A Randomized, Double-blind, Placebo-controlled Multicenter Study of Secukinumab (AIN457) to Examine the Clinical Efficacy and the NSAID-sparing Effect of Secukinumab Over 16 Weeks in Patients With Ankylosing Spondylitis (ASTRUM)
Phase: PHASE4
Conditions: Ankylosing Spondylitis
Sponsor: Novartis Pharmaceuticals

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CAIN457FDE03 
Global Clinical Development - General Medicine 
CAIN457/ Secukinumab  
Clinical Trial Protocol CAIN457FDE03 / NCT02763046 
A randomized, double-blind, placebo-controlled multicenter 
study of Secukinumab (AIN457) to examine the clinical 
efficacy and the NSAID-sparing effect of Secukinumab over 
16 weeks in patients with ankylosing spondylitis (ASTRUM) 
Authors: 
 
Document type: 
Clinical Trial Protocol  
EUDRACT number: 
2015-004575-74 
Version number: 
v01 
Development phase: 
Phase IV 
Release date: 
10-Dec-2018
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed  
without the consent of Novartis 
Clinical Trial Protocol Template Version 2.0, November, 2013 

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Table of contents 
 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 5 
Glossary of terms ................................................................................................................. 8 
1 
Introduction ....................................................................................................................... 10 
1.1 
Background ............................................................................................................ 10 
1.2 
Purpose .................................................................................................................. 11 
2 
Study objectives ................................................................................................................. 12 
2.1 
Primary objective ................................................................................................... 12 
2.2 
Secondary objectives ............................................................................................. 12 
2.3 
Exploratory objectives ........................................................................................... 13 
3 
Investigational plan ........................................................................................................... 15 
3.1 
Study design .......................................................................................................... 15 
3.2 
Rationale of study design ...................................................................................... 17 
3.3 
Rationale of dose/regimen, route of administration and duration of treatment ..... 17 
3.4 
Rationale for choice of comparator ....................................................................... 18 
3.5 
Purpose and timing of interim analyses/design adaptations .................................. 18 
3.6 
Risks and benefits .................................................................................................. 18 
4 
Population .......................................................................................................................... 21 
4.1 
Inclusion criteria .................................................................................................... 21 
4.2 
Exclusion criteria ................................................................................................... 22 
5 
Treatment ........................................................................................................................... 25 
5.1 
Protocol requested treatment ................................................................................. 25 
5.1.1 
Investigational treatment ....................................................................... 25 
5.1.2 
Additional study treatment .................................................................... 26 
5.2 
Treatment arms ...................................................................................................... 26 
5.3 
Treatment assignment, randomization ................................................................... 26 
5.4 
Treatment blinding ................................................................................................ 27 
5.5 
Treating the patient ................................................................................................ 27 
5.5.1 
Patient numbering ................................................................................. 27 
5.5.2 
Dispensing the investigational treatment .............................................. 27 
5.5.3 
Handling of study treatment .................................................................. 28 
5.5.4 
Instructions for prescribing and taking study treatment ........................ 28 
5.5.5 
Permitted dose adjustments and interruptions of study treatment ........ 29 
5.5.6 
Rescue medication ................................................................................ 30 
5.5.7 
Concomitant treatment .......................................................................... 30 

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5.5.8 
Prohibited treatment .............................................................................. 31 
5.5.9 
Discontinuation of study treatment ....................................................... 32 
5.5.10 
Withdrawal of consent .......................................................................... 33 
5.5.11 
Loss to follow-up .................................................................................. 34 
5.5.12 
Emergency breaking of assigned treatment code .................................. 34 
5.5.13 
Study completion and post-study treatment .......................................... 34 
5.5.14 
Early study termination ......................................................................... 35 
6 
Visit schedule and assessments ......................................................................................... 35 
6.1 
Information to be collected on Screening failures ................................................. 41 
6.2 
Patient demographics/other baseline characteristics ............................................. 41 
6.3 
Treatment exposure and compliance ..................................................................... 41 
6.4 
Efficacy .................................................................................................................. 41 
6.4.1 
Assessment of ASAS-NSAID score ..................................................... 42 
6.4.2 
Assessment of SpondyloArthritis International Society criteria 
(ASAS) .................................................................................................. 42 
6.4.3 
Patient’s global assessment of disease activity (VAS) ......................... 43 
6.4.4 
Patient’s assessment of back pain intensity (VAS) ............................... 43 
6.4.5 
Bath Ankylosing Spondylitis Functional Index (BASFI) ..................... 43 
6.4.6 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ........ 43 
6.4.7 
Bath Ankylosing Spondylitis Metrology Index (BASMI linear) .......... 43 
6.4.8 
Medical Outcome Short Form Health Survey (SF-36) Version 2 
(Acute Form) ......................................................................................... 44 
6.4.9 
ASAS Health Index ............................................................................... 44 
6.4.10 
High sensitivity C-reactive protein (hsCRP) ......................................... 44 
6.4.11 
Erythrocyte sedimentation rate (ESR) .................................................. 45 
6.4.12 
Appropriateness of efficacy assessments .............................................. 45 
6.5 
Safety ..................................................................................................................... 45 
6.5.1 
QuantiFERON TB-Gold test or PPD skin test ...................................... 45 
6.5.2 
Chest X-ray or MRI .............................................................................. 46 
6.5.3 
Physical examination ............................................................................ 46 
6.5.4 
Vital signs.............................................................................................. 46 
6.5.5 
Height and weight ................................................................................. 46 
6.5.6 
Laboratory evaluations .......................................................................... 46 
6.5.7 
Electrocardiogram (ECG) ..................................................................... 47 
6.5.8 
Pregnancy and assessments of fertility ................................................. 47 
6.5.9 
Local tolerability (Injection site reactions) ........................................... 47 
6.5.10 
Tolerability of Secukinumab ................................................................. 48 
6.5.11 
Appropriateness of safety measurements .............................................. 48 

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6.6 
Other assessments .................................................................................................. 48 
6.6.1 
HLA-B27............................................................................................... 48 
6.6.2 
Resource utilization ............................................................................... 48 
6.6.3 
Pharmacokinetics .................................................................................. 48 
6.6.4 
Other biomarkers ................................................................................... 48 
7 
Safety monitoring .............................................................................................................. 49 
7.1 
Adverse events ....................................................................................................... 49 
7.2 
Serious adverse events ........................................................................................... 49 
7.2.1 
Definition of SAE ................................................................................. 49 
7.2.2 
SAE reporting........................................................................................ 50 
7.3 
Liver safety monitoring ......................................................................................... 52 
7.4 
Renal safety monitoring ......................................................................................... 52 
7.5 
Pregnancy reporting ............................................................................................... 54 
7.6 
Prospective suicidality assessment ........................................................................ 54 
8 
Data review and database management ............................................................................. 54 
8.1 
Site monitoring ...................................................................................................... 54 
8.2 
Data collection ....................................................................................................... 55 
8.3 
Database management and quality control ............................................................ 55 
8.4 
Data Monitoring Committee .................................................................................. 56 
8.5 
Adjudication Committee ........................................................................................ 56 
9 
Data analysis ...................................................................................................................... 56 
9.1 
Analysis sets .......................................................................................................... 56 
9.2 
Patient demographics and other baseline characteristics ....................................... 57 
9.3 
Treatments ............................................................................................................. 57 
9.4 
Analysis of the primary variable(s) ....................................................................... 58 
9.4.1 
Variable(s) ............................................................................................. 58 
9.4.2 
Statistical model, hypothesis, and method of analysis .......................... 58 
9.4.3 
Handling of missing values/censoring/discontinuations ....................... 58 
9.4.4 
Supportive analyses ............................................................................... 59 
9.5 
Analysis of other variables .................................................................................... 59 
9.5.1 
Secondary efficacy variables ................................................................. 59 
9.5.2 
Exploratory efficacy variables .............................................................. 63 
9.5.3 
Safety variables ..................................................................................... 64 
9.5.4 
Resource utilization ............................................................................... 65 
9.5.5 
Pharmacokinetics .................................................................................. 65 
9.5.6 
Pharmacogenetics/pharmacogenomics ................................................. 65 
9.5.7 
Biomarkers ............................................................................................ 65 

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9.5.8 
PK/PD ................................................................................................... 65 
9.6 
Interim analyses ..................................................................................................... 65 
9.7 
Sample size calculation.......................................................................................... 65 
10  Ethical considerations ........................................................................................................ 66 
10.1 
Regulatory and ethical compliance ........................................................................ 67 
10.2 
Informed consent procedures ................................................................................. 67 
10.3 
Responsibilities of the investigator and IRB/IEC .................................................. 67 
10.4 
Publication of study protocol and results............................................................... 68 
11  Protocol adherence ............................................................................................................ 68 
11.1 
Protocol Amendments ........................................................................................... 68 
12  References ......................................................................................................................... 68 
13  Appendices ........................................................................................................................ 69 
13.1 
Appendix 1: Clinically notable laboratory values and vital signs ......................... 69 
13.2 
Appendix 2: Liver event and laboratory trigger definitions and follow-up 
requirements .......................................................................................................... 70 
13.3 
Appendix 3: Modified New York criteria ............................................................. 72 
13.4 
Appendix 4 ............................................................................................................ 72 
13.4.1 
Analysis and report of NSAID intake during clinical trials/studies ...... 72 
13.4.2 
Assessment of SpondyloArthritis International Society criteria 
(ASAS) .................................................................................................. 73 
13.4.3 
Bath Ankylosing Spondylitis Functional Index (BASFI) ..................... 74 
13.4.4 
Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) ........ 74 
13.4.5 
Bath Ankylosing Spondylitis Metrology Index (BASMI) .................... 74 
 
List of tables 
Table 5-1 
Prohibited treatment .............................................................................. 32 
Table 6-1 
Assessment schedule ............................................................................. 36 
Table 7-1 
Specific renal alert criteria and actions ................................................. 53 
Table 13-1 
Safety analyses: expanded limits and notable criteria ........................... 69 
Table 13-2 
Liver event and laboratory trigger definitions ...................................... 70 
Table 13-3 
Follow-up requirements for liver events and laboratory triggers .......... 70 
Table 13-4 
ASAS recommendations for the approach to collection of NSAID 
intake for use in clinical trials/epidemiological studies of 
spondyloarthritis .................................................................................... 73 
 
List of figures 
Figure 3-1 
Study design .......................................................................................... 16 

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List of abbreviations 
AE 
 
adverse event 
ALT 
 
alanine aminotransferase 
AS 
 
Ankylosing spondylitis 
ASAS  
Assessment of SpondyloArthritis international Society 
AST 
 
aspartate aminotransferase 
BASDAI 
Bath Ankylosing Spondylitis Disease Activity Index 
BASFI  
Bath Ankylosing Spondylitis Functional Index 
BASMI 
Bath Ankylosing Spondylitis Metrology Index 
b.i.d.  
twice a day 
BSL 
 
Baseline 
CFR 
 
US Code of Federal Regulations  
CDS 
 
Core Data Sheet (for marketed drugs) 
COX-1 / 2 
Cyclooxygenase-1 / 2 
CPO 
 
Country Pharma Organization 
CRF 
 
Case Report/Record Form (paper or electronic) 
CRO  
Contract Research Organization 
CTC 
 
Common Toxicity Criteria 
CTRD  
Clinical Trial Results Database 
DMARD 
Disease-modifying antirheumatic drugs 
DS&E  
Drug Safety & Epidemiology 
ECG  
Electrocardiogram 
EDC  
Electronic Data Capture 
ESR 
 
Erythrocyte sedimentation rate 
GCP 
 
Good Clinical Practice 
hsCRP  
High sensitivity C-reactive protein 
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 
IEC 
 
Independent Ethics Committee 
IFU 
 
Instructions for Use 
i.v. 
 
intravenous 
IRB 
 
Institutional Review Board 
IRT 
 
Interactive Response Technology 

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LFT 
 
Liver function test (raised serum transaminases and/or bilirubin levels) 
MedDRA 
Medical dictionary for regulatory activities 
MTX  
Methotrexate 
NSAIDs 
Nonsteroidal anti-inflammatory drugs 
OC/RDC 
Oracle Clinical/Remote Data Capture 
o.d. 
 
once a day 
PFS 
 
Pre-filled syringe 
p.o. 
 
per orally 
SAE 
 
serious adverse event 
s.c. 
 
subcutaneous 
SpA 
 
Spondyloarthritides 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TNFα  
tumor necrosis factor alpha, 
VAS  
visual analog scale 
WHO  
World Health Organization  

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Glossary of terms 
Assessment 
A procedure used to generate data required by the study 
Dose level 
The dose of drug given to the patient (total daily or weekly etc.) 
Enrollment 
Point/time of patient entry into the study at which informed 
consent must be obtained (i.e. prior to starting any of the 
procedures described in the protocol) 
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 each investigational/study drug 
package in studies  
Period 
A subdivision of a cross-over study 
Premature subject/patient 
withdrawal 
Point/time when the patient exits from the study prior to the 
planned completion of all study treatment administration and/or 
assessments; at this time all study treatment administration is 
discontinued and no further assessments are planned, unless 
the patient will be followed for progression and/or survival 
Randomization number 
A unique identifier assigned to each randomized patient, 
corresponding to a specific treatment arm assignment 
Study drug/ treatment 
Any single drug or combination of drugs administered to the 
patient as part of the required study procedures; includes 
investigational drug (s), active drug run-ins or background 
therapy  
Study/investigational 
treatment discontinuation 
Point/time when patient permanently stops taking 
study/investigational treatment  for any reason; may or may not 
also be the point/time of premature patient withdrawal 
Subject Number  
A number assigned to each patient who enrolls into the study  
Variable 
A measured value or assessed response that is determined in 
specific assessments and used in data analysis to evaluate the 
drug being tested in the study 
 
 
 
 
 
 
 
 
 

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Amendment 1 
Amendment rationale  
This protocol amendment is issued for the following reasons: 
 Based on results from MEASURE III (CAIN457F2314), MEASURE IV (CAIN457F2320) 
and COAST V (Ixekizumab - NCT02696785) studies, the assumptions for the power 
calculation of the primary and a selection of secondary and exploratory objectives were re-
evaluated, leading to changes in the statistical analysis plan. The three studies mentioned 
above suggest that the placebo response might be somewhat higher, leading to a potentially 
smaller difference between active treatment and placebo than assumed during the planning of 
this trial. Therefore, in order to keep sufficient power, it was decided to pool the two 
Secukinumab arms for the primary analysis. This new evaluation triggered an adaption of a 
set of objectives. The primary objective was adapted so that data of Group 1 (Secukinumab 
150 mg s.c. “delayed tapering”) and of Group 2 (Secukinumab 150 mg s.c. “early tapering”) 
are pooled and ASAS20 response at week 12 are compared against placebo. For the other re-
evaluated secondary and exploratoy objectives, data is pooled and is compared against placebo 
according to the same schema. In the course of this amendment the amount of randomized 
patients can be reduced to a smaller size (approx. 190) than originally expected (approx. 204), 
while maintaining adequate power for primary and secondary analyses.  
 The amendment is used to describe the ASAS Health Index (chapter 6.4.9) in a more detailed 
way. Besides the 17 aspects of health, the 9 questions regarding environmental factors in 
patients with AS are mentioned.   
None of the changes described in this amended protocol are made due to newly emerged safety 
considerations. 
 
 
 
 

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1 
Introduction 
1.1 
Background 
Ankylosing spondylitis (AS) is a chronic inflammatory disease which belongs to a group of 
conditions known as spondyloarthritides (SpA). It is mainly characterized by involvement of 
the axial skeleton and sacroiliac joints, but also affects peripheral joints, entheses and 
extra-articular organs. A significant proportion of patients may present with associated 
extra-articular manifestations such as uveitis, psoriasis, inflammatory bowel disease, 
cardiovascular and pulmonary abnormalities. IL-17A has been shown to play an important role 
in driving the body’s immune response in psoriasis and SpA conditions, including PsA and AS 
(Van Baarsen et al 2011).  
Cosentyx® (Secukinumab) is a recombinant monoclonal antibody that neutralizes the activity 
of IL-17A. Secukinumab is the first IL-17A inhibitor with positive Phase 3 results for the 
treatment of PsA and AS. In January 2015, Secukinumab (at a dose of 300 mg) became the first 
IL-17A inhibitor approved in Europe as a first-line systemic treatment for moderate-to-severe 
plaque psoriasis in adult patients, and in the United States (US) as a treatment for moderate-to-
severe plaque psoriasis in adult patients who are candidates for systemic therapy or 
phototherapy (light therapy). Secukinumab 
Clinical trials of Secukinumab in ankylosing spondylitis 
The safety and efficacy of Secukinumab has been assessed in 590 patients in 2 randomized, 
double-blind, placebo-controlled, Phase 3 studies (MEASURE 1: CAIN457F2305; and 
MEASURE 2: CAIN457F2310, Sieper et al 2015) in patients with active AS with a Bath 
Ankylosing Spondylitis Disease Activity Index (BASDAI) ≥ 4 despite non-steroidal 
anti-inflammatory drugs (NSAIDs), corticosteroid or disease-modifying anti-rheumatic drug 
(DMARD) therapy. The efficacy and safety of Secukinumab 75 mg and 150 mg were evaluated 
vs. placebo with either an i.v. or s.c. loading regimen. In the MEASURE 1 and MEASURE 2 
study, 27.0% and 38.8% of patients, respectively, were previously treated with an anti-TNFα 
agent and discontinued the anti-TNFα agent due to either lack of efficacy or intolerance (anti-
TNFα-IR patients). The primary endpoint was at least a 20% improvement in Assessment of 
Spondyloarthritis International Society (ASAS20) criteria at Week 16.  
In both AS studies, Secukinumab-treated patients (150 mg in MEASURE 2 and both regimens 
in MEASURE 1) demonstrated significantly improved signs and symptoms at Week 16; a 
comparable magnitude of response and efficacy was maintained up to Week 52. The magnitude 
of response (treatment difference versus placebo) with regards to signs and symptoms at Week 
16 was similar in anti-TNFα-naïve and anti-TNFα-inadequate responder patients in both 
studies, with higher absolute response rates in anti-TNFα-naïve patients. Efficacy was 
maintained in anti-TNFα-naïve and anti-TNFα-IR patients up to Week 52 in both studies.  
In MEASURE 2, treatment with Secukinumab 150 mg resulted in greater improvement in 
ASAS20, ASAS40, high-sensitivity C-reactive protein (hsCRP), ASAS 5/6 and BASDAI score 
compared with placebo at Week 16. The onset of action of Secukinumab 150 mg occurred as 
early as Week 1 for ASAS20 (superior to placebo). ASAS20 responses were improved at Week 
16 in both anti-TNFα-naïve patients (68.2% vs. 31.1%; p<0.05) and anti-TNFα-IR patients 
(50.0% vs. 24.1%; p<0.05) for Secukinumab 150 mg compared with placebo, respectively. 

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Non-steroidal anti-inflammatory drugs in ankylosing spondylitis 
NSAIDs (including COX-1 or COX-2 inhibitors) are the standard therapy for patients with AS 
(van der Hejde et al 2011). While effective in relieving pain and improving disease activity in 
many patients, NSAIDs are associated with side effects that may cause concerns particularly in 
the context of a life-long treatment at high daily intake doses for diseases such as AS. For 
example, it has recently been shown that the NSAID diclofenac increases the risk of myocardial 
infarction in patients with SpA (Dubreuil et al 2014). NSAIDs have also been associated with 
gastrointestinal side effects (Lanas et al 2006) and a potential acceleration of chronic kidney 
disease progression (Nderitu et al 2013). 
According to the ASAS / European League Against Rheumatism (EULAR) recommendations 
(van der Hejde et al 2011), patients who show an inadequate response to at least 2 NSAIDs 
administered at the maximum recommended dose over a total period of 4 weeks should be 
treated with a biologic. When switching to a biologic in clinical practice, the refractory NSAID 
treatment is often kept as a concomitant treatment to the biologic. There is currently no clinical 
or scientific guidance on how, when and how fast NSAIDs should be discontinued or tapered 
after initiation of the biologic treatment.  
Clinical trials have already shown that NSAID intake could be considerably reduced in AS 
patients treated with anti- TNF compounds (e.g. Poddubnyy et al 2013, Konttinen et al 2007, 
Braun et al 2002). In these studies, NSAID usage could be reduced in over 50% of patients by 
more than 50% of the baseline value and could even be completely stopped in up to 20% of the 
analyzed patients (Braun et al 2002). However, in these trials, patients were not explicitly 
advised how to reduce NSAIDs. Furthermore, the nonsteroidal anti-inflammatory drug 
assessment of the spondyloarthritis international society score (ASAS-NSAID score), which 
has been developed as a standardized method of evaluating NSAID intake in clinical trials has 
not been used as an endpoint in many of the trials (Dougados et al 2011). 
In a recently published prospective, randomized, placebo-controlled trial on the NSAID sparing 
effect of etanercept (Dougados et al 2014), a dramatic reduction of NSAID intake (up to two 
thirds) was observed. However, the reduction in NSAID intake was associated with 
considerably lower clinical ASAS20 response rates compared to the Phase 3 clinical trial of 
etanercept in AS (i.e. 44% vs. 57% at Week 8). This finding raises questions as to whether or 
not reducing NSAIDs may potentially counteract the achievement of treatment goals (i.e. 
reduction of disease activity) and whether or not there is an optimal time point for starting 
NSAID tapering. 
1.2 
Purpose 
The current study will assess the clinical ASAS20 response to Secukinumab and evaluate to 
which extent concomitant NSAID treatment can be reduced between Week 4 and Week 12 in 
patients treated with Secukinumab 150 mg or placebo. Furthermore, the clinical trial will assess 
the clinical ASAS20 response to Secukinumab and evaluate to which extent concomitant 
NSAID treatment can be reduced between Week 4 and Week 12 in patients treated with 
Secukinumab 150 mg or placebo following an initial run-in phase of 4 weeks on stable NSAID 
therapy. Two different time points of NSAID tapering initiation will be evaluated in this study: 
1. a delayed tapering approach in which NSAID will be tapered following 4 weeks  of 
Secukinumab treatment at stable NSAID therapy.  

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2. an early tapering approach in which NSAID will be tapered immediately after initiation 
of Secukinumab treatment 
These 2 approaches will be evaluated compared to placebo in order to assess whether the early 
or delayed NSAID tapering is superior to placebo in terms of clinical ASAS20 response and 
extent of reduction in NSAID intake. 
As a patient-reported outcome, pain is a major patient-relevant efficacy parameter in clinical 
practice in AS. This study will therefore monitor overall neck, back and hip pain on a continuous 
basis. It will be recommended that NSAID should be tapered if the patient reports an 
improvement in back pain or a level below a certain threshold. It is anticipated that the results 
of this study may provide guidance for the systematic adjustment of concomitant NSAID 
treatment in AS patients based on their initial response to Secukinumab, thereby leading to 
optimization of the therapeutic strategy with Secukinumab. In case of a positive outcome 
concerning the NSAID reduction, e.g. no drop in clinical efficacy for Secukinumab between 
Week 4 and Week 12 at significantly reduced NSAID intake, this study could trigger the 
development of a guidance concerning NSAID reduction applicable for all AS patients starting 
a biologic treatment. 
2 
Study objectives 
2.1 
Primary objective  
 
To demonstrate that the efficacy of Secukinumab 150 mg s.c. (with NSAID tapering) is superior 
to placebo based on the proportion of patients achieving an ASAS20 response at week 12. To 
show superiority, both Secukinumab treatment arms will be pooled and compared against 
placebo. 
2.2 
Secondary objectives 
1. To demonstrate that the change from baseline in ASAS-NSAID score at week 12 is 
superior for Secukinumab 150 mg s.c. as compared to placebo. To show superiority, both 
Secukinumab treatment arms will be pooled and compared against placebo. 
2. To demonstrate that the efficacy of Secukinumab 150 mg s.c at week 12 is superior to 
placebo based on the change from baseline in the total BASDAI. To show superiority, 
both Secukinumab treatment arms will be pooled and compared against placebo. 
3. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 0 
with NSAID tapering allowed from week 4; “delayed tapering”) at Week 12 is superior to 
placebo based on the proportion of patients achieving an ASAS20 response. 
4. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 
with NSAID tapering allowed from week 4; “early tapering”) at Week 12 is superior to 
placebo based on the proportion of patients achieving an ASAS20 response. 
5. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 
with NSAID tapering allowed from week 4; “early tapering”) at Week 16 is superior to 
placebo based on the proportion of patients achieving an ASAS20 response. 

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6. To demonstrate that the change from baseline in ASAS-NSAID score at Week 12 is 
superior for Secukinumab 150 mg s.c. (Secukinumab from week 0 with NSAID tapering 
allowed from week 4; “delayed tapering”) as compared to placebo. 
7. To demonstrate that the change from baseline in ASAS-NSAID score at Week 12 is 
superior for Secukinumab 150 mg s.c . (Secukinumab from week 4 with NSAID tapering 
allowed from week 4; “early tapering”) as compared to placebo.  
8. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 0 
with NSAID tapering allowed from week 4; “delayed tapering”) at Week 12 is superior to 
placebo based on the change from baseline in the total BASDAI. 
9. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 
with NSAID tapering allowed from week 4; “early tapering”) at Week 12 is superior to 
placebo based on the change from baseline in the total BASDAI. 
10. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 
with NSAID tapering allowed from week 4; “early tapering”) at Week 16 is superior to 
placebo based on the change from baseline in the total BASDAI. 
11. To demonstrate that the efficacy of Secukinumab 150 mg s.c. at week 12 is superior to 
placebo based on the change from baseline in health-related Quality of Life as measured 
by the SF-36 PCS. 
12. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 0 
with NSAID tapering allowed from week 4; “delayed tapering”) at Week 12 is superior to 
placebo based on the change from baseline in health-related Quality of Life as measured 
by the SF-36 PCS. 
13. To demonstrate that the efficacy of Secukinumab 150 mg s.c. (Secukinumab from week 4 
with NSAID tapering allowed from week 4; “early tapering”) at Week 12 is superior to 
placebo based on the change from baseline in health-related Quality of Life as measured 
by the SF-36 PCS. 
14. To compare between both Secukinumab regimens concerning the change from baseline in 
ASAS-NSAID score after 12 weeks of Secukinumab exposure (ASAS-NSAID index at 
Week 12 for “delayed tapering” vs. Week 16 for “early tapering”). 
 
2.3 
Exploratory objectives 
1. To compare between both Secukinumab regimens concerning the change from baseline in 
the BASDAI after 12 weeks of Secukinumab exposure (BASDAI at Week 12 for “delayed 
tapering” vs. Week 16 for “early tapering”). 
2. To evaluate change in patient reported neck, back and hip pain (BASDAI question 2; 
Appendix 4) beginning from Secukinumab treatment on a continuous basis in patients 
exposed to Secukinumab 150 mg s.c. for 12 weeks vs. placebo. 
3. To evaluate change in patient reported neck, back and hip pain (BASDAI question 2; 
Appendix 4) from baseline on a continuous basis in patients randomized Secukinumab 
150 mg s.c. (Secukinumab from week 0 with NSAID tapering allowed from week 4; 
“delayed tapering”) vs. placebo from week 0 to week 12. 
4. To evaluate change in patient reported neck, back and hip pain (BASDAI question 2; 
Appendix 4) from baseline on a continuous basis in patients randomized Secukinumab 
150 mg s.c. (early tapering) vs. placebo from week 0 to week 16. 

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5. To compare ASAS20 response rates at week 4 in Secukinumab 150 mg. s.c. 
(Secukinumab from week 0 with NSAID tapering allowed from week 4; “delayed 
tapering”) vs. week 20 in the patients switching from Placebo after 4 weeks of 
Secukinumab exposure each. 
6. Total ASAS-NSAID [Area Under Curve (AUC)] Score from treatment start with 
Secukinumab to a Secukinumab exposure of 12 weeks. 
7. Total ASAS-NSAID [Area Under Curve (AUC)] Score from Week 4 to Week 16 for each 
treatment arm 
8. Proportion of patients with no NSAID intake after Secukinumab exposure of 12 weeks 
9. Proportion of patients with no NSAID intake at week 12 
10. Change from Baseline in the ASAS Health Index after Secukinumab exposure of 12 
weeks 
11. Change from Baseline in the ASAS Health Index at week 12 
12. Spinal mobility assessed by Bath Ankylosing Spondylitis Metrology Index (BASMI) 
linear scores  
13. ASAS40 response rate over time 
14. ASAS20 response rate over time 
15. ASAS5/6 response rate over time 
16. Change from baseline in hsCRP  
17. Change from baseline in total BASDAI over time 
18. BASDAI 50 response over time  
19. ASAS partial remission over time 
20. Change from baseline in ASAS components, including: 
a. Patient’s global assessment of disease activity 
b. Total spinal pain 
c. Inflammation as measured by the mean of BASDAI questions 5 and 6 
d. Bath Ankylosing Spondylitis Functional Index (BASFI)  
21. Change from baseline in Ankylosing Spondylitis Disease Activity Score (ASDAS)-C-
Reactive Protein (CRP) and ASDAS-Erythrocyte Sedimentation Rate (ESR) 
22. ASDAS inactive disease as defined by ASDAS < 1.3 
23. ASDAS clinically important improvement (change in ASDAS ≥ 1.1) and major 
improvement (change in ASDAS ≥ 2.0) 
24. To assess overall tolerability and safety of Secukinumab at reduced NSAID intake.  
25. To evaluate the reasons given by the patient in the patient diary on why he was not able to 
taper NSAIDs despite reduced spinal pain 
26. To compare both Secukinumab regimens between week 12 (delayed tapering) and week 
16 (early tapering) concerning all primary, secondary and exploratory objectives [at these 
timepoints, patients will have had the same exposure time to Secukinumab of 12 weeks] 
 

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3 
Investigational plan 
3.1 
Study design 
This is a 20-week, randomized, double-blind, 3-arm, placebo-controlled, parallel-group, 
multicenter study of Secukinumab (AIN457) to examine the clinical response as measured by 
the ASAS20 and the NSAID-sparing effect of Secukinumab treatment. The clinical efficacy 
(ASAS20 response) and the cumulative NSAID sparing effect of two strategies of NSAID 
tapering after initiation of Secukinumab will be evaluated as compared to placebo:  
Patients will be randomized 1:1:1 to one of the following treatment groups: 
 Secukinumab - delayed NSAID tapering: Secukinumab 150 mg s.c. at weeks 0, 1, 2, 3, 
4, 8, 12, 16 and 20 with placebo injections at Week 5, 6, 7 and 17, 18, 19 to maintain the 
blind. 
 Secukinumab – early NSAID tapering: Placebo at weeks 0, 1, 2, 3 to maintain the blind; 
followed by Secukinumab 150 mg s.c. at Week 4, 5, 6, 7, 8, 12, 16 and 20 with 
intermittent Placebo injections at week 17, 18, 19 to maintain the blind. 
 Placebo: Placebo at weeks 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. After the Week 16 assessments 
of the secondary endpoint have been performed, these patients will receive Secukinumab 
150 mg s.c. at weeks 16, 17, 18, 19 and 20. 
The patients will be stratified at randomization according to their status of prior TNFα inhibitor 
exposure, i.e. TNFα inhibitor naive patients or TNFα inhibitor inadequate responders (TNFα-
IR). The only condition that will be placed on enrollment targets for each stratum is that no less 
than 60% of patients (122 patients) are TNFα inhibitor naïve, i.e., no more than 40% of patients 
(82 patients) are TNFα-IR. In theory the percentage of TNFα inhibitor naïve patients could 
reach 100%, although that is not anticipated. 

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Figure 3-1 
Study design 
 
All patients will be advised to continue on the maximum recommended/tolerated dose of 
NSAIDs for the first 4 weeks of the trial.  
A follow-up visit is to be done 4 weeks after last study treatment administration for all subjects, 
regardless of whether they complete the entire study as planned or discontinue prematurely. 
NSAID tapering strategy 
All patients will be advised to taper/discontinue their NSAID intake starting at Week 4 to Week 
20. Patients may use NSAIDs on an on-demand basis to avoid an unacceptable worsening of 
disease activity. 
From Week 16 on, those patients originally randomized to placebo will self-inject Secukinumab 
150 mg at weeks 17, 18, 19 and 20, while patients originally randomized to either of the 
Secukinumab groups will receive their next Secukinumab injection after Week 16 at Week 20 
with Placebo injections at weeks 17, 18, 19 to maintain the blinding of the treatment assignment 
for the secondary / exploratory endpoint analyses. 
Patients will be asked to capture NSAID intake and level of AS neck, back and hip pain 
(BASDAI question 2; see Appendix 4) on a daily basis in a patient diary. Guidance will be 

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provided to patients that NSAID intake should be reduced upon an improvement in back pain 
and that the reduction should preferably happen step-wise and instead of an abrupt stop of any 
NSAID intake. However, deviance from this guidance will be acceptable and may be discussed 
between investigator and patient. Patients may deviate from this guidance if required, e.g. 
NSAID use necessary for non-spinal pain (e.g. entheses, peripheral joints, and headache). Also, 
if pain levels increase, patients may increase NSAID usage on an on-demand basis. The 
reduction in NSAID intake will be assessed using the ASAS-NSAID score (Dougados et al 
2012). 
3.2 
Rationale of study design 
This phase IV trial utilizes a double-blind, randomized, parallel-group, placebo-controlled 
design. According to the ASAS/EULAR recommendations (van der Hejde et al. 2011); patients 
who show an inadequate response to at least 2 NSAIDs over a 4-week period in total at the 
maximum recommended dose patients should be treated with a biologic unless contraindicated. 
When switching to a biologic, in clinical practice the refractory NSAID treatment is kept as 
concomitant treatment in addition to the biologic treatment. There is currently no clinical or 
scientific guidance on how, when and how fast NSAIDs should be discontinued. 
In the current study it will be evaluated to which extent NSAID treatment can be reduced 
between Week 4 and Week 12 in patients randomized to Secukinumab 150 mg or placebo 
following an initial run-in phase of 4 weeks on stable NSAID therapy. Two NSAID tapering 
approaches will be evaluated in this study: 
1) an early tapering approach in which NSAID will be tapered at the start of Secukinumab 
treatment,  
2) a delayed tapering approach in which NSAID will be tapered following 4 weeks of 
Secukinumab treatment.  
These 2 strategies will be evaluated compared to placebo in order to assess whether the early or 
delayed NSAID tapering is superior in terms of clinical ASAS20 response and NSAID sparing 
strategy. 
The ASAS-NSAID score was developed as a standard method of evaluating NSAID intake in 
clinical studies (Dougados et al 2011; Dougados et al 2012). There, the current study will use 
the ASAS-NSAID score to assess the potential NSAID sparing effect of Secukinumab. 
3.3 
Rationale of dose/regimen, route of administration and duration 
of treatment 
The dosing of Secukinumab in this study with 4-weekly 150 mg s.c injections after weekly 
Secukinumab 150 mg s.c. loading doses for the first 4 weeks of therapy relies upon dose-
efficacy relationships observed in a proof of concept (PoC) trial (CAIN457A2209) and 2 phase 
III trials (CAIN457F2305, CAIN457F2310) in AS, as described below. 
The PoC trial in AS (CAIN457A2209) suggested that after 2 i.v. Secukinumab doses of 10 
mg/kg given 3 weeks apart, Secukinumab demonstrated high efficacy, achieving an ASAS20 
response at Week 6 in 59% of the patients on Secukinumab versus 24% on placebo, and was 
well-tolerated (Baeten 2013). The ongoing trials in AS, CAIN457F2305 and CAIN457F2310, 
assessed the efficacy of both 75 mg and 150 mg s.c. maintenance doses with loading regimens 

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consisting of either intravenous doses (CAIN457F2305: 3 doses of 10 mg/kg given every 2 
weeks at BSL, Weeks 2 and 4) or subcutaneous doses (CAIN457F2310: 4 weekly doses 
matching the maintenance dose of either 75 mg or 150 mg given at BSL, Weeks 1, 2, and 3). 
Given the similarity of the ASAS20 response seen at the Week 16 primary endpoint for the 150 
mg dose in each of these studies, regardless of whether the loading dosing was i.v. 
(CAIN457F2305: 60.8% for IV-150 mg vs 28.7% for placebo) or s.c. (CAIN457F2310: 61.1% 
for IV-150 mg vs 27.0% for placebo), 150 mg is a sufficient dose to provide clinically and 
statistically significant efficacy, whereas higher i.v. loading doses of Secukinumab do not 
appear to confer a greater response on the primary endpoint of ASAS20 at Week 16. Of note, 
the 75 mg s.c. loading/s.c. 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, ASAS40, hsCRP, ASAS5/6, BASDAI, SF-36 PCS, 
ASQoL and ASAS partial remission. Therefore, the 75 mg dose will not be pursued in further 
studies. 
3.4 
Rationale for choice of comparator 
The use of early and delayed tapering arms is to evaluate when and how fast NSAIDs can be 
discontinued after initiating Secukinumab therapy. 
A placebo arm up to week 16 is included in this study. Due to the nature of the disease and the 
outcome measures used (e.g., ASAS20), a placebo arm is necessary to obtain reliable efficacy 
measurements. This is particularly important as all primary and key secondary endpoints of this 
trial are based on patient reported outcomes which may be more susceptible to bias in an open 
label setting.  The continuation of the placebo group up to including the week 12 injection can 
be supported from an ethical standpoint, as patients can continue on a range of concomitant 
treatments. To obtain unbiased results for the primary endpoint analysis and the blinded 
evaluation of different time points of initiation of NSAID tapering, it is necessary to switch 
placebo patients not before all week 16 assessments have been performed and to maintain 
blinding for the initial treatment group assignment. 
Moreover, the inclusion of a placebo group is in accordance with previously implemented 
methodology and in compliance with the EMA/EMEA (European Medicines Agency) 
guidelines for clinical trials in AS (EMA 2009). 
3.5 
Purpose and timing of interim analyses/design adaptations 
Not applicable. 
3.6 
Risks and benefits 
The risk to patients 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 (IB). 
Data from two pivotal trials in ankylosing spondylitis (AS) CAIN457F2305 and 
CAIN457F2310 demonstrate safety and efficacy of Secukinumab in the treatment of AS.  
Based on these data secukinumab was approved on 19 November 2015 by the European 
Commission for the treatment of active ankylosing spondylitis in adults who have responded 
inadequately to conventional therapy. 

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3.6.1.1 
Study CAIN457F2305 in ankylosing spondylitis (AS) 
This 104-week, double-blind, placebo-controlled study randomized 371 patients with moderate 
to severe ankylosing spondylitis (AS) despite current or previous NSAIDs, DMARDs and/or 
TNF-α inhibitor therapy to 10mg/kg IV load (baseline, Week 2, and Week 4)-75 mg sc every 4 
wks maintenance (n=124); IV load regimen-150 mg sc maintenance (n=125), or to placebo IV 
load and sc maintenance (n=122).  At Week 16, non-responder placebo pts would be 
randomized to 75mg or 150mg maintenance dose without a loading regimen and all remaining 
(responder) placebo pts would be randomized to 75mg or 150 mg maintenance regimen at Week 
24.  The primary objective was superiority to placebo based on Assessment of Spondyloarthritis 
International Society criteria (ASAS) 20 response rate at week 16. 
An interim analysis with a cut-off date of 10-Dec-2013 was performed and included efficacy 
data up to Week 52 and all safety data up to that cut-off date of the study for all patients 
(regardless of study visit at that time).  Over the entire treatment period at time of the data cut-
off, the median duration of exposure was 475 days for any 75 mg group and 463 days for any 
150 mg group.  
Both secukinumab arms were superior to placebo for the primary endpoint of ASAS 20 response 
at Week16: 59.7% for IV-75 mg and 60.8% for IV-150 mg ( p<0.0001) vs. 28.7% for placebo. 
Additionally, both secukinumab IV-75 mg and IV-150 mg groups were superior to placebo at 
Week 16 for all endpoints tested in the hierarchical testing strategy. Among those, ASAS 40 
response was 33.1% (p=0.0003) for IV-75 mg and 41.6% (p<0.0001) for IV-150 mg compared 
with 13.1% for placebo and significantly lower ratios of post-baseline to baseline hsCRP values 
for IV-75 (0.45) and IV-150 mg (0.40) vs. placebo (0.97) were reported (both comparisons, 
p<0.0001). 
 
Secukinumab was efficacious through 16 weeks of treatment in both anti-TNF-α naive patients 
and patients with an inadequate response or intolerance to prior anti-TNF-α therapy. ASAS 20 
and ASAS 40 response rates for secukinumab vs. placebo observed  for TNF-α inhibitor naive 
pts were numerically higher (ASAS 20 (60.0% and 66.3%) and ASAS 40 (34.4% and 48.9%)) 
than for TNF-α inhibitor inadequate responders (ASAS 20: 58.8% and 45.5%; ASAS 40: 29.4% 
and 21.2%) for the IV-75 mg and IV-150 mg regimens, respectively. 
All treatment responses on primary and secondary variables at Week 16 were sustained through 
Week 52, with dose-separation observed between the IV-150 mg and IV-75 mg regimens as 
patients approached Week 52, which favored the higher maintenance dose of 150 mg sc on 
higher hurdle clinical efficacy endpoints such as ASAS 40, ASAS partial remission, and 
BASDAI 50.    
The safety profile of secukinumab for both IV loading regimens showed no new or unexpected 
safety signals. Infections were more frequent with secukinumab compared to placebo and 
showed dose dependence in non-serious infections, with the majority consisting of upper 
respiratory tract infections. Serious infections were rare in both secukinumab treatment arms.  
Two deaths were reported: a suicide secondary to depression in a placebo patient, and 
respiratory failure secondary to cardiac failure and pulmonary fibrosis in a patient on IV-75 
mg.  Neither death was suspected to be related to study treatment. 
The incidence of AEs up to Week 16 was higher in both IV-75 mg (66.9%) and IV-150 mg 
(69.6%) groups vs. placebo (55.7%). This was driven primarily by non-serious infections and 

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infestations (mainly nasopharyngitis), which was the most frequently affected primary SOC.  
Comparable crude incidence rates of serious AEs and discontinuations due to AEs were 
reported in the placebo group compared with either secukinumab dose group up to Week 16.  
Over the entire treatment period, treatment-emergent AEs were reported with a higher 
incidence in the Any 150 mg group (85.1%) than in the Any 75 mg group (76.5%), which 
included patient originally randomized to placebo who were later re-randomized to either dose 
of secukinumab from Week 16 onward. This difference was driven primarily by non-serious 
infections and infestations (mainly nasopharyngitis, pharyngitis, influenza, rhinitis). The rate 
of SAEs was similar between the two secukinumab regimens (10.1% in the Any 75 mg group 
and 9.4% in the Any 150 mg group).  
3.6.1.2 
Study CAIN457F2310 in ankylosing spondylitis (AS) 
This 5-year double-blind, placebo-controlled study randomized 219 patients with moderate to 
severe ankylosing spondylitis (AS) despite current or previous NSAIDs, DMARDs and/or 
TNF-α inhibitor therapy to Secukinumab 75 mg s.c. load (baseline, Weeks 1, 2, and 3) and 75 
mg sc maintenance (every 4 weeks starting at Week 4) (n=73); secukinumab 150 mg s.c load 
and maintenance (n=72); or placebo load and maintenance (n=74).  At Week 16 all placebo 
patients were re-randomized 1:1 to 75mg or 150mg s.c. maintenance dose regimen.   
An interim analysis with a cut-off date of 04-Aug-2014 was performed when the last patient 
completed Week 52 of the study.  Efficacy results at Week 52 and safety data up to the cut-off 
date for all patients (regardless of study visit at the time) are described below. 
Secukinumab 150 mg s.c. demonstrated a rapid onset of response and superior efficacy over 
placebo in measures of disease signs and symptoms, physical function, quality of life and 
objective markers of inflammation. The secukinumab 150 mg sc load and maintenance dose 
group, but not the 75 mg sc load and maintenance dose group, had significantly greater 
responses than placebo at Wk 16, with respect to the primary endpoint (ASAS 20; 61.1% for 
SC-150 mg vs 27.0% for placebo) and all secondary endpoints (ASAS 40, hsCRP, ASAS 5/6, 
BASDAI, SF-36 PCS and ASQoL) except for ASAS partial remission. Secukinumab was 
efficacious through 16 weeks of treatment in both anti-TNF-α naive patients and patients with 
an inadequate response or intolerance to prior anti-TNF-α therapy.  Concerning ASAS40, 
Secukinumab 150 mg s.c. was superior to placebo at Week 16, with a rate of 36.1% (adjusted 
p=0.0008) vs. 10.8% for placebo, while 75 mg s.c. (26.0%) was not significant. All treatment 
responses on primary and secondary variables at Week 16 were sustained through Week 52, 
with higher response rates observed for 150 mg s.c compared with 75 mg s.c. for nearly all 
efficacy endpoints.  
Higher ASAS 20 and ASAS 40 response rates for secukinumab vs. placebo were observed 
regardless of previous TNF-α use. TNF-α inhibitor naive patients had numerically higher rates 
of ASAS 20 response (150 mg: 68.2%; 75 mg: 51.1%, placebo: 31.1%) and ASAS 40 
response (150 mg: 43.2%; 75 mg: 31.1%, placebo: 17.8%) than TNF-α inhibitor inadequate 
responder patients (ASAS 20: 50.0% for 150 mg, 25.0% for 75 mg and 24.1% for placebo; 
ASAS 40: 25.0% for 150 mg, 17.9% for 75 mg and 0.0% for placebo), with consistently 
higher response rates for 150 mg compared with 75 mg. 
The safety profile of secukinumab in this study showed no new or unexpected safety signals. 

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One patient in the secukinumab 75 mg group who had a history of CAD, a significant 
smoking history, and elevated LDL and lipoprotein A levels at baseline died from an acute 
myocardial infarction on Day 22, which was not suspected to be related to study treatment. 
AE incidence up to Week 16 was higher in the secukinumab 150 mg group (65.3%) compared 
with the secukinumab 75 mg s.c. group (57.5%) and comparable to the placebo group 
(63.5%). The AE rate in the secukinumab 150 mg s.c. group was driven primarily by non-
serious infections (mainly nasopharyngitis). Rates of SAEs and discontinuations due to AEs 
up to Week 16 were low and comparable in the secukinumab groups compared with the 
placebo group.  
Over the entire treatment period, treatment-emergent AE rates were comparable between the 2 
secukinumab dose groups (83.8% patients in the Any secukinumab 75 mg s.c. group and 
82.1% in the Any secukinumab 150 mg s.c. group). SAE rates over the entire treatment period 
were similar between the two secukinumab dose groups (8.6% with the Any 75 mg group and 
7.5% with the Any 150 mg group). 
Over the entire treatment period, a slightly higher proportion of patients in the Any-
secukinumab-150 mg s.c. arm (5.7%) discontinued due to an AE compared to the Any-
secukinumab-75 mg s.c. arm (3.8%). All AEs that led to discontinuation were single events 
with no trends across treatment arms. No patient discontinued due to an infection event. 
Based on the benefit-risk profile of secukinumab in AS and other approved indications, it is 
considered appropriate to initiate this study. 
The benefit-risk profile of Secukinumab in AS and other approved indications remains 
favorable and unchanged. It is therefore considered appropriate to initiate this study. 
4 
Population 
Men and women ≥ 18 years of age who fulfill the modified New York criteria for AS (described 
in Appendix 3) and have active disease as defined by a BASDAI ≥4 on a scale of 0-10 and 
spinal pain (BASDAI Question 2) of ≥4 cm on a 0–10 numeric rating scale will be included. 
The study will be a multi-centric study planned to be conducted across 30-45 sites in Germany. 
The study is aimed to randomize a total of approximately 204 patients. Due to statistical 
adaptions, the required amount of randomized patients can be reduced to a total of 
approximately 190.  
Subjects may be re-screened but no study-related re-screening procedure should be performed 
prior to written re-consent by the subject. 
4.1 
Inclusion criteria 
Patients eligible for inclusion in this study have to fulfill all of the following criteria: 
1. Patient must be able to understand and communicate with the investigator and comply 
with the requirements of the study and must give a written, signed and dated informed 
consent before any study assessment is performed 
2. Male or non-pregnant, non-lactating female patients at least 18 years of age 
3. Diagnosis of active AS with prior documented radiologic evidence (X-ray or radiologist’s 
report) fulfilling the Modified New York criteria for AS (Appendix 3)  

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4. Active AS assessed by total BASDAI ≥ 4 (0-10) at baseline 
5. Spinal pain as measured by BASDAI Question 2 ≥ 4 cm on a 0-10 cm numeric rating 
scale at baseline 
6. Total back pain as measured by VAS ≥ 40 mm (0-100 mm) at baseline 
7. Patients should have been on at least 2 different NSAIDs at the highest recommended 
dose for at least 4 weeks in total in the past, prior to randomization, with an inadequate 
response or failure to respond, or less if therapy had to be reduced due to intolerance, 
toxicity or contraindications 
8. Patients must report regular intake of NSAIDs of at least 50% of the highest 
recommended dose at Screening. Patients with prior TNFα inhibitor therapy must report 
regular intake of NSAIDs of at least 50% of the highest recommended dose at baseline 
after the appropriate washout 
9. Patients are required to be on a stable dose of NSAIDs  for at least 2 weeks before 
randomization 
10. Patients who have previously been on a TNFα inhibitor will be allowed entry into study 
after an appropriate wash-out period prior to randomization: 
 4 weeks for Enbrel® (etanercept) – 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 
 10 weeks for Cimzia® (certolizumab) – with a terminal half-life of 14 days 
11. Patients who have been on a TNFα inhibitor (not more than two) 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. No more than 40% of patients may have previously received anti-
TNFα agents 
12. Patients 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 be on a stable dose for 
at least 4 weeks prior to randomization 
13. Patients on MTX must be on stable folic acid supplementation before randomization 
14. Patients 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 
15. Patients taking systemic corticosteroids have to be on a stable dose of ≤ 10 mg/day 
prednisone or equivalent for at least 2 weeks before randomization 
4.2 
Exclusion criteria 
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. No 
additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients. 

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3. 
Chest X-ray or MRI with evidence of ongoing infectious or malignant process, obtained 
within 3 months of screening and evaluated by a qualified physician 
4. 
Patients 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 or participation in 
another clinical study (interventional or non-interventional) in the same indication during 
enrollment in this study 
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. Patients previously treated with any biological immunomodulating agents, except those 
targeting TNFα 
11. Patients who have taken more than two anti-TNFα agents 
12. Previous treatment with any cell-depleting therapies including but not limited to anti-
CD20 or investigational agents (e.g., CAMPATH, 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 (e.g. 20 
weeks in EU). Effective contraception methods include: 
 Total abstinence, when this is in line with the preferred and usual lifestyle of the 
patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception  
 Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy) or tubal ligation at least 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 patients on the 
study, the vasectomized male partner should be the sole partner for that patient  
 Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository  
 Use of oral, injected or implanted hormonal methods of contraception or other forms 
of hormonal contraception that have comparable efficacy (failure rate <1%), for 
example hormone vaginal ring or transdermal hormone contraception 
 Placement of an intrauterine device or intrauterine system 

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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) 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 child 
bearing potential.  
15. Active ongoing inflammatory diseases other than AS 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 patient and/or places the patient at unacceptable risk for 
participation in an immunomodulatory therapy 
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 SGOT (AST), SGPT (ALT), alkaline phosphatase, or serum 
bilirubin. The Investigator should be guided by the following criteria: 
 Any single parameter may not exceed 2 x upper limit of normal (ULN). A single 
parameter elevated up to and including 2 x ULN should be re-checked once more as 
soon as possible, and in all cases, at least prior to enrollment/randomization, to rule 
out 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 patients with one kidney only, or a serum 
creatinine level exceeding 1.5 mg/dL (132.6 µmol/L) 
20. Screening total 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 6-1. 
Patients with a positive test may participate in the study if further work up (according to 
local practice/guidelines) establishes conclusively that the patient has no evidence of 
active tuberculosis. If presence of latent tuberculosis is established, then treatment 
according to local country guidelines must have been initiated 
23. Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C 
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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 patient 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 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 
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  
32. Patients who are intolerant to NSAIDs 
5 
Treatment 
5.1 
Protocol requested treatment 
5.1.1 
Investigational treatment 
Novartis/CRO will supply the following study treatments: 
 Investigational treatment: 
 Secukinumab 150 mg provided in a 1 mL PFS  (1 PFS for 150 mg dose) 
 Reference therapy:  
 Secukinumab placebo (Placebo) provided in a 1 mL PFS 
At the BSL visit, patients will be instructed by the site staff, utilizing the IFU, on how to self-
inject using a PFS. Patients will be asked to raise any questions and then to proceed with self-
injection. At the Week 1 visit, patients will be asked to refer to the IFU and to proceed directly 
with self-injection of the study drug (i.e., no prior retraining) for the remainder of the trial. 
However, if the patient is not comfortable self-injecting the study treatment, then the site staff 
may administer it for the patient. From Week 3, patients will be allowed to self-administer the 
study treatment at home during the optional visits in which there are no scheduled assessments 
at the site (see Table 6-1 below). If the patient is not comfortable self-injecting the study 
treatment, then a caregiver may administer it for the patient or the patient can come to the site 
at an optional visit to have the study drug administered by the study staff. 
Note: The Secukinumab PFSs are packed in double-blinded fashion until the end of the trial 
and therefore, do not need to be prepared by the study site. The study medication will be labeled 
as follows: 

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 Double-blind Secukinumab and Placebo PFS will be labeled AIN457 
150mg/1mL/Placebo. 
For detailed instructions on storage of the investigational treatments, please refer to 
Section 5.5.3. 
5.1.2 
Additional study treatment 
Continuation of the concomitant administration of NSAIDs as prescribed before inclusion into 
the trial is planned beyond the investigational treatment to evaluate the extent of NSAID sparing 
effect of Secukinumab in this trial. 
5.2 
Treatment arms 
Patients will be assigned to one of the following three treatment arms in a ratio of 1:1:1. 
 Group 1: Secukinumab 150 mg s.c. at Week 0, 1, 2, 3, 4, 8, 12, 16 and 20; Placebo 
injections at Week 5, 6, 7 and 17, 18, 19 to maintain the blind for the initial treatment 
assignment 
 Group 2: Placebo at Weeks 0, 1, 2, 3 followed by Secukinumab 150 mg s.c. at 
Week 4, 5, 6, 7, 8, 12, 16 and 20 with Placebo at Week 17, 18, 19 to maintain the blind 
for the initial treatment assignment 
 Group 3: Placebo at Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. From Week 16, patients 
will be switched to receive Secukinumab 150 mg s.c. at Week 16, 17, 18, 19, and 20 
 
5.3 
Treatment assignment, randomization 
At baseline visit, all eligible patients will be randomized via Interactive Response Technology 
(IRT) to 1 of the treatment arms. The investigator or his/her delegate will contact the IRT after 
confirming that the patient fulfills all the inclusion/exclusion criteria. The IRT will assign a 
randomization number to the patient, which will be used to link the patient to a treatment arm 
and will specify a unique medication number for the first package of investigational treatment 
to be dispensed to the patient. The randomization number will not be communicated to the 
caller. 
From Week 16 onwards, all patients will receive Secukinumab 150 mg. Those patients 
originally randomized to placebo will self-inject Secukinumab 150 mg after Week 16 at Week 
17, 18, 19 and 20, while patients originally randomized to either of the Secukinumab groups 
will receive their next Secukinumab injection at Week 20 with Placebo injections at weeks 17, 
18, 19 to maintain the blinding of initial treatment assignment. 
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from patients and investigator staff. A patient 
randomization list will be produced using a validated system that automates the random 
assignment of patient numbers to randomization numbers. These randomization numbers are 
linked to the different treatment arms, which in turn are linked to medication numbers. A 
separate medication list will be produced by or under the responsibility of Novartis Biometry 
using a validated system that automates the random assignment of medication numbers to packs 
containing the investigational drug(s).  

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Original treatment assignment, as per baseline randomization, will remain double-blinded to 
the patient, investigator, and site personnel until after the Week 24 database lock and analyses. 
 
5.4 
Treatment blinding 
This is a double-blind randomized treatment trial. However, after completion of Week 16 
assessments of the primary endpoint, patients initially randomized to placebo will be switched 
to receive Secukinumab 150 mg s.c. every week with intermittent placebo injections in both 
active arms at weeks 17, 18, 19 to maintain the blind for the initial treatment assignment. 
Until the end of the trial, all original randomized treatment assignments will be double-blinded 
to patients, investigators, and site personnel.  
Unblinding of treatment dose or original randomized treatment assignment will only occur in 
the case of patient emergencies (see Section 5.5.12). 
The hsCRP results from samples collected during the treatment period will not be revealed to 
the site.  
5.5 
Treating the patient 
5.5.1 
Patient numbering 
Each patient is uniquely identified in the study by a combination of his/her center number and 
patient number. The center number is assigned by Novartis to the investigative site. Upon 
signing the informed consent form, the patient is assigned a patient number by the IRT.  Upon 
signing of the ICF by the patient, the investigator or his/her staff will contact the IRT and 
provide the requested identifying information for the patient to register them into the IRT. Only 
the assigned patient number should be entered in the field labeled “Patient ID” on the EDC data 
entry screen. Once assigned to a patient, the Patient ID will not be reused.  If the patient fails to 
be randomized for any reason, the IRT must be notified within 2 days that the patient was not 
randomized. The reason for not being randomized will be entered on the Screening Log, and 
the Demography eCRF should also be completed. 
 
5.5.2 
Dispensing the investigational treatment 
Each study site will be supplied by Novartis with study treatment in packaging of identical 
appearance. 
The study treatment packaging for Secukinumab/placebo has a 2-part label. A unique 
medication number is printed on each part of this label. Investigator staff will identify the 
investigational treatment package(s) to dispense to the patient by contacting the IRT and 
obtaining the medication number(s). 
 

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5.5.3 
Handling of study treatment 
5.5.3.1 
Handling of investigational treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly, and kept in a secured location to which only the investigator and designees 
have access. Upon receipt, all investigational treatment should be stored according to the 
instructions specified on the labels. Clinical supplies are to be dispensed only in accordance 
with the protocol. Technical complaints are to be reported to the respective Novartis CPO 
Quality Assurance. 
Medication labels will be in German and comply with the legal requirements of Germany. They 
will include storage conditions for the study treatment but no information about the patient 
except for the medication number. The PFS (150 mg active/placebo) sealed in an outer box 
must be stored in a access controlled/locked refrigerator between 2°C and 8°C and protected 
from light. They must be carefully controlled in accordance with regulations governing 
investigational medicinal products and local regulations. The investigator must maintain an 
accurate record of the shipment and dispensing of study treatment in a drug accountability log. 
Monitoring of drug accountability will be performed by monitors during site visits or remotely 
and at the completion of the trial. Patients will be asked to return all unused study treatment and 
packaging at the end of the study or at the time of discontinuation of study treatment. 
At the conclusion of the study, and as appropriate during the course of the study, the investigator 
will return all unused study treatment, packaging, drug labels, and a copy of the completed Drug 
Accountability log to the Novartis monitor or to the Novartis address provided in the 
investigator folder at each site. 
Destruction of the unused drug should be done according to local requirements and after 
approval by Novartis/CRO clinical team. 
5.5.3.2 
Handling of other study treatment 
Not applicable. 
5.5.4 
Instructions for prescribing and taking study treatment 
Study treatment (150 mg Secukinumab and placebo) will be administered s.c. by 1 mL PFS 
throughout the study as 1 mL/150 mg Secukinumab or 1 mL placebo, respectively. 
Administration of study treatment will occur via self-injection by the patient from Baseline 
through to Week 20. Administration of study treatment must occur after the study assessments 
for the visit have been completed. The PFS with the ready-to-use study treatment solution will 
be provided by the site staff to the patient. Detailed instructions on the self-administration of 
the study treatment will be described in the IFU for Secukinumab and provided to each patient. 
At the Baseline visit, patients will be instructed by the site staff, utilizing the IFU, on how to 
self-inject using a PFS. Patients will be asked to raise questions, if they have any, and then to 
proceed with self-injection. At the Week 1 visit, patients will be asked to refer to the IFU and 
to proceed directly with self-injection of the study drug (i.e. no prior retraining) for the 
remainder of the trial. However, if the patient is not comfortable self-injecting the study 
treatment, then the site staff may administer it for the patient. 
All kits of study treatment assigned by the IRT will be recorded in the IRT. 

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The investigator should promote compliance by instructing the patient to take the study 
treatment exactly as prescribed and by stating that compliance is necessary for the patient’s 
safety and the validity of the study. The patient should be instructed to contact the investigator 
if he/she is unable for any reason to take the study treatment as directed. 
Subcutaneous administration with pre-filled syringe (PFS) 
Secukinumab solution for s.c. injection (150 mg in 1 mL active/placebo) will be provided in a 
PFS.  
The study treatment solution must be injected into normal areas of the skin. 
Patients will be instructed by the site staff on how to self-inject study treatment using a PFS, 
following the IFU. After training at the Baseline visit, the injections will be self-administered 
into an appropriate site of the body (thighs, arms, abdomen), and each injection should be given 
at a different injection site to reduce the risk of injection reaction. Each new injection should be 
given at least 2.5 cm from the previously used site. If the patient chooses the abdomen, the area 
5 cm around the navel should be avoided. Investigational drug should not be injected into areas 
where the skin is tender, bruised, red, or hard, or where patient has scars or stretch marks. 
Injection sites should be rotated among appropriate sites to reduce the risk of injection reactions. 
The PFSs with study treatment solution should be kept at 2 to 8°C, protected from light and 
should not be stored frozen. Prior to administration the boxes containing the PFSs with study 
treatment solution should be allowed to come to room temperature unopened for about 20 
minutes before administration. Used PFSs should be disposed immediately after use in a sharps 
container or according to the regulatory needs of the respective countries.  
Any PFS for which a defect or malfunction is noticed prior to or during the injection at any of 
the study visits must be kept at the site until guidance is received from Novartis/CRO on 
whether it should be returned to Novartis/CRO for investigation or discarded. Devices identified 
as defective should be stored according to local guidelines, until specific instruction is discussed 
with Novartis/CRO personnel. Additionally, from baseline onwards, any noticed defect, 
malfunction, problem during the injections or product complaints with the PFS should be 
recorded in the source document. Sites should detail the issue, the date, the kit number and the 
visit number. The site will be asked to record, based on their judgment, whether the observed 
issue was primarily related to the device or to the user. Device malfunctions should also be 
immediately reported to Novartis/CRO personnel as a necessary replacement kit may need to 
be provided. 
5.5.5 
Permitted dose adjustments and interruptions of study treatment 
Investigational treatment dose adjustments are not permitted. 
Investigational treatment interruption is only permitted if, in the opinion of the investigator, a 
patient is deemed to be placed at a significant safety risk unless administration of investigational 
treatment is temporarily interrupted. In such cases study treatment should be interrupted only 
during the time that this risk is present and ongoing. Investigational treatment can be restarted 
at the next scheduled visit after resolution of the safety risk. 
The effect of Secukinumab on live vaccines is unknown; therefore live vaccines should not be 
administered during participation in the study. In case a live vaccine has been administered due 
to a medical urgency, study treatment should be interrupted for 12 weeks. 

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Any study treatment interruption must be recorded on the Dosage Administration Record eCRF. 
5.5.6 
Rescue medication 
Rescue medication is defined as any new therapeutic intervention or a significant change to 
ongoing therapy made because a patient is experiencing either no benefit from participation in 
the trial or worsening/exacerbation of their disease. Rescue medication must not be used before 
completion of Week 12 assessments. Although no patient will be restricted from receiving 
necessary rescue medications for lack of benefit or worsening of disease, if rescue with 
prohibited biologics (as described in Section 5.5.8) occurs, patients will be discontinued from 
the study and enter into the follow-up period after an end of study visit. Efficacy will be assessed 
in detail at every study visit, and patients who are deemed not to be benefiting from the study 
treatment based upon safety and efficacy assessments by the investigator or for any reason on 
their own accord will be free to discontinue the study at any time. Changes in NSAID 
concomitant therapy are permitted after Week 4 assessments and should ideally be performed 
according to the non-binding NSAID tapering guidelines provided to the patient at the week 4 
visit. Please see Section 5.5.7 and Section 5.5.8 for details. 
Use of rescue medication must be recorded on the Prior and Concomitant medications in the 
eCRF page. 
5.5.7 
Concomitant treatment 
The investigator should instruct the patient to notify the study site about any new medications 
he/she takes after the patient was enrolled into the study. All medications, procedures and 
significant non-drug therapies (including physical therapy and blood transfusions) administered 
after the patient was enrolled into the study must be recorded on the Prior and Concomitant 
medications or Procedures and Significant Non Drug Therapy eCRF. The reason, name of the 
drug, procedure or non-drug therapy should be listed. 
Guidelines for the use of specific medications are provided below: 
Methotrexate 
Patients taking MTX (up to 25 mg/week) must be on a stable dose for at least 4 weeks before 
randomization and maintained stable until Week 12, except if MTX-related adverse events 
develop. 
Folic acid 
Patients on MTX must be taking folic acid supplementation before randomization and during 
the trial to minimize the likelihood of MTX associated toxicity. 
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 may be considered. Cholestyramine could be given orally to wash-
out the drug at a dose of 8 g 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 3 
healthy volunteers. The administration of cholestyramine is recommended in patients who 

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require a drug elimination procedure. If a patient receives 8 g t.i.d. for 11 days he/she could be 
safely randomized 4 weeks after the beginning of the 11- day treatment period. 
Systemic corticosteroids 
Treatment with systemic corticosteroids is permitted up to a maximum daily dose of 10 mg 
prednisone equivalent and if the dose was stable within the 2 weeks preceding randomization. 
Corticosteroid dose reductions below 10 mg prednisone equivalent are permitted after Week 12, 
although the corticosteroid dose should not be reduced by more than 1 mg prednisone equivalent 
every 4 weeks. 
After Week 12, the dose and regimen of systemic corticosteroids may be modified as per 
investigator’s judgment and patient need. 
Any change in the dose of systemic corticosteroids during the trial must be recorded on the 
corresponding eCRF page. 
Intra-articular corticosteroids are not permitted within the 4 weeks preceding randomization 
and up to Week 12. After Week 12, no more than 1 joint per 24-week period may be injected. 
No single injection should exceed 40 mg of triamcinolone (or equivalent) and the total dose of 
intra-articular corticosteroid may not exceed 80 mg of triamcinolone (or equivalent) during any 
20-week period. Injection of intra-articular steroids is not permitted within 8 weeks prior to 
Week 20. 
Non-steroidal anti-inflammatory drugs (NSAIDs) (including COX-1 or COX-2 
inhibitors), low strength opioids and acetaminophen/paracetamol 
Patients regularly using NSAIDs, low strength opioids, or paracetamol/acetaminophen should 
be on stable dose for at least 2 weeks before randomization to allow inclusion. They should 
remain on a stable dose in the study up to Week 4. 
Changes in the NSAID intake will be captured by the patient in the patient diary and checked 
and be transferred into the eCRF at all scheduled study visits after week 4. 
Patients taking low strength opioids or paracetamol/acetaminophen PRN within the 2 weeks 
before randomization can continue to do so in the study; however, they have to refrain from any 
intake during at least 24 hours before a visit with disease activity assessment. 
After Week 12 assessments are completed, a change in the low strength opioids, or 
paracetamol/acetaminophen treatment regimen is permitted. 
Any change of the low strength opioids, or paracetamol/acetaminophen treatment during the 
trial should be recorded on the appropriate Prior and Concomitant medication eCRF page. 
5.5.8 
Prohibited treatment 
Use of the treatments displayed in Table 5-1 is NOT allowed after the start of the washout 
period unless otherwise specified below. 
Live vaccines should not be given until 12 weeks after last study treatment administration. 

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Table 5-1 
Prohibited treatment 
Prohibited treatments 
Washout period  
(before randomization) 
Etanercept* 
4 weeks 
Infliximab* 
8 weeks 
Adalimumab, golimumab, certolizumab* 
10 weeks 
Unstable dose of MTX or sulfasalazine 
(until Week 12) 
4 weeks 
Other DMARD (except MTX or sulfasalazine) 
4 weeks  
Leflunomide 
8 weeks  
Leflunomide with cholestyramine washout 
4 weeks 
Systemic corticosteroids > 10 mg prednisone equivalent** 
(until Week 12) 
2 weeks  
Intra-articular steroids injections  
(until Week 12) 
4 weeks 
Any investigational treatment or participation in any interventional 
trial 
4 weeks or 5 half-lives 
(whichever is longer)  
Analgesics other than paracetamol/acetaminophen or low strength 
opioids PRN 
4 weeks 
Live vaccinations  
6 weeks 
*These agents fall under the category of biologic immunomodulators and are prohibited 
medications. Administration of these agents requires study discontinuation (see Section 5.5.8). 
**See details about corticosteroid management in Section 5.5.7. 
5.5.9 
Discontinuation of study treatment 
Patients may voluntarily discontinue investigational treatment for any reason at any time. 
Patients who prematurely discontinue the study should undergo an end of treatment visit 
(corresponds to the Week 20 visit and also return for the end of study visit at Week 24 (4 weeks 
after last study treatment (see Table 6-1). The final follow-up visit (Week 24) should be 
performed before any new treatment is initiated. Study treatment discontinuation must also be 
recorded in the eCRF and in the IRT. 
For patients who are lost to follow-up (i.e., those patients whose status is unclear because they 
fail to appear for study visits without stating an intention to withdraw from the study), the 
investigator should show "due diligence" by documenting in the source documents steps taken 
to contact the patient, e.g., dates of telephone calls, registered letters, etc. 
Patients who are prematurely withdrawn from the study will not be replaced. 

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Discontinuation of study treatment 
Study treatment must be discontinued if the investigator determines that continuation of study 
treatment would result in a significant safety risk for a patient. The following circumstances 
require study treatment discontinuation: 
 Withdrawal of informed consent 
 Emergence of the following AEs: 
 Any severe or serious adverse event that is not compatible with administration of 
study medication, including adverse events that require treatment with an 
unacceptable concomitant 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 patient at a safety risk for continuation in the 
study (A general guidance on clinically notable laboratory values is provided in 
Appendix 1). 
 Pregnancy 
 Use of  any biologic immunomodulating agent except Secukinumab 
 Any protocol deviation that results in a significant risk to the patient’s safety 
In addition to these requirements for study treatment discontinuation, the investigator should 
discontinue study treatment for a given patient if there is a lack of improvement or worsening 
of their symptoms, or if on balance, he/she thinks that continuation would be detrimental to the 
patient’s well-being. 
For patients who discontinue study treatment, a Dosage Administration Record eCRF should 
be completed, giving the date and primary reason for stopping study treatment. 
The investigator must also contact the IRT to register the patient’s discontinuation from study 
treatment. 
5.5.10 
Withdrawal of consent 
Patients may voluntarily withdraw consent to participate in the study for any reason at any time. 
Withdrawal of consent occurs only when a patient does not want to participate in the study 
anymore and does not want any further visits or assessments and does not want any further 
study related contacts and does not allow analysis of already obtained biologic material. 
If a patient withdraws consent, the investigator must make every effort (e.g. telephone, e-mail, 
letter) to determine the primary reason for this decision and record this information. 
Investigational treatment must be discontinued and no further assessments conducted. All 
biological material that has not been analyzed at the time of withdrawal must not be used. 
Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow-up. 

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5.5.11 
Loss to follow-up 
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to withdraw, the investigator should show "due diligence" by contacting the patient, 
family or family physician as agreed in the informed consent and by documenting in the source 
documents steps taken to contact the patient, e.g. dates of telephone calls, registered letters, etc. 
A patient should not be formally considered lost to follow-up until his/her scheduled end of 
treatment visit would have occurred. 
5.5.12 
Emergency breaking of assigned treatment code 
Emergency treatment code breaks should only be undertaken when it is essential to treat the 
patient safely and efficaciously. Most often, investigational treatment discontinuation and 
knowledge of the possible treatment assignments are sufficient to treat a study patient who 
presents with an emergency condition. Emergency treatment code breaks are performed using 
the IRT. When the investigator contacts the system to break a treatment code for a patient, 
he/she must provide the requested patient identifying information and confirm the necessity to 
break the treatment code for the patient. The investigator will then be able to unblind details of 
the investigational drug treatment for the specified patient in the IRT system.  
It is the investigator’s responsibility to ensure that there is a procedure in place to allow access 
to the IRT in case of emergency. The investigator will inform the patient how to contact his/her 
backup in cases of emergency when he/she is unavailable. The investigator will provide 
protocol number, investigational treatment name if available, patient number, and instructions 
for contacting the sponsor (or any entity to which it has delegated responsibility for emergency 
code breaks) to the patient in case an emergency treatment code break is required at a time when 
the investigator and backup are unavailable. 
Study patient must be discontinued after emergency unblinding. 
As per Novartis standard operating procedures (SOPs) it is one of the primary responsibilities 
of each investigator to be available in case of an urgent emergency unblinding for one of his/her 
patients. 
5.5.13 
Study completion and post-study treatment 
A patient will be considered to have completed the study if he/she received a maximum of 20 
weeks of study treatment and upon completion of the scheduled study assessments and 
procedures up to and including the follow up visit (Week 24). 
Information on the patient’s completion or discontinuation from the study and the reason for 
discontinuation of the study will be recorded on the appropriate Study Phase Completion eCRF 
page. 
In any case, the investigator or site staff must contact the IRT as soon as possible to record the 
patient’s study completion (Week 24) and/or discontinuation. 
The investigator must provide follow-up medical care for all patients who are prematurely 
withdrawn from the study, or must refer them for appropriate ongoing care. This care may 
include initiating another treatment outside of the study as deemed appropriate by the 
investigator. This treatment may be any non-biologic DMARD. In case of a biologic treatment, 
a waiting period of 3 months before initiating the treatment is recommended. 

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5.5.14 
Early study termination 
The study can be terminated at any time for any reason by Novartis for any reason specified in 
the clinical trial study contract. Should this be necessary, the patient should be seen as soon as 
possible and treated for a prematurely withdrawn patient. The investigator may be informed of 
additional procedures to be followed in order to ensure that adequate consideration is given to 
the protection of the patient’s interests. The sponsor will be responsible for informing the 
Institutional Review Board/Independent Ethics Committee (IRBs/IECs) of the early termination 
of the trial. 
6 
Visit schedule and assessments 
Table 6-1 lists all of the assessments and indicates with an “x” when the Visits are performed. 
For visits scheduled through Week 4, the study treatment should not be administered less than 
7 days after the previous administration. For visits scheduled after Week 4, the study treatment 
should not be administered less than 14 days after the previous administration. At a minimum, 
patients will be contacted for safety evaluations during the 30 days following the end of 
treatment visit at Week 20, including a final contact at the 30-day point. Documentation of 
attempts to contact the patient should be recorded in the source documentation.  
Subjects who prematurely discontinue should return for the End-of-treatment visit (corresponds 
to the week 20 visit) 4 weeks after the last study treatment administration, as well as return for 
the follow-up (week 24). 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. 
Screening will be flexible (up to 10 weeks) in duration based on the time required to washout 
prior anti-rheumatic and other medications and will have a duration, during which time the 
patient 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 6-1. 
Screening will consist of 2 consecutive visits. During Screening Visit 1, initial assessments will 
be performed as outlined in Table 6-1. 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 patient 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 and should ideally be performed no less than 2 weeks prior to randomization to 
allocate time for laboratory analyses and shipment of medication. 
All patients evaluated at Screening Visit 1 and 2 for eligibility should not be screen failed on 
the basis of a medication requiring washout, unless the patient will be unable to complete the 
washout in the appropriate time frame before randomization. 

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Table 6-1 
Assessment schedule 
 
Screening1 
Treatment 1 
Treatment 2 
Follow Up 
Screening 
Visit 1 
Screening 
Visit 2 
Week 
-10 
to -4 
 -4 to 
-2 
BSL 
1 
2 
3 
4 
5 
6 
7 
8 
12 
16 
17 
18 
19 
20 
F24 
Obtain informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Optional Site visit 
 
 
 
 
 
X 
 
X 
 
X 
 
 
 
X 
X 
X 
 
 
Inclusion/Exclusion 
criteria2 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant medical 
history/ current 
medical condition 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Prior medication 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
AS assessment3 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Cardiovascular 
medical history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Smoking history 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
ECG4 
 
X 
 
 
 
 
 
 
 
 
 
X 
 
 
 
 
 
 
Physical exam4 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
 
 
X 
X 
Height, weight 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital signs 
X 
X 
X 
 
X 
 
X 
 
X 
 
X 
X 
X 
 
 
 
X 
X 

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Screening1 
Treatment 1 
Treatment 2 
Follow Up 
Screening 
Visit 1 
Screening 
Visit 2 
Week 
-10 
to -4 
 -4 to 
-2 
BSL 
1 
2 
3 
4 
5 
6 
7 
8 
12 
16 
17 
18 
19 
20 
F24 
PPD skin test5 or 
QuantiFERON TB-
Gold test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Chest X-ray or 
MRI6 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Hematology, blood 
chemistry, 
urinalysis 
 
X 
X 
 
X 
 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
Serum pregnancy 
test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy 
test 
 
 
X 
 
 
 
X 
 
 
 
X 
X 
 
 
 
 
X 
X 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Administration of 
s.c. study treatment 
via  PFS 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant 
medication/ non-
drug therapy 
X 
Update as necessary 

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Screening1 
Treatment 1 
Treatment 2 
Follow Up 
Screening 
Visit 1 
Screening 
Visit 2 
Week 
-10 
to -4 
 -4 to 
-2 
BSL 
1 
2 
3 
4 
5 
6 
7 
8 
12 
16 
17 
18 
19 
20 
F24 
Adverse 
events/SAEs (if 
applicable, 
including injection 
site reactions)7 
X 
NSAID intake 
reported in eCRF 
 
X 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
X 
Provide NSAID 
Diary to patient and 
instruct patient 
 
 
 
 
 
 
X 
 
 
 
X 
X 
X 
 
 
 
 
 
NSAID intake 
captured in patient 
diary 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Check NSAID diary 
 
 
 
 
 
 
 
 
X 
 
X 
X 
X 
 
 
 
X 
 
Patient’s global 
assessment of 
disease activity 
(VAS) 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
 
 
X 
X 
Patient’s 
assessment of back 
pain intensity (VAS) 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
 
 
X 
X 
BASFI 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
 
 
X 
X 

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Screening1 
Treatment 1 
Treatment 2 
Follow Up 
Screening 
Visit 1 
Screening 
Visit 2 
Week 
-10 
to -4 
 -4 to 
-2 
BSL 
1 
2 
3 
4 
5 
6 
7 
8 
12 
16 
17 
18 
19 
20 
F24 
BASDAI 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
X 
X 
 
 
 
X 
X 
Spinal mobility 
(BASMI Linear + 
chest expansion) 
 
 
X 
 
X 
 
X 
 
 
 
X 
X 
X 
 
 
 
X 
 
SF-36 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
ASAS Health Index 
 
 
X 
 
 
 
X 
 
 
 
 
X 
 
 
 
 
X 
 
Erythrocyte 
Sedimentation Rate 
(ESR) 
 
X 
X 
 
X 
 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
High sensitivity  
C-reactive protein 
(hsCRP) 
 
X 
X 
 
X 
 
X 
 
 
 
X 
X 
X 
 
 
 
X 
X 
HLA-B27 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 If the patient’s washout period ≤ 4 weeks, Screening visit 1 (SV1) and Screening visit 2 (SV2) can be performed on the same day. 
2 Eligibility and relevant medical history assessments are conducted at SV1, SV2 and Baseline (BSL) / Day 1’. The data for all three visits should be 
recorded on the corresponding eCRFs available at SV1. 
3 The following eCRFs are to be completed: AS Disease background eCRF, Modified New York criteria for AS eCRF 
4 These assessments are source documentation only and will not be entered into the eCRF. 
5 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. 

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Screening1 
Treatment 1 
Treatment 2 
Follow Up 
Screening 
Visit 1 
Screening 
Visit 2 
Week 
-10 
to -4 
 -4 to 
-2 
BSL 
1 
2 
3 
4 
5 
6 
7 
8 
12 
16 
17 
18 
19 
20 
F24 
6 A chest X-ray or MRI 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 patient meets inclusion/exclusion criteria in order to minimize unnecessary exposure to radiation. The X-ray may be replaced by an MRI 
assessment. 
7 AEs/SAEs occurring after the patient has signed the informed consent must be captured on the appropriate eCRF page. SAEs must be recorded from 
signing of informed consent, AEs must be captured from the BSL visit on. 
* For all patients who discontinue or withdraw from the study, the investigator should ensure that the patient completes an end of treatment visit. 

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6.1 
Information to be collected on Screening failures 
Patients may discontinue from the study prior to randomization. These patients are considered 
Screening failures. 
If a patient discontinues before entering the double-blind treatment period at baseline, the IRT 
must be notified within 2 days and the reason for not being randomized will be entered on the 
Screening Phase Disposition eCRF page.  
In addition, only demography data, the reason for failing (screening failure log) and informed 
consent will be collected for those patients who fail to enter the treatment phase.  
Reporting of potential SAE which may have occurred from time of signing informed consent 
until screening failure time should be followed as described in Section 7.2 
6.2 
Patient demographics/other baseline characteristics 
Patient demographic and baseline characteristics data to be collected on all patients and to be 
recorded in the eCRF include: 
 Year of birth, age, sex, race and source of patient referral 
 Relevant AS and general medical history/current medical condition data until the start of 
study treatment, number of previous DMARDs used, date of diagnosis of AS, previous AS 
therapies, functional status class according to the New York criteria, cardiovascular 
medical history and smoking history 
Whenever possible, diagnoses and not symptoms will be recorded. 
6.3 
Treatment exposure and compliance 
All dates and times of study treatment administration will be recorded on the appropriate 
Dosage Administration Record eCRF page. 
Drugs administered prior to start of treatment and other drugs continuing or started during the 
study treatment period will be entered in the Prior/Concomitant medications or Significant non-
drug therapies eCRF page.  
Compliance is expected to be 100%, unless temporary interruption is needed for safety reasons 
as described in (Section 5.5.5). Compliance will also be assessed by a Novartis/CRO monitor 
using information provided by the authorized site personnel. 
6.4 
Efficacy 
 Assessment of SpondylArthritis International Society criteria (ASAS)20 
 ASAS-NSAID score  
 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) 
 Spinal mobility assessed by Bath Ankylosing Spondylitis Metrology Index (BASMI) 

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 hsCRP and ESR 
6.4.1 
Assessment of ASAS-NSAID score 
The ASAS-NSAID score will be calculated in accordance with the ASAS recommendations 
(Dougados et al 2011). NSAID intake will be collected in accordance with the ASAS 
recommendations (i.e., name, mean dose, number of days of intake during a period of time). 
Thereafter, the ASAS-NSAID score will be calculated considering both the daily dose of the 
specific NSAID(s) and the percentage of days of intake of the NSAID(s) during a given period 
of time. 
Detailed information for calculating the ASAS-NSAID score is given in Appendix 4. 
6.4.2 
Assessment of SpondyloArthritis International Society criteria (ASAS) 
The ASAS response measures consist of the following assessment domains (Sieper 2009). 
The main ASAS domains are as follows: 
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 
The additional assessment domains are as follows: 
5. Spinal mobility represented by the BASMI lateral spinal flexion assessment 
6. C-reactive protein (acute phase reactant) 
Investigator must review the results timely and document adverse events, if applicable.  
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 3 of the 4 main domains and no worsening of ≥ 20% and ≥ 1 unit on a scale of 10 in the 
remaining domain. 
6.4.2.1 
ASAS Response Criteria-40% (ASAS40) 
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. 
6.4.2.2 
ASAS 5/6 improvement criteria 
The ASAS 5/6 improvement criteria is an improvement of ≥20% in at least five of all six 
domains. 
6.4.2.3 
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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6.4.3 
Patient’s 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?”. 
6.4.4 
Patient’s assessment of back pain intensity (VAS) 
The patient’s assessment of back pain will be performed using a 100 mm VAS ranging from no 
pain to unbearable pain, after the question “Based on your assessment, please indicate what is 
the amount of back pain at any time that you experienced during the last week?” and “Based 
on your assessment, please indicate what is the amount of back pain at night that you 
experienced during the last week?” 
6.4.5 
Bath Ankylosing Spondylitis Functional Index (BASFI) 
The BASFI is a set of 10 questions designed to determine the degree of functional limitation in 
those patients with AS. The ten questions were chosen with major input from patients with AS. 
The first 8 questions consider activities related to functional anatomy. The final 2 questions 
assess the patients’ ability to cope with everyday life. A 0 through 10 scale (captured 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. 
6.4.6 
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 patients 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. 
6.4.7 
Bath Ankylosing Spondylitis Metrology Index (BASMI linear) 
The BASMI is a validated instrument that uses the minimum number of clinically appropriate 
measurements that assess accurately axial status, with the goal to define clinically significant 
changes in spinal movement. Parameters include: 

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1. Lateral spinal flexion 
2. Tragus-to-wall distance 
3. Lumbar flexion (modified Schober)  
4. Maximal intermalleolar distance  
5. Cervical rotation angle 
Additionally, the following assessments should be taken: 
6. Chest expansion 
7. Occiput-to-wall distance 
Detailed information on the assessments is described in Appendix 4. 
6.4.8 
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 patients and patients with acute and chronic conditions. It consists of eight 
subscales that can be scored individually: Physical Functioning, Role-Physical, Bodily Pain, 
General Health, Vitality, Social Functioning, Role-Emotional, and Mental Health (Ware 1993). 
Two overall summary scores, the Physical Component Summary (PCS) and the Mental 
Component Summary (MCS) also can be computed (Ware 1994). The SF-36 has proven useful 
in monitoring general and specific populations, comparing the relative burden of different 
disease, differentiating the health benefits produced by different treatments, and in screening 
individual patients. 
The purpose of the SF-36 in this study is to assess the health-related QoL of patients. Given the 
acute nature of this disease, version 2, with a 1-week recall period, will be used in this study. 
Investigator must review the results timely and document adverse events, if applicable. 
6.4.9 
ASAS Health Index 
The ASAS Health Index (ASAS HI) is an index that measures an individual’s status of 
functioning, disability and health in individuals and is designed specifically for 
spondyloarthritis patients. (ASAS HI) (12). 
The ASAS HI is a linear composite measure that contains 17 items of functioning and health 
and 9 environmental factors addressing categories of support/relationships, attitudes and health 
services with dichotomous response options: “I agree” and “I do not agree”. The result forms a 
unidimensional scale providing a sum score representing a wide spectrum of different levels of 
functioning (Kiltz et al. 2014). 
6.4.10 
High sensitivity C-reactive protein (hsCRP) 
This assessment will be performed in order to identify the presence of inflammation, to 
determine its severity, and to monitor response to treatment. 
Since the results of this test may unblind study personnel, results from the central laboratory 
will be provided for Screening and baseline only. The hsCRP results from samples collected 
during the treatment period will be revealed following database lock only. 

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6.4.11 
Erythrocyte sedimentation rate (ESR) 
ESR is helpful in diagnosing inflammatory diseases and is used to monitor disease activity and 
response to therapy. ESR will be performed locally at the investigative site using a centrally 
provided assessment kit. 
6.4.12 
Appropriateness of efficacy assessments  
The ASAS-NSAID score is used to determine the NSAID sparing effect of biologic i.e. the 
timing of discontinuation/tapering of NSAID(s) after initiating treatment with Secukinumab. 
The other efficacy outcome measures used in this study are the standard measures used across 
all AS trials. 
6.5 
Safety 
 QuantiFERON TB-Gold test or PPD skin test 
 Chest X-ray or MRI 
 Physical examination 
 Vital signs 
 Height and weight 
 Laboratory evaluations 
 Pregnancy and assessment of fertility 
 Local tolerability (injection site reactions) 
 Tolerability of Secukinumab 
All blood draws and safety assessments should be done prior to study treatment administration. 
Appropriate safety assessments (e.g. evaluation of AEs and SAEs including injection site 
reactions) should be repeated after the dose is administered. 
6.5.1 
QuantiFERON TB-Gold test or PPD skin test 
Either a QuantiFERON TB-Gold test or a PPD skin test must be performed at Screening. 
Patients with a positive test may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that the patient has no evidence of active 
tuberculosis, or if presence of latent tuberculosis is established then treatment according to local 
country guidelines must have been initiated. 
QuantiFERON TB-Gold test 
 A QuantiFERON TB-Gold test is to be performed at the second Screening visit and the 
results to be known prior to randomization to determine the patient’s eligibility for the trial. 
The test will be used to screen the patient population for latent tuberculosis infection.  
 The test will be analyzed by the central laboratory. Details on the collection, processing and 
shipment of samples and reporting of results by the central laboratory are provided in the 
laboratory manual. 
PPD skin test 
 A PPD skin test is to be performed at Screening and read before randomization to determine 
the patient’s eligibility for the trial. The test dose is bioequivalent to 5 tuberculin units of 

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standard PPD injected intradermally, usually into the volar surface of the forearm. The site 
is cleaned and the PPD extract is then injected into the most superficial layer under the skin. 
If given correctly, the injection should raise a small wheal of about 5 mm, which resolves 
within 10-15 minutes. 
Because the reaction (induration) will take 48-72 hours to develop, the patients must return to 
the study center within that time for a proper evaluation of the injection site. This will determine 
whether the patient has had a significant reaction to the PPD test. A reaction is measured in 
millimeters of induration (hard swelling) at the site. A PPD skin induration ≥5 mm (or according 
to local practice/guidelines) is interpreted as a positive result. 
6.5.2 
Chest X-ray or MRI 
A chest X-ray or MRI at Screening (or within 3 months prior to Screening) will be performed 
to rule out the presence of a pulmonary malignancy of infectious process, in particular 
tuberculosis. 
6.5.3 
Physical examination  
The physical examination will include the examination of general appearance, skin, neck, eyes, 
ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular and 
neurological system. 
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present before signing the ICF must be included in the 
relevant medical history eCRF. Significant findings made after signing the ICF which meet the 
definition of an SAE must be recorded in the Adverse Event eCRF. All findings meeting the 
definition of an AE must be recorded from the first administration of study drug on.  
6.5.4 
Vital signs  
This 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. 
6.5.5 
Height and weight  
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram (kg) in indoor clothing, 
but without shoes) will be measured. 
If possible, body weight assessments should be performed by the same study site staff member 
using the same scale throughout the study. 
6.5.6 
Laboratory evaluations  
A central laboratory will be used for analysis of all specimens collected as listed in the 
sub-sections below (except for urinalysis and ESR). Details on the collections, shipment of 
samples and reporting of results by the central laboratory are provided to investigators in the 
laboratory manual. Clinically significant abnormalities must be recorded on the relevant section 
of the medical history/Current medical conditions/AE CRF page as appropriate. All patients 
with laboratory tests containing clinically significant abnormal values are to be followed until 

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the values return to normal ranges or until a valid reason, other than treatment related AE, is 
defined. 
Clinically notable laboratory results are defined in Appendix 1. 
6.5.6.1 
Hematology 
Hemoglobin, hematocrit, red blood cell count, white blood cell count with differential counts, 
and platelet count will be measured at scheduled visits. 
6.5.6.2 
Clinical chemistry 
Serum chemistries will include glucose, urea, creatinine, total bilirubin, AST (SGOT), ALT 
(SGPT), GGT, alkaline phosphatase, sodium, potassium, bicarbonate, calcium, phosphorous, 
total protein, albumin, and uric acid. 
6.5.6.3 
Urinalysis 
Dipsticks will be provided by the central laboratory to the sites for local urinalysis assessments. 
The urinalysis results for standard parameters such as protein, glucose, blood and WBCs will 
be recorded in the appropriate eCRF page. 
 
6.5.7 
Electrocardiogram (ECG) 
A standard 12 lead ECG will be performed as indicated in Table 6-1. 
ECGs can be performed externally at a qualified physician but the investigator/qualified site 
staff must review the tracing. The tracing must then be stored with the subject's source 
documents. If the ECG findings at screening are clinically relevant and would prevent the 
subject from participating in the study (taking into account the subject's overall status as well 
as the medication profile), the subject should be recorded a screen failure and should not receive 
treatment. Findings at the later ECG readings will be reported as adverse or serious adverse 
events. If these findings constitute a reason for premature patient withdrawal or would render 
the overall risk-benefit evaluation of continued participation and treatment in the study 
unfavorable for the patient, the patient must discontinue study medication. 
6.5.8 
Pregnancy and assessments of fertility  
All pre-menopausal women who are not surgically sterile will have a serum β-hCG test (serum 
pregnancy test) performed at the second Screening visit and local urine pregnancy tests as 
indicated in Table 6-1. 
A positive urine pregnancy test requires immediate interruption of study drug until serum β-
hCG is performed and found to be negative. 
6.5.9 
Local tolerability (Injection site reactions) 
The local tolerability at the site of s.c. injection of the study treatment will be assessed in case 
of any local reaction, until this has disappeared.  

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The assessment of pain, redness, swelling, induration, hemorrhage and itching will be 
performed by a physician and will be recorded on the Adverse Events eCRF, including the 
severity (mild, moderate, severe) and the duration. 
6.5.10 
Tolerability of Secukinumab  
Tolerability will be assessed by adverse events, laboratory values and injection site reaction. 
6.5.11 
Appropriateness of safety measurements  
The safety measures used in this study are reliable and relevant standard measures for a 
biologic in AS. According to local recommendations, a chest X-ray should be performed in 
clinical practice before initiation of an immunomodulating biologic therapy for AS (DGRh 
2009). The radiation exposure that results from the chest X-ray safety measurements at 
Screening are estimated to be far below 1 mS. For effective radiation doses under 3 mS 
(300 mrem), the risk is considered to be minimal. Therefore, the radiation exposure in this 
study involves minimal risk and is necessary to ensure reliable safety measures before the 
treatment with a biologic. 
While hsCRP results are not automatically communicated to the site by the central lab, it will 
be acceptable to perform a CRP measurement at a local lab in case this is warranted for safety 
reasons. 
 The safety assessments selected are standard and adequate for this indication/patient 
population.  
6.6 
Other assessments 
 HLA-B27 
6.6.1 
HLA-B27 
A blood sample to analyze Human Leukocyte Antigen-B27 (HLA-B27) will be obtained from 
all patients at baseline. 
Details on the collection, handling and shipment of the sample to the central laboratory will be 
provided to investigators in the laboratory manual. 
6.6.2 
Resource utilization 
No measures of Healthcare Resource Utilization (RU) will be collected in the study. 
6.6.3 
Pharmacokinetics 
Not applicable. 
6.6.4 
Other biomarkers 
Not applicable. 

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7 
Safety monitoring 
7.1 
Adverse events 
An AE is the appearance or worsening of any undesirable sign, symptom, or medical condition 
occurring after first intake of study drug even if the event is not considered to be related to study 
drug. Study drug includes the investigational drugs under evaluation that are given during any 
period of the study. 
Medical conditions/diseases present before first intake of study drug are only considered 
adverse events if they worsen after study start. Abnormal laboratory values or test results 
constitute AEs only if they induce clinical signs or symptoms, require dose reduction or 
temporary or permanent study drug discontinuation or require therapy. 
All AEs with a date of onset up to 30 days following after the patient has stopped study 
participation (defined as time of last dose of study drug taken or last visit whichever is later) 
must be reported. 
The occurrence of AEs should be sought by non-directive questioning of the patient at each 
visit during the study. AEs may also be detected when they are volunteered by the patient during 
or between visits or through physical examination, laboratory test, or other assessments. All 
adverse events must be recorded on the Adverse Events CRF with the following information: 
1. the severity grade (mild, moderate, severe) 
2. its relationship to the study drug(s) (suspected/not suspected) 
3. its duration (start and end dates or if continuing at final exam) 
4. whether it constitutes a serious adverse event (SAE) 
All AEs should be treated appropriately. Treatment may include 1 or more of the following: no 
action taken (i.e. further observation only); study drug dosage adjusted/temporarily interrupted; 
study drug permanently discontinued due to this adverse event; concomitant medication given; 
non-drug therapy given; patient hospitalized/patient’s hospitalization prolonged. The action 
taken to treat the AE should be recorded on the Adverse Event CRF.  
Once an adverse event is detected, it should be followed until its resolution or until it is judged 
to be permanent, and assessment should be made at each visit (or more frequently, if necessary) 
of any changes in severity, seriousness, the suspected relationship to the study drug, the 
interventions required to treat  it, and the outcome. 
The investigator should also instruct each patient to report any new AE (beyond the protocol 
observation period) that the patient, or the patient’s personal physician, believes might 
reasonably be related to 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. 
7.2 
Serious adverse events 
7.2.1 
Definition of SAE 
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 1 of the following 
criteria: 

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 is fatal or life-threatening  
 results in persistent or significant disability/incapacity 
 constitutes a congenital anomaly/birth defect 
 requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
 routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition (specify what this includes) 
 elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
 treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission  
 social reasons and respite care in the absence of any deterioration in the patient’s 
general condition 
 is medically significant, i.e. defined as an event that jeopardizes the patient or may require 
medical or surgical intervention. 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 
Life-threatening in the context of a SAE refers to a reaction in which the patient was at risk of 
death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if more severe (see Annex IV, ICH-E2D Guideline). 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life threatening or result in death or hospitalization but might jeopardize the patient or might 
require intervention to prevent 1 of the other outcomes listed above. Examples of such events 
are intensive treatment in an emergency room or at home for allergic bronchospasm, blood 
dyscrasias or convulsions that do not result in hospitalization or development of dependency or 
abuse (see Annex IV, ICH-E2D Guideline). 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All AEs (serious and non-serious) are captured on the CRF, SAEs also require individual 
reporting to DS&E as per Section 7.2.2. 
Information about common side effects already known about the investigational drug can be 
found in the Investigator Brochure (IB) or will be communicated between IB updates in the 
form of Investigator Notifications. This information will be included in the patient informed 
consent and should be discussed with the patient during the study as needed. 
7.2.2 
SAE reporting 
To ensure patient safety, every SAE, regardless of suspected causality, occurring after the 
patient has provided informed consent and until 30 days after the patient has stopped study 
participation (defined as time of last dose of study drug taken or last visit whichever is later) 
must be reported to Novartis within 24 hours of learning of its occurrence.  

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Any SAEs experienced after this 30 day period should only be reported to Novartis if the 
investigator suspects a causal relationship to the study drug. For patients who discontinue study 
medication, SAEs still need to be reported until the end of study, regardless of their suspected 
relationship to study medication.  
Recurrent episodes, complications, or progression of the initial SAE must be reported as follow-
up to the original episode, regardless of when the event occurs.  This report must be submitted 
within 24 hours of the investigator receiving the follow-up information. An SAE that is 
considered completely unrelated to a previously reported one should be reported separately as 
a new event. 
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form.  The investigator must assess the relationship to study drug, complete the SAE Report 
Form in English, and send the completed, signed form by fax within 24 hours to the German 
Novartis Clinical Safety & Epidemiology Department. The SAE form should also include 
information about the concomitant NSAID medication. The telephone and telefax number of 
the contact persons in the German department of Clinical Safety and Epidemiology, are listed 
in the investigator folder provided to each site. The original copy of the SAE Report Form and 
the fax confirmation sheet must be kept with the case report form documentation at the study 
site. 
All SAEs occurring during the follow-up period will be entered in the Adverse Events CRF 
pages. In addition, an SAE Report Form should be completed. Follow-up information will be 
sent to the same person to whom the original SAE Report Form was sent, using a new SAE 
Report Form stating that this is a follow-up to the previously reported SAE and giving the date 
of the original report.  The follow-up information should describe whether the event has 
resolved or continues, if and how it was treated, whether the blind was broken or not, and 
whether the patient continued or withdrew from study participation. 
Adverse reactions under a Novartis drug of which investigator became aware prior to or during 
Screening and which were not yet reported should be forwarded to the local Novartis Clinical 
Safety & Epidemiology Department. This adverse reaction report including the administered 
Novartis drug and causality assessment should be forwarded independently from the described 
procedure. Serious adverse reactions occurring under non-Novartis drugs which are not 
investigational medicinal product (IMP) should be forwarded either to the national competent 
authority (BfArM or PEI), the Drug Commission of the German Medical Association or the 
respective marketing authorization holder. 
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 Novartis study drug, a Clinical Safety & 
Epidemiology 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 drug that this 
SAE has been reported. 
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant Ethics Committees in accordance with 
Directive2001/20/EC or as per national regulatory requirements in participating countries. 

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7.3 
Liver safety monitoring 
Secukinumab has not been studied specifically in patient with hepatic impairments. No 
pharmacokinetic data are available in these patients. However IgGs are mainly eliminated via 
catabolism and hepatic impairment is not expected to influence clearance of Secukinumab. 
To ensure patient safety and enhance reliability in determining the hepatotoxic potential of an 
investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed.  
The following two categories of abnormalities / adverse events have to be considered during 
the course of the study: 
 Liver laboratory triggers, which will require repeated assessments of the abnormal 
laboratory parameter 
 Liver events, which will require close observation, follow-up monitoring and completion 
of the standard base liver CRF pages 
Please refer to Table 13-1 in Appendix 2 for complete definitions of liver laboratory triggers 
and liver events.  
Every liver laboratory trigger or liver event as defined in Table 13-1 of Appendix 2 should be 
followed up by the investigator or designated personal at the trial site as summarized below. 
Detailed information is outlined in Table 13-2 in Appendix 2. 
For the liver laboratory trigger: 
 Repeating the LFT (Liver Function Test) within the next week to confirm elevation. 
Repeat laboratory tests should be entered on the appropriate unscheduled local laboratory CRF 
page. 
 If the elevation is confirmed, close observation of the patient will be initiated, including 
consideration of treatment interruption if deemed appropriate. 
For the liver events: 
 Repeating the LFT to confirm elevation as appropriate 
 Discontinuation of the investigational drug if appropriate 
 Hospitalization of the patient if appropriate 
 A causality assessment of the liver event via exclusion of alternative causes (e.g., disease, 
co-medications) 
 An investigation of the liver event which needs to be followed until resolution.  
These investigations can include serology tests, imaging and pathology assessments, 
hepatologist’s consultancy, based on investigator’s discretion. All follow-up information, and 
the procedures performed should be recorded on appropriate CRF pages, including the liver 
event overview eCRF pages. 
7.4 
Renal safety monitoring 
Secukinumab has not been studied specifically in patient with renal impairments. No 
pharmacokinetic data are available in patients with renal impairment. The renal elimination of 

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intact Secukinumab, an IgG monoclonal antibody, is expected to be low and of minor 
importance. 
To ensure patient safety and enhance reliability in determining the nephrotoxic potential of an 
investigational drug, a standardized process for identification, monitoring and evaluation of 
renal events has to be followed.  
The following two categories of renal adverse events have to be considered during the course 
of the study: 
1. Serum event: 
 confirmed (after ≥ 24h) increase in serum creatinine of ≥ 25% compared to baseline 
during normal hydration status 
2. Urine event:  New onset (≥1+) proteinuria, hematuria or glucosuria; or 
 Doubling in the urinary albumin-creatinine ratio (ACR) or urinary protein-creatinine 
ratio (PCR) (if applicable). 
Every renal laboratory trigger or renal event as defined in Table 7-1 should be followed up by 
the investigator or designated personnel at the trial site as summarized below. 
Table 7-1 
Specific renal alert criteria and actions 
Serum Event 
Serum creatinine increase 
25 – 49% compared to baseline 
Confirm 25% increase after 24-48h  
Follow up within 2-5 days 
Acute Kidney Injury: Serum creatinine 
increase   50 % compared to baseline 
Follow up within 24-48h if possible 
Consider drug interruption  
Consider patient hospitalization /specialized treatment 
Urine Event 
New dipstick proteinuria ≥ 1+ 
Albumin- or Protein-creatinine ratio 
increase ≥ 2-fold 
Albumin-creatinine ratio (ACR) ≥ 30 
mg/g or ≥ 3 mg/mmol; 
Protein-creatinine ratio (PCR )≥ 150 
mg/g or >15 mg/mmol 
Confirm value after 24-48h 
Perform urine microscopy 
Consider drug interruption / discontinuation  
New dipstick glucosuria ≥ 1+ not due to 
diabetes 
Blood glucose (fasting) 
Perform serum creatinine, ACR  
New dipstick hematuria ≥ 1+ not due to 
trauma 
Urine sediment microscopy 
Perform serum creatinine, ACR  
 
For all renal events: 

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Document contributing factors in the CRF: co-medication, other co-morbid conditions, and 
additional diagnostic procedures performed  
Monitor patient regularly (frequency at investigator’s discretion) until either:  
Event resolution: sCr within 10% of baseline or protein-creatinine ratio within 50% of baseline, or 
Event stabilization: sCr level with ±10% variability over last 6 months or protein-creatinine ratio 
stabilization at a new level with ±50% variability over last 6 months. 
7.5 
Pregnancy reporting 
All pre-menopausal women who are not surgically sterile will have a urine pregnancy test. A 
positive urine pregnancy test requires immediate interruption of study drug until serum β-hCG 
is performed and found to be negative. 
To ensure patient safety, each pregnancy occurring while the patient is on study treatment 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 on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the local Novartis Drug Safety and Epidemiology Department. Pregnancy 
follow-up should be recorded on the same form and should include an assessment of the 
possible relationship to the investigational treatment. 
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form.  
7.6 
Prospective suicidality assessment 
Not applicable 
8 
Data review and database management 
8.1 
Site monitoring  
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative/CRO will review the protocol and CRFs with the investigators and their staff. 
During the study, Novartis/CRO employs several methods of ensuring protocol and GCP 
compliance and the quality/integrity of the sites’ data. The field monitor will visit the site to 
check the completeness of patient records, the accuracy of entries on the eCRFs, 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. 
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on eCRFs must be traceable to these source documents in the 
patient's file. The investigator must also keep the original informed consent form signed by the 
patient (a signed copy is given to the patient). 

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The investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the eCRF entries. Novartis/CRO monitoring standards require full verification 
for the presence of informed consent, adherence to the inclusion/exclusion criteria, 
documentation of SAEs, and of data that will be used for all primary variables. Additional 
checks of the consistency of the source data with the eCRFs are performed according to the 
study-specific monitoring plan. No information in source documents about the identity of the 
patients will be disclosed. 
8.2 
Data collection 
Designated investigator staff will enter the data required by the protocol into the OC/RDC 
system. Designated investigator site staff will not be given access to the system until they have 
been trained.  
Automatic validation procedures within the system check for data discrepancies during and 
after data entry and, by generating appropriate error messages, allow the data to be confirmed 
or corrected online by the designated investigator site staff. The Investigator must certify that 
the data entered into the electronic Case Report Forms are complete and accurate. After 
database lock, the investigator will receive copies of the patient data for archiving at the 
investigational site.  
8.3 
Database management and quality control 
Novartis staff / CRO staff review the data entered into the CRFs by investigational staff for 
completeness and accuracy and instruct the site personnel to make any required corrections or 
additions. Queries are sent to the investigational site using an electronic data query. Designated 
investigator site staff is required to respond to the query and confirm or correct the data.  
Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system. 
Concomitant procedures, non-drug therapies and adverse events will be coded using the 
Medical dictionary for regulatory activities (MedDRA) terminology. 
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated CRO). 
ECG records will be kept at the site as source data. 
Diary data will be entered into a paper diary by the patient. The study staff will check the diary 
and enter the data into the eCRF. The database will be sent electronically to Novartis (or a 
designated CRO). 
Randomization codes and data about all study drug(s) dispensed to the patient and all dosage 
changes will be tracked using an Interactive Response Technology (IRT). The system will be 
supplied by a vendor, who will also manage the database. The database will be sent 
electronically to Novartis (or a designated CRO). 
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.  
The occurrence of relevant protocol deviations will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 

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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 Trial 
Statistician and Statistical Reporting and the Clinical Trial Leader. 
8.4 
Data Monitoring Committee 
Not required. 
8.5 
Adjudication Committee 
Not required. 
9 
Data analysis  
Summary statistics for continuous variables will generally include the number of subjects (N), 
minimum, lower quartile, mean, median, upper quartile, and maximum. For categorical or 
binary variables, the number and percent of subjects in each category will be presented. P-values 
presented will be two-sided unless otherwise specified. 
Inferential efficacy comparisons with placebo will generally focus on the first 12-weeks of 
treatment.  
Data analyses will be presented by treatment regimen. Efficacy and safety data for the placebo-
controlled period (or the entire treatment period as appropriate) will be presented by the 
following 3 treatment groups. These treatment groups represent the regimens subjects will be 
eligible to be randomized to.  
Secukinumab (“delayed tapering”) regimen: Secukinumab 150 mg s.c. at Week 0, 1, 2, 3, 4, 
8, 12, 16 and 20; Placebo injections at Week 5, 6 and 7 and 17, 18. 19. 
Secukinumab  (“early tapering”) regimen: Placebo at Weeks 0, 1, 2, 3 followed by 
Secukinumab 150 mg s.c. at Week 4, 5, 6, 7, 8, 12, 16 and 20 with additional Placebo injections 
at week 17, 18. 19. 
Placebo regimen: Placebo at Weeks 0, 1, 2, 3, 4, 5, 6, 7, 8 and 12. From Week 16, patients will 
be switched to receive Secukinumab 150 mg s.c. at Week 16, 17, 18, 19, and 20. 
9.1 
Analysis sets  
Randomized set: The randomized set will be defined as all subjects who were randomized.  
Full analysis set (FAS): The FAS will be comprised of all subjects from the randomized set to 
whom study treatment has been assigned. Following the intent-to-treat principle, subjects will 
be evaluated according to the treatment assigned to at randomization, and in the actual stratum 
if stratified randomization is used. 
Safety set: The safety set includes all subjects who took at least one dose of study treatment 
during the treatment period. Subjects will be evaluated according to treatment received. 

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9.2 
Patient demographics and other baseline characteristics  
Demographics and baseline characteristics 
The following common background and demographic variables will be summarized: 
 Gender, age, race, weight, height, and BMI 
Baseline disease characteristics will also be summarized for the following variables: 
 Duration of disease, TNF- alpha inhibitor status (naïve or inadequate responder), Patient’s 
global assessment of disease activity and other ASAS components, hsCRP, ESR, number 
of prior biologic AS therapies, dose of methotrexate or other DMARD at randomization 
Medical history 
Any significant prior or active medical condition at the time of signing informed consent will 
be coded using the MedDRA dictionary. These medical conditions will be summarized by 
primary system organ class and preferred term. 
9.3 
Treatments  
Study treatment 
The analysis of study treatment data will be based on the safety set. The number of active and 
placebo injections received will be presented by treatment group. 
The duration of exposure to study treatment will also be summarized by treatment group. In 
addition, the number and percentage of subjects with cumulative exposure levels (e.g. any 
exposure, ≥ 1 week, ≥ 2 weeks, ≥ 3 weeks, ≥ 4 weeks, ≥ 8 weeks, etc.) will be presented. 
Prior and concomitant medication 
Prior and concomitant medications will be summarized in separate tables by treatment group. 
Prior medications are defined as treatments taken and stopped prior to first dose of study 
treatment. Any medication given at least once between the day of first dose of randomized study 
treatment and the date of the last study visit will be a concomitant medication, including those 
which were started pre-baseline and continued into the period where study treatment is 
administered. 
Medications will be presented in alphabetical order, by Anatomical Therapeutic Classification 
(ATC) codes and grouped by anatomical main group. Tables will show the overall number and 
percentage of subjects receiving at least one treatment of a particular ATC code and at least one 
treatment in a particular anatomical main group. 
Significant prior and concomitant non-drug therapies and procedures will be summarized by 
primary system organ class and MedDRA preferred term. 
The number and percentage of subjects receiving prior and concomitant ankylosing spondylitis 
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 ankylosing spondylitis therapies previously. 

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9.4 
Analysis of the primary variable(s) 
Details of the testing strategy including primary and secondary endpoints are provided in 
Section 9.4.1 and Section 9.5.1. 
9.4.1 
Variable(s) 
The primary efficacy variable is response to treatment according to the ASAS20 criteria at 
Week 12. The analysis of the primary variable will be based on the FAS subjects. The analysis 
of the primary variable will be based on the following estimand: 
o Analysis set: FAS 
o Variable of interest: proportion of patients achieving treatment response as defined by the 
ASAS20 criteria at Week 12. 
o Intervention effect: effect between a secukinumab pooled groups vs. placebo regardless of 
adherence to randomized treatment. 
Summary measure: Odds ratio (OR) 
9.4.2 
Statistical model, hypothesis, and method of analysis 
The statistical hypothesis for ASAS20 being tested is that there is no difference in the proportion 
of subjects fulfilling the ASAS20 criteria in the pooled Secukinumab groups at week 12 versus 
placebo regimen. 
In statistical terms, H1: p1 = p0, HA: p1 ≠ p0, where p0 and p1 denotes the proportion of ASAS20 
responders at Week 12 in the placebo and pooled Secukinumab groups. .Secukinumab groups 
will be pooled using their measurements at week 12. 
H1: Secukinumab ( pooled) is not different to placebo with respect to ASAS20 response at week 
12. 
The primary analysis will be conducted via logistic regression with treatment, TNF-α status 
(previously exposed / never exposed), and CRP status (above central lab ULN / equal or below 
central lab ULN) as factors. The two Secukinumab groups will be pooled using a linear contrast. 
Odds ratios and 95% CI will be presented comparing Secukinumab (pooled) to placebo. 
9.4.3 
Handling of missing values/censoring/discontinuations 
Missing data for ASAS20 response and other binary efficacy variables (e.g. ASAS5/6, etc.) for 
data up to Week 20 will be handled as follows: 
1. Subjects who drop out of the trial for any reason will be considered non-responders from 
the time they drop out through Week 20 
2. Subjects who do not have the required data to compute response (e.g. ASAS components) 
at baseline and at the specific time point will be classified as non-responders. 
Patients who were unblinded prior to the scheduled timepoint will be considered non-responders 
from the time of unblinding up to Week 16. The primary analysis will use the non-responder 
imputation. 
Continuous variables (e.g. ASAS components) up to Week 20 will be analyzed using a mixed-
effects model repeated measures (MMRM) which is valid under the missing at random (MAR) 
assumption. For analyses of these parameters, if all post-baseline values are missing then these 

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missing values will not be imputed and this subject will be removed from the analysis of the 
corresponding variable, i.e. it might be that the number of subjects providing data to an analysis 
is smaller than the number of subjects in the FAS. 
Additionally, under the assumption of missing at random, multiple imputation by treatment may 
be performed for baseline weight as well as for all baseline and post-baseline efficacy variables 
of interest during the trial. 
9.4.4 
Supportive analyses 
Sensitivity analyses and supportive analyses will be conducted in order to provide evidence that 
the results seen from the primary analysis are robust. These analyses will center on the 
deviations in model assumptions, and the treatment of missing data.  
In addition, further logistic regression models may be conducted which explore the impact of 
other baseline or disease characteristics on response. 
In case of a substantial number of missing values, their impact on the analysis results may be 
assessed as well by repeating the logistic regression model using ways to handle missing data. 
These may include, but are not limited to: 
a) Tipping point analysis 
b) Observed data analysis 
9.5 
Analysis of other variables 
9.5.1 
Secondary efficacy variables  
The secondary efficacy variables are listed below. Secondary efficacy variables will be 
analyzed using the FAS population. 
 ASAS20 response at Week 12/16. 
 ASAS-NSAID response at Week 12. 
 Change from baseline in BASDAI at Week 12/16. 
 Change from baseline in SF36 physical component score at Week 12/16. 
 Change from baseline in ASAS-NSAID score at Week 12 for Secukinumab (delayed 
tapering) vs. change from baseline in ASAS-NSAID score at Week 16 for Secukinumab 
(early tapering) 
 Change from baseline in BASDAI at Week 12 for Secukinumab (delayed tapering) vs 
change from baseline in BASDAI at Week 16 for Secukinumab (early tapering). 
 Change from baseline in BASDAI question 2 
 ASAS20 response at Week 4 for Secukinumab (delayed tapering) vs. ASAS20 response at 
Week 20 for placebo group 
Testing strategy 
The following hypotheses will be included in the testing strategy, and type-I-errors will be set 
such that a family-wise type-I-error of 5% is kept: 
Primary objective: 

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H1: Secukinumab 150 mg s.c. (pooled Secukinumab groups) is not different to placebo regimen 
with respect to signs and symptoms (ASAS20 response) at Week 12 
Secondary objectives: 
H2: Secukinumab 150 mg s.c. (pooled Secukinumab groups) is not different to placebo regimen 
with respect to change from baseline in ASAS-NSAID score at Week 12 
H3: Secukinumab 150 mg s.c. (pooled Secukinumab groups) is not different to placebo regimen 
with respect to change from baseline in total BASDAI score at Week 12 
H4: Secukinumab 150 mg s.c. (delayed tapering) is not different to placebo regimen with respect 
to signs and symptoms (ASAS20 response) at Week 12 
H5: Secukinumab 150 mg s.c. (early tapering) is not different to placebo regimen with respect 
to signs and symptoms (ASAS20 response) at Week 12 
H6: Secukinumab 150 mg s.c. (early tapering) is not different to placebo regimen with respect 
to signs and symptoms (ASAS20 response) at Week 16 
H7: Secukinumab 150 mg s.c. (delayed tapering) is not different to placebo regimen with respect 
to change from baseline in ASAS-NSAID score at Week 12 
H8: Secukinumab 150 mg s.c. (early tapering) is not different to placebo regimen with respect 
to change from baseline in ASAS-NSAID score at Week 12 
H9: Secukinumab 150 mg s.c. (delayed tapering) is not different to placebo regimen with respect 
to change from baseline in total BASDAI score at Week 12 
H10: Secukinumab 150 mg s.c. (early tapering) is not different to placebo regimen with respect 
to change from baseline in total BASDAI score at Week 12 
H11: Secukinumab 150 mg s.c. (early tapering) is not different to placebo regimen with respect 
to change from baseline in total BASDAI score at Week 16 
 
These hypotheses will in principal be tested hierarchically in ascending order. However, since 
some hypotheses for individual group comparisons are already contained in the higher-ranked, 
pooled comparisons for the same endpoint (i.e. H4 and H5 are contained in H1, H7 and H8 are 
contained in H2 and H9 and H10 are contained in H3) these individual hypothesis can be tested 
simultaneously. The justification is that as soon as the pooled hypothesis has been rejected 
(e.g. H1 ), at least one of the two contained individual hypotheses (e.g. H4 and H5) must be 
false and there is only a potential for at most one type-I-error. Therefore H4 and H5 can be 
tested simultaneously once all higher-ranked hypotheses have been rejected. The same 
argument applies to H7 and H8 and to H9 and H10. The following chart displays the testing 
strategy graphically: 
 

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First the hypotheses (H1) for the primary objective (ASAS20 for Secukinumab pooled at week 
12) versus placebo will be tested. If this hypothesis can be rejected at level α, H2 will be tested 
and so on  until H4. H4. and H5 will be tested simultaneously. If both can be rejected, H6 will 
be tested and so on. As soon as a hypothesis fails to be rejected at level α, all tests of the 
following hypotheses (except the paired hypothesis in the same knot) will be regarded as 
exploratory only and will not provide any confirmatory evidence, irrespective of their nominal 
p-values. Of note, in the description above, rejection of a hypothesis refers to rejection of the 
two-sided hypothesis; however the level of a rejected hypothesis is only passed on according 

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to the procedure for the test of another hypothesis if the treatment effect is in favor of the 
Secukinumab regimen. The family-wise error will be set to α=5% and it will be controlled 
with the proposed semi-hierarchical testing strategy. 
ASAS20 at week 12  
Response at Week 12 to ASAS20 for Secukinumab (delayed-tapering) versus placebo will be 
evaluated using a logistic regression model with treatment as a factor and baseline weight as a 
covariate. 
ASAS20 at week 16  
Response at Week 16 to ASAS20 for Secukinumab (early-tapering) versus placebo will be 
evaluated using a logistic regression model with treatment as a factor and baseline weight as a 
covariate. 
ASAS-NSAID at Week 12 
Between-treatment differences in the change in ASAS-NSAID relative to baseline will be 
evaluated using a mixed-effect model repeated measures (MMRM). Treatment group and 
analysis visit as factors, baseline ASAS-NSAID and weight as continuous covariates. Treatment 
by analysis visit and baseline ASAS-NSAID by analysis visit will be included as interaction 
terms in the model. An unstructured covariance structure will be assumed for the model. The 
significance of the Secukinumab pooled treatment effect will be determined from a linear 
contrast comparing the (mean of the) two Secukinumab regimens to placebo. The significance 
of the two individual Secukinumab treatment group effects will be determined from the pairwise 
comparisons performed between Secukinumab regimens and placebo. 
BASDAI at Week 12/16 
The change from baseline to Week 12/16 in total BASDAI will be analyzed using a MMRM 
with treatment regimen and analysis visit as factors and weight and baseline score as continuous 
covariates. Treatment by analysis visit and baseline by analysis visit will be included as 
interaction terms in the model. An unstructured covariance structure will be assumed for this 
model. The significance of the Secukinumab treatment effect will be determined from the 
pairwise comparisons performed between Secukinumab regimens and placebo. 
Other secondary variables 
SF-36 PCS  
For the change in SF-36 PCS, between-treatment differences will be evaluated using a mixed 
effect repeated measures model (MMRM). Treatment group and analysis visit will be included 
as categorical factors and baseline SF-36 PCS score and weight as continuous covariates. 
Treatment by analysis visit and baseline SF-36 PCS score by analysis visit will be included as 
interaction terms in the model. An unstructured covariance structure will be assumed for the 
model. The significance of the Secukinumab treatment effect will be determined from the 
pairwise comparisons performed between Secukinumab regimens and placebo. 

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Between-treatment comparisons for binary variables in the FAS population (e.g. ASAS20) at 
individual analysis visits will be evaluated using a logistic regression model with treatment as 
a factor and weight as a covariate for any analysis up to end of study. 
Continuous variables (e.g. change from baseline in BASDAI question 2) will be evaluated using 
a MMRM with treatment regimen and analysis visit as factors and weight and baseline score as 
continuous covariates. Treatment by analysis visit and baseline by analysis visit will be included 
as interaction terms in the model. An unstructured covariance structure will be assumed for this 
model. The significance of the treatment effects for Secukinumab regimens at different analysis 
visits will be determined from the pairwise comparisons performed between Secukinumab 
regimens and placebo and/or Secukinumab at the appropriate analysis visits.  
9.5.2 
Exploratory efficacy variables 
The exploratory efficacy variables are listed below. Exploratory efficacy variables will be 
analyzed using the FAS population. 
 Total ASAS-NSAID [Area Under Curve (AUC)] Score from treatment start with 
Secukinumab to a Secukinumab exposure of 12 weeks. 
 Total ASAS-NSAID [Area Under Curve (AUC)] Score From Week 4 to Week 16  
 Proportion of patients with no NSAID intake after Secukinumab exposure of 12 weeks 
 Proportion of patients with no NSAID intake at week 12. 
 Change from Baseline in the ASAS Health Index after Secukinumab exposure of 12 
weeks 
 Change from Baseline in the ASAS Health Index at week 12 
 Change from baseline in BASMI 
 ASAS40 response  
 ASAS20 response  
 ASAS5/6 response  
 Change from baseline in hsCRP  
 Change from baseline in total BASDAI  
 BASDAI 50 response  
 ASAS partial remission  
 Change from baseline in ASAS components including: 
a. Patient global disease activity 
b. Total spinal pain 
c. Inflammation (average of BASDAI questions 5 and 6) 
d. BASFI 
 Change from baseline in ASDAS-CRP and ASDAS-ESR 
 ASDAS inactive disease as defined by ASDAS < 1.3 
 ASDAS clinically important improvement (change in ASDAS ≥ 1.1) and major 
improvement (change in ASDAS ≥ 2.0)  
 Reasons given in the patient diary on why he was not able to taper NSAIDs despite 
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Secukinumab groups at week 12 (delayed tapering) and week 16 (early tapering) will be 
compared for all primary, secondary and exploratory variables that have not been outlined. 
Variables such as hsCRP whose distribution is not anticipated to be normal will be transformed 
and analyzed on the loge scale. All other details and analyses regarding the exploratory efficacy 
variables will be outlined in the statistical analysis plan. 
9.5.3 
Safety variables  
Adverse events 
Treatment emergent adverse events (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) will be summarized.  
AEs will be summarized by presenting, for each treatment group, the number and percentage 
of subjects 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 subject reported more than one adverse event with the same 
preferred term, the adverse event with the greatest severity will be presented. If a subject 
reported more than one adverse event within the same primary system organ class, the subject 
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 will be presented separately by study periods, i.e. Weeks 1-16 and after Week 
16. 
As appropriate, the incidence of AEs will be presented per 100 subject years of exposure. 
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, serum chemistry and urinalysis). Descriptive summary statistics for the change 
from baseline to each study visit will be presented. These descriptive summaries will be 
presented by test group, laboratory test and treatment group. Change from baseline will only be 
summarized for subjects 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 subject’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 

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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 descriptive summary statistics for the change 
from baseline for each post-baseline visit will be performed. These descriptive summaries will 
be presented by vital sign and treatment group. Change from baseline will only be summarized 
for subjects with both baseline and post-baseline values. 
HLA-B27 
Human Leukocyte Antigen-B27 (HLA-B27) will be summarized at baseline and listed. 
9.5.4 
Resource utilization 
Not applicable. 
9.5.5 
Pharmacokinetics  
Not applicable. 
9.5.6 
Pharmacogenetics/pharmacogenomics  
Not applicable. 
9.5.7 
Biomarkers  
Not applicable. 
9.5.8 
PK/PD  
Not applicable. 
9.6 
Interim analyses  
Not applicable. 
9.7 
Sample size calculation 
All sample size and power considerations are performed using EAST 6. 
The sample size was calculated based on the phase III results of the MEASURE2 study, which 
used the same dose and loading regimen as will be applied in this trial. Under the assumption 
of 56.9% ASAS20 responders in the Secukinumab (delayed tapering) group and 27.0% in the 
placebo group, a sample size of 62 patients per group is required to have 90% power to show 
superiority of Secukinumab over placebo at a two sided α=5%. 
For the comparison of the the early tapering group at week 16 vs. placebo, the same treatment 
effect is expected, leading to the same sample size. To compensate for some dropout and other 
protocol deviations, the sample size will be increased to 68 per arm. The total sample size of 
this trial will thus be 204. At the time of writing this amendment, about 190 patients have been 
recruited into this trial and it seems unlikely that a sample > 200 can be recruited within 
reasonable time. With this sample size, the (newly introduced) comparison of pooled 

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Secukinumab groups vs. placebo, the trial would still have almost 80 % (78%) power if the 
placebo response was somewhat higher (35%) than originally assumed..  
Other secondary endpoints 
It will be assumed that the amount of NSAID reduction observed in the etanercept SPARSE 
trial (Dougados et al. 2014), of 63.9 vs. baseline (etanercept) and 36.6 for placebo, with an 
estimated standard deviation of 40 will be seen in this trial for both Secukinumab groups versus 
placebo. Based on this assumption both secukinmab groups will have >90% power to show 
superiority over placebo for NSAID reduction. 
For the total BASDAI parameter, 62 patients per treatment group should yield a power of 
approximately 91%, assuming a a treatment difference of 1.8 with a standard deviation of 2.8 
(van der Heijde 2006). For SF-36 PCS, 62 patients per treatment group yield a power of 
approximately 87.5%, assuming mean change of 6.9 on both Secukinumab regimen and mean 
change of 1.6 on placebo with common standard deviation of 8.7 (Davis 2007).    
10 
Ethical considerations 
Study documentation, record keeping and retention of documents 
Each participating site will maintain appropriate medical and research records for this trial, in 
compliance with Section 4.9 of the ICH E6 GCP, and regulatory and institutional requirements 
for the protection of confidentiality of patients. As part of participating in a Novartis-sponsored 
study, each site will permit authorized representatives of the sponsor(s) and regulatory agencies 
to examine (and when required by applicable law, to copy) clinical records for the purposes of 
quality assurance reviews, audits and evaluation of the study safety and progress. 
Source data are all information, original records of clinical findings, observations, or other 
activities in a clinical trial necessary for the reconstruction and evaluation of the trial. Examples 
of these original documents and data records include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, patients’ diaries or evaluation 
checklists, pharmacy dispensing records, recorded data from automated instruments, copies or 
transcriptions certified after verification as being accurate and complete, microfiches, 
photographic negatives, microfilm or magnetic media, x-rays, and patient files and records kept 
at the pharmacy, at the laboratories, and medico-technical departments involved in the clinical 
trial. 
Data collection is the responsibility of the clinical trial staff at the site under the supervision of 
the site Principal Investigator. The study case report form (CRF) is the primary data collection 
instrument for the study. The investigator should ensure the accuracy, completeness, legibility, 
and timeliness of the data reported in the CRFs and all other required reports. Data reported on 
the CRF, that are derived from source documents, should be consistent with the source 
documents or the discrepancies should be explained. All data requested on the CRF must be 
recorded. Any missing data must be explained. Any change or correction to a paper CRF should 
be dated, initialed, and explained (if necessary) and should not obscure the original entry. For 
electronic CRFs an audit trail will be maintained by the system. The investigator should retain 
records of the changes and corrections to paper CRFs. 
The investigator/institution should maintain the trial documents as specified in Essential 
Documents for the Conduct of a Clinical Trial (ICH E6 Section 8) and as required by applicable 

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regulations and/or guidelines. The investigator/institution should take measures to prevent 
accidental or premature destruction of these documents. 
Essential documents (written and electronic) should be retained for a period of not less than 
fifteen (15) years from the completion of the Clinical Trial unless Sponsor provides written 
permission to dispose of them or, requires their retention for an additional period of time 
because of applicable laws, regulations and/or guidelines. 
Confidentiality of study documents and patient records 
The investigator must ensure anonymity of the patients; patients must not be identified by names 
in any documents submitted to Novartis. Signed informed consent forms and patient enrollment 
log must be kept strictly confidential to enable patient identification at the site. 
10.1 
Regulatory and ethical compliance  
This clinical study was designed and shall be implemented 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 Japanese Ministry of 
Health, Labor, and Welfare), and with the ethical principles laid down in the Declaration of 
Helsinki. 
10.2 
Informed consent procedures  
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent. Informed consent must be 
obtained before conducting any study-specific procedures (i.e. all of the procedures described 
in the protocol). The process of obtaining informed consent should be documented in the patient 
source documents.  
Novartis will provide to investigators in a separate document an informed consent form that 
complies with the ICH GCP guideline and regulatory requirements and is considered 
appropriate for this study.  
Women of child bearing potential should 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 requirement for the 
duration of the study or longer if required by locally approved prescribing information (e.g. 20 
weeks in EU). If there is any question that the patient will not reliably comply, they should not 
be entered in the study. 
10.3 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution should 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, patient recruitment procedures 
(e.g., advertisements) and any other written information to be provided to patients. Prior to 
study start, the investigator is required to sign a protocol signature page confirming his/her 
agreement to conduct the study in accordance with these documents and all of the instructions 
and procedures found in this protocol and to give access to all relevant data and records to 
Novartis monitors, auditors, Novartis Quality Assurance representatives, designated agents of 

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Novartis, IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site 
is requested by a regulatory authority, the investigator must inform Novartis immediately that 
this request has been made. 
10.4 
Publication of study protocol and results  
Novartis assures that the key design elements of this protocol will be posted in a publicly 
accessible database such as clinicaltrials.gov. In addition, upon study completion and 
finalization of the study report the results of this trial will be either submitted for publication 
and/or posted in a publicly accessible database of clinical trial results. 
11 
Protocol adherence 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of patients should be 
administered as deemed necessary on a case by case basis. Under no circumstances should an 
investigator collect additional data or conduct any additional procedures for any research related 
purpose involving any investigational drugs. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be implemented. 
All significant protocol deviations will be recorded and reported in the CSR. 
11.1 
Protocol Amendments  
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, Health Authorities where required, and the IRB/IEC prior to 
implementation. Only amendments that are intended for patients safety may be implemented 
immediately provided the Health Authorities are subsequently notified by protocol amendment 
and the reviewing IRB/IEC is notified. Notwithstanding the need for approval of formal 
protocol amendments, the investigator is expected to take any immediate action required for the 
safety of any patient included in this study, even if this action represents a deviation from the 
protocol. In such cases, the reporting requirements identified in section 7 Safety Monitoring 
should be followed. 
12 
References 
References are available upon request 
Blauvelt A, Prinz J, Gottlieb AB, et al (2014) Secukinumab administration by pre-filled 
syringe: efficacy, safety, and usability results from a randomized controlled trial in psoriasis 
(FEATURE). Br J Dermatol.(published online ahead of print August 16, 2014). 
Braun et al. Treatment of active ankylosing spondylitis with infliximab: a randomised 
controlled multicentre trial; Lancet 2002; 359: 1187–93. 
Dougados M, Simon P, Braun J et al (2011) ASAS recommendations for collecting, analysing 
and reporting NSAID intake in clinical trials/epidemiological studies in axial 
spondyloarthritis. Ann Rheum Dis;70(2):249-51. 

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Dougados M, Wood E, Combe B et al (2014) evaluation of the nonsteroidal anti-inflammatory 
drug-sparing effect of etanercept in axial spondyloarthritis: results of the multicenter, 
randomized, double-blind, placebo-controlled SPARSE study. Arthritis Res Ther;16(6):481. 
Dubreuil M (2014) myocardial infarction risk with diclofenac use in spondyloarthropathy 
versus non-inflammatory low back pain. ACR/ARHP Annual Meeting 2014; Boston, MA.  
Arthritis Rheumatol. Supplement 66(10):Abstract no. 554;S243. 
Kiltz U, van der Heijde D, Boonen A, Braun J (2014) The ASAS Health Index (ASAS HI) – a 
new tool to assess the health status of patients with spondyloarthritis; Clin Exp Rheumatol 
2014; 32 (Suppl. 85):S105-S108 
Konttinen L, Tuompo R, Uusitalo T et al (2007) anti-TNF therapy in the treatment of 
ankylosing spondylitis: the Finnish experience; Clin Rheumatol (2007)26(10):1693–1700. 
Nderitu P, Doos L, Jones PW et al (2013) non-steroidal anti-inflammatory drugs and chronic 
kidney disease progression: a systematic review. Fam Practice;30(3):247–55. 
Poddubnyy D, Hermann KG, Callhoff J et al (2014) ustekinumab for the treatment of patients 
with active ankylosing spondylitis: results of a 28-week, prospective, open-label, proof-of-
concept study (TOPAS); Ann Rheum Dis;73(5):817-23. 
Sieper et al. 2015. Secukinumab significantly improves signs and symptoms of active 
ankylosing spondylitis: 52-Week Data from MEASURE 2, A Randomized, Double-Blind, 
Placebo-Controlled Phase 3 Trial with Subcutaneous Loading and Maintenance Dosing. 
EULAR Annual Meeting, Rome Italy, 2015. Oral presentation (presentation number 168) 
Van der Hejde D, Sieper J, Maksymowych WP et al (2011) update of the international ASAS 
recommendations for the use of anti-TNF agents in patients with axial spondyloarthritis. Ann 
Rheum Dis;70(6):905-8. 
Van Baarsen LGM, Lebre MC, van der Coelen D, et al (2011) IL-17 levels in synovium of 
patients with rheumatoid arthritis, psoriatic arthritis and osteoarthritis: Target validation in 
various forms of arthritis. Ann Rheum Dis;70:A79.  
13 
Appendices 
13.1 
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/CRO personnel. 
 
 
 
Table 13-1 
Safety analyses: expanded limits and notable criteria 
 
Final Harmonization 

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Notable Criteria 
Laboratory Variable 
 
Standard Units 
SI Units 
LIVER FUNCTION AND RELATED VARIABLES 
SGOT (AST) 
 
>3 x ULN 
>3 x ULN 
SGPT (ALT) 
 
>3 x ULN 
>3 x ULN 
Bilirubin 
 
>2 x ULN 
>2 x ULN 
Alkaline phosphatase 
 
>2.5 x ULN 
>2.5 x ULN 
 
 
 
 
RENAL FUNCTION, METABOLIC AND ELECTROLYTE VARIABLES 
Creatinine (serum) 
 
>2 x ULN 
>2 x ULN 
HEMATOLOGY VARIABLES 
Hemoglobin:  
20 g/L decrease from baseline 
Platelet count:  
<100x10E9/L 
White blood cell count: 
<0.8 x LLN 
Neutrophils:  
<0.9 x LLN 
13.2 
Appendix 2: Liver event and laboratory trigger definitions and 
follow-up requirements 
Table 13-2 
Liver event and laboratory trigger definitions 
 
Definition/ threshold 
LIVER LABORATORY 
TRIGGERS 
3 x ULN < ALT / AST  5 x ULN 
 1.5 x ULN < TBL  2 x ULN 
LIVER EVENTS 
ALT or AST > 5 × ULN 
 
ALP > 2 × ULN (in the absence of known bone pathology) 
 
TBL > 2 × ULN (in the absence of known Gilbert syndrome) 
 
ALT or AST > 3 × ULN and INR > 1.5  
 
Potential Hy’s Law cases (defined as ALT or AST > 3 × ULN and 
TBL > 2 × ULN [mainly conjugated fraction] without notable 
increase in ALP to > 2 × ULN) 
 
Any clinical event of jaundice (or equivalent term) 
 
ALT or AST > 3 × ULN accompanied by (general) malaise, fatigue, 
abdominal pain, nausea, or vomiting, or rash with eosinophilia 
 
Any adverse event potentially indicative of a liver toxicity *  
 
Table 13-3 
Follow-up requirements for liver events and laboratory triggers 
Criteria 
Actions required 
Follow-up monitoring 
Potential Hy’s 
Law casea 
Discontinue the study drug 
immediately 
Hospitalize, if clinically appropriate 
Establish causality 
Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc 
(frequency at investigator 
discretion) 
 

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Criteria 
Actions required 
Follow-up monitoring 
ALT or AST 
> 8 × ULN 
Discontinue the study drug 
immediately 
Hospitalize if clinically appropriate 
Establish causality 
Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc 
(frequency at investigator 
discretion) 
> 3 × ULN and 
INR > 1.5 
Discontinue the study drug 
immediately 
Hospitalize, if clinically appropriate 
Establish causality 
Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc 
(frequency at investigator 
discretion) 
> 5 to ≤ 8 × ULN 
Repeat LFT within 48 hours 
If elevation persists, continue follow-up 
monitoring 
If elevation persists for more than 2 
weeks, discontinue the study drug 
Establish causality 
Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc 
(frequency at investigator 
discretion) 
> 3 × ULN 
accompanied by 
symptomsb 
Discontinue the study drug 
immediately 
Hospitalize if clinically appropriate 
Establish causality 
Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc 
(frequency at investigator 
discretion) 
> 3 to ≤ 5 × ULN  
(patient is 
asymptomatic) 
Repeat LFT within the next week 
If elevation is confirmed, initiate close 
observation of the patient 
Investigator discretion 
Monitor LFT within 1 to 4 weeks  
ALP (isolated) 
 
 
> 2 × ULN (in the 
absence of 
known bone 
pathology) 
Repeat LFT within 48 hours 
If elevation persists, establish 
causality 
Complete liver CRF 
Investigator discretion 
Monitor LFT within 1 to 4 weeks 
or at next visit 
TBL (isolated) 
 
 
> 2 × ULN (in the 
absence of 
known Gilbert 
syndrome) 
Repeat LFT within 48 hours 
If elevation persists, discontinue the 
study drug immediately 
Hospitalize if clinically appropriate 
Establish causality 
Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc 
(frequency at investigator 
discretion) 
Test for hemolysis (e.g., 
reticulocytes, haptoglobin, 
unconjugated [indirect] bilirubin) 
> 1.5 to ≤ 2 × 
ULN 
(patient is 
asymptomatic) 
Repeat LFT within the next week 
If elevation is confirmed, initiate close 
observation of the patient  
Investigator discretion 
Monitor LFT within 1 to 4 weeks 
or at next visit 
Jaundice 
Discontinue the study drug 
immediately 
Hospitalize the patient 
Establish causality 
Complete liver CRF 
ALT, AST, TBL, Alb, PT/INR, ALP 
and γGT until resolutionc 
(frequency at investigator 
discretion) 

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Criteria 
Actions required 
Follow-up monitoring 
Any AE 
potentially 
indicative of a 
liver toxicity* 
Consider study drug interruption or 
discontinuation  
Hospitalization if clinically appropriate 
Establish causality 
Complete liver CRF 
Investigator discretion 
*These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver 
damage-related conditions; the non-infectious hepatitis; the benign, malignant and unspecified 
liver neoplasms 
aElevated ALT/AST > 3 × ULN and TBL > 2 × ULN but without notable increase in ALP to > 2 × 
ULN 
b(General) malaise, fatigue, abdominal pain, nausea, or vomiting, or rash with eosinophilia  
cResolution is defined as an outcome of one of the following: (1) return to baseline values, (2) 
stable values at three subsequent monitoring visits at least 2 weeks apart, (3) remain at 
elevated level after a maximum of 6 months, (4) liver transplantation, and (5) death. 
13.3 
Appendix 3: Modified New York criteria 
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. 
13.4 
Appendix 4 
13.4.1 
Analysis and report of NSAID intake during clinical trials/studies 
1. As soon as the information contained in Table 13-4 is available (eg, name, mean dose, 
number of days of intake during a period of time), the recommendation is to analyse/report 
the data in terms of NSAID equivalent dose in mg/day on a 0–100 scale. The 150 mg 
equivalent diclofenac is set to 100. When the exact number of days with NSAID intake is 
not known (usually when the interval of time between 2 visits exceeds 2 weeks), it is 
recommended to refer to the semi-quantitative estimation summarised in Table 13-4. In 
this case, a score of 7/7 is proposed for the answer ‘every day’, 6/7 for >5 days/week, 4/7 
for >3 to ≤5 days/week, 2 for >1 to ≤3 days/ week, 0.5 for ≤1 day/week and 0 if the patient 
did not take any NSAID during the study period (Dougados et al 2011). 
The general formula for the calculation is: 
(equivalent NSAID score) × (days of intake during period of interest) × (days per week)/(period 
of interest in days) 

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For example, if during a period of interest (between 2 visits) of 6 months, the patient has taken 
piroxicam 20 mg during 4 months and if during this 4-month period he has taken piroxicam 3–
5 days per week the calculation is as follows: 
100 (20 mg piroxicam score) × 120 (4 months) × 4/7 (3–5 days/week)/180 (6 months) = 38.1 
If the patient has used 10 mg piroxicam during the remaining 2 months on 2 days a week, the 
NSAID score for this period is: 
50 (10 mg piroxicam score) ×60 (2 months) × 2/7 (1–3 days/week)/180 (6 months) = 4.8 
In this example the total score for the 6 month period is 42.9 (38.1 plus 4.8). 
Table 13-4 
ASAS recommendations for the approach to collection of NSAID 
intake for use in clinical trials/epidemiological studies of 
spondyloarthritis 
NSAID intake since the last visit  
Yes □   
 
No □ 
NSAID name 
Average daily 
intake 
Days with intake 
Starting date 
Ending date 
 
------------------- 
 
 
 
I___I___I___I 
mg 
□ <1 day/week 
□ 1–3 days/week 
□ 3–5 days/week 
□ ≥5 days/week 
□ Everyday 
 
I__I__II__I__II__I__I 
 
 
I__I__II__I__II__I__I 
 
Ongoing 
 
27. When the name and the dose of the NSAID intake are not available but the number of 
days with NSAID intake is available, the recommendation is to present the results as the 
percentage days with at least NSAID intake during a period of time. 
28. When the only available data are the NSAID intake at a specific visit, the recommendation 
is to present the results as the percentage patients taking an NSAID at a specifi c visit. 
13.4.2 
Assessment of SpondyloArthritis International Society criteria (ASAS) 
The ASAS response measures consist of the following assessment domains (Sieper 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: 
5. Spinal mobility represented by the BASMI lateral spinal flexion assessment 
6. C-reactive protein (acute phase reactant) 

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13.4.3 
Bath Ankylosing Spondylitis Functional Index (BASFI) 
The BASFI is a set of 10 questions designed to determine the degree of functional limitation in 
those patients with AS. The 10 questions were chosen with a major input from patients with 
AS. The first 8 questions consider activities related to functional anatomy. The final 2 questions 
assess the patient’s ability to cope with everyday life. A 10 cm visual analog scale (VAS) is 
used to answer the questions. The mean of the 10 scales gives the BASFI score – a value 
between 0 and 10. 
13.4.4 
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: 
 How would you describe the overall level of fatigue/tiredness you have experienced? 
 How would you describe the overall level of AS neck, back or hip pain you have had? 
 
 How would you describe the overall level of pain/swelling in joints other than neck, back, 
hips you have had? 
 How would you describe the overall level of discomfort you have had from any areas 
tender to touch or pressure? 
 How would you describe the overall level of morning stiffness you have had from the 
time you wake up? 
 How long does your morning stiffness last from the time you wake up? 
To give each symptom equal weighting, the mean (average) of the 2 scores relating to morning 
stiffness (questions 5 and 6) is taken. The mean of questions 5 and 6 is added to the scores from 
questions 1-4. The resulting 0 to 50 score is divided by 5 to give a final 0 – 10 BASDAI score. 
Scores of 4 or greater suggest suboptimal control of disease, and patients with scores of 4 or 
greater are usually good candidates for either a change in their medical therapy or for enrollment 
in clinical trials evaluating new drug therapies directed at Ankylosing Spondylitis. BASDAI is 
a quick and simple index (taking between 30 seconds and 2 minutes to complete). 
13.4.5 
Bath Ankylosing Spondylitis Metrology Index (BASMI) 
Cervical rotation 
Cervical rotation is measured twice with the patient supine on plinth, head in neutral position, 
forehead horizontal (if necessary, with the head on a pillow or foam block, which must be 
documented for future reassessments). A goniometer (preferably a gravity goniometer) is placed 
centrally on the forehead. Patient rotates head as far as possible to the right, keeping shoulders 
still; ensure no neck flexion or side flexion occurs. The angle between the sagittal plane and the 
new plane after rotation is recorded. The higher reading of 2 assessments is recorded in degrees. 
The same procedure is repeated twice for the left side. Record the mean of the higher reading 
from the right side and the higher reading from the left side. 

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Protocol No. CAIN457FDE03 
 
Tragus to wall distance 
Tragus to wall distance is measured twice with the patient’s heels and back rested against the 
wall. The chin should be at usual carrying level and the patient takes maximal effort to touch 
the head against the wall. The distance between the tragus and the wall is assessed on each side, 
and an average of the 2 distances from each side is calculated. The procedure is repeated, and 
the shorter of the 2 average assessments is reported. 
Spinal lateral flexion (lumbar lateral flexion) 
Patient stands with heels and buttocks touching the wall, knees straight, shoulders back, and 
hands by the side. The patient bends to the right side as far as possible, without lifting the left 
foot/heel or flexing the right knee and maintaining a straight posture with heels, buttocks, and 
shoulders against the wall. The distance from the third fingertip to the floor when patient bends 
to the side is subtracted from the distance when patient stands upright. The higher of 2 tries is 
recorded. The maneuver is repeated on the left side. Record the mean of the larger difference 
from the right side and the larger difference from the left side.  
Lumbar flexion (modified Schober index) 
Patient is standing erect. Set marks in upright position 5 cm below and 10 cm above lumbosacral 
junction (spinal section of a line joining the dimples of Venus). Measure the difference between 
the distance between marks in a standing position (15 cm) versus a forward flexed position 
when the patient bends forward as far as possible, keeping the knees straight. The procedure is 
repeated, and the higher difference of the 2 tries is reported. 
Maximal intermalleolar distance 
Patient is lying down with the legs separated as far as possible with knees straight and toes 
pointing upwards. Alternatively, the patient stands and separates the legs as far as possible. 
Distance between medial malleoli is measured, and the higher of the 2 readings is recorded. 
Chest expansion 
Chest expansion is measured with the patient’s hands resting on or behind the head. The 
measurement is taken at the fourth intercostal level anteriorly. The difference between maximal 
inspiration and expiration in cm (to the nearest 0.1 cm) is recorded twice, and the higher 
difference of the 2 tries is reported. 
Occiput-to-wall distance 
Occiput to wall distance is measured twice with the patient’s heels and back rested against the 
wall. The chin should be at usual carrying level, and the patient takes maximal effort to touch 
the head against the wall. The distance between the occiput and the wall is assessed, and the 
shorter of the 2 readings is reported.