hepatitis B or hepatitis C at screening or randomization 
24. 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) 
25. Current severe progressive or uncontrolled disease which in the judgment of the clinical 
investigator renders the participant unsuitable for the trial 
26. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor 
tolerability or lack of access to veins) 
27. Inability or unwillingness to receive subcutaneous injections with PFS 
28. 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 
29. Donation or loss of 400 mL or more of blood within 8 weeks before dosing 

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30. History or evidence of ongoing alcohol or drug abuse, within the last six months before 
randomization 
31. Plans for administration of live vaccines during the study period or 6 weeks prior to 
randomization 
 
6 
Treatment 
6.1 
Study treatment 
Novartis Global Clinical Supply will supply the following study treatments: 
• Investigational Treatment: 
• Secukinumab 150 mg provided in a 1 mL PFS (one PFS for 150 mg dose) 
• Reference Therapy: 
• Secukinumab placebo (Placebo) provided in a 1 mL PFS 
At Week 16, all participants will switch to open label secukinumab 150 mg, including all 
placebo participants; however, all participants, investigators and site staff will remain blinded 
to the original randomized treatment group assignment (150 mg vs placebo) until the end of the 
trial. 
At Week 24, non-responders (defined as not achieving ASAS20) will be escalated to 
secukinumab 300 mg (two PFS for 150 mg dose). Responders will continue secukinumab 150 
mg treatment. 
6.1.1 
Investigational and control drugs 
Table 6-1 
Investigational and control drug 
 
Investigational/ 
Control Drug 
(Name and Strength) 
Pharmaceutical 
Dosage Form 
Route of 
Administration 
Supply Type 
Sponsor (global 
or local) 
Secukinumab 150 mg 
PFS 
subcutaneous injection 
Double Blind Supply 
Sponsor (global) 
Secukinumab 150 mg 
PFS 
subcutaneous injection 
Open label 
Sponsor (global) 
Secukinumab placebo 
PFS 
subcutaneous injection 
Double Blind Supply 
Sponsor (global) 
In the double blind period, the Secukinumab/Placebo PFSs are packaged in a double-blinded 
fashion to meet dosing requirements until including Week 12 dispensing, thereafter at Week 16 
and onwards open label treatment will start. 
In the open label period (starting at Week 16), the study medication will be provided in open 
label fashion for the 150 mg and from Week 24 onwards for the 300 mg doses. Open label 
medications will be supplied until the last dose is given at Week 48. 
The double blind period medication will be labeled as follows: 
• Double-blind Secukinumab and Placebo PFS will be labeled as AIN457 
150mg/1mL/Placebo. 
The open label period study medication will be labeled as follows: 
• Open label Secukinumab PFS will be labeled as AIN457 150mg/1mL 

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For detailed instructions on storage of the investigational treatments, please refer to medication 
label. 
6.1.2 
Additional study treatments 
Not Applicable 
6.1.3 
Treatment arms/group 
Double Blind Period (Treatment Period 1) 
Participants in double-blind period will be assigned to one of the following two treatment 
groups in a ratio of 1:1. Participants will receive study treatment at BSL, Weeks 1, 2, 3, and 4, 
followed by treatment every 4 weeks through Week 12. 
• Group 1: secukinumab 150 mg (1 mL, 150 mg/mL) s.c. PFS at BSL, Weeks 1, 2, and 3, 
followed by administration every 4 weeks starting at Week 4. 
• Group 2: placebo (1 mL) s.c. PFS at BSL, Weeks 1, 2 and 3, followed by administration 
every 4 weeks starting at Week 4. 
Open Label Period (Treatment Period 2 and 3) 
Treatment Period 2: At Week 16, Group 1 participants will continue using secukinumab 150 
mg and Group 2 participants will start receiving secukinumab 150 mg dosing every four weeks. 
Treatment will be provided open label from Week 16 onward, as all participants will be taking 
150 mg s.c. every 4 weeks. However, all participants and investigators/site staff will remain 
blinded to the original randomized treatment group assignment (150 mg vs placebo). 
Treatment Period 3: At Week 24, participants in open label period will be assessed as being 
Open Label Period Responder or Open Label Period non-responder and will receive the study 
treatment every 4 weeks through Week 48 as follows. 
• Open Label Period Responder: Secukinumab 150 mg provided in a 1 mL PFS (one PFS 
for 150 mg dose, s.c.), administration every 4 weeks starting at Week 24. 
• Open Label Period non-responder: Secukinumab 150 mg provided in a 1 mL PFS (two 
PFS for 300 mg dose, s.c.), administration every 4 weeks starting at Week 24. 
6.1.4 
Treatment duration 
The planned study duration is 60 weeks with the last secukinumab treatment administration at 
Week 48. Participants may be discontinued from treatment earlier due to unacceptable toxicity, 
disease progression and/or if the treatment is discontinued at the discretion of the investigator 
or the participant. For participants who in the opinion of the investigator are still deriving 
clinical benefit from the study drug, every effort will be made to continue provision of study 
treatment. 
Participants should continue to receive the study treatment until one or more criteria for 
treatment discontinuation described in Section 9.1.1 are met. 

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6.2 
Other treatments 
6.2.1 
Concomitant therapy 
During this study, NSAIDs, selected analgesics, selected disease-modifying anti-rheumatic 
drugs (DMARDs), i.e. MTX and sulfasalazine, and systemic corticosteroids are permitted as 
part of participants’ routine medical care and will not be provided by Novartis. The 
investigational site and / or the participant's treating physician are responsible for prescribing 
and providing any background therapy. 
The investigator should instruct the participant to notify the study site about any new 
medications he/she takes after the participant was enrolled into the study. All medications, 
procedures and significant non-drug therapies (including physical therapy and blood 
transfusions) administered after the participant was enrolled into the study must be recorded in 
the Prior/Concomitant medications electronical case report form (eCRF) page. 
6.2.1.1 
Permitted concomitant therapy requiring caution and/or action 
Guidelines for the use of specific medications are provided below: 
Methotrexate 
Participants taking MTX (≤ 25 mg/week) must be on a stable dose for at least 4 weeks before 
randomization and maintained stable until Week 24. Any changes in dose or initiation after 
Week 24 must be recorded in the Prior/Concomitant medications eCRF page. 
Folic acid 
Participants on MTX must be taking folic acid supplementation before randomization and 
during the trial to minimize the likelihood of MTX associated toxicity. 
Sulfasalazine 
Participants taking sulfasalazine (≤ 3 g/day) must be on a stable dose for at least 4 weeks before 
randomization and maintained stable until Week 24. Any changes in dose or initiation after 
Week 24 must be recorded in the Prior/Concomitant medications eCRF page. 
Leflunomide wash-out with cholestyramine 
In case of leflunomide treatment, a drug wash-out of 8 weeks has to be performed. However, 
another wash-out procedure might be considered. Cholestyramine could be given orally to 
wash-out the drug at a dose of 8 g three times a day (t.i.d.) Cholestyramine reduced plasma 
levels of the active leflunomide metabolite by approximately 40% in 24 hours and by 49 % to 
65 % in 48 hours in three healthy volunteers. The administration of cholestyramine is 
recommended in participants who require a drug elimination procedure. If a participant receives 
the dose of 8 g t.i.d. for 11 days, he/she could be safely randomized 4 weeks after the beginning 
of the 11 days treatment period. 
After all Week 24 assessments are completed, leflunomide therapy may be initiated as a 
background medication. Any initiation or changes in dose after Week 24 must be recorded in 
the Prior/Concomitant medications eCRF page. 
Systemic corticosteroids 

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Medication 
Prohibition period 
Action taken 
Infliximab 
8 weeks washout period prior to 
randomization to until Week 28 
Delay randomization or discontinue 
from study treatment 
Adalimumab, golimumab, 
certolizumab 
Unstable dose of MTX or 
sulfasalazine 
 
 
Other DMARD (except MTX or 
sulfasalazine) 
10 weeks washout period prior to 
randomization to until Week 28 
4 weeks prior to randomization to 
until Week 24 
 
 
4 weeks washout period prior to 
randomization to until Week 24, 
Delay randomization or discontinue 
from study treatment 
Achieve stable dose for at least 4 
weeks prior to randomization and 
remain on a stable dose up to 
Week 24 
Delay randomization or discontinue 
from study treatment 
Leflunomide 
8 weeks washout period prior to 
randomization to until Week 24 
Delay randomization or discontinue 
from study treatment 
Leflunomide with Cholestyramine 
washout 
Unstable dose of NSAIDs (COX1 
or COX2 inhibitors) 
 
 
Systemic corticosteroids > 10 mg 
prednisone equivalent* 
4 weeks washout period prior to 
randomization to until Week 24 
2 weeks prior to randomization to 
until Week 24 
 
 
2 weeks prior to randomization to 
until Week 24 
Delay randomization or discontinue 
from study treatment 
Achieve stable dose for at least 2 
weeks prior to randomization and 
remain on a stable dose up to 
Week 24 
Achieve stable dose for at least 2 
weeks prior to randomization and 
remain on a stable dose up to 
Week 24 
Intra-articular steroid injections 
4 weeks prior to randomization to 
until Week 24 
Delay randomization or discontinue 
from study treatment 
Any biological immunomodulating 
agents, except those targeting 
TNFα** 
Any cell-depleting therapies 
including but not limited to anti-
CD20 or investigational agents 
(e.g., anti-CD52, anti-CD4, anti-
CD5, anti-CD3, anti-CD19) 
From screening to follow up visit 
No prior exposure allowed 
 
 
From screening to follow up visit 
No prior exposure allowed 
Any investigational treatment or 
participation in any interventional 
trial 
Analgesics other than 
paracetamol/acetaminophen or low 
strength opioids PRN(Pro re nata) 
4 weeks or 5 half-lives (whichever 
is longer) prior to randomization to 
follow up visit 
4 weeks prior to randomization to 
follow up visit 
Delay randomization or 
discontinue from study treatment 
 
Delay randomization or 
discontinue from study treatment 
Live vaccinations 
6 weeks prior to randomization to 
follow up visit 
Traditional Chinese Medicines*** 
Until Week 24, if adjustment 
needed by investigator’s 
judgement 
*See details about corticosteroid management in Section 6.2.1. 
Delay randomization or 
discontinue from study treatment 
Delay randomization or 
discontinue from study treatment 
**These agents fall under the category of biologic immunomodulators and are prohibited medications. 
Administration of these agents requires study treatment discontinuation (see Section 9.1) 
***Traditional Chinese herb medicines, Chinese patent medicines etc. 
 
6.2.3 
Escape Medication 
Escape medication is defined as any new therapeutic intervention or a significant change to 
ongoing therapy made because a participant is experiencing either no benefit from participation 
in the trial or worsening/exacerbation of their disease. 

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From Week 28 on, based on the clinical judgment of disease activity by the investigator and the 
participant, participants may be considered as inadequate responders. Participants who are 
repeatedly (e.g. two or more consecutive visits) considered to be inadequate responders will 
have the option to enter escape. Upon entering “escape”, participants can be switched to 
treatment according to locally applicable clinical practice. 
Participants have the option to either discontinue study treatment (escape to locally applicable 
clinical practice treatment but continue study participation) or completely discontinue from the 
study (no further study participation) for any reason. 
While all participants have already switched to open label treatment with secukinumab 150 mg 
at Week 16, the originally randomized treatment assignment before Week 16 (secukinumab 150 
mg or placebo) will remain blinded until the end of study. From Week 24 onward, if based on 
the clinical practice, the participants escape to include the use of a biologic such as a TNFα 
inhibitor, it should be prescribed in accordance with investigator practice and local treatment 
guidelines. Participants switching to a biologic therapy (e.g. anti-TNFα) other than 
secukinumab must not receive any further study medication and the investigator will be 
recommended to consider a wash out period after the last administration of study treatment prior 
to starting any other biologic treatment. All other participants will continue their original 
assigned treatment. 
Any use of escape medication must be recorded in the Prior/Concomitant medications eCRF. 
6.3 
Participant numbering, treatment assignment, randomization 
6.3.1 
Participant numbering 
Each participant is identified in the study by a Participant Number (Participant No.), that is 
assigned when the participant is enrolled for screening and is retained for the participant 
throughout his/her participation in the trial. A new Participant No. will be assigned at every 
subsequent enrollment if the participant is re-screened. The Participant No. consists of the 
Center Number (Center No.) (as assigned by Novartis to the investigative site) with a sequential 
participant number suffixed to it, so that each participant’s participation is numbered uniquely 
across the entire database. Upon signing the informed consent form, the participant is assigned 
to the next sequential Participant No. available. 
Participants numbers are assigned when the site creates the first entry for the participant in the 
CRF, therefore CRF entry must be created prior to contacting the Interactive Response 
Technology system. 
A new ICF will need to be signed if the investigator chooses to re-screen the participant after a 
participant has screen failed, and the participant will be assigned a new Participant No. 
6.3.2 
Treatment assignment, randomization 
At baseline visit, all eligible participants will be randomized via Interactive Response 
Technology (IRT) to one of the treatment groups. The investigator or his/her delegate will 
contact the IRT after confirming that the participant fulfills all the inclusion/exclusion criteria. 
The IRT will assign a randomization number to the participant, which will be used to link the 

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For details regarding the planned primary endpoint analysis, refer to Section 12.7. 
The reading of MRI scan and X-ray will be performed in a blinded fashion by independent 
readers and post screening results will only be provided to the sites after full unblinding of the 
study after completion of the study. 
Unblinding of original randomized treatment assignment (at the site level and below) before the 
final database lock and analyses are completed will only occur in the case of participant 
emergencies. 
Unblinding of the sponsor staff (except field monitor) will occur at the time of the primary 
endpoint analysis. The study will be conducted in an open label fashion after Week 16, however, 
original group assignment from the randomization will remain blinded until the end of study 
for site staf and field monitors. 
Table 6-3 
Blinding Level 
 
Time or Event 
Randomization 
Treatment 
allocation 
Safety event 
(single participant 
Primary 
Endpoint 
Role 
list generated 
& dosing 
unblinded) 
Analysis 
Participants 
B 
B 
B 
B 
Site staff 
B 
B 
B 
B 
Field Monitor 
B 
B 
B 
B 
Drug Supply and Randomization Office 
UI 
UI 
UI 
UI 
Statistician/statistical programmer/data 
analysts 
B 
B 
B 
UI 
All other sponsor staff not identified above 
B 
B 
B 
UI 
B: Remains blinded UI: Allowed to be unblinded on individual participant level 
 
6.5 
Dose escalation and dose modification 
Study treatment dose adjustments are not permitted. Study treatment interruption is also not 
permitted with the following exceptions: 
Study treatment interruption is only permitted if, in the opinion of the investigator, a participant 
is deemed to be placed at a significant safety risk unless dosing is temporarily interrupted. In 
such cases study treatment should be interrupted only during the time that this risk is present 
and ongoing. Study treatment can be restarted at the next scheduled visit after resolution of the 
safety risk. 
The effect of secukinumab on live vaccines is unknown; therefore, live vaccines should not be 
administered during participation in the study. In case a live vaccine has been administered due 
to a medical urgency, the participant must discontinue the study treatment. 
Any study treatment interruption must be recorded on the Dosage Administration Record eCRF. 
In all cases the original visit schedule should be maintained (no recalculation from the last 
visit). 

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6.5.1 
Dose escalation guidelines 
Only at the Week 24 visit, any participant who does not meet ASAS20 criteria per IRT 
confirmation is categorized as non-responder to the secukinumab 150 mg q4wk dose and will 
be escalated to 300 mg q4wk in an open label fashion. 
6.6 
Additional treatment guidance 
Treatment modifications as new therapeutic interventions or a significant change to ongoing 
therapy must not be made before completion of Week 24 assessments. 
From Week 24 on, if the participant or investigator feels the level of disease activity requires 
an escalation in therapy, background medications such as NSAIDs and DMARDs may be 
modified or added to treat signs and symptoms of nr-axSpA as outlined in Section 6.2.1. All 
medication changes must be recorded in the Prior/Concomitant medications eCRF page. 
Participants who do not achieve ASAS 20 response at Week 24 visit will be escalated to 300 
mg secukinuimab s.c. through Week 48 to assess if secukinumab 300 mg will provide further 
benefit to participants. 
While nr-axSpA is a multifaceted disease and the assessment of responder status should be 
based on the global clinical picture and not on a single efficacy parameter; repeatedly (e.g. at 
two or more consecutive visits) not achieving a clinically meaningful improvement in the 
BASDAI of ≥ 20% or ≥ 1 unit (0 – 10 scale) (Pavy et al 2005) may be considered as a general 
guidance for considering a participant inadequate responder or non-responder to study treatment. 
Although no participant will be restricted from receiving necessary medications for lack of 
benefit or worsening of disease, if treatment with prohibited biologics (as described in 
Section 6.2.2) occurs, participants may remain in the trial but must discontinue study treatment. 
Efficacy will be assessed in detail at every study visit, and participants who are deemed not to 
be benefiting from the study treatment based on safety and efficacy assessments (see 
Section 9.1.1) or for any reason on their own accord will be free to discontinue participation in 
the study at any time. Changes in NSAID, non-biologic DMARDs and corticosteroid 
concomitant therapy are permitted as per investigator's and participant's clinical judgment after 
all Week 24 assessments are completed. Please see Section 6.2.1, Section 6.2.2 and 
Section 9.1.1 for details. 
Any treatment modifications or new therapeutic interventions must be recorded in the 
Prior/Concomitant medications eCRF page. 
6.6.1 
Treatment compliance 
Every time the study treatment is to be administered, IRT needs to be accessed for the 
medication (kit) number. The date and time of all study treatment administered during the study 
and any deviations from the protocol treatment schedule will be captured by the investigator 
staff on the appropriate Dosage Administration Record eCRF page. 
In this study, the compliance to the planned administration schedule is expected to be high since 
the study treatment will be administered on site by self-administration by the participants or the 
trained site staff. 

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Exposure to the study treatment will be based on the number of injections administered. 
Compliance with the study treatment will be assessed by the field monitor at each visit using 
information provided by the pharmacist or by the investigator. Compliance is expected to be 
100%, unless temporary interruption is needed for safety reasons as described in Section 6.5. 
6.6.2 
Recommended treatment of adverse events 
Medication used to treat AE must be recorded on the appropriate CRF. 
6.6.3 
Emergency breaking of assigned treatment code 
Emergency code breaks must only be undertaken when it is required to in order to treat the 
participant safely. Blinding codes may also be broken after a participant discontinues treatment 
due to disease progression if deemed essential to allow the investigator to select the participant’s 
next treatment regimen, and after discussion and agreement with the sponsor. Most often, study 
treatment discontinuation and knowledge of the possible treatment assignments are sufficient 
to treat a study participant who presents with an emergency condition. Emergency treatment 
code breaks are performed using the IRT. When the investigator contacts the system to break a 
treatment code for a participant, he/she must provide the requested participant identifying 
information and confirm the necessity to break the treatment code for the participant. The 
investigator will then receive details of the investigational drug treatment for the specified 
participant and a fax or email confirming this information. The system will automatically inform 
the Novartis monitor for the site and the study team that the code has been broken. 
It is the investigator's responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT at any time in case of emergency. The investigator will provide: 
• protocol number 
• site number 
• participant number 
In addition, oral and written information to the participant must be provided on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable, to ensure that un-blinding 
can be performed at any time. 
After an emergency unblinding, study medication must be discontinued. 
In the case of accidental unblinding, participants will not be replaced by newly enrolled 
participants. 
6.7 
Preparation and dispensation 
Each study site will be supplied with study drug of identical appearance in packaging as 
described under investigational and control drugs section. 
A unique medication number is printed on the study medication label. 
Investigator staff will identify the study medication kits to dispense to the participant by 
contacting the IRT and obtaining the medication number(s). The study medication has a 2-part 
label (base plus tear-off label), immediately before dispensing the medication kit to the 
participant, site personnel will detach the outer part of the label from the packaging and affix it 
to the source document. 

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All doses of study treatment (secukinumab and placebo) will be administered at the study site, 
and it is preferred that participants self-administer. However, if the participant is not able or not 
willing to self-administer, administration will be performed by study site staff. The injections 
will be self-administered by the participant at the study site under the supervision of a site staff 
member after the study assessments for the visit have been completed. Participants will be 
instructed by the site staff on how to self-inject study treatment using a PFS, following the 
Instructions for Use (IFU). Home administration is not allowed in this study except when there 
is global health disruptive event, such as pandemic/epidemic (e.g. COVID-19). The instructions 
and procedures are outlined in Section 16.9. 
Any PFS for which a defect or malfunction is noticed prior to or during the administration at 
any of the study visits, must be kept at the site until guidance is received from Novartis on 
whether it should be returned to Novartis for investigation or discarded. PFS identified as 
defective should be stored according to local guidelines, until specific instruction is discussed 
with Novartis personnel. Additionally, from BSL onwards, any noticed defect, malfunction, 
problem during the injections or product complaints with the PFS should be recorded in the 
source document. Sites should detail the issue, the date, the kit number and the visit number. 
Site will be asked to record based on their judgment whether the observed issue was primarily 
related to the PFS device or to the user. PFS malfunctions should also be immediately reported 
to Novartis personnel as a necessary replacement kit may need to be provided. 
Prior to administration the boxes containing the PFSs with study treatment, it should be allowed 
to come to room temperature unopened for 15-30 minutes prior to injection. 
The injections will be administered into the appropriate site of the body (thighs, arms, abdomen), 
and each injection should be given at a different injection site to reduce the risk of reaction. 
Each new injection should be given at least one inch from the previously used site. 
Used safety syringes should be disposed immediately after use in a sharps container or 
according to the local regulatory requirements. 
 
7 
Informed consent procedures 
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation), Institutional Review Board (IRB)/Independent Ethics 
Committee (IEC)-approved informed consent. 
If applicable, in cases where the participants’ representative(s) gives consent (if allowed 
according to local requirements), the participant must be informed about the study to the extent 
possible given his/her understanding. If the participant is capable of doing so, he/she must 
indicate agreement by personally signing and dating the written informed consent document. 
Informed consent must be obtained before conducting any study-specific procedures (e.g., all 
of the procedures described in the protocol). The process of obtaining informed consent must 
be documented in the participant source documents. 
Novartis will provide to investigators in a separate document a proposed informed consent form 
that complies with the ICH GCP guidelines and regulatory requirements and is considered 
appropriate for this study. Any changes to the proposed consent form suggested by the 
investigator must be agreed by Novartis before submission to the IRB/IEC. 

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Information about common side effects already known about the investigational drug can be 
found in the IIB. This information will be included in the participant informed consent and 
should be discussed with the participant during the study as needed. Any new information 
regarding the safety profile of the investigational drug that is identified between IB updates will 
be communicated as appropriate, for example, via an investigator notification (IN) or an 
aggregate safety finding. New information might require an update to the informed consent and 
then must be discussed with the participant. 
The following informed consents are included in this study: 
• Main study consent, which also included: 
• A subsection that requires a separate signature for the ‘Optional Consent for 
Additional Research’ to allow future research on data/samples collected during this 
study 
• As applicable, Pregnancy Outcomes Reporting Consent for female participants who 
took study treatment 
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 after IRB/IEC 
approval. 
When there is global health disruptive event, such as pandemic/epidemic (e.g. COVID-19) that 
may challenge the ability to obtain a standard written informed consent due to limits that prevent 
an on-site visit, the instructions and procedures of this situation are outlined in Section 16.9. 
 
8 
Visit schedule and assessments 
The Assessment Schedule Table 8-1 lists all of the assessments and when they are performed. 
Participants should be seen for all visits/assessments as outlined in the assessment schedule 
Table 8-1 or as close to the designated day/time as possible. Missed or rescheduled visits should 
not lead to automatic discontinuation. 
Participants who prematurely discontinue study should return for end of treatment visit 4 weeks 
after the last study treatment administration, as well as return for the follow-up visit 12 weeks 
after the last study treatment administration. 
If they refuse to return for these assessments or are unable to do so, every effort should be made 
to contact them or a knowledgeable informant by telephone to determine the reason. 
At a minimum, participants will be contacted for safety evaluations during the 30 days 
following the last study visit, however preferably for a follow-up visit 12 weeks after last study 
treatment. Attempts to contact the participant should be recorded in the source documentation. 
If a global health disruptive event, such as a pandemic/epidemic (e.g. COVID-19) limits or 
prevents on-site study visits, study treatment dispensing and other study assessments may be 
impacted. The instructions and procedures of this situation are outlined in Section 16.9. 

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X Assessment to be recorded in the clinical database or received electronically from a vendor 
S Assessment to be recorded in the source documentation only 
1 If the participant’s washout period ≤ 4 weeks, Screening visit 1 (SV1) and Screening visit 2 (SV2) can be performed on the same day. 
2 For all participants who discontinue the study prematurely, the investigator should ensure that the participant completes an end of treatment visit 4 weeks after last 
study treatment and also returns after an additional 8 weeks for a final follow-up visit (12 weeks after last study treatment). 
3 Eligibility and relevant medical history assessments are conducted at SV1, SV2 and BSL. The data for all three visits should be recorded on the corresponding eCRF. 
4 Extra-axial involvement such as uveitis, psoriasis, inflammatory bowel disease, dactylitis, enthesitis, peripheral arthritis 
5 Unless MRI according to the imaging criteria was taken within the past 3 months prior to targeted Baseline. A copy of MRI or radiologist’s report must be kept in the 
source documentation. 
6 Unless X-ray according to the imaging criteria was taken within the past 3 months prior Screening. A copy of the x-ray or radiologist’s report must be kept in the source 
documentation 
7 The PPD skin test can be performed at any time during the screening period, but it must be read within 72 hours and before randomization. 
8 A chest X-ray or CT is required if it was not performed and evaluated within 3 months prior to screening. The X-ray should be performed after it is certain, the 
participant meets inclusion/exclusion criteria in order to minimize unnecessary exposure to radiation. The X-ray may be replaced by a CT assessment. A copy of the x-
ray/ CT or radiologist’s report must be kept in the source documentation. 
9 Hepatitis B and/or hepatitis C and/or HIV serology testing to be performed during screening period only if required as per local medical practice or local regulations 
prior to initiation of therapy. These assessments will be documented in source records only and will not be entered into the eCRF. 
10 All the assessments need to be completed before the administration. 
11 AEs/SAEs occurring after the participant has signed the informed consent must be captured on the appropriate eCRF page. 
12 Sample must be obtained fasting 

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8.1 
Screening 
Re-screening of a participant who has failed screening may be allowed. In such cases, a new 
ICF must be signed. A new participant number will be assigned to the participant. The re-screen 
form will have to be completed in the eCRF and in IRT to provide the original participant 
number. An individual participant can only be re-screened once for the study. 
All required screening assessments must be repeated if they do not meet the allowed time 
window for screening when the participant is re-screened for participation in the study. 
Once the number of participants screened and enrolled is likely to ensure target enrollment, the 
Sponsor may close the study to further screening. In this case, the participants who screen failed 
will not be permitted to re-screen. 
The study IRB/IEC approved informed consent form must be signed and dated before any 
screening procedures are performed, except for radiological evaluations which were performed 
as part of the participant's clinical standard of care within the acceptable screening window. 
Participants will be evaluated against study inclusion and exclusion criteria and safety 
assessments (refer to Table 8-1). Screening assessments must be repeated if performed outside 
of the specified screening window (refer to Table 8-1). Participants must meet all inclusion and 
none of the exclusion criteria at screening in order to be eligible for the study. 
Screening will be flexible in duration based on the time required to washout prior anti-rheumatic 
and other medications and will have a duration of up to 10 weeks, during which time the 
participant will sign the informed consent form (ICF), be evaluated for eligibility and sufficient 
time is allowed for potential medication washout, in addition to all other assessments indicated 
in Table 8-1. 
Screening will consist of two consecutive visits. During Screening visit 1, initial assessments 
will be performed as outlined in Table 8-1. At that visit, the duration of the washout period will 
be determined and Screening visit 2 will be performed as follows: 
• If the washout period is ≤ 4 weeks, the investigator should proceed directly to Screening 
visit 2 on the same day and complete all assessments in the next 4 weeks prior to 
randomization. 
• If the washout period is more than 4 weeks, the participant will be instructed to initiate the 
necessary washout regimen and return for Screening visit 2 at 4 weeks prior to 
randomization. 
The rationale is that in all cases Screening visit 2 must occur within the 4 weeks prior to 
randomization. 
All participants evaluated at Screening visits 1 and 2 for eligibility should not be screen failed 
on the basis of a medication requiring washout, unless the participant will be unable to complete 
the washout in the appropriate time frame before randomization. 
Investigators will have the discretion to record abnormal test findings on the medical history 
eCRF whenever in their judgment, the test abnormality occurred prior to the informed consent 
signature. 

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8.1.1 
Information to be collected on screening failures 
Participants who sign an informed consent form may discontinue from the study prior to 
randomization will be considered a screen failure. The reason for screen failure should be 
recorded on the appropriate Case Report Form. 
The demographic information, informed consent, and Inclusion/Exclusion pages must also be 
completed for screen failure participants. No other data will be entered into the clinical database 
for participants who are screen failures, unless the participant experienced a serious adverse 
event during the screening phase (see SAE section for reporting details). Adverse events that 
are not SAEs will be followed by the investigator and collected only in the source data. If the 
participant fails to be randomized in the double-blind treatment period at baseline, the IRT must 
be notified within 2 days of the screen fail that the participant was not randomized and the 
reason for not being randomized will be entered on the Screening Phase Disposition eCRF page. 
Participants who are randomized and fail to start treatment, e.g. participants randomized in error, 
will be considered an early terminator. The reason for early termination should be recorded on 
the appropriate Case Report Form. 
8.2 
Participant demographics/other baseline characteristics 
Country-specific (China) regulations should be considered for the collection of demographic 
and baseline characteristics in alignment with eCRF. 
Participant demographic and baseline characteristic data to be collected on all participants 
include: 
• Age, sex, race and ethnicity 
• Relevant nr-axSpA and general medical history/current medical condition present before 
inform consent was signed, history of extra-axial involvement (uveitis, psoriasis, 
inflammatory bowel disease, dactylitis, enthesitis, peripheral arthritis), date of onset of 
inflammatory back pain, number of previous DMARDs used, date of diagnosis of nr-
axSpA, previous nr-axSpA therapies, cardiovascular medical history and smoking history. 
Whenever possible, diagnoses and not symptoms will be recorded here. 
Participant race and ethnicity are collected and analyzed to identify variations in safety or 
efficacy due to these factors as well as to assess the diversity of the study population as required 
by Health Authorities 
Investigators will have the discretion to record abnormal test findings on the medical history 
eCRF if, in their judgment, the test abnormality occurred prior to the informed consent signature. 
8.3 
Efficacy 
• Assessment of SpondyloArthritis International Society criteria (ASAS) 
• Patient’s global assessment of disease activity (VAS) 
• Patient’s assessment of back pain intensity (VAS) 
• Bath Ankylosing Spondylitis Functional Index (BASFI) 
• Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
 
 

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8.3.1 
Assessment of SpondyloArthritis International Society criteria (ASAS) 
The ASAS response measures consist of the following assessment domains (Sieper et al 2009). 
Main 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 
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: 
 
2. C-reactive protein (acute phase reactant) 
8.3.1.1 
ASAS Response Criteria-20% (ASAS20) 
ASAS20 response is defined as an improvement of ≥20% and ≥1 unit on a scale of 10 in at least 
three of the four main domains and no worsening of ≥20% and ≥1 unit on a scale of 10 in the 
remaining domain. 
8.3.1.2 
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 three of the four main domains and no worsening at all in the remaining domain. 
8.3.1.3 
ASAS 5/6 improvement criteria 
The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six 
domains. 
8.3.1.4 
ASAS partial remission criteria 
The ASAS partial remission criteria are defined as a value not above 2 units in each of the four 
main domains on a scale of 10. 

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8.3.2 
Patients global assessment of disease activity (VAS) 
The patient’s global assessment of disease activity will be performed using a 100 mm visual 
analog scale (VAS) ranging from not severe to very severe, after the question, "How active was 
your disease on average during the last week?” 
8.3.3 
Patients 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?” 
8.3.4 
Bath Ankylosing Spondylitis Functional Index (BASFI) 
The BASFI is a set of 10 questions designed to determine the degree of functional limitation in 
those participants with AS. The ten questions were chosen with major input from participants 
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 
by a continuous VAS) is used to answer the questions. The mean of the ten scales gives the 
BASFI score – a value between 0 and 10. 
8.3.5 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
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 duration 
6. Morning stiffness severity 
To give each symptom equal weighting, the mean (average) of the two scores relating to 
morning stiffness is taken (questions 5 and 6). The resulting 0 to 10 score 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 participants 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 AS. BASDAI is a quick 
and simple index taking between 30 seconds and 2 minutes to complete. 
8.3.5.1 
BASDAI 50 
The BASDAI 50 is defined as an improvement of at least 50% in the BASDAI compared to 
baseline. 

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When there is global health disruptive event, such as pandemic/epidemic (e.g. COVID-19) that 
may limit or prevent on-site study visits to collect images, the instructions and procedures of 
this situation are outlined in Section 16.9. 
8.3.13 
Appropriateness of efficacy assessments 
The efficacy outcome measures used in this study are the standard measures used across all AS 
and nr-axSpA trials and are considered to be required for filing. 
8.4 
Safety and Tolerability 
Safety assessments are specified below with the assessment schedule detailing when each 
assessment is to be performed. If global health disruptive event, such as pandemic/epidemic 
(e.g. COVID-19) limits or prevents on-site study visits, the safety assessment may not be 
performed. The instructions and procedures of this situation are outlined in Section 16.9. 
• QuantiFERON TB-Gold test or PPD skin test 
• Chest X-ray or CT 
• Physical examination 
• Vital signs 
• Height and weight 
• Laboratory evaluations 
 
 
• Electrocardiogram 
• Pregnancy and assessment of fertility 
• Local tolerability (Injection site reactions) 
• Tolerability of secukinumab 
For details on AE collection and reporting, refer to AE Section 10.1.1. 
Table 8-2 
Safety and tolerability assessments 
Assessment 
Specification 
Physical 
examination 
The physical examination will include the examination of general appearance, skin, neck, 
eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular 
and neurological system. 
Information for all physical examinations must be included in the source documentation at 
the study site. Significant findings that are present before signing the ICF must be included in 
the relevant medical history eCRF. Significant findings made after signing the ICF that meet 
the definition of an AE must be recorded in the Adverse Event eCRF and if SAE criteria are 
met, also reported as a SAE. 
Vital signs 
Vital signs will include blood pressure and pulse rate measurements after 5 minutes rest in 
sitting position. 
If possible, vital signs assessments should be performed by the same study site staff 
member using the same validated device throughout the study. 
Height and 
weight 
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram [kg] in indoor 
clothing) (both without shoes) will be measured. 
If possible, body weight assessments should be performed by the same study site staff 
member using the same scale throughout the study. 
 

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8.4.1 
Laboratory evaluations 
A central laboratory will be used for analysis of all specimens collected listed below (except 
urinalysis, urine/serum pregnancy test and erythrocyte sedimentation rate). Details on the 
collection, shipment of samples and reporting of results by the central laboratory are provided 
in the laboratory manual. For the identification of clinically notable values, see Section 16.1. 
All participants with laboratory tests containing clinically significant abnormal values are to be 
followed until the values return to normal ranges or until a valid reason, other than treatment 
related AE, is defined. 
Table 8-3 
Clinical Laboratory Assessments 
 
Test Category 
Test Name 
 
Hematology 
Hematocrit, Hemoglobin, MCH, MCHC, MCV, Platelets, Red blood cells, White blood cells, 
Red Blood Cell, Morphology, Differential (Basophils, Eosinophils, Lymphocytes, Monocytes, 
Neutrophils, white blood cell counts) 
Chemistry 
Albumin, Alkaline phosphatase, ALT(SGPT), AST (SGOT), Gamma-glutamyl-transferase 
(GGT), Lactate dehydrogenase (LDH), Bicarbonate, Calcium, Magnesium, Phosphorus, 
Sodium, Potassium, Creatinine, Direct Bilirubin, Total Bilirubin, Total Protein, Blood Urea 
Nitrogen (BUN) or Urea, Uric Acid, Glucose (fasting) 
Urinalysis 
Microscopic Panel (Red Blood Cells, White Blood Cells, Casts, Crystals, Bacteria, Epithelial 
cells) 
Macroscopic Panel (Dipstick) (Color, Bilirubin, Blood, Glucose, Ketones, Leukocytes 
esterase, Nitrite, pH, Protein, Specific Gravity, Urobilinogen) 
The urinalysis results for standard parameters such as protein, glucose, blood and WBCs 
will be recorded in the appropriate eCRF page. 
Lipid panel and 
marker 
A lipid profile including High Density Lipoprotein, Low Density Lipoprotein, cholesterol and 
triglycerides will be measured from a fasting blood sample. 
A cardiovascular profile including lipoprotein (a), apolipoprotein B, apolipoprotein A-1, and 
adiponectin will be measured from a fasting blood sample. 
Pregnancy Test 
Serum / Urine pregnancy test 
8.4.2 
Electrocardiogram (ECG) 
A standard 12 lead ECG will be performed as indicated in Table 8-1. In this study, ECG will 
be performed locally. ECGs must be recorded after 10 minutes rest in the supine position to 
ensure a stable baseline. The preferred sequence of cardiovascular data collection during study 
visits is ECG collection first, followed by vital signs, and blood sampling. 
Each ECG tracing should be labeled with the study number, participant number, and date. The 
original ECG tracing on non-heat-sensitive paper or its certified copy appropriately signed, 
must be collected and kept in the source document at the study site. 
Although there is no exclusion criterion based on ECG results, the baseline ECG at the 
Randomization visit must be reviewed locally for major abnormalities before administration of 
study treatment. 
Clinically significant abnormalities must be recorded on the CRF as either medical 
history/current medical conditions or adverse events as appropriate. 
8.4.3 
Pregnancy 
All pre-menopausal women who are not surgically sterile will have a serum β-hCG test (serum 
pregnancy test) performed at the second screening visit in central lab, the rest pregnancy 

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assessments as indicated in Table 8-1 can be urine pregnancy test or serum pregnancy test as 
applicable in local lab. A positive urine pregnancy test requires immediate interruption of study 
drug until serum β-hCG is performed and found to be negative. If positive, the participant must 
be discontinued from the study treatment. Additional pregnancy testing might be performed if 
requested by local requirements. 
8.4.4 
Chest X-ray or CT 
A chest X-ray or CT scan at screening (or within 3 months prior to screening) is performed to 
rule out the presence of a pulmonary malignancy or infectious process, in particular, TB. 
When there is global health disruptive event, such as pandemic/epidemic (e.g. COVID-19) that 
may limit or prevent on-site study visits to collect images, the instructions and procedures of 
this situation are outlined in Section 16.9. 
8.4.5 
QuantiFERON TB-Gold test or PPD skin test 
Either a QuantiFERON TB-Gold test or a PPD skin test must be performed at screening. 
Participants with a positive test may participate in the study if further work up (according to 
local practice/guidelines) establishes conclusively that the participant has no evidence of active 
TB, or if presence of latent TB is established then treatment according to local guidelines must 
have been initiated. 
QuantiFERON TB-Gold test 
A QuantiFERON TB-Gold test is to be performed at the second screening visit and the results 
to be available prior to randomization to determine the participant’s eligibility. The test will be 
used to screen the participant population for latent TB infection. 
The test will be analyzed by the central laboratory. Details on the collection, processing and 
shipment of samples and reporting of results by the central laboratory are provided in the 
laboratory manual. 
PPD skin test 
A PPD skin test is to be performed at screening and read before randomization to determine the 
participant's eligibility for the trial. The test dose is bioequivalent to 5 tuberculin units of 
standard PPD injected intradermally, usually into the volar surface of the forearm. The site is 
cleaned and the PPD extract is then injected into the most superficial layer under the skin. If 
given correctly, the injection should raise a small wheal of about 5 mm, which resolves within 
10-15 minutes. 
Since the reaction (induration) will take 48-72 hours to develop, the participants must return to 
the investigators’ site within that time for a proper evaluation of the injection site. This will 
determine whether the participant has had a significant reaction to the PPD test. A reaction is 
measured in millimeters of induration (hard swelling) at the site. A PPD skin induration ≥5 mm 
(or according to local practice/guidelines) is interpreted as a positive result. 

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8.5.1 
Clinical Outcome Assessments (COAs) 
The impact of nr-axSpA on various aspects of participant's health-related quality of life (QoL) 
will be assessed by the following instruments: 
• SF-36 
• ASQoL 
All questionnaires will be available, in the local languages. 
All questionnaires will be completed at the scheduled study visit prior to the participant seeing 
the investigator for any other clinical assessment or evaluation. The participant should be given 
sufficient instruction, space, time and privacy to complete the questionnaires. The study 
coordinator should check each questionnaire for completeness and encourage the participant to 
complete any missing responses. Guidelines for administering the PRO questionnaires can be 
found in Section 16.8. 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 participant. If AEs or SAEs are confirmed, then the physician must 
record the events as per instructions given in Section 16.8 of the protocol. Investigators should 
not encourage the participants to change the responses reported in the completed questionnaires. 
The language in which each of the questionnaires to be completed will also be captured the first 
time a questionnaire is administered. 
In the event of global health disruptive event, such as pandemic/epidemic (e.g. COVID-
19) that limits or prevents on-site study visits, selected efficacy assessments including 
PPROs can alternatively be done as per the instructions and procedures of this situation outlined 
in Section 16.9. 
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 quality 
of life among healthy participants 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 participants. 
The purpose of the SF-36 in this study is to assess the health-related QoL of participants. Given 
the acute nature of this disease, version 2, with a 1-week recall period, will be used in this study. 
The use of the SF-36, especially the SF-36 PCS, in patients with nr-axSpA can be supported. 
While SF-36 was widely used to assess the health related quality of life in AS patients, a recent 

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Study treatment must be discontinued under the following circumstances: 
• Participant decision 
• Pregnancy 
• Use of prohibited treatment as per recommendations in the prohibited treatment section 
• Any situation in which study participation might result in a safety risk to the participant 
• Following emergency unblinding 
• Emergence of the following adverse events: 
• Any severe or serious adverse event that is not compatible with administration of 
study medication, including adverse events that require treatment with prohibited co-
medication 
• Onset of lymphoproliferative disease or any malignancy except for treated basal cell 
carcinoma, treated actinic keratoses, treated in situ carcinoma of the cervix or non-
invasive malignant colon polyps which are being or have been removed 
• Life-threatening infection 
• Any laboratory abnormalities that in the judgment of the investigator are clinically 
significant and are deemed to place the participant at a safety risk for continuation in 
the study (A general guidance on clinically notable laboratory values is provided in 
Section 16.1.) 
• Use of any prohibited treatment as defined in Section 6.2.2 
• Any protocol deviation that results in a significant risk to the participant’s safety 
• Any laboratory abnormalities that in the judgment of the investigator, taking into 
consideration the participant’s overall status, prevents the participant from continuing 
participation in the study 
In addition to these requirements for study treatment discontinuation, the investigator should 
discontinue study treatment for a given participant if on balance, he/she thinks that continuation 
would be detrimental to the participant’s well-being. 
If discontinuation of study treatment occurs, the investigator should make a reasonable effort 
to understand the primary reason for the participant’s premature discontinuation of study 
treatment and record this information. 
Participants who discontinue study treatment or who decide they do not wish to participate in 
the study further should NOT be considered withdrawn from the study UNLESS they withdraw 
their consent (see 'Withdrawal of Informed Consent' section). 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 participant/pre-designated contact as specified in the lost to follow-up 
section. This contact should preferably be done according to the study visit schedule. 
If the participant cannot or is unwilling to attend any visit(s), the site staff should maintain 
regular telephone contact with the participant, or with a person pre-designated by the participant. 
This telephone contact should preferably be done according to the study visit schedule. 
After study treatment discontinuation, at a minimum, in abbreviated visits, the following data 
should be collected at clinic visits or via telephone/email contact: 

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• New / concomitant treatments 
• Adverse Events / Serious Adverse Events 
Participants who discontinue study should undergo an end of treatment visit at 4 weeks after 
last study treatment and then also return after an additional 8 weeks for a final follow-up visit, 
corresponding to Week 60 (12 weeks after last study treatment; see Table 8-1). 
The investigator must also contact the IRT to register the participant’s discontinuation from 
study treatment. 
If discontinuation occurs because treatment code has been broken, please refer to Emergency 
breaking of treatment code section. 
9.1.2 
Withdrawal of informed consent 
Participants may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent occurs only when a participant: 
• Does not want to participate in the study anymore, 
and 
• Does not want any further visits or assessments 
and 
• Does not want any further study related contacts 
In this situation, the investigator should make a reasonable effort (e.g. telephone, e-mail, letter) 
to understand the primary reason for the participant’s decision to withdraw his/her consent and 
record this information. 
Where consent to the use of personal and coded data is not required, participant therefore cannot 
withdraw consent. They still retain the right to object to the further use of personal data. 
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing. 
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study discontinuation. A final 
evaluation at the time of the participant’s study discontinuation should be made as detailed in 
the assessment table. 
Novartis will continue to retain and use all research results (data) that have already been 
collected for the study evaluation. 
9.1.3 
Lost to follow-up 
For participants whose status is unclear because they fail to appear for study visits without 
stating an intention to discontinue or withdraw, the investigator must show "due diligence" by 
documenting in the source documents steps taken to contact the participant, e.g. dates of 
telephone calls, registered letters, etc. A participant should not be considered as lost to follow-
up until due diligence has been completed or until his/her scheduled End of Study visit would 
have occurred. 

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9.1.4 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time. 
Reasons for early termination: 
• Unexpected, significant, or unacceptable safety risk to participants enrolled in the study 
• Practical reasons (including slow enrollment), or for regulatory or medical reasons 
• Discontinuation of study drug development 
In taking the decision to terminate, Novartis will always consider participant welfare and safety. 
Should early termination be necessary, participants must be seen as soon as possible and treated 
as a prematurely withdrawn participant. The investigator may be informed of additional 
procedures to be followed in order to ensure that adequate consideration is given to the 
protection of the participant’s interests. The investigator or sponsor depending on local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial. 
9.2 
Study completion and post-study treatment 
Study completion is defined as when the last participant finishes their Study Completion or end 
of study (i.e Week 60) visit and any repeat assessments associated with this visit have been 
documented and followed-up appropriately by the Investigator or, in the event of an early study 
termination decision, the date of that decision. 
Continuing care should be provided by the investigator and/or referring physician based on 
participant availability for follow-up. This care may include: 
• Enrollment in a rollover extension program or equivalent program, as applicable, provided 
the participant completed end of study visit (i.e Week 60) and could still deriving benefit 
from the study treatment based on investigator’s decision. 
A participant will be considered to have completed the double blind period if he/she received a 
maximum of 16 weeks of study treatment and upon completion of the scheduled study 
assessments and procedures up to and including Follow Up visit (i.e. Week 60) or continuation 
into the open label period. 
A participant will be considered to have completed the open label period if he/she has received 
a maximum of 48 weeks of study treatment and has completed the scheduled study assessments 
and procedures up to and including Follow Up visit (i.e. Week 60). 
Information on the participant's completion or discontinuation of the study and the reason for 
discontinuation of the study will be recorded on the study disposition eCRF page. 
In any case, the investigator or site staff must contact the IRT as soon as possible to record the 
participant's study completion and/or discontinuation. 
The investigator must provide follow-up medical care for all participants who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care. This care may 
include initiating another treatment outside of the study as deemed appropriate by the 
investigator. This treatment may be any non-biologic DMARD. In case of a biologic treatment, 
a waiting period of 3 months before initiating the treatment is recommended. 

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10 
Safety monitoring and reporting 
10.1 
Definition of adverse events and reporting requirements 
10.1.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical 
investigation participant after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. 
The investigator has the responsibility for managing the safety of individual participant and 
identifying adverse events. 
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
The occurrence of adverse events must be sought by non-directive questioning of the participant 
at each visit during the study. Adverse events also may be detected when they are volunteered 
by the participant during or between visits or through physical examination findings, laboratory 
test findings, or other assessments. Patient-Reported Outcomes are considered as other 
assessments to detect adverse events, see Section 8.5.1. 
Adverse events must be recorded under the signs, symptoms, or diagnosis associated with them, 
accompanied by the following information (as far as possible) (if the event is serious refer to 
Section 10.1.2): 
1. The severity grade include the following: 
• mild: usually transient in nature and generally not interfering with normal activities 
• moderate: sufficiently discomforting to interfere with normal activities 
• severe: prevents normal activities 
2. Its relationship to the study treatment. If the event is due to lack of efficacy or progression 
of underlying illness (i.e. progression of the study indication) the assessment of causality 
will usually be ‘Not suspected.’ The rationale for this guidance is that the symptoms of a 
lack of efficacy or progression of underlying illness are not caused by the trial drug, they 
happen in spite of its administration and/or both lack of efficacy and progression of 
underlying disease can only be evaluated meaningfully by an analysis of cohorts, not on a 
single participant 
3. Its duration (start and end dates) or if the event is ongoing, an outcome of not 
recovered/not resolved or recovering/resolving must be reported 
4. Whether it constitutes a SAE (see Section 10.1.2 for definition of SAE) and which 
seriousness criteria have been met 
5. Action taken regarding with study treatment. 
All adverse events must be treated appropriately. Treatment may include one or more of the 
following: 
• Dose not changed 
• Dose Reduced/increased 

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• 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 
medical history of the participant. 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Adverse event monitoring should be continued for at least 30 days following the last dose of 
study treatment. 
Once an adverse event is detected, it must be followed until its resolution or until it is judged to 
be permanent (e.g. continuing at the end of the study), and assessment must be made at each 
visit (or more frequently, if necessary) of any changes in severity, the suspected relationship to 
the interventions required to treat it, and the outcome. 
Information about adverse drug reactions for the investigational drug can be found in the 
Investigator's Brochure (IB) or will be communicated between IB updates in the form of IN. 
This information will be included in the participant informed consent and should be discussed 
with the participant during the study as needed. 
The investigator should also instruct each participant to report any new adverse event (beyond 
the protocol observation period) that the participant, or the participant's personal physician, 
believes might reasonably be related to study treatment. This information should be recorded 
in the investigator’s source documents, however, if the AE meets the criteria of an SAE, it must 
be reported to Novartis. 
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria: 
• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results 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 participant 
with the underlying disease. Alert ranges for laboratory and other test abnormalities are included 
in Section 16.1. 
10.1.2 
Serious adverse events 
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] 
undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following 
criteria: 
• fatal 
• life-threatening 

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Life-threatening in the context of a SAE refers to a reaction in which the participant was at risk 
of death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to the ICH-E2D Guidelines). 
• results in persistent or significant disability/incapacity 
• constitutes a congenital anomaly/birth defect 
• requires in-patient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
• routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition 
• elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
• social reasons and respite care in the absence of any deterioration in the participant’s 
general condition 
• treatment on an emergency out-patient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission 
• is medically significant, e.g. defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant.” Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that 
do not result in hospitalization or development of dependency or abuse (please refer to the ICH-
E2D Guidelines). 
All new malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All reports of intentional misuse and abuse of the product are also considered serious adverse 
event irrespective if a clinical event has occurred. 
10.1.3 
SAE reporting 
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
has provided informed consent and until 12 weeks following the last administration of study 
treatment must be reported to Novartis safety within 24 hours of learning of its occurrence. 
Detailed instructions regarding the submission process and requirements are to be found in the 
investigator folder provided to each site. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at a 

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different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event. 
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert (new 
occurrence) and is thought to be related to the study treatment, a CMO & PS Department 
associate may urgently require further information from the investigator for health authority 
reporting. Novartis may need to issue an Investigator Notification (IN) to inform all 
investigators involved in any study with the same study treatment that this SAE has been 
reported. 
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with European Union 
(EU) Guidance 2011/C 172/01 or as per China national regulatory requirements. 
10.1.4 
Pregnancy reporting 
Pregnancies 
All pre-menopausal women who are not surgically sterile will have a urine pregnancy test. A 
positive urine pregnancy test requires immediate interruption of study drug until serum β-hCG 
is performed and found to be negative. 
If a female trial participant becomes pregnant, the study treatment should be stopped, and the 
trial participant must be asked to read and sign pregnancy consent form to allow the Study 
Doctor ask about her pregnancy. To ensure participant 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 (CMO&PS). Pregnancy follow-up should be recorded on the same 
form and should include an assessment of the possible relationship to the study treatment any 
pregnancy outcome. Any SAE experienced during pregnancy must be reported. Information 
will be collected at three time points after the estimated date of delivery and for a period of 12 
months. 
Follow up of the pregnancy (female participant) should be according to the following schedule: 
Tracking of pregnancy cases occurs until after Expected Delivery Date (EDD) for all 
prospective pregnancy cases received from clinical studies (including pregnancies where the 
participant was exposed to placebo and pregnancies due to the conduct of the study). 
• EDD + 1 month (mandatory for all cases). Requesting the pregnancy outcome and other 
clinically relevant pregnancy data or changes in data. 
• EDD + 2 month (mandatory if no answer is obtained after request at EDD+1 month). A 
reminder letter for the outcome. 
• The follow-up at EDD + 3 months is mandatory for all cases of live birth. Information on 
the status of the baby 3 months after delivery and information on any development issue 
or abnormality that would not be seen at birth must be collected. 

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• The follow up at EDD + 12 months is mandatory for all cases of live birth. Information on 
the status of the baby 12 months after delivery and information on any development issue 
or abnormality that would not be seen at birth must be collected. If the pregnancy case is 
lost to follow-up (e.g., no response after 3 attempts) this information must be transferred 
to the Safety Desk of the Country participant Safety. 
10.1.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal product, 
which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate CRF irrespective of whether or not associated with an AE/SAE and reported to 
Safety only if associated with an SAE. Misuse or abuse will be collected and reported in the 
safety database irrespective of it being associated with an AE/SAE within 24 hours of 
Investigator’s awareness. 
Table 10-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
 
Document in Dosing 
Treatment error type 
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 clinical trial 
participants who were 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 Section 16.1. 
10.2.2 
Renal safety monitoring 
There has been no safety signal for nephrotoxicity with secukinumab in clinical trial participants 
who were exposed, and from a mechanism of action standpoint, there is no known effect of 
blocking IL-17A on the kidney. All participant with laboratory tests containing clinically 

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significant abnormal values (see Section 16.1 for notable laboratory values) are to be followed 
until the values return to normal ranges or until a valid reason, other than treatment related AE, 
is defined. Standard renal function tests (blood urea nitrogen, serum creatinine) will be obtained 
at regular intervals, but special measures for renal safety monitoring are not planned. 
 
11 
Data Collection and Database management 
11.1 
Data collection 
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRF). The eCRFs have been built using fully validated secure web-
enabled software that conforms to 21 Code of Federal Regulation (CFR) Part 11 requirements. 
Investigator site staff will not be given access to the 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 participant data for 
archiving at the investigational site. 
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification. 
11.2 
Database management and quality control 
Novartis personnel (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 
World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions and 
adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology. 
Dates of screenings, randomizations, screen failures and study completion, as well as 
randomization codes and data about all study treatment(s) dispensed to the participant and all 
dosage changes will be tracked using an IRT. The system will be supplied by a vendor, who 
will also manage the database. The data will be sent electronically to Novartis (or a designated 
CRO) at specific timelines. 
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. The 
code break functionality will remain available until study shut down or upon request of Novartis. 

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Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked and the treatment codes will be unblinded and made 
available for data analysis. Any changes to the database after that time can only be made after 
written agreement by Novartis development management. 
11.3 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and data capture requirements (i.e. eSource DDE or 
eCRFs) with the investigators and their staff. During the study, Novartis employs several 
methods of ensuring protocol and GCP compliance and the quality/integrity of the sites’ data. 
The field monitor will visit the site to check the completeness of participant records, the 
accuracy of data capture / data entry, the adherence to the protocol and to Good Clinical Practice, 
the progress of enrollment, and to ensure that study treatment is being stored, dispensed, and 
accounted for according to specifications. Key study personnel must be available to assist the 
field monitor during these visits. Continuous remote monitoring of each site’s data may be 
performed by a centralized Novartis/CRA organization. Additionally, a central analytics 
organization may analyze data & identify risks & trends for site operational parameters, and 
provide reports to Novartis clinical teams to assist with trial oversight. 
The investigator must maintain source documents for each participant in the study, consisting 
of case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
participant's file. The investigator must also keep the original informed consent form signed by 
the participant (a signed copy is given to the participant). 
The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. Novartis monitoring standards require full 
verification for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the CRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
participants will be disclosed. 
 
12 
Data analysis and statistical methods 
The primary endpoint analysis will be performed after all participants complete Week 16 as 
described in Section 12.7 and the final analysis will be conducted on all participant data at the 
time the study ends. Any data analysis carried out independently by the investigator should be 
submitted to Novartis before publication or presentation. 
Summary statistics for continuous variables will generally include the number of participants 
(N), minimum, lower quartile, mean, standard deviation (SD), median, upper quartile, and 
maximum. For categorical or binary variables, the number and percent of participants in each 
category will be presented. 
In case of a global health disruptive event, such as pandemic/epidemic (e.g., COVID-19), 
affecting the ability of the participant or the site to adhere to protocol requirements and 

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assessments and therefore leading to a potential increase in the number of missing 
measurements, additional analysis populations may be defined as per the instructions and 
procedures outlined in Section 16.9. 
The efficacy evaluation of secukinumab relative to placebo will generally focus on the first 16 
weeks of treatment unless otherwise specified. 
Data analyses will be presented by treatment group. Efficacy and safety data for the 16-week 
placebo-controlled period and the entire treatment period as appropriate will be presented by 
the following two treatment groups. Participants may be included in more than one treatment 
group for some analyses (e.g., exposure adjusted adverse events over the entire treatment 
period). 
These treatment groups represent the regimens to which participants will be eligible to be 
randomized: 
• Secukinumab 150 mg regimen 
• Placebo regimen 
Note that the treatment groups above for a participant may differ depending on the time period 
of the analysis and whether one assesses the participant for efficacy or safety (see Section 12.1 
for details). Data may be presented by a combination of the ‘original’ and ‘switch’ treatment 
groups. These treatment groups represent the treatment combinations the participants 
experience over the course of the entire trial (e.g., placebo participants who are reassigned to 
secukinumab 150 mg, non-responders who are escalated to secukinumab 300 mg). 
12.1 
Analysis sets 
The following analysis sets will be used in this study: 
Randomized set: The randomized set will be defined as all participants who were randomized. 
Unless otherwise specified, mis-randomized participants (mis-randomized in IRT) will be 
excluded from the randomized set. 
Mis-randomized participants are defined as those participants who were mistakenly randomized 
into the IRT prior to the site confirming all eligibility criteria had been met and to whom no 
study medication was given. Mis-randomized participants are treated as screen failures. 
Full analysis set (FAS): The FAS will be comprised of all participants from the randomized 
set to whom study treatment has been assigned. Following the intent-to-treat principle, 
participants will be evaluated according to the treatment assigned to at randomization. 
Safety set: The safety set includes all participants who took at least one dose of study treatment 
during the treatment period. Participants will be evaluated according to treatment received. 
12.2 
Participant demographics and other baseline characteristics 
Demographics and baseline characteristics 
The following common background and demographic variables will be summarized: 
• Gender, age, race, ethnicity, weight, height, and BMI. 
Baseline disease characteristics will also be summarized for the following variables: 

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Significant prior and concomitant non-drug therapies and procedures will be summarized by 
primary system organ class and MedDRA preferred term. 
Prior surgeries and procedures are defined as surgeries and procedures done prior to first dose 
of study treatment. Any surgeries and procedures done between the day of first dose of study 
treatment and within 84 days after the last dose will be a concomitant surgeries and procedures, 
including those which were started pre-baseline and continued into the period where study 
treatment is administered. 
The number and percentage of participants receiving prior and concomitant nr-axSpA therapy 
will be presented by randomized treatment group as well as the reasons for stopping their 
therapies (primary lack of efficacy, secondary lack of efficacy, lack of tolerability, other) and 
the total duration of exposure to nr-axSpA therapies previously. NSAID, glucocorticoid and 
DMARD (MTX, Leflunomide, Sulfasalazine) use will be summarized. 
12.4 
Analysis of the primary endpoints/estimands 
The primary objective of this study is to assess the efficacy of secukinumab relative to placebo 
at week 16 based on the proportion of participants achieving an ASAS40 response in TNF-α 
naïve participants. The consistency of the treatment difference between this bridging study and 
the global study will be evaluated. 
12.4.1 
Definition of primary endpoints/estimands 
The primary efficacy variable is response to treatment according to the ASAS40 criteria at 
Week 16 in TNF-α naïve participants with active nr-axSpA. The analysis of the primary 
variable will be based on the FAS participants. 
12.4.2 
Statistical model, hypothesis, and method of analysis 
The primary analysis will be conducted via logistic regression with treatment and stratification 
factor (CRP+/MRI+, CRP+/MRI-, CRP-/MRI+) as factors and weight as a 
covariate. Difference in response proportions between secukinumab regimen and placebo 
regimen and the corresponding 95% confidence interval (CI) will be computed utilizing the 
logistic regression model fitted. 
12.4.3 
Handling of missing values/censoring/discontinuations 
Missing data for ASAS40 response and other binary efficacy variables (e.g., ASAS5/6, etc.) for 
data up to Week 16 will be handled as follows: 
1. Participants who discontinue from treatment or study for any reason will be considered 
as non-responders from the time of discontinuation through Week 16 
2. Participants who do not have the required data to compute responses (e.g., ASAS 
components) at baseline and at the specific time point will be classified as non-responders 
at the specific time point. 
Participants who are unblinded prior to the scheduled time point will be considered non-
responders from the time of unblinding up to Week 16. The primary analysis will use the non-
responder imputation. 

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12.5 
Analysis of secondary endpoints/estimands 
12.5.1 
Efficacy and/or Pharmacodynamic endpoints 
The secondary efficacy variables are described below. Secondary efficacy variables will be 
analyzed using the FAS population. Handling of missing data for secondary variables included 
in the testing strategy will be the same as for the primary variable. 
ASAS40 at Week 16 
The proportion of participants meeting the response criteria will be evaluated using a logistic 
regression model with treatment group and stratification factor (CRP+/MRI+, CRP+/MRI-, 
CRP-/MRI+) as factors and weight as a covariate. 
ASAS 5/6 at Week 16 
The proportion of participants meeting the response criteria will be evaluated using a logistic 
regression model with treatment group and stratification factor (CRP+/MRI+, CRP+/MRI-, 
CRP-/MRI+) as factors and weight as a covariate. 
BASDAI at Week 16 
Between-treatment differences in the change from baseline in BASDAI will be evaluated using 
MMRM with treatment group, stratification factor (CRP+/MRI+, CRP+/MRI-, CRP-/MRI+) 
and analysis visit as factors and baseline BASDAI score and weight as continuous covariates. 
Treatment by analysis visit and baseline BASDAI score by analysis visit will be included as 
interaction terms in the model. An unstructured covariance structure will be assumed for the 
model. 
BASDAI50 at Week 16 
The proportion of participants meeting the response criteria at Week 16 will be evaluated using 
a logistic regression model with treatment group and stratification factor (CRP+/MRI+, 
CRP+/MRI-, CRP-/MRI+) as factors and baseline weight and baseline BASDAI score as 
covariates. 
hsCRP at Week 16 
For the change in hsCRP, since evidence from the literature would suggest that the data are not 
normally distributed (Huffman et al 2006), analysis will be performed on the loge ratio of the 
treatment value vs baseline value (calculated by dividing the post-baseline value by the baseline 
value and then applying the loge transformation) to normalize the distribution of hsCRP at each 
analysis visit. Between-treatment differences in the change in hsCRP relative to baseline will 
be evaluated using MMRM with treatment group, stratification factor (CRP+/MRI+, 
CRP+/MRI-, CRP-/MRI+) and analysis visit as factors and loge baseline hsCRP and weight as 
continuous covariates. Treatment by analysis visit and loge baseline hsCRP by analysis visit 
will be included as interaction terms in the model. An unstructured covariance structure will be 
assumed for the model. The estimate and the 2-sided 95% confidence intervals obtained from 
the model will be back transformed to the original scale. 

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BASFI at Week 16 
Between-treatment differences in the change from baseline in BASFI will be evaluated using 
MMRM with treatment group, stratification factor (CRP+/MRI+, CRP+/MRI-, CRP-/MRI+) 
and analysis visit as factors and baseline BASFI score and weight as continuous covariates. 
Treatment by analysis visit and baseline BASFI score by analysis visit will be included as 
interaction terms in the model. An unstructured covariance structure will be assumed for the 
model. 
SI joint edema on MRI at Week 16 
The change from baseline to Week 16 in inflammation measured by SI joint total edema score 
will be evaluated using an analysis of covariance (ANCOVA)model with treatment group, 
stratification factor (CRP+/MRI+, CRP+/MRI-, CRP-/MRI+) as factors, and weight and 
baseline inflammation score as covariates. 
ASAS20 at Week 16 
The proportion of participants meeting the response criteria will be evaluated using a logistic 
regression model with treatment group and stratification factor (CRP+/MRI+, CRP+/MRI-, 
CRP-/MRI+) as factors and weight as a covariate. 
SF-36 PCS at Week 16 
See Section 12.5.4 Patient Reported Outcomes. 
ASQoL at Week 16 
Summary statistics of observed data by visit and change from baseline in ASQoL will be 
provided for each treatment regimen. Between-treatment differences will be evaluated using 
MMRM. Treatment group, stratification factor (CRP+/MRI+, CRP+/MRI-, CRP-/MRI+) and 
analysis visit will be included as categorical factors and baseline ASQoL scores and weight as 
continuous covariates. Treatment by analysis visit and baseline ASQoL scores by analysis visit 
will be included as interaction terms in the model. An unstructured covariance structure will be 
assumed for the model. 
ASAS partial remission at Week 16 
Response at Week 16 to ASAS partial remission criteria will be evaluated using a logistic 
regression model with treatment and stratification factor (CRP+/MRI+, CRP+/MRI-, CRP- 
/MRI+) as factors and weight as a covariate. 
12.5.2 
Safety endpoints 
Adverse events 
Treatment-emergent adverse events (i.e., events started after the first dose of study treatment or 
events present prior to the first dose of study treatment but increased in severity based on 
preferred term and on or before last dose + 84 days) will be summarized. 

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Adverse events will be summarized by presenting, for each treatment group, the number and 
percentage of participants having any AE, having an AE in each primary system organ class 
and having each individual AE (preferred term). Summaries will also be presented for AEs by 
severity and for study treatment related AEs. If a participant reported more than one adverse 
event with the same preferred term, the adverse event with the greatest severity will be presented. 
If a participant reported more than one adverse event within the same primary system organ 
class, the participant will be counted only once with the greatest severity at the system organ 
class level, where applicable. Serious adverse events will also be summarized. 
These summaries may be presented separately by different study periods, e.g., Week 1-16 and 
entire treatment period. 
As appropriate, the incidence of AEs will be presented per 100 patient years of exposure 
(exposure-adjusted incidence rates). 
Separate summaries will be provided for death, serious adverse event, other significant adverse 
events leading to discontinuation and adverse events leading to dose adjustment (including 
study treatment discontinuation). 
A graphical display of relative frequencies within system organ classes and relative risks, as 
appropriate, will be presented. 
When adjudication is required of major cardiovascular events, a summary of those types of 
events as reported by the investigator and confirmed by adjudication will be provided. 
Laboratory data 
The summary of laboratory evaluations will be presented for three groups of laboratory tests 
(hematology and serum chemistry). Descriptive summary statistics for the change from baseline 
to each study visit will be presented. These descriptive summaries will be presented by test 
group, laboratory test and treatment group. Change from baseline will only be summarized for 
participants with both baseline and post baseline. 
For each parameter, the maximum change from baseline within each study period will be 
evaluated analogously. 
In addition, shift tables will be provided for all parameters to compare a participant’s baseline 
laboratory evaluation relative to the visit’s observed value. For the shift tables, the normal 
laboratory ranges will be used to evaluate whether a particular laboratory test value was normal, 
low, or high for each visit value relative to whether or not the baseline value was normal, low, 
or high. These summaries will be presented by laboratory test and treatment group. Shifts will 
be presented by visit as well as for most extreme values post-baseline. 
 
 
Vital signs 
Analysis of the vital sign measurements using summary statistics for the change from baseline 
for each post-baseline visit will be performed. These descriptive summaries will be presented 

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12.7 
Interim analyses 
Not applicable. 
12.8 
Sample size calculation 
12.8.1 
Primary endpoints 
As it is a bridging study for China registration, this study will pursue an estimation strategy 
rather than formal hypothesis testing of treatment difference. 

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Analysis of an unpublished phase III study with secukinumab in nr-axSpA showed a placebo 
response rate of about 29.2% and a secukinumab 150 mg response rate of 41.5% after 16 weeks 
for ASAS40 in TNF-α naïve participants. Assuming 10% of randomized participants will be 
TNF-α IR and 90% of randomized participants will be TNF-α naïve. With 134 participants, 120 
of them are TNF-α naïve (1:1 ratio to two groups), then there are approximately 77.3% 
probability to show at least 50% global treatment difference (6.15%) and approximately 90.7% 
probability to show positive treatment difference. 
Table 12-1 
Probability of Success with Different Observed Response Rates of 
ASAS40 in TNF-α naïve participants 
 
Observed Response Rate 
Criterion 1 
Criterion 2 
Secukinumab 
Placebo 
95% CI 
of (p1- 
Aimed 
Treatment 
Aimed 
Treatment 
(p1) 
(p2) 
p1-p2 
p2) 
Difference 
PoS 
Difference 
PoS 
Scenario 1 
0.395 
0.292 
0.103 
(-0.066, 
> 0.0615 
0.699 
> 0 
0.864 
0.272) 
Scenario 2 
0.415 
0.292 
0.123 
(-0.046, 
> 0.0615 
0.773 
> 0 
0.907 
0.293) 
Scenario 3 
0.435 
0.292 
0.143 
(-0.027, 
> 0.0615 
0.835 
> 0 
0.939 
0.313) 
Scenario 4 
0.455 
0.292 
0.163 
(-0.008, 
> 0.0615 
0.885 
> 0 
0.962 
0.334) 
 
12.9 
Primary endpoint analysis 
The primary endpoint analysis will be performed after all participants have completed the Week 
16 visit. The investigators, site personnel and monitors will continue to remain blinded to the 
original treatment assignment that each participant received at randomization until after the 
database lock for Week F60 analysis. The primary endpoint analysis will be used for regulatory 
submission. 
Subsequent to the primary endpoint analysis, the final analysis is planned after participants have 
completed the Week F60 assessments and may be used for regulatory submission and/or 
publication purposes. Additional analyses may be performed to support interactions with health 
authorities, as necessary. 
 
13 
Ethical considerations and administrative procedures 
13.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations (including European Directive 2001/20/EC, US CFR 21), and with the ethical 
principles laid down in the Declaration of Helsinki. 
13.2 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion from 
the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial protocol, 
written informed consent form, consent form updates, participant recruitment procedures (e.g., 

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

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Novartis and approved by the IRB/IEC and Health Authorities, where required, it cannot be 
implemented. 
14.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. 
Only amendments that are required for participant safety may be implemented immediately 
provided the health 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 participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations. 

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Van Tubergen A, Black PM, Coteur G (2015) Are patient-reported outcome instruments for 
ankylosing spondylitis fit for purpose for the axial spondyloarthritis patient? A qualitative and 
psychometric analysis. Rheumatology; 54:1842-51. 
Van der Heijde D, Landewé R, Baraliakos X, et al (2008) Radiographic findings following 
two years of infliximab therapy in patients with ankylosing spondylitis. Arthritis Rheum; 
58(10):3063-70. 
Van der Heijde D, Ramiro S, Landewé R, et al (2017) 2016 update of the ASAS-EULAR 
management recommendations for axial spondyloarthritis. Ann. Rheum. Dis; 76:978-991. 
Van der Linden S, Valkenburg HA, Cats A (1984) Evaluation of diagnostic criteria for 
ankylosing spondylitis. A proposal for modification of the New York criteria. Arthritis 
Rheum; 27(4):361-8. 
Ward MM, Deodhar A, Akl EA, et al (2016) American College of Rheumatology/Spondylitis 
Association of America/Spondyloarthritis Research and Treatment Network 2015 
Recommendations for the Treatment of Ankylosing Spondylitis and Nonradiographic Axial 
Spondyloarthritis.Arthritis Rheumatol; 68(2):282-98. 
Ware JE, Sherbourne CD (1992) The MOS 36-item short-form health survey (SF-36). I. 
Conceptual framework and item selection. Med Care; 30(6):473-83. 

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16 
Appendices 
16.1 
Appendix 1: Clinically notable laboratory values and vital signs 
The following criteria will be used to define expanded limits and notable abnormalities of key 
laboratory tests. 
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 
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) 
SGPT (ALT) 
>3 x ULN 
>3 x ULN 
>3 x ULN 
>3 x ULN 
Bilirubin 
>2 x ULN 
>2 x ULN 
Alkaline phosphatase 
>2.5 x ULN 
>2.5 x ULN 
RENAL FUNCTION VARIABLES 
Creatinine (serum) 
>2 x ULN 
>2 x ULN 
Blood Urea Nitrogen (BUN) 
≥ 5 × ULN 
≥ 5 × ULN 
HEMATOLOGY VARIABLES 
Hemoglobin 
Platelet Count 
20 g/L decrease from baseline 
<100x10E9/L 
White blood cell count 
<0.8 x LLN 
Neutrophils 
<0.9 x LLN 
SGOT (AST) = serum glutamic oxaloacetic transaminase (aspartate aminotransferase), SGPT (ALT) = 
serum glutamic pyruvic transaminase (alanine aminotransferase), LLN=lower limit of normal, 
ULN=upper limit of normal, SI Unit = The International System of Units 

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16.2 
Blood collection log 
Refer to the central laboratory manual for sample collection, preparation and shipping 
information. 
 
16.3 
Modified New York criteria 
According to Exclusion Criteria 1, participants meeting clinical criteria must not have below 
described radiological changes. 
Clinical criteria 
• 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 
• Sacroiliitis grade ≥2 bilaterally or grade 3–4 unilaterally 
Definite AS if the radiological criterion is associated with at least one clinical criterion. 

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16.4 
ASAS Classification Criteria for Axial Spondyloarthritis (axSpA) 
ASAS Classification Criteria for Axial Spondyloarthritis (axSpA) 
 
Sacroiliitis on imaging* plus ≥ 1 SpA 
feature 
*Sacroiliitis on imaging: 
● Active (acute) inflammation on MRI 
highly suggestive of sacroiliitis 
associated with SpA 
● Definite radiographic sacroiliitis 
according to the modified NY criteria 
OR 
HLA-B27 plus ≥ 2 other SpA 
features 
SpA features: 
● Inflammatory back pain 
● Arthritis 
● Enthesitis (heel) 
● Uveitis 
● Dactylitis 
● Psoriasis 
● Crohn’s / colitis 
● Good respons to NSAIDs 
● Family history for SpA 
● HLA-B27 
● Elevated CRP 
 
16.5 
Assessment of SpondyloArthritis International Society criteria 
(ASAS) 
The ASAS response measures consist of the following assessment domains (Sieper et al 2009). 
Main 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 
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: 
 
6. C-reactive protein (acute phase reactant) 
16.5.1 
Bath Ankylosing Spondylitis Functional Index (BASFI) 
The BASFI is a set of 10 questions designed to determine the degree of functional limitation in 
those participants with AS. The ten questions were chosen with a major input from participants 
with AS. The first 8 questions consider activities related to functional anatomy. The final 2 
questions assess the participants’ ability to cope with everyday life. A 10 cm visual analog scale 
is used to answer the questions. The mean of the ten scales gives the BASFI score – a value 
between 0 and 10. 
16.5.2 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) 
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: 

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16.8 
Guidelines for administering the questionnaires for patient 
reported outcomes 
Before trial start 
Study coordinators should familiarize themselves with the PRO questionnaires in the trial and 
identify any items where a participant’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 participant responds ‘most or all of the time’, then the 
study coordinator should inform the study investigator. 
Before completion 
Participants should be provided with the correct questionnaire at the appropriate visits and in 
the appropriate language 
Participants should have adequate space and time to complete the forms 
Questionnaire should be administered before the clinical examination 
During completion 
Administrator may clarify the questions but should not influence the response 
Only one response for each question 
Also see “Addressing Problems and Concerns” 

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After completion 
Check for completeness and not for content* 
Check for multiple responses that were made in error 
*However, any response which may directly impact or reflect the participant’s medical 
condition (e.g., noting of depression) should be communicated by the study coordinator to the 
investigator). 
Addressing problems and concerns 
Occasionally a participant may have concerns or questions about the questionnaires 
administered. Guidance related to some of the most common concerns and questions are given 
below. 
The participant does not want to complete the questionnaires 
Tell the participant that completion of the questionnaires is voluntary. The goal is to better 
understand the physical, mental and social health problems of participants. Emphasize that such 
information is as important as any other medical information and that the questionnaires is 
simple to complete. Suggest that the questionnaires may be different from anything the 
respondent has filled in the past. If the participant still declines, retrieve the questionnaires. 
Record the reason for the decline and thank the participant. 
The participant is too ill or weak to complete the questionnaires 
In these instances, the coordinator may obtain participant responses by reading out loud each 
question, followed by the corresponding response categories, and entering the participant’s 
response. No help should be provided to the participant by any person other than the designated 
study coordinator. The coordinator should not influence participant responses. The study 
coordinator cannot translate the question into simpler language and has to be read verbatim. 
The participant wants someone else to complete the questionnaires 
In no case should the coordinator or anyone other than the participant provide responses to the 
questions. Unless specified in the study protocol, proxy data are not an acceptable substitute for 
participant self-report. Participants should be discouraged from asking a family member or 
friend for help in completing a questionnaire. 
The participant does not want to finish completing the questionnaires 
If non-completion is a result of the participant having trouble understanding particular items, 
ask the participant to explain the difficulty. Re-read the question for them verbatim but do not 
rephrase the question. If the respondent is still unable to complete the questionnaire, accept it 
as incomplete. Thank the participant. 

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The participant is concerned that someone will look at his/her responses 
Emphasize that all responses are to be kept confidential. Point out that their names do not appear 
anywhere on the questionnaire, so that their results will be linked with an ID number and not 
their name. Tell the participant that his/her answers will be pooled with other participants’ 
answers and that they will be analyzed as a group rather than as individuals. Tell the participant 
that completed forms are not routinely shared with treating staff and that their responses will 
only be seen by you (to check for completeness) and by the investigator. Any response which 
may directly impact on or reflect their medical condition (e.g., noting of severe depression) will 
be communicated by the coordinator to the physician. 
The participant asks the meaning of a question/item 
While completing the questionnaire, some participants might ask the meaning of specific items 
so that they can better understand and respond. If this happens, assist the participant by 
rereading the question for them verbatim. If the participant asks to interpret the meaning of an 
item, do not try to explain it, but suggest that he/she use his/her own interpretation of the 
question. Participants should answer the questions based on what they think the questions mean. 
General information about all questionnaires 
All questionnaires have to be completed by the participants in their local languages using an 
electronic device. The questionnaires should be completed by the participants in a quiet area 
free from disturbance, and before any visit assessments. Participants should receive no help 
from family members; if questions cannot be answered alone (due to problems with reading or 
understanding), then the doctor or nurse should read the questions and record the participant’s 
responses without influencing their answers. The information provided is strictly confidential 
and will be treated as such. If a participant has missed a question or given more than one 
response per question, then this should be brought to participant. Incomplete questions should 
not be accepted without first encouraging the participant to complete unanswered questions. 
The investigator must complete the participant/visit information on the electronic device and 
ensure that the center number, participant’s number and initials are identical to the Case Record 
Form. As there are no source data for this questionnaire, the data queries will be restricted to 
participant/visit information. 
16.9 
Guidance of Study management during potential future 
pandemic/epidemic 
Scope 
The instructions and procedures outlined in this appendix are applicable only in case of global 
health disruptive event, such as pandemic/epidemic [e.g. severe acute respiratory syndrome 
coronavirus 2 (SARS-CoV-2) or coronavirus disease/COVID-19]. In order to maintain the 
study data integrity and ensure the safety of participants, investigators should inform and 
discuss with the sponsor’s monitor about its applicability prior to implementing any of the 
following procedures. 

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Screening (Screening to Randomization) 
In case of a global health disruptive event, such as pandemic/epidemic (e.g. COVID-19), 
affecting the ability of the participant or the site to adhere to protocol requirements and 
assessments, investigators should only randomize participants if they expect them to be able to 
adhere to assessments and protocol-related activities. Evaluation of the eligibility of the 
participant should consider the ability to attend study visits and adhere to protocol assessments. 
If the latter is not anticipated, screening and randomization should not proceed, and re-screening 
(as allowable per protocol) should be considered when conditions allow for proper trial 
management. 
During Treatment Period (Baseline to EOT) 
In case of a global health disruptive event, such as pandemic/epidemic (e.g. COVID-19), 
affecting the ability of the participantor the site to adhere to protocol requirements and 
assessments and therefore leading to a potential increase in the number of missing 
measurements, the Sponsor may consider recruiting additional participants to restore the sample 
size only after consultation with local regulatory authority. 
Risks and Benefits 
Active infection should be excluded in order to comply with eligibility criteria (see Section 5.2). 
The potential of secukinumab to increase the risk of infections has been identified (see IB 
Section 7.1). COVID-19 has similar impact on risk-benefit as other infections. No additional 
risk is anticipated due to COVID-19 infection. 
Visits 
If the COVID-19 pandemic or similar situations that limits or prevents on-site study visits, 
alternative methods of providing continuing care may be implemented only for the visits 
outlined in the table above. Phone calls, virtual contacts (e.g. teleconsult) or visits by site staff 
to the participant´s home depending on local regulations and capabilities, can replace on-site 
study visits, for the duration of the pandemic until it is safe for the participant to visit the site 
again. Any safety or efficacy assessments, which could not be feasible to perform or evaluate 
conduct remotely or virtually, the protocol deviation need to be recorded. Such data will treated 
as missing data. 
This will not apply to Screening, BSL, all clinic visits up to including Week 16, Week 24, Week 
52 and Week 60 visit. For remaining visits per protocol, the above exceptions may be 
implemented, however, every effort need to be made to ensure on-site visit. If on-site visit is 
prevented at Screening or Baseline visit, the participants should not be randomized. 
Laboratory assessments 
If the designated central laboratory is unable to operate, collection of samples may be modified 
by Novartis and if modified, will be communicated to the investigator. In such cases, it is 
acceptable to collect and perform laboratory tests at local laboratories that are certified for these 

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diagnostics. Similarly, sites should inform to the Sponsor of proposed changes to sample 
management/collection. 
IMP (administration and dispensation) 
In case of a major health care event (e.g., COVID-19 pandemic, epidemic) that limits or 
prevents on-site study visits, delivery of IMP directly to a participant’s home is generally 
permitted (if allowed by local regulations) in the event the Investigator has decided that an on-
site visit by the participant is no longer appropriate or possible, and that it is in the interest of 
the participant’s health to administer the study treatment even without performing an on-site 
visit. For changes in the distribution of trial drugs, the primary goal is to provide IMP to 
participants based on protocol to ensure participant safety and the integrity of clinical trials. 
Implementation will need to be discussed with Novartis. The dispatch of IMP from the site to 
the participant’s home remains under the accountability of the Investigator. Each 
shipment/provisioning will be for a maximum of 1-month supply. In this case, regular phone 
calls or virtual contacts (every 4 weeks or more frequently if needed) will occur between the 
site and the participant for instructional purposes, safety monitoring, and discussion of the 
participant´s health status until the participants can again visit the site. 
IMP home administration is allowed only for the scheduled dosing visits (outlined in Table 8-1) 
if the participant or caregiver is trained on subcutaneous self-administration. 
Changes in transportation and storage arrangements will not violate the blind design of 
treatment. The investigator should make relevant records such as the inventory and storage 
conditions of trial drugs. 
Efficacy and Clinical Outcomes Assessments (COAs) 
In  the  event  of  a  pandemic/epidemic  that limits  or  prevents  on-site study 
visits, selected efficacy assessments including Patient Reported Outcomes (PROs) can 
alternatively be done via web-based backup portal or visits of site staff to the participant´s home, 
depending on local regulations and capabilities, and following any applicable training in the 
required process. 
Exceptionally, if the electronic device is not working, the efficacy assessments and Patient 
Reported Outcomes may be completed using web-based backup portal for PROs. The data 
would then be transcribed in the vendor database. 
For individual cases where the efficacy endpoint is not collected, the reasons for not obtaining 
the efficacy evaluation should be documented. 
Imaging 
During the COVID-19 pandemic that limits or prevents on-site study visits, the collection of 
images may be modified by Novartis and will be communicated to the investigator. 

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Safety 
During the COVID-19 pandemic that limits or prevents on-site study visits, regular phone or 
virtual calls will occur (every 4 weeks or more frequently if needed) for safety monitoring and 
discussion of the participant´s health status until the participant can again visit the site. 
Female participants would be advised to perform the urine pregnancy test at home and report 
the result to the site. It is important that participants are instructed to perform the urine 
pregnancy test first and only if the test result is negative proceed with the administration of the 
study treatment. 
Informed Consent Procedures 
During the COVID-19 pandemic that may challenge the ability to obtain a standard written 
informed consent due to limits that prevent an on-site visit, the Investigator may conduct the 
informed consent discussion remotely (e.g. telephone, videoconference). Guidance issued by 
local regulatory bodies on this aspect prevail and must be implemented and appropriately 
documented (e.g. the presence of an impartial witness, sign/dating separate ICFs by trial 
participant and person obtaining informed consent, etc.). Remote informed consent should be 
appropriately documented and confirmed by way of standard informed consent procedures at 
the earliest opportunity when the participant will be back at the trial sites. 
Site monitoring 
In the event of a major health care disruption (e.g. pandemic, epidemic), requiring social 
distancing or limited travel/attendance to the clinical trial site, remote site initiation and 
monitoring could be considered. 
Note: The details on operationalizing above-mentioned study management aspects during 
potential future pandemic/epidemic will be supplemented by study specific guidance to the 
clinical trial sites.