Clinical trial NCT03765788
Conditions: Giant Cell Arteritis
Keywords: GCA ain457 Secukinumab Subcutaneous Vessel Inflammation corticosteroid tapering newly diagnosed or relapsing giant cell arteritis prednisolone taper regimen "escape"
Sponsor: Novartis Pharmaceuticals
Start date: 2019-01-30; Completion date: 2021-06-08
Enrollment: 52 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
This study was designed to evaluate the efficacy and safety of secukinumab compared to placebo to maintain disease remission up to 28 weeks including corticosteroid tapering, as well as up to 1 year (52 weeks) in patients with newly diagnosed or relapsing giant cell arteritis (GCA) who were naïve to biological therapy.

Detailed description:
This randomized, parallel-group, double-blind, placebo-controlled, multicenter, Phase II study was designed to evaluate the efficacy of secukinumab compared to placebo in combination with a 26-week prednisolone taper regimen in terms of sustained remission in patients with newly diagnosed or relapsing Giant Cell Arteritis (GCA) who were naïve to biological therapy. The study consisted of a Screening Period of up to 6 weeks (maximum duration), a 52-week Treatment Period and an 8-week Safety Follow-up Period

Patients who did not achieve remission by Week 12, experienced a flare after remission or could not adhere to the prednisolone taper regimen entered "escape". Upon entering "escape", patients received prednisolone at a dose determined by the physician's clinical judgment and continued to receive secukinumab or placebo in a blinded manner.

Safety evaluation was included in all visits including two safety follow-up visits performed 8 and 12 weeks after the last study drug administration.

Arms: arm 1: Participants received secukinumab at a dose of 300 milligrams (mg) as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen. arm 2: Participants received placebo as subcutaneous (s.c.) injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter through to week 48 along with a 26-week prednisolone tapering regimen.
Interventions: intervention 1: Secukinumab 300 mg, s.c. intervention 2: Prednisolone intervention 3: Placebo
Intervention descriptions: intervention 1: Secukinumab 300 mg was administered by subcutaneous (s.c.) injections using 1 mL pre-filled syringes (PFSs) throughout the study. intervention 2: Prednisolone was provided as tablets (1 mg, 5 mg, 10 mg, 20 mg tablets) for daily administration as tapered regimen from a dose of 25 mg to 60 mg at Baseline to 1 mg at Week 26 (last dose) intervention 3: Placebo 300 mg was administered by subcutaneous (s.c.) injections using 1 mL pre-filled syringes (PFSs) throughout the study.

Protocol documents:
Prot_000.pdf: 
Clinical Development & Medical Affairs Region Europe 
AIN457/Secukinumab 
Clinical Trial Protocol CAIN457ADE11C / NCT03765788
A randomized, parallel-group, double-blind, placebo-
controlled, multicenter phase 2 trial to investigate the 
safety and efficacy of secukinumab (AIN457) in patients 
with giant cell arteritis (TitAIN) 
Document type: 
Clinical Trial Protocol 
EUDRACT number: 
2018-002610-12 
Version number: 
 03 CLEAN 
Clinical trial phase: 
Phase II 
Release date: 
29. Nov 2019
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 3.4 (May 2017) 


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Table of contents 
Table of contents ................................................................................................................. 2 
List of tables ........................................................................................................................ 5 
List of figures ...................................................................................................................... 5 
Glossary of terms ................................................................................................................. 8 
Amendment 3 .................................................................................................................... 10 
Amendment 2 .................................................................................................................... 11 
Amendment 1 .................................................................................................................... 12 
Protocol summary .............................................................................................................. 13 
1 
Introduction ....................................................................................................................... 20 
1.1 
Background ............................................................................................................ 20 
1.2 
Purpose .................................................................................................................. 22 
2 
Study objectives and endpoints ......................................................................................... 22 
2.1 
Objectives and related endpoints ........................................................................... 22 
3 
Investigational plan ........................................................................................................... 24 
3.1 
Study design .......................................................................................................... 24 
3.2 
Rationale for study design ..................................................................................... 25 
3.2.1 
Rationale for choice of background therapy ......................................... 26 
3.3 
Rationale for dose/regimen, route of administration and duration of treatment .... 27 
3.4 
Rationale for choice of comparator ....................................................................... 28 
3.5 
Purpose and timing of interim analyses/design adaptations .................................. 28 
3.6 
Risks and benefits .................................................................................................. 29 
4 
Population .......................................................................................................................... 30 
4.1 
Inclusion criteria .................................................................................................... 31 
4.2 
Exclusion criteria ................................................................................................... 31 
5 
Treatment ........................................................................................................................... 34 
5.1 
Study treatment ...................................................................................................... 34 
5.1.1 
Investigational and control drugs .......................................................... 34 
5.1.2 
Additional treatment.............................................................................. 35 
5.2 
Treatment arms ...................................................................................................... 35 
5.3 
Treatment assignment and randomization ............................................................. 35 
5.4 
Treatment blinding ................................................................................................ 36 
5.5 
Treating the patient ................................................................................................ 36 
5.5.1 
Patient numbering ................................................................................. 36 
5.5.2 
Dispensing the study drug ..................................................................... 36 
5.5.3 
Handling of study and additional treatment .......................................... 37 


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5.5.4 
Instructions for prescribing and taking study treatment ........................ 37 
5.5.5 
Permitted dose adjustments and interruptions of study treatment ........ 41 
5.5.6 
Rescue medication ................................................................................ 41 
5.5.7 
Concomitant medication ....................................................................... 41 
5.5.8 
Prohibited medication ........................................................................... 42 
5.5.9 
Emergency breaking of assigned treatment code .................................. 44 
5.6 
Study completion and discontinuation .................................................................. 45 
5.6.1 
Study completion and post-study treatment .......................................... 45 
5.6.2 
Discontinuation of study treatment ....................................................... 45 
5.6.3 
Withdrawal of informed consent ........................................................... 46 
5.6.4 
Loss to follow-up .................................................................................. 47 
5.6.5 
Early study termination by the sponsor ................................................. 47 
6 
Visit schedule and assessments ......................................................................................... 47 
6.1 
Screening ............................................................................................................... 55 
6.1.1 
Information to be collected on screening failures ................................. 55 
6.1.2 
Medical history and demographic data ................................................. 56 
6.1.3 
Height .................................................................................................... 56 
6.1.4 
Alcohol test/drug screen ........................................................................ 56 
6.1.5 
Tuberculosis screening .......................................................................... 56 
6.2 
Treatment exposure and compliance ..................................................................... 56 
6.3 
Efficacy .................................................................................................................. 57 
6.3.1 
Primary efficacy assessment ................................................................. 57 
6.3.2 
Secondary efficacy assessments ............................................................ 57 
 
 
 58 
 
 58 
 
 58 
6.3.6 
Appropriateness of efficacy assessments .............................................. 59 
6.4 
Safety/tolerability .................................................................................................. 59 
6.4.1 
Physical examination ............................................................................ 59 
6.4.2 
Vital signs.............................................................................................. 59 
6.4.3 
Weight ................................................................................................... 59 
6.4.4 
Tolerability of investigational treatments ............................................. 60 
6.4.5 
Laboratory evaluations .......................................................................... 60 
6.4.6 
Electrocardiogram ................................................................................. 61 


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6.4.7 
Pregnancy and assessments of fertility ................................................. 61 
6.4.8 
Other safety evaluations ........................................................................ 62 
6.4.9 
Appropriateness of safety measurements .............................................. 62 
6.5 
Additional assessments .......................................................................................... 62 
6.5.1 
Clinical outcome assessments ............................................................... 62 
6.5.2 
Patient reported outcomes ..................................................................... 63 
 
 65 
 
 65 
6.5.5 
Other assessments ................................................................................. 66 
7 
Safety monitoring and reporting ........................................................................................ 66 
7.1 
Definition of adverse events and reporting requirements ...................................... 66 
7.1.1 
Adverse events ...................................................................................... 66 
7.1.2 
Serious adverse events .......................................................................... 68 
7.1.3 
SAE reporting........................................................................................ 69 
7.1.4 
Pregnancy reporting .............................................................................. 70 
7.1.5 
Reporting of study treatment errors including misuse/abuse ................ 70 
7.2 
Additional safety monitoring ................................................................................. 71 
7.2.1 
Liver safety monitoring ......................................................................... 71 
7.2.2 
Renal safety monitoring ........................................................................ 71 
7.2.3 
Data monitoring committee ................................................................... 71 
8 
Data review and database management ............................................................................. 71 
8.1 
Site monitoring ...................................................................................................... 71 
8.2 
Data collection ....................................................................................................... 72 
8.3 
Database management and quality control ............................................................ 72 
9 
Data analysis ...................................................................................................................... 73 
9.1 
Analysis sets .......................................................................................................... 73 
9.2 
Patient demographics and other baseline characteristics ....................................... 74 
9.3 
Treatments ............................................................................................................. 74 
9.4 
Analysis of the primary variable............................................................................ 75 
9.4.1 
Primary variable .................................................................................... 75 
9.4.2 
Statistical model, hypothesis, and method of analysis .......................... 75 
9.4.3 
Handling of missing values/censoring/discontinuations ....................... 75 
9.4.4 
Sensitivity analyses ............................................................................... 76 
9.4.5 
Subgroup analyses ................................................................................. 76 
9.5 
Analysis of secondary variables ............................................................................ 76 
9.5.1 
Efficacy variables .................................................................................. 76 


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9.5.2 
Safety variables ..................................................................................... 78 
9.5.3 
Resource utilization ............................................................................... 79 
 
 79 
 
 79 
9.5.6 
Biomarkers ............................................................................................ 80 
 
 80 
 
 80 
9.8 
Sample size calculation.......................................................................................... 81 
10 Ethical considerations ........................................................................................................ 81 
10.1 
Regulatory and ethical compliance ........................................................................ 81 
10.2 
Informed consent procedures ................................................................................. 82 
10.3 
Responsibilities of the investigator and IRB/IEC .................................................. 82 
10.4 
Publication of study protocol and results............................................................... 83 
10.5 
Quality Control and Quality Assurance ................................................................. 83 
11 Protocol adherence ............................................................................................................ 83 
11.1 
Protocol amendments............................................................................................. 83 
12 References ......................................................................................................................... 84 
13 Appendix 1: Clinically notable laboratory values and vital signs ..................................... 86 
 
List of tables 
Table 2-1 
Objectives and related endpoints .......................................................... 22 
Table 5-1 
Overview of study treatment ................................................................. 34 
Table 5-2 
Study treatment schedule ...................................................................... 38 
Table 5-3 
60-40 mg/day at Baseline ...................................................................... 39 
Table 5-4 
40-25 mg/day at Baseline ...................................................................... 40 
Table 5-5 
Prohibited treatment .............................................................................. 43 
Table 6-1 
Assessment schedule ............................................................................. 49 
Table 7-1 
Guidance for capturing the study treatment errors including 
misuse/abuse ......................................................................................... 70 
Table 9-1 
Sensitivity to changes in assumptions in observed response rates ........ 81 
Table 13-1 
Safety Analyses: Expanded Limits and Notable Criteria ...................... 86 
 
List of figures 
Figure 3-1 
Study design .......................................................................................... 25 
 


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List of abbreviations 
 
ACR 
American College of Rheumatology 
AE 
Adverse Event 
ALT 
Alanine Aminotransferase 
ALP 
Alkaline Phosphatase 
AS 
Ankylosing Spondylitis 
AST 
Aspartate Aminotransferase 
AUC 
Area under the Curve 
AUClast 
The AUC from time zero to the last measurable concentration sampling time (tlast) 
(mass x time x volume-1) 
AUCinf 
The AUC from time zero to infinity (mass x time x volume-1) 
AUCtau 
The AUC calculated to the end of a dosing interval (tau) at steady-state (amount x 
time x volume-1) 
BUN 
Blood Urea Nitrogen 
CDS 
Core Data Sheet 
Cmax 
The maximum (peak) observed plasma, blood, serum, or other body fluid drug 
concentration after single dose administration (mass x volume-1) 
CL/F 
The total body clearance of drug from the plasma (volume x time-1) 
CMO & PS  
Chief Medical Office and Patient Safety 
CO 
Country Organization 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CRP 
C-reactive protein 
CTA 
Computed tomography angiography 
CTCAE 
Common toxicity criteria for adverse events 
CV 
Coefficient of variation 
DMC 
Data Monitoring Committee 
ECG 
Electrocardiogram 
EDC 
Electronic Data Capture 
EQ-5D 
EuroQol-5D 
eSource  
Electronic Source 
ESR 
Erythrocyte Sedimentation Rate 
FACIT-Fatigue 
Functional Assessment of Chronic Illness Therapy Fatigue Score 
GCA 
Giant Cell Arteritis 
GCP 
Good Clinical Practice 
GGT 
Gamma-Glutamyl Transferase 
 
 
hCG 
Human Chorionic Gonadotropin 
HIV 
Human immunodeficiency virus 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use 


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IEC 
Independent Ethics Committee 
IL-17A 
Interleukin 17A 
IRB 
Institutional Review Board 
LFT 
Liver Function Test  
LLN 
Lower Limit of Normal 
MedDRA 
Medical Dictionary for Regulatory Activities  
 
 
 
 
 
 
NYHA 
New York Heart Association 
PFS 
Prefilled Syringes 
PET-CT 
Positron Emission Tomography-Computed Tomography 
PGA 
Patient’s Global Assessment 
PhGA 
Physician’s Global Assessment 
 
 
PMR 
Polymyalgia Rheumatica 
PPD 
Purified Protein Derivative 
PRO 
Patient Reported Outcomes 
PsA 
Psoriatic Arthritis 
QTcF 
QT interval corrected by Fridericia’s formula 
SAP 
Statistical Analysis Plan 
RBC 
Red Blood Cell(s) 
SAE 
Serious Adverse Event 
s.c. 
Subcutaneous 
SD 
Standard Deviation 
SF-36 
Short Form 36 
SmPC 
Summary of Product Characteristics 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
Tmax 
The time to reach maximum (peak) plasma, blood, serum, or other body fluid drug 
concentration after single dose administration (time) 
T1/2 
The elimination half-life associated with the terminal slope (λz) of a semi logarithmic 
concentration-time curve (time). Use qualifier for other half-lives 
TNFα 
Tumor Necrosis Factor Alpha 
ULN 
Upper Limit of Normal 
USA 
United States of America 
VAS 
Visual Analog Scale 
Vz/F 
The apparent volume of distribution during terminal phase (associated with λz) 
(volume) 
WBC 
White Blood Cell(s) 
WHO 
World Health Organization  
 


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Glossary of terms 
Additional treatment 
Medicinal products that may be used during the clinical trial as described in 
the protocol, but not as an investigational medicinal product (e.g. any 
background therapy) 
Assessment 
A procedure used to generate data required by the study 
Biologic samples 
A biological specimen including, for example, blood (plasma, serum), 
saliva, tissue, urine, stool, etc. taken from a study patient  
Control drug 
A study drug (active or placebo) used as a comparator to reduce 
assessment bias, preserve blinding of investigational drug, assess internal 
study validity, and/or evaluate comparative effects of the investigational 
drug 
Dosage 
Dose of the study treatment given to the patient in a time unit (e.g. 100 mg 
once a day) 
Electronic data capture 
(EDC) 
Electronic data capture (EDC) is the electronic acquisition of clinical study 
data using data collection systems, such as Web-based applications, 
interactive voice response systems and clinical laboratory interfaces. EDC 
includes the use of Electronic Case Report Forms (eCRFs) which are used 
to capture data transcribed from paper source forms used at the point of 
care. 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last patient.  
Enrollment 
Point/time of patient entry into the study at which informed consent must be 
obtained  
Investigational 
drug/treatment 
The drug whose properties are being tested in the study 
Medication number 
A unique identifier on the label of medication kits 
Patient 
An individual with the condition of interest for the study. 
Period 
The subdivisions of the trial design (e.g. screening, treatment, follow-up) 
which are described in the Protocol. Periods define the study phases and 
will be used in clinical trial database setup and eventually in analysis. 
Personal data 
Patient information collected by the Investigator that is transferred to 
Novartis for the purpose of the clinical trial. This data includes patient 
identifier information, study information and biological samples. 
Premature patient 
withdrawal 
Point/time when the patient exits from the study prior to the planned 
completion of all study drug administration and/or assessments; at this time 
all study drug administration is discontinued and no further assessments 
are planned. 
Randomization number 
A unique identifier assigned to each randomized patient 
Run-in failure 
A patient who is screened but not randomized/treated after the run-in 
period (where run-in period requires adjustment to patient’s intervention or 
treatment). 
Screen failure 
A patient who did not meet one or more criteria that were required for 
participation in the study. 
Source data/document 
Source data refers to the initial record, document, or primary location from 
where data comes. The data source can be a database, a dataset, a 
spreadsheet or even hard-coded data, such as paper or eSource. 
Start of the clinical trial 
The start of the clinical trial is defined as the signature of the informed 
consent by the first patient. 


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


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Amendment 3 
Amendment rationale 
This protocol amendment is issued to  
  
 
 
 
 
 
 
 
 
 
Additionally, this protocol amendment includes the correction of typographical errors, 
formatting errors and editorial changes to increase clarity and consistency of the text. 
Consequently, changes were incorporated directly in the protocol with track changes, even if 
not listed specifically in this section. None of the changes described in this amended protocol 
are made due to newly emerged safety considerations. 
 
Changes to the protocol 
Changes to specific sections of the protocol are shown in track changes version of the 
protocol using strike through red font deletions and red underlined for insertions. 
A copy of this amended protocol will be sent to the Independent Ethics Committee (IEC) and 
Health Authorities (HA). 
The changes described in this amended protocol require IEC/HA approval prior to 
implementation. 
 


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Amendment 2 
Amendment rationale 
This protocol amendment is issued to  
1) add an extension phase to the current core phase to assess the effect of secukinumab 
after completed steroid tapering with regards to sustained remission, the potential 
steroid sparing effect, the potential vascular effect on imaging 
, 
quality of life, safety and tolerability up to Week 52. Blinded treatment will be given 
until Week 48 for final assessments in Week 52. Two Follow-up visits will be 
conducted in Weeks 56 and 60. In accordance with the current core phase, patients can 
enter the escape arm at any time in case of flare in order to receive additional 
prednisolone as per the investigator´s clinical judgement. 
2) add an additional secondary endpoint to assess the proportion of patients receiving 
prednisolone ≤ 5mg/day at Week 19, Week 28 and Week 52 
Changes to the protocol 
Changes to specific sections of the protocol are shown in track changes version of the 
protocol using strike through red font deletions and red underlined for insertions. 
The protocol amendment includes the correction of typographical and formatting errors and 
minor editorial changes for increased clarity of the text. Consequently, a small number of 
changes were implemented throughout the protocol. 
None of the changes described in this amended protocol are made due to newly emerged 
safety considerations. 
A copy of this amended protocol will be sent to the Independent Ethics Committee (IEC) and 
Health Authorities (HA). 
The changes described in this amended protocol require IEC/HA approval prior to 
implementation. 


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Amendment 1 
Amendment rationale  
This protocol amendment is issued for the following reasons: 
 
 
 
 
 
 
 
Changes to the protocol 
Changes to specific sections of the protocol are shown in the track changes version using 
strike through red font for deletions and red underlined for insertions. 
Additionally, this protocol amendment includes the correction of typographical errors, 
formatting errors and editorial changes to increase clarity and consistency of the text. 
Consequently, changes were incorporated directly in the protocol with track changes, even if 
not listed specifically in this section. 
None of the changes made are due to safety concern and none of the changes have an impact 
on the conduct of the trial or alter in any way the treatment of study subjects.  


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Protocol summary 
 
Protocol number 
CAIN457ADE11C 
Full title 
A randomized, parallel-group, double-blind, placebo-controlled, multicenter 
phase 2 trial to investigate the safety and efficacy of secukinumab (AIN457) 
in patients with giant cell arteritis (TitAIN) 
Brief title 
TitAIN 
Sponsor and 
Clinical phase 
Novartis Pharma GmbH/ 
Phase II 
Investigation type 
Biological 
Study type 
Interventional 
Purpose and rationale 
This randomized, placebo-controlled, multicenter, Phase II trial in patients 
with newly diagnosed or relapsing giant cell arteritis (GCA) is proposed in 
order to investigate the potential effects of secukinumab in GCA. To date, 
no information on the safety and efficacy of secukinumab in GCA has been 
reported in a clinical trial setting. Secukinumab is a selective high-affinity 
fully human monoclonal antibody that neutralizes interleukin 17A ( IL-
17A) and is approved in adults in more than 70 countries for the following 
indications:  moderate to severe plaque psoriasis, active psoriatic arthritis 
(PsA), and active ankylosing spondylitis (AS). Approval for these 
indications was obtained in Europe in 2015. Secukinumab has shown 
significant improvements of signs and symptoms of these IL-17A driven 
diseases and provided a very favorable safety profile (of over 5 years) in 
these indications. Therefore, IL-17A inhibition with secukinumab could be a 
new potent and safe treatment option for patients suffering from GCA. 
Primary objective 
The primary objective is to evaluate the efficacy of secukinumab compared 
to placebo, in combination with a 26-week prednisolone taper regimen, 
based on the proportion of patients with GCA who have sustained 
remission until Week 28 
• Definition of remission: absence of flare.  
• Definition of sustained remission: patients without flare until 
Week 28 and in adherence to the protocol prednisolone taper 
regimen. 
• Definition of flare: determined by the investigator and defined as 
the recurrence after remission of signs or symptoms of GCA 
and/or erythrocyte sedimentation rate (ESR) ≥ 30 mm/hr and/or 
CRP ≥ 10 mg/L attributable to GCA. 
Secondary objectives 
The secondary objectives are as follows: 
• 
To evaluate the efficacy of secukinumab in combination with a 26-week 
prednisolone taper regimen versus placebo in patients with GCA, 
measured by the following: 
• Remission rate at Week 12 
• Time to first flare after remission 
• Cumulative corticosteroid dose up to Week 28 and up to Week 52 
• Patients in sustained remission up to Week 52 


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- 
Definition of remission: absence of flare.  
- 
Definition of sustained remission: patients without flare until 
Week 52 and in adherence to the protocol prednisolone taper 
regimen + prednisolone-free phase from Week 27 onwards. 
- 
Definition of flare: determined by the investigator and defined 
as the recurrence after remission of signs or symptoms of GCA 
and/or erythrocyte sedimentation rate (ESR) ≥ 30 mm/hr and/or 
CRP ≥ 10 mg/L attributable to GCA. 
• Proportion of patients on prednisolone dose ≤ 5mg/day at Week 
19/ Week 28 / Week 52 
• Changes from baseline in disease activity and quality of life 
measures at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 for each 
of the following: 
• 
Physician’s global assessment (PhGA) visual analog scale 
(VAS) 
• 
Patient reported outcomes (PROs): 
• Patient global assessment (PGA) VAS 
• Functional Assessment of Chronic Illness Therapy Fatigue 
(FACIT-Fatigue) 
• Short form 36 (SF36) 
• EuroQoL 5D (EQ-5D) 
• 
Laboratory parameters (Baseline vs. Week 4, 8, 12, 16, 20, 24, 28, 32, 
36, 40, 44, 48 and 52): 
• 
CRP 
• 
ESR 
• 
To evaluate the safety/ tolerability and immunogenicity of secukinumab 
in patients with newly diagnosed or relapsing GCA. 
Study design 
This 
randomized, 
parallel-group, 
double-blind, 
placebo-controlled, 
multicenter, Phase II study is designed to evaluate the efficacy and safety 
of secukinumab compared to placebo in combination with a 26-week 
prednisolone taper regimen in terms of sustained remission in patients with 
newly diagnosed or relapsing GCA who are naïve to biological therapy. 
The study will consist of a maximum 6-week screening period, a 52-week 
treatment period and a 8-week safety follow-up period. 


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At Baseline, patients will be assigned to one of the following 2 arms in a 1:1 
ratio: 
• 
Group 1: secukinumab 300 mg s.c. + 26-week prednisolone taper 
regimen 
• 
Group 2: placebo s.c. + 26-week prednisolone taper regimen 
Patients who do not achieve remission by Week 12, experience a flare after 
remission or cannot adhere to the prednisolone taper regimen will enter 
“escape”. Upon entering “escape”, patients will receive prednisolone at a 
dose determined by the investigator’s clinical judgment and will continue to 
receive secukinumab or placebo in a blinded manner. Patients in “escape” 
should continue to attend all subsequent scheduled visit assessments. 
Population 
The study population will consist of 50 patients diagnosed with GCA (in 
accordance with inclusion criterion no. 4) and fulfilling all other entry 
criteria. Both patients with new onset GCA (diagnosed within 6 weeks of 
Baseline) and those with relapsing disease (diagnosed > 6 weeks of 
Baseline) will be included. Enrollment of patients with relapsing GCA will be 
preferentially limited to 50% but may be increased depending on the rate of 
enrollment of new-onset versus relapsing patients.  
Inclusion criteria 
Patients eligible for inclusion in this study must meet all of the following 
criteria: 
1. Signed informed consent must be obtained prior to participation in 
the study. 
2. Patient must be able to understand and communicate with the 
investigator and comply with the requirements of the study. 
3. Male or non-pregnant, non-lactating female patients at least 
50 years of age. 
4. Diagnosis of GCA classified according to the following criteria: 
• 
Age at onset of disease ≥ 50 years. 
• 
History of ESR ≥ 30 mm/hr or CRP ≥ 10 mg/L. 
• 
Unequivocal cranial symptoms of GCA (new-onset localized 
headache, scalp or temporal artery tenderness, ischemia-
related vision loss, or otherwise unexplained mouth or jaw 
pain upon mastication) AND/OR symptoms of polymyalgia 
rheumatica (PMR) defined as shoulder and/or hip girdle 
pain associated with inflammatory morning stiffness. 
• 
Temporal artery biopsy revealing features of GCA AND/OR 
evidence of large-vessel vasculitis by angiography or cross-
sectional imaging study such as magnetic resonance 
angiography (MRA), computed tomography angiography (CTA), 
positron emission tomography-computed tomography 
(PET-CT), or ultrasound. 
5. Patients with new onset GCA or relapsing GCA: 
• 
Definition new onset: diagnosis of GCA within 6 weeks of 
Baseline Visit. 
• 
Definition relapsing GCA: diagnosis of GCA (in accordance 
with inclusion criterion no. 4) > 6 weeks before Baseline Visit 
and in the meantime achieved remission (absence of signs 
and symptoms attributable to GCA and normalization of ESR 
(< 30 mm/hr) and CRP (<10.0mg/L) included) including 
previous treatment with ≥ 25 mg/day prednisolone equivalent 


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for ≥ 2 weeks.  
6. Active disease as defined by the presence of signs and symptoms 
of GCA (cranial or PMR) and elevated ESR ≥ 30 mm/hr, or 
CRP ≥ 10 mg/L, attributed to active GCA within 6 weeks of 
Baseline. 
7. Prednisolone dose of 25-60 mg/day at Baseline. 
8. Patients taking methotrexate (MTX) ≤ 25 mg/week are allowed to 
continue their medication provided they have taken it for at least 3 
months and are on a stable dose for at least 4 weeks prior to 
randomization and if they are on a stable folic acid treatment 
before randomization. 
Exclusion criteria 
Patients who fulfill any of the following criteria are not eligible for inclusion 
in this study: 
1. Pregnant or nursing (lactating) women where pregnancy is defined 
as the state of a female after conception and until the termination 
of gestation, confirmed by a positive human chorionic gonadotropin 
(hCG) laboratory test. 
2. Women of childbearing potential, defined as all women 
physiologically capable of becoming pregnant, unless they are 
using effective methods of contraception during dosing of study 
treatment and for a minimum of 20 weeks after the last dose of 
secukinumab. Effective contraception methods include: 
• 
Total abstinence (when this is in line with the preferred and 
usual lifestyle of the patient. Periodic abstinence (e.g. 
calendar, ovulation, symptothermal, post-ovulation methods) 
and withdrawal are not acceptable methods of contraception. 
• 
Female sterilization (have had surgical bilateral 
oophorectomy with or without hysterectomy), total 
hysterectomy or tubal ligation at least 6 weeks before taking 
investigational drug. In case of oophorectomy alone, only 
when the reproductive status of the woman has been 
confirmed by follow-up hormone level assessment. 
• 
Male sterilization (at least 6 months prior to screening). For 
female patients on the study, the vasectomized male partner 
should be the sole partner for that patient. 
• 
Barrier methods of contraception: condom or occlusive cap 
(diaphragm or cervical/vault caps).  
• 
Use of oral, (estrogen and progesterone), injected or 
implanted hormonal methods of contraception or other 
forms of hormonal contraception that have comparable 
efficacy. 
Women are considered post-menopausal and not of child bearing 
potential if they have had at least 12 months of natural 
(spontaneous) amenorrhea with an appropriate clinical profile 
(e.g. age appropriate, history of vasomotor symptoms) or have 
had surgical bilateral oophorectomy (with or without 
hysterectomy), total hysterectomy or tubal ligation at least 6 
weeks ago. In the case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by follow 
up hormone level assessment is she considered not of child 
bearing potential. 
3. Previous exposure to secukinumab or other biologic drug directly 


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targeting IL-17 or IL-17 receptor. 
4. Patients treated with any cell-depleting therapies including but not 
limited to anti-CD20 or investigational agents (e.g. anti-CD3, anti-
CD4, anti-CD5 or anti-CD19). 
5. Patients who have previously been treated with any biologic agent 
including but not limited to tocilizumab, sirukumab, abatacept, or 
tumor necrosis factor alpha (TNFα) inhibitors (infliximab, 
adalimumab, etanercept, certolizumab, golimumab). 
6. Patients who have previously been treated with tofacitinib or 
baricitinib. 
7. Patients treated with i.v. immunoglobulins or plasmapheresis within 
8 weeks prior to Baseline. 
8. Patients treated with cyclophosphamide, tacrolimus or everolimus 
within 6 months prior to Baseline. 
9. Patients treated with hydroxychloroquine, cyclosporine A, 
azathioprine, sulfasalazine or mycophenolate mofetil within 4 
weeks of Baseline. 
10. Patients treated with leflunomide within 8 weeks of Baseline unless 
a cholestyramine washout has been performed in which case the 
patient must be treated within 4 weeks of Baseline. 
11. Patients treated with an alkylating agent except for 
cyclophosphamide as mentioned above. 
12. Patients requiring systemic chronic glucocorticoid therapy for any 
other reason than GCA. 
13. Chronic systemic glucocorticoid therapy over the last 4 years or 
longer; or inability, in the opinion of the investigator, to withdraw 
glucocorticoid therapy through protocol-defined taper regimen due 
to suspected or established adrenal insufficiency. 
14. Patients requiring chronic (i.e. not occasional “prn”) high potency 
opioid analgesics for pain management. 
15. Patients treated with any investigational agent within 4 weeks or 
within 5 half-lives of the drug (whichever is longer) prior to 
Baseline. 
16. Contraindication or hypersensitivity to secukinumab. 
17. Active ongoing inflammatory diseases other than GCA that might 
confound the evaluation of the benefit of secukinumab therapy. 
18. Active ongoing inflammatory diseases or underlying metabolic, 
hematologic, renal, hepatic, pulmonary, neurologic, endocrine, 
cardiac, infectious or gastrointestinal conditions, which in the 
opinion of the investigator immunocomprises the patient and/or 
places the patient at unacceptable risk for participation in an 
immunomodulatory therapy. 
19. Significant medical problems or diseases, including but not limited 
to the following: uncontrolled hypertension (≥ 160/95 mmHg), 
congestive heart failure (New York Heart Association (NYHA) 
status of class III or IV) and uncontrolled diabetes. 
20. History of clinically significant liver disease or liver injury as 
indicated by abnormal liver function tests (LFTs) such as aspartate 
aminotransferase (AST), alanine aminotransferase (ALT), alkaline 
phosphatase (ALP) or serum bilirubin. The investigator should be 
guided by the following criteria: 
a. Any single parameter may not exceed 2 x upper limit of 


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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 randomization, 
to rule out any possible laboratory error. 
b. If the total bilirubin concentration is increased above 2 x ULN, 
total bilirubin should be differentiated into the direct and 
indirect reacting bilirubin. 
21. History of renal trauma, glomerulonephritis, or patients with one 
kidney only, or a serum creatinine level exceeding 1.8 mg/dL 
(159.12 μmol/L).  
22. Screening total white blood cell (WBC) count < 3000/μL, or 
platelets < 100 000/μL or neutrophils < 1500/μL or hemoglobin 
< 8.3 g/dL (83 g/L).  
23. Active systemic infections during the last 2 weeks (exception: 
common cold) prior to randomization. 
24. Major ischemic event, unrelated to GCA, within 12 weeks of 
screening. 
25. Any major infection requiring oral antibiotic treatment within 
2 weeks prior to Baseline. 
26. Major surgery within 8 weeks prior to screening or planned major 
surgery within 12 months after randomization. 
27. 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 ≥ 5mm or according to local practice/guidelines), or 
a positive QuantiFERON TB-Plus test. Patients with a positive test 
may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that the patient has no 
evidence of active tuberculosis. If presence of latent tuberculosis is 
established then treatment according to local country guidelines 
must be initiated prior to randomization. 
28. Known infection with human immunodeficiency virus (HIV), 
hepatitis B or hepatitis C at screening or randomization. 
29. 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). 
30. Life vaccinations within 6 weeks prior to Baseline or planned 
vaccination during study participation until 12 weeks after last study 
treatment administration. 
31. Current severe progressive or uncontrolled disease which in the 
judgment of the clinical investigator renders the patient unsuitable 
for the trial. 
32. Inability or unwillingness to undergo repeated venipuncture 
(e.g. because of poor tolerability or lack of access to veins). 
33. 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. 
34. Donation or loss of 400 mL or more of blood within 8 weeks before 


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randomization. 
35. History or evidence of ongoing alcohol or drug abuse, within the 
last 6 months before randomization. 
No additional exclusions may be applied by the investigator, in order to 
ensure that the study population will be representative of all eligible 
patients. 
Study treatment 
Investigational drug: secukinumab 300 mg supplied in prefilled syringes 
(PFS) each containing 150 mg of secukinumab.  
Control: placebo supplied in PFS to match secukinumab dose 
Co-administered treatment: prednisolone tablets for tapered oral 
administration (taper regimen from a dose of 25 mg to 60 mg at Baseline to 
0 mg at Week 27. Prednisolone will be supplied as 1 mg, 5 mg, 10 mg, 20 
mg tablets. 
Efficacy assessments 
• 
GCA assessment (signs and symptoms) 
• 
PhGA 
• 
ESR 
• 
CRP 
• 
Patient reported outcomes:  
• PGA 
• EQ-5D 
• SF-36 
• FACIT-Fatigue 
Immunogenicity 
assessment 
Immunogenicity assessment of anti-AIN457 antibodies. 
Safety assessments 
• 
Physical examination 
• 
Vital signs 
• 
Laboratory parameters 
• 
Adverse events (AEs)/serious adverse events (SAEs) 
 
Data analysis 
The primary endpoint is the proportion of GCA patients who adhere to the 
prednisolone taper regimen and are in sustained remission until Week 28. 
The response rate of the comparable placebo-arm of the GIACTA study will 
be used as the prior distribution for the placebo response rate for the 
primary endpoint in this study. The prior distribution for the response rate 
on secukinumab will be a uniform Beta distribution. 
Posterior distributions for the estimate of the odds ratio, risk-ratio and risk 
difference will be derived by sampling from the posterior distributions of the 
response rates of secukinumab and placebo.  
Key words 
IL-17A, secukinumab, GCA, giant cell arteritis 


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1 
Introduction 
1.1 
Background 
Giant cell arteritis (GCA) is the most common form of primary systemic vasculitis in people 
over the age of 50 years (Koster et al 2016). GCA is an inflammatory chronic disease with a 
prevalence between 24 and 278 per 100,000 in the European Union (EU) and the United 
States of America (USA). Typical clinical manifestations of new-onset GCA related to the 
inflammation of large- and medium-sized arteries are new onset of headaches, jaw 
claudication, 
scalp 
tenderness, 
and 
visual 
disturbances. 
Characteristic 
systemic 
manifestations include fever, malaise, weight loss, and polymyalgia (Ness et al 2013). 
Ischemic anterior optic neuropathy resulting in irreversible visual loss is a common and feared 
symptom of GCA. Therefore, prompt and effective immunosuppressive treatment is 
crucial in GCA (Hoffmann et al 2002, Jover et al 2001).  
High dose glucocorticoids are the mainstay of GCA therapy and effectively reduce vascular 
inflammation (Salvarani et al 2004, Petri et al 2014). While glucocorticoids remain the 
mainstay of treatment, relapses are common and morbidity related to treatment frequently 
occurs (Koster et al 2016). High cumulative glucocorticoid doses have the major drawback of 
a high rate of adverse events (AEs) with more than 80% of patients suffering from serious 
adverse events (SAEs). High glucocorticoid sum doses are of major concern as they 
result in a substantial increase of infections, osteoporosis, and severe metabolic side 
effects. Furthermore, treatment failures occur in 
more than 50% of patients 
(Salvarani et al 2004, Petri et al 2014). There is an unmet need for immunosuppressive 
therapies that are able to induce long-term remission while avoiding the adverse effects of 
glucocorticoids (Koster et al 2016). 
Studies on anti-tumor necrosis factor alpha (TNFα) therapies and azathioprine have failed to 
demonstrate a consequential effect while results of studies on methotrexate as glucocorticoid-
sparing agents are conflicting (Petri et al 2014, De Silvia et al 1986, Hayat 2008). The 
GIACTA-trial (Stone et al 2017) showed that tocilizumab, an interleukin-6 receptor 
antagonist, (administered weekly or every other week) combined with a 26-week prednisolone 
taper was superior to either 26-week or 52-week prednisolone tapering plus placebo with 
regard to sustained glucocorticoid-free remission in patients with GCA. Nonetheless, there 
were some drawbacks regarding tocilizumab therapy in GCA patients which should be 
considered. The primary endpoint (sustained remission at Week 52) was achieved in 56% of 
patients in the group that received tocilizumab weekly and 53% of patients in the group that 
received tocilizumab every other week; therefore, almost half of patients did not achieve 
remission. Furthermore, high sensitivity CRP, which was chosen as part of the definition of 
remission in the GIACTA trial, is not reliable as an inflammation marker (for indicating 
disease relapses or infectious complications) in GCA patients treated with tocilizumab as CRP 
is suppressed under tocilizumab therapy. Moreover, a magnetic resonance imaging (MRI) 
follow-up of the phase II study by Reichenbach et al (2018) on the use of tocilizumab in 
GCA showed persistent large vessels contrast-media enhancement, which indicates ongoing 
large-vessel inflammation. Thus additional treatment alternatives besides glucocorticoids and 
tocilizumab are needed in GCA. 


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The cause of GCA has still not been clearly identified but it is thought that GCA occurs 
based on a genetic background and is triggered by unknown environmental factors that 
can activate and lead to maturation of dendritic cells localized in the adventitia of normal 
arteries. Activated dendritic cells then lead to the activation, proliferation and polarization of 
Th1 and Th17 cells, which produce interferon-gamma and interleukin 17 (IL-17), 
respectively (Samson et al 2017). Interleukin 17A (IL-17A) seems to be implicated in the 
pathogenesis of GCA; increased IL-17A expression in temporal artery lesions is a predictor 
of sustained response to glucocorticoid treatment in patients with GCA (Espigol-Frigole et 
al 2013, Samson et al 2012). Recent evidence suggests that there is heterogeneity of 
histological lesions in GCA, which is correlated with Th9 and especially Th17 (Ciccia et al 
2017). Marquez et al found a novel association between polymorphisms within the IL-17A 
locus and GCA that supports the relevant role of Th17 cells in this vasculitis 
pathophysiology (Marquez et al 2014). Another study shows hyperproliferation of regulatory 
T-cells that overexpress the FoxP3∆2 domain, lacking the ∆2. The dysfunctional FoxP3∆2 
domain is known to contribute to an enhanced Th17 differentiation and therefore IL-17A 
overproduction. In line with that observation, IL-17A is upregulated in active GCA patients of 
that study. The IL-6 receptor antagonist tocilizumab is able to reestablish the functional 
FoxP3 domain in regulatory T-cells leading to less IL-17A production and effective control of 
GCA. This observation implicates IL-17A to be an important cytokine in active GCA and its 
direct inhibition to be a new therapeutic target for patients suffering from active disease. 
(Miyabe et al 2017).  
Secukinumab is a selective high-affinity fully human monoclonal antibody that neutralizes 
IL-17A and is approved in more than 70 countries for the following indications: 1) Moderate 
to severe plaque psoriasis in adult patients, including pustular psoriasis (Japan only); 2) adults 
with active psoriatic arthritis (PsA); 3) adults with active ankylosing spondylitis (AS). 
Approval for these indications was obtained in Europe in 2015. Two case reports of patients 
suffering from GCA and PsA in remission (either glucocorticoid-free remission or low-dose 
glucocorticoid remission) after treatment with secukinumab strengthens the idea of IL-17A 
inhibition to be the new mode of action in the treatment of GCA (Rotar et al 2018, Sammut et 
al 2018).  
This randomized, placebo-controlled, multicenter, Phase II trial in patients with newly 
diagnosed or relapsing GCA is proposed in order to investigate the potential effects of 
secukinumab in GCA. To date, no information on the safety and efficacy of secukinumab in 
GCA has been reported in a clinical trial setting. Nonetheless, as of 25-Jun-2017, over 28000 
patients with chronic inflammatory diseases, such as psoriasis, PsA and AS have been 
enrolled in studies with secukinumab with over 25000 having received active drug at doses 
ranging from single and/or multiple doses of 0.1 mg/kg to 30 mg/kg i.v. and 25 mg to 300 mg 
s.c.. Secukinumab has shown significant improvements in the signs and symptoms of these 
IL17A-driven diseases and provided a very favorable safety profile (of over 5 years) in these 
indications. Therefore, IL-17A inhibition with secukinumab could be a new potent and safe 
treatment option for patients suffering from GCA. 


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1.2 
Purpose 
The purpose of this study is to evaluate the efficacy and safety of secukinumab treatment in 
adults with newly diagnosed or relapsing GCA who are naïve to biologic therapies in a 
double-blind placebo-controlled trial. The study will evaluate the effect of secukinumab 
treatment to maintain disease remission up to 28 weeks including corticosteroid (i.e. 
prednisolone) tapering, as well as up to 1 year (52 weeks). 
2 
Study objectives and endpoints 
2.1 
Objectives and related endpoints 
Table 2-1 
Objectives and related endpoints 
Objectives 
Endpoints 
Primary objective 
Endpoint for primary objective 
• 
To evaluate the efficacy of secukinumab 
compared to placebo, in combination with a 
26-week prednisolone taper regimen, based on 
the proportion of patients with GCA who have 
sustained remission. 
• 
Definition of remission: Absence of flare.  
• 
Definition of sustained remission: patients 
without flare until Week 28 and in 
adherence to the protocol prednisolone 
taper regimen. 
• 
Definition of flare: Determined by the 
investigator and defined as the recurrence 
after remission of signs or symptoms of 
GCA and/or ESR ≥ 30 mm/hr and/or CRP 
≥ 10 mg/L attributable to GCA.  
• 
Proportion of GCA patients in sustained 
remission at Week 28. 
Secondary objectives: 
Endpoint for secondary objectives: 
• 
To evaluate the efficacy of secukinumab in 
combination with a 26-week prednisolone taper 
regimen versus placebo in patients with GCA, 
measured by the following: 
 
• 
Remission rate at Week 12 
• 
Remission rate at Week 12 
• 
Time to first flare after remission 
• 
Time to first GCA flare after clinical 
remission (up to Week 52) 
• 
Cumulative corticosteroid dose up to Week 28 
and up to Week 52 
• 
Proportion of patients with GCA who have 
sustained remission  
- 
Definition of remission: absence of flare.  
- 
Definition of sustained remission: patients 
without flare until Week 52 and in 
adherence to the protocol prednisolone 
taper regimen + prednisolone-free phase 
from Week 27 onwards. 
• 
Total cumulative prednisolone dose over 28 
weeks and 52 weeks 
• 
Proportion of GCA patients in sustained 
remission at Week 52 
 
 
 
 
 


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Objectives 
Endpoints 
- 
Definition of flare: determined by the 
investigator and defined as the recurrence 
after remission of signs or symptoms of 
GCA and/or erythrocyte sedimentation rate 
(ESR) ≥ 30 mm/hr and/or CRP ≥ 10 mg/L 
attributable to GCA. 
• 
Proportion of patients on prednisolone 
dose ≤ 5mg/day at Week 19/ Week 28 / 
Week 52 
 
 
 
 
 
 
 
 
• 
Proportion of patients on prednisolone dose 
≤ 5mg/day at Week 19, Week 28 and Week 
52 
• Changes from baseline in disease activity 
and quality of life measures at Week 4, 8, 
12, 16, 20, 24, 28, 36, 44 and 52 for each 
of the following: 
• 
Changes from Baseline in disease activity 
and quality of life measures at Week 4, 8, 
12, 16, 20, 24, 28, 36, 44 and 52 for each of 
the following: 
• 
PhGA, VAS 
• 
PhGA, VAS 
 
 
• 
PROs: 
• 
PROs: 
• PGA, VAS 
• FACIT-Fatigue 
• SF36 
• EQ-5D 
• 
PGA, VAS 
• 
FACIT-Fatigue 
• 
SF-36 
• 
EQ-5D 
• 
Laboratory parameters  
(Baseline vs. Week 28 and 52): 
• 
CRP 
• 
ESR 
• 
Change from Baseline in CRP and ESR at 
Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 
44, 48 and 52 
• 
To evaluate the safety/ tolerability and 
immunogenicity of secukinumab in patients 
with newly diagnosed or relapsing GCA. 
• 
Safety and tolerability assessments over 
time: incidence and severity of AEs and 
SAEs; routine safety laboratory parameters  
 


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CRP=C-reactive protein, ESR=erythrocyte sedimentation rate, EQ-5D=EuroQoL 5D, GCA=giant cell 
arteritis, 
 FACIT-Fatigue=Functional Assessment of Chronic Illness 
Therapy Fatigue, 
 PhGA=physician’s global assessment, 
 PGA=patient’s global assessment, 
SF-36=short form 
36, VAS=visual analog scale 
3 
Investigational plan 
3.1 
Study design 
This randomized, parallel-group, double-blind, placebo-controlled, multicenter, Phase II study 
is designed to evaluate the efficacy of secukinumab compared to placebo in combination with 
a 26-week prednisolone taper regimen in terms of sustained remission in patients with newly 
diagnosed or relapsing GCA who are naïve to biological therapy. 
The study will consist of 6-week (maximum duration) screening period, a 52-week treatment 
period and a 8-week safety follow-up period (Figure 3-1). Patients who do not achieve 
remission by Week 12, experience a flare after remission or cannot adhere (as described 
below) to the prednisolone taper regimen will enter “escape”. Upon entering “escape”, 
patients will receive prednisolone at a dose determined by the physician’s clinical judgment 
and continue to receive secukinumab or placebo in a blinded manner. Patients in “escape” 
should continue to attend all subsequent scheduled visit assessments.  
Patients who have received an additional corticosteroid as stated in the taper regimen will be 
considered as not having adhered to the protocol-defined prednisolone taper regimen. Patients 
not adhering to the prednisolone taper will be classified as non-responders in the primary 
analysis, regardless of their status of sustained remission. Patients receiving less than the full 
amount of prednisolone as required by the taper (due to missing tablets) will not be classified 
as non-responders, unless other non-response criteria are fulfilled.  
Screening period: During the screening period, patients may receive glucocorticoids for the 
treatment of GCA at the discretion of the investigator. By the end of the screening period 
patients should be able to switch to the Sponsor-provided prednisolone in order to follow 
the protocol-defined prednisolone tapering regimens. 
Randomization: Patients will be assigned to one of the following 2 arms in a 1:1 ratio: 
• Group 1: secukinumab 300 mg s.c. + 26-week prednisolone taper regimen 
• Group 2: placebo s.c. + 26-week prednisolone taper regimen 
Patients will receive secukinumab/placebo at Baseline, Week 1, 2, 3, 4, then every 4 weeks 
thereafter through to Week 48 (last dose) at the study center. Assessments will be performed 
in accordance to the study schedule. Patients in both groups will follow the protocol-defined 
prednisolone taper regimen. 


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At every visit, each patient’s disease activity and condition will be assessed in order to 
determine whether the patient can adhere to the defined prednisolone taper regimen 
(open-label fashion). If they cannot adhere to the taper regimen or are experiencing a 
flare (definition above), they must enter the “escape” arm and receive prednisolone at a 
dose determined by the physician based on clinical need and will continue to receive 
secukinumab 300 mg or placebo s.c. (still blinded). 
Safety evaluation will be included in all visits including two safety follow-up visits 
performed 8 and 12 weeks after the last study drug administration at Week 48 (this will be 
at Week 56 and Week 60 for patients completing the study according to the protocol). 
Figure 3-1 
Study design 
 
 
3.2 
Rationale for study design 
A randomized, parallel-group, double-blind, placebo-controlled trial design is considered 
appropriate for determining the effectiveness of secukinumab (combined with prednisolone 
tapering) in a new indication (i.e. GCA). This design is aligned with the design of the 
GIACTA trial (Stone et al 2017), which demonstrated the efficacy and safety of another 
humanized monoclonal antibody (i.e. tocilizumab) in combination with prednisone tapering 
for the treatment of patients with GCA. In addition, it is closely aligned with the design of 
Phase II clinical trials in the clinical development program for secukinumab for other chronic 
inflammatory diseases.  
Patients with newly diagnosed or relapsing GCA who are naïve to biological therapy and who 
are already receiving prednisolone (at a dose of 25-60 mg/day) are considered to be an 
appropriate patient population for assessing the effectiveness of secukinumab compared with 
placebo in GCA. It is expected that this population will achieve a good response to first-time 
biological therapy with secukinumab based on the role of IL-17A in the pathogenesis of GCA, 


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and the proven efficacy and safety of secukinumab for the treatment of a variety of other 
chronic inflammatory diseases (through the inhibition of IL-17A) as described in Section 1.1. 
Two case reports of patients suffering from GCA and PsA in remission (either 
glucocorticoid-free remission or low-dose glucocorticoid remission) after treatment with 
secukinumab strengthens the idea of IL-17A inhibition being a new mode of action in the 
treatment of GCA (Rotar et al 2018, Sammut et al 2018).  
3.2.1 
Rationale for choice of background therapy 
High-dose corticosteroid therapy is the mainstay of treatment for GCA; however, additional 
treatments that would effectively reduce the dose and duration of corticosteroid therapy are 
needed, thus avoiding the associated long-term toxicity and providing more durable remission 
of GCA. This study aims to show that secukinumab can enable patients with GCA to achieve 
and maintain disease control. A specific (i.e. prednisolone) taper regimen was selected for this 
study as a similar treatment strategy (i.e. with prednisone) proved to be effective in 
combination with another humanized monoclonal antibody (i.e. tocilizumab) for achieving 
sustained glucocorticoid-free remission in patients with GCA in the GIACTA-trial.  
In this phase-3 trial, the percentage of placebo patients in remission following the 26-week 
taper regimen vs. 52-week taper regimen was the same (14% vs. 18%). More AEs/SAEs were 
recorded in the placebo groups than in the tocilizumab groups with the highest numbers in the 
52-week taper regimen placebo group, which may have been the results of the effects of 
glucocorticoids. In the 26-week-taper regiment group, no ischemic events and in particular no 
cases of anterior ischemic optic neuropathy were reported. (Stone et al 2017) Due to the 
glucocorticoid-therapy-associated AEs and their substantial increase when it comes to long 
term treatment and thereby raised total glucocorticoid dose, efforts should be made to use the 
lowest doses of glucocorticoids for the shortest time possible when treating patients GCA 
(Proven et al 2003). Therefore, the 26-week corticosteroid (i.e. prednisolone) taper regimen, 
with a low-stringency escape strategy, was selected for this study.  
In addition, a corticosteroid tapering strategy is in line with EULAR recommendations for the 
management of GCA (Mukhtyar et al 2009, Ponte et al 2015).  
The 26-week corticosteroid (i.e. prednisolone) taper is considered long enough to avoid risk 
of uncontrolled disease in patients. The risk of uncontrolled disease is mitigated further by the 
low-stringency escape criteria (i.e. any patient with active disease or flare will be allowed to 
receive escape treatment with prednisolone). Patients who do not achieve remission until 
Week 12, cannot adhere to the taper regimen, or have recurrent disease will be able to adjust 
their corticosteroid dose to control disease activity and will no longer follow a protocol-
defined taper regimen. 
The 26-week prednisolone taper regimen will be administered to all patients in this study, i.e. 
in parallel with secukinumab injections in the investigational treatment group, and in parallel 
with placebo injections in the control group, unless they escape. This will allowing a 
comparison of the efficacy and safety of secukinumab compared to placebo in patients with 
GCA under controlled corticosteroid conditions. 


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3.3 
Rationale for dose/regimen, route of administration and duration 
of treatment 
The dose/regimen, route of administration and duration of secukinumab treatment 
(i.e. 300 mg s.c. with initial dosing at Week 0 (Baseline), 1, 2, 3, and 4, followed by 4-weekly 
maintenance dosing) has been selected based on its proven effectiveness and safety with 
approved chronic inflammatory diseases. Secukinumab 300 mg s.c. is the approved dose for 
moderate to severe plaque psoriasis, and for patients with PsA who are anti-TNF-alpha 
inadequate responders or who have concomitant moderate to severe plaque psoriasis. 
Secukimumab 150 mg is also approved for the treatment of other patients with PsA (i.e. those 
not meeting 300 mg dose requirements) and for patients with AS.   
The Phase III studies in patients with active PsA (CAIN457F2306 and CAIN457F2312) 
demonstrated the superior efficacy of secukinumab 150 mg s.c. and 300 mg s.c. 
(CAIN457F2312 only) regimens over placebo. Secukinumab 150 mg s.c. and 300 mg s.c. 
regimens had a rapid onset of response and showed significant and clinically meaningful 
efficacy compared with placebo on the primary endpoint and several secondary endpoints.  
While secukinumab 150 mg and 300 mg regimens are both more efficacious than placebo, the 
300 mg regimen provided the greatest efficacy across multiple PsA domains in tumor necrosis 
factor-α inhibitor (TNF) incomplete responder (TNF-IR) patients and showed higher efficacy 
on skin endpoints and physical function as measured by HAQ-DI in both TNF-naïve patients 
and TNF-IR patients. Evidence of dose response was shown in TNF-IR patients favoring 
secukinumab 300 mg over 150 mg at the Week 24 efficacy endpoint used for the primary and 
secondary efficacy analyzes of CAIN457F2312 study. Indeed, ACR20/50/70 response rates at 
Week 24 in TNF-IR patients were higher with secukinumab 300 mg compared to 150 mg 
(45.5% vs 29.7%, 27.3% vs 18.9% and 15.2% vs 10.8% respectively). This trend was 
maintained up to Week 52. 
Furthermore, secukinumab 300 mg was more efficacious than 150 mg in achieving 
clinically meaningful improvements in skin disease, particularly with respect to clear/almost 
clear skin (PASI 90, IGA mod 2011 0/1) in patients with moderate to severe psoriasis (defined 
as ≥ 10% BSA). There was a clear dose response favoring secukinumab 300 mg in the higher 
thresholds of skin clearance. The difference between 300 mg and 150 mg secukinumab 
regimens was more pronounced in the more difficult-to-achieve PASI 90 and IGA mod 2011 
0/1 endpoints, with 21.9% and 27.4% more patients with ≥ 10% BSA compared to 8.2% and 
3.3% more patients with < 10 % BSA reaching PASI 90 and IGA mod 2011 0/1 responses, 
respectively, at Week 24. Therefore, secukinumab 300 mg afforded greater improvement in 
plaque psoriasis than 150 mg, particularly in the achievement of clear/almost clear skin, in 
patients with moderate to severe psoriasis (≥ 10% body surface area). 
Two case reports of patients suffering from GCA and PsA in remission (either 
glucocorticoid-free remission or low-dose glucocorticoid remission) after treatment with 
secukinumab strengthens the idea of IL-17A inhibition to be a new mode of action in the 
treatment of GCA (Rotar et al 2018, Sammut et al 2018).  
In addition, pertaining to safety assessment, there were no clinically meaningful differences 
among the secukinumab doses of 300 mg and 150 mg in the exposure adjusted incidences 
rates of the key risks over the entire treatment period in the 2 Phase III trials in PsA patients. 


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The overall safety in the PsA population was consistent with prior extensive experience in 
psoriasis, and showed that secukinumab 300 mg and 150 mg are acceptable for chronic use in 
adult patients with active PsA. 
For the primary analysis,  a treatment duration of 24 weeks was selected for this study. This is 
shorter than the 52-week treatment duration in the GiACTA trial (Stone et al 2017); however, 
most flares occurred within the first 6 months in the GiACTA trial. Therefore, the time point 
for primary analysis is at Week 28, to evaluate the effect of secukinumab in patients are on 
study treatment or placebo for 24 weeks. Assessments for the primary analysis will be 
conducted at Week 28, 2 weeks after last prednisolone dose in Week 26. 
Secondary endpoints address both assessments at Week 28, after 24 weeks of treatment 
including a 26-week-prednisolone taper and also assessments at Week 52, after a total of 48 
weeks of treatment, without concomitant prednisolone from Week 27 onwards. 
From Week 27 up to Week 52, it will be assessed whether secukinumab is effective to provide 
sustained remission, decreased vessel involvement (assessed by imaging) and improved 
quality of life without concomitant prednisolone.  Patients will receive double-blind treatment 
consisting of two injections per time point up to Week 48, final efficacy assessments will be 
performed at Week 52. 
Regular assessments ensure that the patients who may experience a flare in any of the 
treatment groups can enter the escape arm in order to receive prednisolone based on the 
investigator´s clinical judgement. 
The 8-week follow-up period after the end of study treatment is included to generate follow–
up data for potential relapse and to have treatment safety follow-up data in the GCA 
indication. The 26-week prednisolone taper regimen was selected as this proved to be 
sufficiently effective in combination with tocilizumab for achieving sustained glucocorticoid-
free remission in patients with GCA in the GIACTA-trial (Stone et al 2017). Pivotal Phase III 
trials of secukinumab in other chronic inflammatory diseases (e.g. psoriasis, PsA) have 
demonstrated peak efficacy (i.e. remission of disease) at Week 12, which has been sustained 
until Week 24. In this Phase II trial, those patients who do not achieve remission at Week 12 
will be entered into an “escape” treatment arm where they will continue to receive 
secukinumab or placebo in a blinded fashion but their prednisolone treatment may be adjusted 
by the investigator based on their clinical needs.  
3.4 
Rationale for choice of comparator 
A placebo arm is included in this study because it is not known whether secukinumab can 
improve GCA. However, standard of care with corticosteroids (i.e. prednisolone as 
described in Section 3.2.1 will be given to both treatment groups throughout the study. Due 
to the nature of the disease and the outcome measures used, a placebo arm is necessary to 
obtain reliable efficacy measurements, to judge the size of the active treatment compared 
to change over time in the placebo group, and to reasonably attribute AEs to 
secukinumab.  
3.5 
Purpose and timing of interim analyses/design adaptations  
Three interim analyses will be conducted after  


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• 50% of patients complete Week 28  
• 50% of patients complete Week 52 
• 100% of patients complete Week 28 
to receive preliminary results whether secukinumab is effective in GCA and to support 
Phase III program activities.  
The final analysis will be conducted after all subjects complete the study at Week 60. All 
available data from all patients will be analyzed and summarized in one final CSR. 
 
3.6 
Risks and benefits 
As of 25-Jun-2017, over 28000 subjects have been enrolled in clinical studies with 
secukinumab with over 25000 healthy volunteers and patients having received active drug. 
In an analysis of completed, unblinded/open label trials and trials analyzed up to the primary 
efficacy endpoint, (not including blinded trials or trials with healthy volunteers) a total of 
9632 patients were treated with secukinumab. Of these, 6319 patients were exposed for at 
least 1 year. Overall, 16134.63 patient-years of exposure to secukinumab are reported in 
this analysis. Overall, patients have received secukinumab across various indications 
(rheumatoid arthritis, AS, PsA, psoriasis, multiple sclerosis, uveitis, Crohn’s disease, dry 
eye, polymyalgia rheumatica) at doses ranging from single and multiple doses of 0.1 mg/kg 
to 30 mg/kg i.v. and 25 mg to 300 mg s.c. Full safety results from all PsA, AS and 
psoriasis completed studies show that secukinumab generally is safe and well tolerated. 
The safety profile observed in the latest DSUR (Issue 007: 26-Jun-2016 to 25-Jun-2017) is in 
line with the current known safety profile of secukinumab in moderate to severe psoriasis, 
PsA and AS.  
For all 3 indications, secukinumab has shown an imbalance vs. placebo in total AEs, which 
was driven by infections, mainly non-serious upper respiratory tract infections during the 
placebo-controlled epoch of the trials (12 to 16 weeks depending on the protocol). This 
imbalance was not translated into infection SAEs and there was also no difference between 
300 mg and 150 mg secukinumab in the overall rate of infections or in upper respiratory tract 
infections. In all indications, Candida infections were more frequent with secukinumab when 
compared to placebo and, in psoriasis trials, Candida infections were more common with the 
300 mg dose compared to the 150 mg secukinumab regimen. The imbalance between the 
doses was limited to non-serious, localized mucosal or cutaneous candidiasis, with no reports 
of chronic or systemic disease in any treatment group. Across indications, Candida infections 
were responsive to standard treatment and did not necessitate discontinuation. No serious 
opportunistic infections were reported. No tuberculosis reactivation or viral hepatitis 
reactivation were observed in clinical trials, regardless of indication (psoriasis, PsA or AS).  
Neutropenia was more frequently observed with secukinumab than with placebo, but most 
cases were mild, transient and reversible spontaneously. 


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The incidence of hypersensitivity AEs was slightly higher with secukinumab compared with 
placebo, with the difference mostly due to mild to moderate urticaria and eczema non-
associated with systemic symptoms. 
The incidence of selected rare events of interest (major adverse cardiovascular events 
(MACE) and malignancies) adjusted for exposure over 52 weeks was comparable to placebo 
in clinical trials across multiple indications. 
There was no clear association between treatment with secukinumab and new onset of 
inflammatory bowel disease, but due to the potential involvement of the IL -17A pathway in 
the pathogenesis of the disease, it is not possible to rule out a potential increased risk of 
exacerbation. 
Secukinumab 300 mg was comparable to 150 mg and both doses showed comparable safety to 
placebo and etanercept over 52 weeks of treatment.  
Infections, neutropenia and hypersensitivity are important identified risks, while 
malignancies, major adverse cardiovascular events, immunogenicity, Crohn’s disease, and 
hepatitis B reactivation are important potential risks. Interaction with live vaccines is an 
important potential interaction (and also included as an important potential risk).  
No new safety signal was identified and no actions were taken for safety reasons during the 
reporting period of the latest DSUR. 
It is anticipated that secukinumab will have beneficial effects for patients with GCA by 
inhibiting IL-17A-driven inflammation and thereby enabling patients to achieve and 
maintain remission. The placebo patients in the study will not have this benefit, however, 
they will be followed closely in order to identify any progress or need for additional therapy. 
The risk to patients in this trial will be minimized by compliance with the eligibility criteria, 
close clinical monitoring and extensive guidance to the investigators, provided in the current 
version of the Investigator’s Brochure (IB). 
Taking into account the individual risks, the expected risk profile of secukinumab from 
a mechanism of action perspective in GCA is anticipated to be similar to that of the 
approved indications. 
From the standpoint of the overall risk benefit assessment, the current trial with 
secukinumab is justified. 
Women of child bearing potential must be informed that taking the study treatment 
may involve unknown risks to the fetus if pregnancy were to occur during the study, and 
agree that in order to participate in the study they must adhere to the contraception 
requirements outlined in Section 4.2 (Exclusion criteria). If there is any question that the 
patient will not reliably comply, they should not be entered or continue in the study. 
4 
Population 
The study population will consist of 50 patients diagnosed with GCA (in accordance with 
inclusion criterion no. 4) and fulfilling all other entry criteria. Both patients with new onset 
GCA (diagnosed within 6 weeks of Baseline) and those who have relapsing disease 


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(diagnosed > 6 weeks before Baseline) will be included. Enrollment of patients with 
relapsing GCA will be preferentially limited to 50% but may be increased depending on the 
rate of enrollment of new-onset versus relapsing patients.  
4.1 
Inclusion criteria 
Patients eligible for inclusion in this study must meet all of the following criteria: 
1. Signed informed consent must be obtained prior to participation in the study. 
2. Patient must be able to understand and communicate with the investigator and comply 
with the requirements of the study. 
3. Male or non-pregnant, non-lactating female patients at least 50 years of age. 
4. Diagnosis of GCA classified according to the following criteria: 
• Age at onset of disease ≥ 50 years. 
• History of ESR ≥ 30 mm/hr or CRP ≥ 10 mg/L. 
• Unequivocal cranial symptoms of GCA (new-onset localized headache, scalp or 
temporal artery tenderness, ischemia-related vision loss, or otherwise unexplained 
mouth or jaw pain upon mastication) AND/OR symptoms of polymyalgia rheumatica 
(PMR defined as shoulder and/or hip girdle pain associated with inflammatory 
morning stiffness). 
• Temporal artery biopsy revealing features of GCA AND/OR evidence of large-vessel 
vasculitis by angiography or cross-sectional imaging study such as magnetic resonance 
angiography (MRA), computed tomography angiography (CTA), positron emission 
tomography-computed tomography (PET-CT), or ultrasound. 
5. Patients with new onset GCA or relapsing GCA: 
• Definition new onset: diagnosis of GCA within 6 weeks of Baseline Visit. 
• Definition relapsing GCA: diagnosis of GCA (in accordance with inclusion 
criterion no. 4) > 6 weeks before Baseline Visit and in the meantime achieved 
remission (absence of signs and symptoms attributable to GCA and normalization 
of ESR (< 30 mm/hr) and CRP (< 10.0 mg/L) included) including previous 
treatment with ≥ 25 mg/day prednisolone equivalent for ≥ 2 weeks.  
6. Active disease as defined by the presence of signs and symptoms of GCA (cranial or 
PMR) and elevated ESR ≥ 30 mm/hr, or CRP ≥ 10 mg/L, attributed to active GCA within 
6 weeks of Baseline. 
7. Prednisolone dose of 25-60 mg/day at Baseline. 
8. Patients taking MTX (≤ 25 mg/week) are allowed to continue their medication provided 
they have taken it for at least 3 months and are on a stable dose for at least 4 weeks prior 
to randomization and if they are on a stable folic acid treatment before randomization. 
4.2 
Exclusion criteria 
Patients who fulfill any of the following criteria are not eligible for inclusion in this study: 
1. Pregnant or nursing (lactating) women where pregnancy is defined as the state of a 
female after conception and until the termination of gestation, confirmed by a positive 
human chorionic gonadotropin (hCG) laboratory test. 


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2. Women of childbearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during 
dosing of study treatment and for a minimum of 20 weeks after the last dose of 
secukinumab. Effective contraception methods include: 
• Total abstinence (when this is in line with the preferred and usual lifestyle of the 
patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable methods of contraception. 
• Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy), total hysterectomy or tubal ligation at least 6 weeks before taking 
investigational drug. In case of oophorectomy alone, only when the reproductive 
status of the woman has been confirmed by follow-up hormone level assessment. 
• Male sterilization (at least 6 months prior to screening). For female patients on the 
study, the vasectomized male partner should be the sole partner for that patient 
• Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps).  
• Use of oral, (estrogen and progesterone), injected or implanted hormonal methods 
of contraception or other forms of hormonal contraception that have comparable 
efficacy. 
Women are considered post-menopausal and not of child bearing potential if they have 
had at least 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical 
bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal 
ligation at least 6 weeks ago. In the case of oophorectomy alone, only when the 
reproductive status of the woman has been confirmed by follow up hormone level 
assessment is she considered not of child bearing potential. 
3. Previous exposure to secukinumab or other biologic drug directly targeting IL-17 or IL-17 
receptor. 
4. Patients treated with any cell-depleting therapies including but not limited to anti-CD20 or 
investigational agents (e.g. anti-CD3, anti-CD4, anti-CD5 or anti-CD19). 
5. Patients who have previously been treated with any biologic agent including but not 
limited to tocilizumab, sirukumab, abatacept or TNFα inhibitors (infliximab, adalimumab, 
etanercept, certolizumab, golimumab). 
6. Patients who have previously been treated with tofacitinib or baricitinib. 
7. Patients treated with i.v. immunoglobulins or plasmapheresis within 8 weeks prior to 
Baseline. 
8. Patients treated with cyclophosphamide, tacrolimus or everolimus within 6 months prior 
to Baseline. 
9. Patients treated with hydroxychloroquine, cyclosporine A, azathioprine, sulfasalazine, 
mycophenolate mofetil within 4 weeks of Baseline. 
10. Patients treated with leflunomide within 8 weeks of Baseline unless a cholestyramine 
washout has been performed in which case the patient must be treated within 4 weeks of 
Baseline. 
11. Patients treated with an alkylating agent. 


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12. Patients requiring systemic chronic glucocorticoid therapy for any other reason than GCA. 
13. Chronic systemic glucocorticoid therapy over the last 4 years or longer, or inability, in the 
opinion of the investigator, to withdraw glucocorticoid therapy through protocol-defined 
taper regimen due to suspected or established adrenal insufficiency. 
14. Patients requiring chronic (i.e. not occasional “prn”) high potency opioid analgesics for 
pain management. 
15. Patients treated with any investigational agent within 4 weeks or within 5 half-lives of the 
drug (whichever is longer) prior to Baseline. 
16. Contraindication or hypersensitivity to secukinumab. 
17. Active ongoing inflammatory diseases other than GCA that might confound the evaluation 
of the benefit of secukinumab therapy. 
18. Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, 
hepatic, pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal 
conditions, which in the opinion of the investigator immunocomprises the patient and/or 
places the patient at unacceptable risk for participation in an immunomodulatory therapy. 
19. Significant medical problems or diseases, including but not limited to the following: 
uncontrolled hypertension (≥ 160/95 mmHg), congestive heart failure (New York Heart 
Association (NYHA) status of class III or IV) and uncontrolled diabetes. 
20. History of clinically significant liver disease or liver injury as indicated by abnormal liver 
function tests (LFTs) such as aspartate aminotransferase (AST), alanine aminotransferase 
(ALT), alkaline phosphatase or serum bilirubin. The investigator should be guided by the 
following criteria: 
a. Any single parameter may not exceed 2 x upper limit of normal (ULN). A single 
parameter elevated up to and including 2 x ULN should be re-checked once more as 
soon as possible and in all cases, at least prior to randomization, to rule out any 
possible laboratory error. 
b. If the total bilirubin concentration is increased above 2 x ULN, total bilirubin should 
be differentiated into the direct and indirect reacting bilirubin. 
21. History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum 
creatinine level exceeding 1.8 mg/dL (159.12 μmol/L). 
22. Screening total white blood cell (WBC) count < 3000/μL, or platelets < 100 000/μL or 
neutrophils < 1500/μL or hemoglobin < 8.3 g/dL (83 g/L). 
23. Active systemic infections during the last 2 weeks (exception: common cold) prior to 
randomization. 
24. Major ischemic event, unrelated to GCA, within 12 weeks of screening. 
25. Any major infection requiring oral antibiotic treatment within 2 weeks prior to Baseline. 
26. Major surgery within 8 weeks prior to screening or planned major surgery within 
12 months after randomization. 
27. 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 ≥ 5mm or according to local practice/guidelines), or a positive 
QuantiFERON TB-Plus test. Patients with a positive test may participate in the study if 


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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 be initiated prior to 
randomization. 
28. Known infection with human immunodeficiency virus (HIV), hepatitis B or hepatitis C at 
screening or randomization. 
29. 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). 
30. Life vaccinations within 6 weeks prior to Baseline or planned vaccination during study 
participation until 12 weeks after last study treatment administration. 
31. Current severe progressive or uncontrolled disease which in the judgment of the clinical 
investigator renders the patient unsuitable for the trial. 
32. Inability or unwillingness to undergo repeated venipuncture (e.g. because of poor 
tolerability or lack of access to veins). 
33. 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. 
34. Donation or loss of 400 mL or more of blood within 8 weeks before randomization. 
35. History or evidence of ongoing alcohol or drug abuse, within the last 6 months before 
randomization. 
No additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients. 
5 
Treatment 
5.1 
Study treatment 
5.1.1 
Investigational and control drugs 
An overview of study treatment is presented in Table 5-1. Patients will be given all 
secukinumab and placebo injections by the site staff on site. The PFSs are packed in a double-
blind fashion and do not need to be prepared. The study treatments will be labeled as follows: 
• Double-blind secukinumab and placebo PFSs will be labeled AIN457 150 mg/1ml/ 
Placebo for dosing up to and including Week 48. 
Patients will also receive open-label prednisolone tablets for tapered dosing from Baseline to 
Week 26. Patients will be given prednisolone tablets by the site staff on site at study site 
visits, and will be supplied with sufficient tablets for home administration between study 
visits.   
Table 5-1 
Overview of study treatment 
Study drug name 
Formulation 
Unit dose 
Packaging 
Provided by 


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Secukinumab 300 mg  
(2 injections of 150 mg) 
2 x 1 mL PFS 
1 mL  
(150 mg) 
Double-blind supply 
Novartis 
Placebo, 2 injections 
2 x 1 mL PFS 
 
Double-blind supply 
Novartis 
Prednisolone, (taper 
regimen from a dose of 
25 mg to 60 mg at 
Baseline to 1 mg at 
Week 26 [last dose]) 
Tablets for oral 
administration 
1 mg, 5 mg, 
10 mg, 
20 mg 
Open-label supply 
Novartis 
5.1.2 
Additional treatment 
Prednisolone will be administered alongside the investigational drug (secukinumab) and 
placebo in this trial as described in Section 5.1.2. No further additional treatment is included 
in this trial. 
5.2 
Treatment arms 
Patients will be assigned to one of the following 2 treatment arms in a 1:1 ratio, with 
approximately 25 patients per arm. 
• Group 1: Secukinumab 300 mg s.c. (2 x 150 mg) + 26-week prednisolone taper regimen 
• Group 2: Placebo s.c. (2 injections) + 26-week prednisolone taper regimen 
Patients will receive secukinumab or placebo at Week 0 (Baseline), Week 1, 2, 3, 4, then 
every 4 weeks thereafter through to Week 48 (last dose) at the study center.  
Patients will receive a daily dose of prednisolone, which will be decreased (i.e. tapered down) 
from Baseline to Week 26.  
Patients who do not achieve remission by Week 12, experience a flare after remission or 
cannot adhere to the prednisolone taper regimen will enter “escape”. Upon entering “escape”, 
patients will receive prednisolone at a dose determined by the physician’s clinical judgment 
and continue to receive secukinumab 300 mg s.c. in a double-blind manner. Patients in 
“escape” should continue to attend all subsequent scheduled visit assessments.  
Patients who have received an additional corticosteroid as stated in the taper regimen will be 
considered as not having adhered to the protocol-defined prednisolone taper regimen. Patients 
not adhering to the prednisolone taper will be classified as non-responders in the primary 
analysis, regardless of their status of sustained remission. Patients receiving less than the full 
amount of prednisolone as required by the taper (due to missing tablets) will not be classified 
as non-responders.  
5.3 
Treatment assignment and randomization 
At the randomization visit (Baseline) all eligible patients will be given a randomization 
number that assigns them to one of the 2 treatment arms. All patients will be given an 
available randomization number. This number assigns the patient to one of the treatment arms 
while treatment assignment is unbiased and concealed from patients and investigator staff. 
Subsequently, the investigator will enter the randomization number in the eCRF.  


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The patient randomization list will be produced by or under the responsibility of Novartis 
Biometry using a validated system ensuring assignment of treatment arms to randomization 
numbers in the specified ratio. The randomization scheme will be reviewed and approved by a 
member or delegate of the Novartis Biometry Randomization Group. 
5.4 
Treatment blinding 
Patients, investigator staff, persons performing the assessments, and the clinical trial team 
(CTT) will remain blind to the identity of the treatment from the time of randomization until 
database lock, using the following methods:  
1. Randomization data are kept strictly confidential until the time of unblinding, and will not 
be accessible by anyone else involved in the study.  
2. The identity of the treatments will be concealed by the use of study treatment that are all 
identical in packaging, labeling, schedule of administration, appearance, taste and odor. 
A double-blind supply of secukinumab and placebo PFSs, and open-label supply of 
prednisolone tablets will be provided to sites.  
Unblinding will occur in the case of patient emergencies and at the conclusion of the study. 
A selected Novartis clinical team will be unblinded to the interim analyses results. Details will 
be specified in an Interim Analyses Charters. 
5.5 
Treating the patient 
Sponsor qualified medical personnel will be readily available to advise on trial related 
medical questions or problems. The planned duration of treatment is 48 weeks for 
investigational drug (secukinumab)/ placebo and 26 weeks for co-administered treatment with 
prednisolone. Patients may be discontinued from treatment earlier due to unacceptable 
toxicity, disease progression and/or treatment is discontinued at the discretion of the 
investigator or the patient. For patients who in the opinion of the investigator are still deriving 
clinical benefit from secukinumab every effort will be made to continue provision of study 
treatment. 
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. When the 
patient has signed the informed consent form the investigator or his/her staff will create a new 
patient record in the eCRF and provide the identifying information for the patient. The eCRF 
will then assign the patient number. Once assigned to a patient, the patient number will not be 
reused. If the patient fails to be randomized, the reason must be documented in the eCRF 
immediately. In addition, the Screening Log should be completed for these patients. 
5.5.2 
Dispensing the study drug 
Each study site will be supplied by Novartis with study treatment in packaging of identical 
appearance. The investigational treatment packaging for each patient will consist of individual 
boxes (one per study drug administration visit) each containing 2 PFSs in one of the following 
combinations:  


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Type I: 150 mg secukinumab + 150 mg secukinumab  
Type II: placebo + placebo 
The study treatment packaging has a 2-part label. A unique medication number is printed on 
each part of this label which corresponds to the assigned treatment. Investigator staff will 
identify the study drug to dispense to the patient using the medication number on the label. 
Immediately before dispensing study drug to the patient, investigator staff will detach the 
outer part of the label from the packaging and affix it to the source document (Drug Label 
Form) containing that patient’s unique Patient Number. Immediately after dispensing study 
drug to the patient, investigator staff will access the eCRF to confirm administration of the 
assigned medication pack. 
5.5.3 
Handling of study and additional treatment  
5.5.3.1 
Handling of study treatment  
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly, and kept in a secured location to which only the investigator and 
designees have access. Upon receipt, all study treatment must 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 Country 
Pharma Organization (CPO) Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of 
Germany. They will include storage conditions for the study treatment but no information 
about the patient except for the medication number. 
The 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 (for prednisolone) at the end of the study 
or at the time of discontinuation of study treatment. Note: all injections of 
secukinumab/placebo will be administered by site staff at the scheduled treatment visits.  
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. 
5.5.3.2 
Handling of additional treatment  
Not applicable. 
5.5.4 
Instructions for prescribing and taking study treatment  
The study treatment schedule is presented in Table 5-2. Secukinumab (2 × 150 mg in 1.0 mL 
PFS) or matching placebo will be administered s.c. to the patient throughout the study. 
Patients will be given the injections on site by qualified staff at all scheduled study visits.  


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The injections will be administered into the appropriate site of the body (thighs, arms, 
abdomen) and each injection should be given at a different injection site to reduce the risk of 
reaction. Each new injection should be given at least one inch from the previously used site. 
If the abdomen is chosen, a 2-inch area around the navel should be avoided. The study 
treatment should not be injected into areas where the skin is tender, bruised, red or hard, or 
where the subject has scars or stretch marks. 
Single PFS will be packaged in boxes. Prior to administration the boxes containing the PFS 
with study treatment solution should be allowed to come to room temperature unopened for 
15 to 30 minutes prior to injection. Used PFS should be disposed immediately after use in a 
sharps container OR according to local regulations. 
For visits scheduled through Week 4, the study treatment should not be administered less 
than 7 days from the previous administration. For visits scheduled after Week 4, the study 
treatment should not be administered less than 14 days from the previous administration. 
Prenisolone will be co-administered to all patients in a tapered regimen from their Baseline 
dose (i.e. 25 mg to 60 mg) to 1 mg at Week 26 (last dose of prednisolone, 0 mg from Week 
27 onwards).  
Patients will be given prednisolone tablets by the site staff on site at study site visits, and will 
be supplied with sufficient tablets for home administration between study visits. The 
investigator must promote compliance by instructing the patient to take prednisolone exactly 
as prescribed and by stating that compliance is necessary for the patient’s safety and the 
validity of the study. The patient must be able to contact the investigator at any time if he/she 
is unable for any reason to take prednisolone as prescribed. 
Sponsor qualified medical personnel will be readily available to advise on trial related 
medical questions or problems. 
All dosages prescribed and dispensed to the patient and all dose changes during the study 
must be recorded on the eCRF.  
Table 5-2 
Study treatment schedule  
Investigational / Control Drug 
(Name and Strength) 
Dose 
Frequency and/or 
Regimen 
Secukinumab 300 mg  
(2 injections of 150 mg) 
300 mg (2 x 1 mL PFS each 
containing 150 mg secukinumab) 
Week 0 to 4: weekly 
From Week 4 to 
Week 48: every 
4 weeks 
Placebo, 2 injections 
Not applicable.  
As above. 
Prednisolone,  
(taper regimen from a dose of 25 mg to 
60 mg at Baseline to 1 mg at Week 26 
[last dose]) 
Tapered from Baseline to 
Week 26 (see Table 5-3 and 
Table 5-4) 
Daily 
Prednisolone 
Two different prednisolone taper regimens (Table 5-3 for patients on 40 to 60 mg/day 
prednisolone at Baseline; and Table 5-4 for patients on 25 to 40 mg/day prednisolone at 


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Baseline) will be used for both treatment arms depending on patients’ prednisolone levels at 
Baseline. From Week 8, all patients will receive the same prednisolone level (15 mg/day) and 
will continue to be tapered down. 
Prednisolone will be supplied by the Sponsor in an open-label fashion. Prednisolone intakes 
at weeks, which are not part of the assessment schedule need to be reported (date/, home 
administration form). 
Table 5-3 
60-40 mg/day at Baseline 
Week Dose 
mg/day 
Prednisolone 
n/visit 
 
 
20 mg, n(tablets) 
10mg, n(tablets) 5 mg, n(tablets) 
1mg, n(tablets) 
 
0 
60-40 
Supplied by sponsor, patients start tapering on individual level within the 
ranges, from Week 7 in accordance with the taper regimen 
1 
55-35 
2 
50-30 
3 
45-28 
4 
35-25 
5 
30-22 
6 
25-21 
7 
20 
 
2 
 
 
2 
8 
15 
 
1 
1 
 
2 
9 
13 
 
1 
 
3 
4 
10 
12 
 
1 
 
2 
3 
11 
10 
 
2 
 
2 
12 
9 
 
1 
4 
5 
13 
8 
 
1 
3 
4 
14 
7 
 
1 
2 
3 
15 
6 
 
1 
1 
2 
16 
6 
 
1 
1 
2 
17 
5 
 
1 
 
1 
18 
5 
 
1 
 
1 
19 
4 
 
 
4 
4 
20 
4 
 
 
4 
4 
21 
3 
 
 
3 
3 
22 
3 
 
 
3 
3 
23 
2 
 
 
2 
2 
24 
2 
 
 
2 
2 
25 
1 
 
 
1 
1 
26 
1 
 
 
1 
1 
27 
0 
 
 
 
 
28 
0 
 
 
 
 
Grey: no site visit 
 


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Table 5-4 
40-25 mg/day at Baseline 
Week 
Dose 
mg/day 
Prednisolone 
n/vi
sit 
 
 
20 mg, n(tablets) 10mg, n(tablets) 5 mg, n(tablets) 1mg, n(tablets) 
 
0 
40-25 
Supplied by sponsor, patients start tapering on individual level within the 
ranges, from week 7 in accordance with the taper regimen 
1 
35-22 
2 
30-21 
3 
27-20 
4 
25-19 
5 
22-18 
6 
20-17 
7 
16 
 
1 
1 
1 
3 
8 
15 
 
1 
1 
 
2 
9 
13 
 
1 
 
3 
4 
10 
12 
 
1 
 
2 
3 
11 
10 
 
 
2 
 
2 
12 
9 
 
 
1 
4 
5 
13 
8 
 
 
1 
3 
4 
14 
7 
 
 
1 
2 
3 
15 
6 
 
 
1 
1 
2 
16 
6 
 
 
1 
1 
2 
17 
5 
 
 
1 
 
1 
18 
5 
 
 
1 
 
1 
19 
4 
 
 
 
4 
4 
20 
4 
 
 
 
4 
4 
21 
3 
 
 
 
3 
3 
22 
3 
 
 
 
3 
3 
23 
2 
 
 
 
2 
2 
24 
2 
 
 
 
2 
2 
25 
1 
 
 
 
1 
1 
26 
1 
 
 
 
1 
1 
27 
0 
 
 
 
 
 
28 
0 
 
 
 
 
 
grey: no site visit 


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5.5.5 
Permitted dose adjustments and interruptions of study treatment  
Study treatment interruption should be avoided with the following exceptions: 
• Study 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 dosing is temporarily 
interrupted. In such cases study treatment should be interrupted only during the time 
that this risk is present and ongoing. Study treatment can be restarted at the next 
scheduled visit after resolution of the safety risk. 
Any study treatment interruption must be recorded on the corresponding CRF page. 
No dose escalation is permitted in this study. Prednisolone dosing will be tapered down 
weekly from Baseline through to Week 26 as indicated in Section 5.5.4. 
5.5.6 
Rescue medication 
This study includes an “escape” arm involving prednisolone treatment. Patients who do not 
achieve remission by Week 12, experience a flare after remission or cannot adhere to the 
prednisolone taper regimen will enter “escape” as described in Section 5.2. Upon entering 
“escape”, patients will receive prednisolone at a dose determined by the investigator’s clinical 
judgment and will continue to receive secukinumab or placebo in a blinded manner. 
5.5.7 
Concomitant medication 
The investigator must 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 in the appropriate 
eCRF. 
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt the investigator should contact the Novartis medical monitor before 
randomizing a patient or allowing a new medication to be started. 
5.5.7.1 
Permitted concomitant therapy  
Prednisolone prior and up to Baseline 
Patients must be on prednisolone dose of 25-60 mg/day at Baseline in order to be included in 
the study.  
Prednisolone from Baseline 
Patients will receive a daily dose of prednisolone, which will be decreased (i.e. tapered down) 
from Baseline to Week 26 as described in Section 5.5.4. No additional prednisolone or 
equivalent is permitted.  


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Methotrexate 
Patients taking MTX (≤ 25 mg/week) at study entry are allowed to continue their medication 
provided they have taken it for at least 3 months and are on a stable dose for at least 4 weeks 
prior to randomization and throughout the study. 
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 can be given orally at a dose 
of 8 g three times daily to wash out leflunomide. Cholestyramine has been shown to reduce 
plasma levels of the active leflunomide metabolite by approximately 40% in 24 hours and by 
49% to 65% in 48 hours in 3 healthy volunteers. The administration of cholestyramine is 
recommended in patients who require a drug elimination procedure. If a patient receives 
8 g three times daily for 11 days he/she can be safely randomized 4 weeks after the beginning 
of the 11-day cholestyramine treatment period. 
Vitamin D 
Vitamin D (1000 I.E. per day) is strongly recommended during the study.  
5.5.8 
Prohibited medication 
Use of the treatments displayed in Table 5-5 is NOT allowed after the start of the washout 
period unless otherwise specified below.  
Regarding action to be taken with respect to use of prohibited treatments, the s.c. study 
treatment (i.e. secukinumab or placebo) may be either temporarily or permanently 
discontinued depending on the safety risk due to the prohibited medication. However, 
treatment with oral prednisolone may be continued at a dose determined by the Investigator. 
In case of temporary discontinuation of s.c. study treatment due to prohibited medication, s.c. 
study treatment is interrupted during the time the safety risk is present and ongoing but can be 
restarted at the next scheduled visit after resolution of the safety risk. In case of permanent 
discontinuation of s.c. study treatment due to use of prohibited medication, the patient may 
continue to stay in the study and complete all study assessments up to Week 52 (and follow-
up) but without receiving any s.c. study treatment. Live vaccines should not be given until 12 
weeks after the last study drug administration. 


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Table 5-5 
Prohibited treatment 
Prohibited treatments 
Prohibition1/ 
Washout period 
before randomization2 
Action to be taken 
Biologic drugs directly targeting IL-17 or IL-17 
receptor* 
Never 
Discontinue s.c. study 
treatment 
Any cell-depleting therapies including but not 
limited to anti-CD20 or investigational agents 
(e.g. anti-CD3, anti-CD4, anti-CD5 or anti-CD19* 
Never 
Discontinue s.c. study 
treatment 
Tofacitinib or baricitinib 
Never 
Discontinue s.c. study 
treatment 
Leflunomide 
Leflunomide with cholestyramine washout 
8 weeks 
4 weeks 
Discontinue s.c. study 
treatment 
Other cDMARDs (except MTX if taken as 
outlined in 5.5.7.1) 
4 weeks 
Discontinue s.c. study 
treatment 
Biological agent including but not limited to 
tocilizumab, sirukumab, abatacept or TNFα 
inhibitors (infliximab, adalimumab, etanercept, 
certolizumab, golimumab, ) 
Never 
Discontinue s.c. study 
treatment 
Intravenous immunoglobulins or plasmapheresis 
8 weeks 
Discontinuation s.c. 
study treatment may be 
required on a 
case by case basis. 
Cyclophosphamide, tacrolimus or everolimus 
6 months 
Discontinue s.c. study 
treatment 
Hydroxychloroquine, cyclosporine A, 
azathioprine, sulfasalazine or mycophenolate 
mofetil 
4 weeks 
Discontinue s.c. study 
treatment 
Alkylating agents, except for cyclophosphamide 
Never 
Discontinue s.c. study 
treatment 
Additional systemic glucocorticoid therapy 
At Baseline, patients 
shall be able to adhere 
to the taper regimen 
Patient enters ESCAPE 
High potency opioid analgesics (except for PRN 
use; patients have to refrain from any intake 
during at least 24 hours before a visit) 
 2 weeks 
Discontinuation of 
s.c. study treatment 
may be required on a 
case by case basis. 
Any investigational treatment other than study 
medication or participation in any interventional 
trial 
4 weeks or 5 half-lives 
(whichever is longer) 
Discontinue s.c. study 
treatment 
Live vaccinations 
6 weeks 
If administered due to a 
medical urgency, s.c. 
study treatment should 
be 
interrupted for 4 
months. If administered 
not for a medical 


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Prohibited treatments 
Prohibition1/ 
Washout period 
before randomization2 
Action to be taken 
urgency then s.c. study 
treatment should be 
discontinued 
 
Abbreviations: DMARDs: disease modifying anti-rheumatic drugs MTX: methotrexate,  
1 Never = medication is prohibited from any time point prior to study start and up to and including 
follow-up visit.  
2 Period in weeks refers to washout of prohibited medications during Screening counted from 
randomization visit. Administration of these agents requires study discontinuation.  
5.5.9 
Emergency breaking of assigned treatment code 
Emergency unblinding should only be done when necessary in order to treat the patient. Most 
often, study drug discontinuation and knowledge of the possible treatment assignments are 
sufficient to treat a study patient who presents with an emergency condition. Two complete 
sets of emergency code break cards are provided by Novartis. One set is to be retained by 
Novartis and one set is to be distributed to the investigators. They must be stored in a secure 
place but accessible in case of emergency. The investigator will receive a blinded code break 
card for each patient, with the details of drug treatment covered by a sealed tear-off cover. In 
an emergency, the tear-off cover can be removed to determine the treatment. The tear-off 
covers are not to be removed for any reason other than an emergency. When the investigator 
removes the tear-off cover he/she must note the date, time, and reason for removing it and 
retain this information with the case report form documentation.  
The unblinded treatment code should not be recorded on the eCRF. The investigator must also 
immediately inform the Novartis monitor that the code has been broken.  
It is the investigator’s responsibility to ensure that there is a procedure in place to allow access 
to the emergency code breaks for his/her patients at the site. 
Furthermore he/she need to provide a telephone number by which he/she can be reached 
throughout the trial in case of an emergency unblinding request for one of his/her patients 
(e.g. a mobile number) code break cards in case of emergency. The investigator will inform 
the patient how to contact his/her backup in cases of emergency when he/she is unavailable. 
The protocol number, study drug name if available, patient number, and instructions for 
contacting Novartis (or any entity to which it has delegated responsibility for emergency code 
breaks) will be provided to the patient in case emergency unblinding is required at a time 
when the investigator and backup are unavailable. As per Novartis standard operating 
procedures (SOPs) it is one of the primary responsibilities of each investigator to be available 
in case of an urgent emergency unblinding for one of his/her patients. 
 


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5.6 
Study completion and discontinuation  
5.6.1 
Study completion and post-study treatment 
A subject will be considered to have completed the study when the subject has completed the 
last visit planned in the protocol. (i.e. 52-week treatment period, and 8-week follow-up 
period). As per the study design, patients who do not achieve remission by Week 12, 
experience a flare after remission or cannot adhere to the prednisolone taper regimen will 
enter “escape”. Upon entering “escape”, patients will receive prednisolone at a dose 
determined by the Investigator’s clinical judgment and continue to receive secukinumab or 
placebo in a blinded manner until Week 48. No further secukinumab treatment will be 
provided after Week 48. No further prednisolone treatment will be provided after Week 52.    
Study completion is defined as when the last patient completes their End of Study Visit, and 
any repeat assessments associated with this visit have been documented and followed-up 
appropriately by the Investigator, or in the event of an early study termination decision, the 
date of that decision. 
Normally, all randomized and/or treated patients should have a safety follow-up call 
conducted 60 days after last administration of study treatment; however, the 60 days 
falls within the study 8-week follow-up period, where no s.c. study treatment is given; 
therefore, the safety follow-up is part of the End of Study. As so far, no indication for an 
increased incidence or progression of malignancies was observed in clinical studies of 
secukinumab, no further monitoring after the two follow-up visits is required. 
All SAEs reported during this time period must be reported as described in Section 7.1.3.  
After study participation, the patients will continue to be treated at the investigators discretion 
according to local practice. The investigator must provide follow-up medical care for all 
patients who prematurely withdraw from the study, or must refer them for appropriate 
ongoing care. 
5.6.2 
Discontinuation of study treatment 
Discontinuation of study treatment for a patient occurs when study treatment is stopped 
earlier than the protocol planned duration. Discontinuation of study treatment can be decided 
by either the patient or the investigator. 
Study treatment must be discontinued under the following circumstances: 
• Patient decision - patients may choose to discontinue study treatment for any reason at 
any time. 
• The investigator believes that continuation would negatively impact the safety of the 
patient or the risk/benefit ratio of trial participation. 
• Emergence of the following AEs: 
• Any severe AE or SAE that is not compatible with administration of study 
medication, including AEs that require treatment with an unacceptable co - 
medication 
• Life-threatening infection 


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• Onset of lymphoproliferative disease or any malignancy except for treated basal cell 
carcinoma, treated actinic keratosis, treated in situ carcinoma of the cervix, or non-
invasive malignant colon polyps which are being or have been removed 
• Any protocol deviation that results in a significant risk to the patient’s safety. 
• Pregnancy (see Section 6.4.7 and Section 7.1.4) 
• Use of prohibited treatment as per recommendations in Section 5.5.8.  
• AEs, abnormal laboratory values or abnormal test results that indicate a safety risk to 
the patient. 
• Any laboratory abnormalities that in the judgment of the investigator, taking into 
consideration the patient’s overall status, prevents the patient from continuing 
participation in the study. 
If discontinuation of study treatment occurs, the investigator must determine the primary 
reason for the patient’s premature discontinuation of study treatment and record this 
information on the Dosage Administration CRF. 
If study treatment discontinuation occurs because of study treatment unblinding, please refer 
to Section 5.5.9.   
Discontinuation of study treatment does not require the patient to be discontinued from the 
study and all ongoing visit assessments except in case of withdrawal of informed consent 
(see Section 5.6.3). Refer to Section 6 for the visit schedule and assessments. 
Patients who prematurely discontinue the study treatment (s.c. secukinumab or placebo) are 
encouraged to remain in the study to continue the study-related assessments until completion 
of the study. 
Patients who prematurely discontinue completely from the study for any reason should return 
for the End-of-Study-Visit (EOS) to conduct the Week 52 assessments (4 weeks after the last 
study treatment administration of secukinumab), as well as return for the follow-up visits 
(Week 56 and Week 60).   
If patients refuse to return for these assessments or are unable to do so, every effort (e.g. 
telephone, e-mail, letter) should be made to contact the patient/pre-designated contact as 
specified in Section 5.6.4. This contact should preferably be done according to the study 
visit schedule. 
Replacement policy 
Patients who discontinued will not be able to rejoin.  
5.6.3 
Withdrawal of informed consent 
Patients may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent occurs only when a patient: 
• Does not want to participate in the study anymore, and 
• Does not allow further collection of personal data. 


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In this situation, the investigator should make a reasonable effort (e.g. telephone, e-mail, 
letter) to understand the primary reason for the patient’s decision to withdraw his/her consent 
and record this information.  
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing.  
Further attempts to contact the patient are not allowed unless safety findings require 
communicating or follow-up. 
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the patient’s study withdrawal should be made as detailed in the 
assessment table (Table 6-1). 
Novartis will continue to keep and use collected study information (including any data 
resulting from the analysis of a patient’s samples until their time of withdrawal) according to 
applicable law. 
All biological samples not yet analyzed at the time of withdrawal will no longer be used, 
unless permitted by applicable law. They will be stored according to applicable legal 
requirements. 
5.6.4 
Loss to follow-up 
For patients whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the investigator must show “due diligence” by 
documenting in the source documents steps taken to contact the patient, e.g. dates of 
telephone calls, registered letters, etc. A patient should not be considered as lost to follow-up 
until due diligence has been completed or until the end of the study. 
5.6.5 
Early study termination by the sponsor  
The study can be terminated by Novartis at any time for any reason. This may include reasons 
related to the benefit risk assessment of participating in the study, practical reasons, or for 
regulatory or medical reasons (including slow enrolment). Should this be necessary, the 
patient must be seen as soon as possible and treated as a prematurely discontinued patient. 
The investigator may be informed of additional procedures to be followed in order to ensure 
that adequate consideration is given to the protection of the patient’s interests. The 
investigator 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. 
Assessment schedule lists all of the assessments when they are performed. All data obtained 
from these assessments must be supported in the patient’s source documentation. 
• All questionnaires will be completed prior to the subject seeing the investigator for 
any clinical assessment or evaluation. 


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• All efficacy assessments should be performed prior to administration of study 
treatment. 
Patients should be seen for all visits/assessments as outlined in the assessment schedule or as 
close to the designated day/time as possible. Missed or rescheduled visits should not lead to 
automatic discontinuation.  
Patients who prematurely discontinue the study treatment (s.c. secukinumab or placebo) are 
encouraged to remain in the study to continue the study-related assessments until completion 
of the study. 
Patients who prematurely discontinue completely from the study for any reason should return 
for the End of Treatment visit (EOT) to conduct the Week 52 assessments (4 weeks after the 
last study treatment administration of secukinumab), as well as return for the follow-up visits 
(Week 56 and Week 60).   
At the End of Treatment visit, all dispensed prednisolone should be reconciled, and the AE 
and concomitant medications recorded on the eCRF. 
 
 


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Table 6-1 
Assessment schedule 
Period 
Screening† 
Screening† 
Baseline 
Treatment period 
Visit No.  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
Week 
-6 to  
Baseline 
≤ 4 weeks 
from 
Baseline 
0 (Rnd)  
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
Inclusion/exclusion criteria 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
Information and informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Relevant medical history/current medical 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Washout evaluation/instruction 
S 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Alcohol test/drug screen 
 
S 
 
 
 
 
 
 
 
 
 
 
 
GCA medical history and previous 
therapies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
S 
Vital signs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Smoking History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
QuantiFERON TB-Plus test 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test 
 
 X 
 
 
 
 
 
 
 
 
 
 
 
Urine pregnancy test 
 
 
X* 
 
 
X* 
 
 
 
X* 
 
 
X* 
ECG 
 
S 
 
 
 
 
 
 
 
 
 
 
 
Prior/concomitant medications/non-drug 
therapy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Period 
Screening† 
Screening† 
Baseline 
Treatment period 
Visit No.  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
Week 
-6 to  
Baseline 
≤ 4 weeks 
from 
Baseline 
0 (Rnd)  
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
AEs/SAEs  
(including injection site reactions) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Administration of s.c. study treatment‡ 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prednisolone treatment‡‡ 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
GCA assessment  
(signs and symptoms) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Patient’s global assessment of disease 
activity 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Physician’s global assessment of disease 
activity 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
EQ-5D 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
SF-36 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
FACIT-Fatigue 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
X 
X 
ESR 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CRP 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anti-AIN457 antibodies  
 
 
X 
 
 
 
X 
 
X 
 
 
 
X 


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Period 
Screening† 
Screening† 
Baseline 
Treatment period 
Visit No.  
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
Week 
-6 to  
Baseline 
≤ 4 weeks 
from 
Baseline 
0 (Rnd)  
1 
2 
3 
4 
8 
12 
16 
20 
24 
28 
(pre-dose at Baseline, Week 4, Week 12, 
Week 28, Week 36, Week 44; any time at 
Week 52 and Week 60) 
Hematology, blood chemistry, urinalysis 
 
X 
X 
 
 
 
X 
 
X 
 
 
 
X 
Lipids (Fasted) 
 
X 
X 
 
 
 
X 
 
X 
 
 
 
X 
S=collected as source data only. 
† Screening Visit 1 and Visit 2 can be performed on the same day if appropriate. 
‡ For visits scheduled through Week 4, the study treatment should not be administered less than 7 days from the previous administration. 
For visits scheduled after Week 4, the study treatment should not be administered less than 14 days from the previous administration. 
‡‡ Note: sufficient prednisolone tablets will be provided to the patient for daily home administration between the scheduled study visits. 
* Kits will be provided by central lab and test is to be performed locally, only in women who are not surgically sterile or in menopause 
 
 
 
 
 
 
 
 
 


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Period 
Treatment period 
EOT 
Safety FU 
Visit No.  
14 
15 
16 
17 
18 
19 
20 
21 
Week 
32 
36  
40 
44 
48 
52 
56 
60 
Inclusion/exclusion criteria 
 
 
 
 
 
 
 
 
Information and informed consent 
 
 
 
 
 
 
 
 
Relevant medical history/current medical 
history 
 
 
 
 
 
 
 
 
Washout evaluation/instruction 
 
 
 
 
 
 
 
 
Demography 
 
 
 
 
 
 
 
 
Alcohol test/drug screen 
 
 
 
 
 
 
 
 
GCA medical history and previous 
therapies 
 
 
 
 
 
 
 
 
Physical examination 
S 
S 
S 
S 
S 
S 
S 
S 
Vital signs 
X 
X 
X 
X  
X 
X 
X 
X 
Height 
 
 
 
 
 
 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test 
 
X* 
 
 
 
X* 
 
 
Prior/concomitant medications/non-drug 
therapy 
X 
X 
X 
X 
X 
X 
X 
X 
AEs/SAEs  
(including injection site reactions) 
X 
X 
X 
X 
X 
X 
X 
X 
Administration of s.c. study treatment‡ 
X 
X 
X 
X 
X 
 
 
 
Prednisolone treatment 
 
 
 
 
 
 
 
 


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Period 
Treatment period 
EOT 
Safety FU 
Visit No.  
14 
15 
16 
17 
18 
19 
20 
21 
Week 
32 
36  
40 
44 
48 
52 
56 
60 
GCA assessment  
(signs and symptoms) 
X 
X 
X 
X 
X 
X 
X 
X 
Patient’s global assessment of disease 
activity 
 
X 
 
X 
 
X 
 
 
Physician’s global assessment of disease 
activity 
 
X 
 
X 
 
X 
 
 
EQ-5D 
 
X 
 
X 
 
X 
 
 
SF-36 
 
X 
 
X 
 
X 
 
 
FACIT-Fatigue 
 
X 
 
X 
 
X 
 
 
ESR 
X 
X 
X 
X 
X 
X 
 
 
CRP 
X 
X 
X 
X 
X 
X 
 
 
Anti-AIN457 antibodies  
(pre-dose at Baseline, Week 4, Week 12, 
Week 28, Week 36, Week 44; any time at 
Week 52 and Week 60) 
 
X 
 
X 
 
X 
 
X 
Hematology, blood chemistry, urinalysis 
 
X 
 
X 
 
X 
 
 
Lipids (Fasted) 
 
X 
 
X 
 
X 
 
 
 EOT=end of treatment, FU=follow-up, S=collected as source data only. 
† Screening Visit 1 and Visit 2 can be performed on the same day if appropriate. 


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‡ For visits scheduled through Week 4, the study treatment should not be administered less than 7 days from the previous administration. 
For visits scheduled after Week 4, the study treatment should not be administered less than 14 days from the previous administration. 
* Kits will be provided by central lab and test is to be performed locally, only in women who are not surgically sterile or in menopause 
 
 


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6.1 
Screening 
Screening will be flexible (up to 6 weeks in duration) to be able to adhere to the 
protocol-defined prednisolone taper regimen (maximum dose of 60 mg at Baseline) and to 
allow sufficient time for the washout of relevant medications. During Screening, the patient 
will be evaluated for eligibility 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, it will be determined whether a 
washout period is required. 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. 
Screening Visit 1 and Visit 2 may be performed on the same day if possible.  
It is permissible to re-screen a patient once if s/he fails the initial Screening; however, each 
case must be discussed and agreed with the Sponsor on a case-by-case basis. 
6.1.1 
Information to be collected on screening failures  
Patients who sign an ICF and are subsequently found to be ineligible prior to randomization 
will be considered a screen failure. The reason for screen failure should be recorded on the 
appropriate eCRF. The demographic information, informed consent, and Inclusion/Exclusion 
pages must also be completed for screen failure patients. No other data will be entered into the 
clinical database for patients who are screen failures, unless the patient experienced a SAE 
during the screening phase (see Section 7.1.3 for reporting details).  
Patients who are randomized and fail to start treatment, e.g. patients randomized in error, will 
be considered an early terminator. The reason for early termination should be recorded on the 
appropriate eCRF.  
Baseline assessments may occur during Screening Visit 1, Screening Visit 2, or the Baseline 
Visit depending on the assessment as indicated in Table 6-1.  
German regulations should be considered for the collection of demographic and Baseline 
characteristics in alignment with the CRF. 


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6.1.2 
Medical history and demographic data 
Medical history includes clinically significant diseases within 10 years, surgeries, cancer 
history (including prior cancer therapies and procedures), cardiovascular medical history, 
smoking history, use of alcohol and drugs of abuse, and all medications (e.g. prescription 
drugs, over-the-counter drugs, herbal/homeopathic remedies, nutritional supplements) used by 
the patient within 365 days prior to the Screening Visit 1, except for the history of use of 
corticosteroids for GCA, where all available and related toxicities data should be recorded. 
Demographic data will include age, sex, and self-reported race. 
6.1.3 
Height 
Height in centimeters (cm) will be measured at Screening Visit 1. 
6.1.4 
Alcohol test/drug screen 
All patients will be screened for substances of abuse. These assessments will be documented 
in source records only and will not be entered into the eCRF.  
6.1.5 
Tuberculosis screening 
A central laboratory immunological test (QuantiFERON TB-Plus) must be performed at 
Screening Visit 2 to screen the patient population for latent tuberculosis infection. The 
results must be known prior to randomization to determine the patient’s eligibility for the 
study. 
Patients with a positive test may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that 
• the patient has no evidence of active tuberculosis 
• if presence of latent tuberculosis is established then treatment according to local country 
guidelines must have been initiated. 
6.1.5.1 
Central laboratory test for tuberculosis screening 
The QuantiFERON TB-Plus test will be analyzed by the central laboratory. Details on 
the collection, processing and shipment of samples and reporting of results by the central 
laboratory are provided in the laboratory manual. 
6.2 
Treatment exposure and compliance 
Compliance to the study treatment regimen is ensured by administration of 
secukinumab/placebo at the study site at all visits as per the study schedule (Table 6-1). 
Information on the study treatment administration or any deviation from the dose regimen 
must be recorded in the eCRF. All study treatment dispensed and returned must be recorded in 
the Drug Accountability Log. 


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6.3 
Efficacy 
6.3.1 
Primary efficacy assessment  
The primary efficacy objective is to evaluate the efficacy of secukinumab compared to 
placebo, in combination with a 26-week prednisolone taper regimen, based on the proportion 
of patients with GCA who have sustained remission.  
The primary efficacy endpoint is the proportion of GCA patients in sustained remission (as 
defined below) at Week 28.  
Definition of remission: Absence of flare (see below). Definition of sustained remission: 
patients without flare (see below) until Week 28 and in adherence to the protocol prednisolone 
taper regimen. 
Definition of flare: Determined by the investigator and defined as the recurrence after 
remission of signs or symptoms of GCA (see Section 6.3.1.1) and/or ESR ≥ 30 mm/hr (see 
Section 6.4.5.5) and/or CRP ≥ 10 mg/L (see Section 6.4.5.4) attributable to GCA. 
6.3.1.1 
Signs and symptoms of GCA disease 
Evaluation of clinical signs and symptoms by the Efficacy Assessor at every study visit 
according to the schedule of assessment will include the following: 
• Fever (> 38° C). 
• Symptoms of polymyalgia rheumatica (PMR) (morning stiffness and/or pain, in the 
shoulder and/or hip girdles). 
• Localized headache, temporal artery or scalp tenderness. 
• Visual signs or symptoms such as acute or subacute vision loss due to arteritic anterior 
ischemic optic neuropathy (A-AION), transient blurry vision (generally monocular or at 
least affecting one eye at a time, but potentially affecting both eyes). 
• Jaw or mouth pain. 
• New or worsened extremity claudication. 
• Other features judged by the clinician-investigator to be consistent with a GCA or PMR 
flare. 
6.3.2 
Secondary efficacy assessments 
The following secondary efficacy endpoints will be assessed as herein described or described 
in the respective protocol sections: 
• Remission rate at Week 12 (Section 6.3.1) 
• Time to first GCA flare after clinical remission (up to Week 52) (Section 6.3.1) 
• Total cumulative prednisolone dose up to Weeks  28 and 52 (Section 9.5.1) 
• Proportion of GCA patients in sustained remission at Week 52 
o Definition of remission: absence of flare. . 
o Definition of sustained remission: patients without flare until Week 52 and in 
adherence to the protocol prednisolone taper regimen + prednisolone-free phase 
from Week 27 onwards. 


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o Definition of flare: determined by the investigator and defined as the recurrence 
after remission of signs or symptoms of GCA and/or erythrocyte sedimentation 
rate (ESR) ≥ 30 mm/hr and/or CRP ≥ 10 mg/L attributable to GCA. 
• Proportion of patients on prednisolone dose < 5mg/day at Week 19, Week 28 and Week 
52 (Section 9.5.1) 
• Changes from Baseline in disease activity and quality of life measures at Week 4, 8, 12, 
16, 20, 24,28, 36, 44, 52 for each of the following:  
•  
• PhGA, VAS (Section 6.5.1.1.1) 
•  
• PROs: 
• PGA, VAS (Section 6.5.2.1.1) 
• FACIT-Fatigue (Section 6.5.2.1.2) 
• SF-36 (Section 6.5.2.1.3) 
• EQ-5D (Section 6.5.2.1.4) 
• Change from Baseline at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 in CRP 
(Section 6.4.5.4) and ESR (Section 6.4.5.5). 
All efficacy assessments should be performed prior to administration of study treatment. 
 
 
  
 
 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 


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6.3.6 
Appropriateness of efficacy assessments 
The primary efficacy assessment in this study is aligned with the primary efficacy assessment 
in the GIACTA trial (Stone et al 2017), which demonstrated the efficacy of another 
humanized monoclonal antibody (i.e. tocilizumab) in combination with similar corticosteroid 
tapering (i.e. prednisone) for the treatment of patients with GCA. Other efficacy assessments, 
including the PhGA and PRO assessments, including PGA are closely aligned with those 
included in other Phase II and Phase III clinical trials in the clinical development program for 
secukinumab for other chronic inflammatory diseases.  
6.4 
Safety/tolerability 
Safety assessments are specified below with the assessment schedule detailing when each 
assessment is to be performed. For details on AE collection and reporting, refer to Section 7. 
6.4.1 
Physical examination  
A complete physical examination will include the examination of general appearance, skin, 
neck (including thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, 
extremities, vascular, and neurological systems. If indicated based on medical history and/or 
symptoms, rectal, external genitalia, breast, and pelvic examinations will be performed. 
Information for all physical examinations must be included in the source documentation at the 
study site. Clinically relevant findings that are present prior to signing informed consent must 
be recorded on the appropriate eCRF that captures medical history. Significant findings made 
after first administration of investigational drug which meet the definition of an AE must be 
recorded as an AE. 
6.4.2 
Vital signs 
Vital signs include blood pressure (both arms) and pulse measurements, respiratory rate and 
temperature. After the patient has been sitting for 5 minutes, with back supported and both 
feet placed on the floor, systolic and diastolic blood pressure will be measured 3 times per 
arm using a validated device, with an appropriately sized cuff. The repeat sitting 
measurements will be made at 1 to 2 minute intervals and the mean of the 3 measurements 
(per arm) will be used. In case the cuff sizes available are not large enough for the patient’s 
arm circumference, a sphygmomanometer with an appropriately sized cuff may be used. 
Blood pressure assessments will be performed on both arms.  
Clinically notable vital signs are defined in Appendix 1. 
6.4.3 
Weight 
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. 


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6.4.4 
Tolerability of investigational treatments 
Tolerability will be assessed by AEs, laboratory values, injection site reaction and 
immunogenicity. 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. The assessment of 
pain, redness, swelling, induration, hemorrhage and itching will be performed by a 
physician and will be recorded on the appropriate eCRF capturing AEs, including the 
severity (mild, moderate, severe) and the duration of the adverse reaction. 
6.4.5 
Laboratory evaluations 
Clinically relevant deviations of laboratory test results occurring during or at completion of 
the study must be reported and discussed with Novartis personnel. The results should be 
evaluated for criteria defining an AE and reported as such if the criteria are met. Repeated 
evaluations are mandatory until normalization of the result(s) or until the change is no longer 
clinically relevant. In case of doubt, Novartis personnel should be contacted. 
Clinically notable laboratory findings are defined in Appendix 1.  
6.4.5.1 
Hematology 
Hemoglobin, hematocrit, red blood cell count, white blood cell (WBC) count with 
differentials and platelet count will be measured. 
6.4.5.2 
Clinical chemistry 
Serum chemistries will include sodium, potassium, blood urea nitrogen (BUN)/urea, 
bicarbonate,  phosphorous, total protein, calcium, albumin, uric acid, creatinine, creatine 
kinase, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT), 
gamma glutamyl transferase (GGT) and alkaline phosphatase (ALP); at all time points 
specified in Table 6-1. 
If the total bilirubin concentration is increased above 2 times the ULN, direct and indirect 
reacting bilirubin should be differentiated. 
Follicle stimulating hormone is only done at Screening Visit 2 and only in patients who are 
not reported post-menopausal at Screening Visit 2.  
6.4.5.3 
Lipid panel and glucose 
A lipid profile including high density lipoprotein, low density lipoprotein, cholesterol, 
triglycerides, HbA1c and glucose will be measured from a fasting blood sample. 
6.4.5.4 
C-reactive protein 
Blood for this assessment will be obtained at the visits indicated in Table 6-1 in order to 
identify the presence of inflammation, to determine its severity, and to monitor response to 
treatment.  


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6.4.5.5 
Erythrocyte sedimentation rate 
Blood for ESR, which is helpful in diagnosing inflammatory diseases and is used to 
monitor disease activity and response to therapy, will be obtained at the visits indicated in 
Table 6-1. ESR tests will be done locally. For details please refer to the Laboratory Manual.  
6.4.5.6 
Urinalysis 
Dipsticks will be provided by the central laboratory to the study sites for local urinalysis 
assessments. Dipstick measurements for standard parameter such as specific gravity, protein, 
glucose, pH, erythrocytes, hemoglobin, nitrite, bilirubin, urobilinogen, ketones and WBC will 
be done at scheduled visits as indicated in Table 6-1. If dipstick measurement results are 
positive (abnormal), results will be captured in the e CRF. 
6.4.6 
Electrocardiogram 
In this study, electrocardiograms (ECGs) will be performed locally. ECGs must be recorded 
after 10 minutes rest in the supine position to ensure a stable Baseline. A single 12 lead ECG 
is collected. The Fridericia QT correction formula (QTcF) should be used for clinical 
decisions. The original ECGs (on non-heat-sensitive paper or a certified copy on non-heat 
sensitive paper), appropriately signed, must be collected and archived at the study site. The 
ECG tracing must be labeled with study number, patient initials, patient number, date and 
time, and filed in the study site source documents.  
Clinically relevant abnormalities should be recorded on the relevant medical history/Current 
medical conditions eCRF page for the Baseline ECG. 
Clinically relevant abnormalities noted after the Baseline ECG should be reported as AE (see 
Section 7). 
6.4.7 
Pregnancy and assessments of fertility 
Pregnancy testing 
Secukinumab must not be given to pregnant women; therefore, effective methods of 
birth control must be used for women of child-bearing potential (see Exclusion Criteria 
definitions, Section 4.2). 
A serum β-hCG test will be performed in all women at Visit 2 (Screening 2). All women 
who are not surgically sterile or in menopause at Screening will have local urine 
pregnancy tests as indicated in Table 6-1. A positive urine pregnancy test requires 
immediate interruption of study treatment until serum β-hCG is performed and found to be 
negative. If positive, the patient must be discontinued from the trial. Additional pregnancy 
testing might be performed if requested per local requirements. Refer to Section 7.1.4 for 
details on reporting of pregnancy. Pregnancy test results are kept in the eCRF. 


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Assessments of fertility 
Refer to Section 4.2 for criteria to determine women that are not of child bearing potential. 
Medical documentation of oophorectomy, hysterectomy, or tubal ligation must be retained as 
source. Subsequent hormone level assessment to confirm the woman is not of child bearing 
potential must also be available as source documentation in the following cases: 
• Surgical bilateral oophorectomy without a hysterectomy. 
• Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile. 
In the absence of the above medical documentation, FSH testing is required of any female 
patient who states that they are of non-child bearing potential, regardless of reported 
reproductive/menopausal status at Screening/Baseline. 
6.4.8 
Other safety evaluations 
6.4.8.1 
Immunogenicity 
Blood samples for immunogenicity (anti-AIN457 antibodies) will be taken pre-dose at the 
scheduled time points as indicated in Table 6-1. Anti-secukinumab antibodies will be assessed 
in serum by MSD assay. Details of the analytical methods to assess anti-secukinumab 
antibodies in serum will be described in the bioanalytical data report. 
In addition, if a patient discontinues from the study at any time point, he/she will need to 
provide a sample at the last visit. The actual sample collection date and exact time will be 
entered on the Immunogenicity Blood collection eCRF. Sampling problems will be noted in 
the Comment section of the eCRF. 
A laboratory manual will be provided to investigators with detailed information on sample 
collection, handling and shipment. Tubes and preprinted labels will be provided by the central 
laboratory to the sites. 
The detailed methods for immunogenicity assessment will be described in the Bioanalytical 
Data Report. 
6.4.9 
Appropriateness of safety measurements 
The safety assessments selected are standard for this indication/patient population. 
6.5 
Additional assessments 
6.5.1 
Clinical outcome assessments 
6.5.1.1 
Clinician reported outcomes 
6.5.1.1.1 Physician’s global assessment of disease activity 
The physician’s global assessment of disease activity (PhGA)will be performed using 
100 mm VAS ranging from no disease activity to maximal disease activity, after the 
question “Considering all the ways the giant cell arteritis affects your patient, please 


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indicate with a vertical mark ( | ) through the horizontal line how well his or her condition 
is today”. To enhance objectivity, the physician must not be aware of the specific patient’s 
global assessment of disease activity (PGA), when performing his own assessment on that 
patient. 
The PhGA is filled in by the investigator at all visits specified in in Table 6-1 prior to study 
drug administration. 
 
 
 
 
 
 
 
 
 
 
 
6.5.2 
Patient reported outcomes 
The patient should be given the PRO measures to be completed at the scheduled visit before 
any clinical assessments are conducted. The patient should be given sufficient space and time 
to complete the PRO measures. 
The site personnel (referring to who could be responsible for administering and checking 
completions of PRO measures) should check PRO measures for completeness and ask the 
patient to complete any missing responses. The responses stored electronically on the 
database will be considered the source file.  
Completed measures and any unsolicited comments written by the patient should be reviewed 
and assessed by the investigator for responses, which may indicate potential AEs or SAEs 
before any clinical study examinations. This assessment should be documented in study 
source records. If AEs or SAEs are confirmed, study investigators should not encourage the 
patient to change responses reported in the completed questionnaires. Study investigators 
must follow reporting instructions outlined in Section 7 of the study protocol. 
6.5.2.1.1 Patient’s global assessment of disease activity 
The patient’s global assessment of disease activity will be performed using 100 mm 
VAS ranging from ”has no effect at all” to ”worst possible effect”, after the question  
“On a scale of 0-100 where would you rate the overall effect your Giant Cell Arteritis has 
on you at this time”. 
The patient’s global assessment of disease activity is filled in by the patient at all visits 
specified in Table 6-1 prior to study drug administration.  


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6.5.2.1.2 Functional assessment of chronic illness therapy fatigue scale 
(FACIT-Fatigue©) 
The FACIT-Fatigue© is a 13-item questionnaire (Cella 1993 and Yellen 1997) that assesses 
self-reported fatigue and its impact upon daily activities and function. 
The purpose of collecting available FACIT-Fatigue© data according to clinical routine of the 
Treating Physician in the eCRF is to assess the impact of fatigue on patients with GCA. The 
questionnaire will be used at  all visits specified in Table 6-1 prior to study drug 
administration. 
6.5.2.1.3 Short Form Health Survey (SF-36) 
The SF-36 is a widely used and extensively studied instrument to measure health-related 
quality of life among healthy subjects 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 quality of life of patients. 
The standard version with a 4-week recall period, will be used at all visits specified in Table 
6-1 prior to study drug administration. 
6.5.2.1.4 EuroQol 5D 
The EQ-5D-5L is a widely used, self-administered questionnaire designed to assess health 
status in adults (Xu et al 2011, Mc Clure et al 2017). The purpose of the EQ-5D-5L in this 
study is to assess the general health status of the patients. The measure is divided into 2 
distinct sections. The first section includes 1 item addressing each of 5 dimensions 
(mobility, self-care, usual activity, pain/discomfort, and anxiety/depression). Patients rate 
each of these items from “no problem”, “slight problems”, “moderate problems”, “severe 
problems”, “extreme problems/unable.” A composite health index is then defined by 
combining the levels for each dimension. The second section of the questionnaire measures 
self-rated (global) health status utilizing a vertically oriented VAS where 100 represents the 
“best possible health state” and 0 represents the “worst possible health state.” Respondents 
are asked to rate their current health by placing a mark along this continuum. The recall 
period is “today,” and the questionnaire requires approximately 5 to 10 minutes to complete. 
The EQ-5D-5L contains 6 items designed to assess health status in terms of a single index 
value or health utility score. One of the strengths of the EQ-5D-5L approach is that it allows 
“weighting” by the patient of particular health states and the generation of patient utilities. 
Published weights are available that allow for the creation of a single summary health utility 
score. Overall scores range from 0 to 1, with lower scores representing a higher level of 
dysfunction. The EQ5D is filled in by the patient at the visits specified in Table 6-1 prior to 
study drug administration.  


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6.5.5 
Other assessments 
No additional tests will be performed on patients entered into this study. 
7 
Safety monitoring and reporting 
7.1 
Definition of adverse events and reporting requirements 
7.1.1 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (e.g. any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a patient or 
clinical investigation patient after providing written informed consent for participation in the 
study. Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product.  In addition, all reports of intentional misuse and abuse of 
the study treatment are also considered an AE irrespective if a clinical event has occurred. See 
Section 7.1.5 for an overview of the reporting requirements.  
The investigator has the responsibility for managing the safety of individual patient and 
identifying AEs. 
Novartis qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
The occurrence of AEs must be sought by non-directive questioning of the patient at each 
visit during the study. Adverse events also may be detected when they are volunteered by the 
patient during or between visits or through physical examination finding, laboratory test 
finding, or other assessments. 
Adverse events must be recorded under the signs, symptoms or diagnosis associated with 
them, accompanied by the following information (as far as possible) (if the event is serious 
refer to Section 7.1.3): 
1. The severity grade: 


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• Mild: Usually transient in nature and generally not interfering with normal activities 
• Moderate: Sufficiently discomforting to interfere with normal activities 
• Severe: Prevents normal activities 
2. Its relationship to the investigational treatment and other treatment (prednisolone). If the 
event is due to lack of efficacy or progression of underlying illness (i.e. progression of the 
study indication) the assessment of causality will usually be ‘not suspected.’ The rationale 
for this guidance is that the symptoms of a lack of efficacy or progression of underlying 
illness are not caused by the trial drug, they happen in spite of its administration and/or 
both lack of efficacy and progression of underlying disease can only be evaluated 
meaningfully by an analysis of cohorts, not on a single patient. 
3. Its duration (start and end dates) or if the event is ongoing an outcome of not 
recovered/not resolved must be reported. 
4. Whether it constitutes a SAE (see Section 7.1.2 for definition of SAE) and which 
seriousness criteria have been met 
5. Action taken regarding investigational treatment and other treatment (prednisolone).  
All AEs must be treated appropriately. Treatment may include one or more of the 
following: 
• Dose not changed 
• Dose Reduced/increased 
• Drug interrupted/withdrawn. 
6. Its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown). 
Conditions that were already present at the time of informed consent should be recorded in the 
patient’s medical history. 
Adverse events (including laboratory abnormalities that constitute AEs) should be described 
using a diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Adverse event monitoring should be continued for at least 20 weeks (or 5 half-lives or end of 
study visit, whichever is longer) following the last dose of study treatment. 
Once an AE is detected, it must be followed until its resolution or until it is judged to be 
permanent(e.g. Continuing at the end of the study), and assessment should be made at each 
visit (or more frequently, if necessary) of any changes in severity, the suspected relationship 
to the investigational drug, the interventions required to treat it, and the outcome. 
Information about common side effects already known about the investigational drug can be 
found in the IB. This information will be included in the patient informed consent and should 
be discussed with the patient during the study as needed. Any new information regarding the 
safety profile of the medicinal product that is identified between IB updates will be 
communicated as appropriate, for example, via an Investigator Notification or an Aggregate 
Safety Finding. New information might require an update to the informed consent and has 
then to be discussed with the patient. 
Abnormal laboratory values or test results constitute AEs only if they fulfill at least one of the 
following criteria: 


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• they induce clinical signs or symptoms 
• they are considered clinically significant 
• they require therapy 
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
Baseline or the previous visit, or values which are considered to be non-typical in patients with 
the underlying disease. Clinically notable laboratory values are presented in Appendix 1.  
7.1.2 
Serious adverse events 
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] 
undesirable sign(s), symptom(s) or medical conditions(s)) which meets any one of the 
following criteria: 
• fatal 
• life-threatening. 
Life-threatening in the context of a SAE refers to a reaction in which the subject was at risk of 
death at the time of the reaction, it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to Annex IV, ICH-E2D Guideline) 
• Results in persistent or significant disability/incapacity. 
• Constitutes a congenital anomaly/birth defect. 
• Requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
• Routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition. 
• Elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent . 
• Treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission. 
• Social reasons and respite care in the absence of any deterioration in the patient’s 
general condition. 
• Is medically significant, e.g. defined as an event that jeopardizes the patient or may 
require medical or surgical intervention to prevent one of the outcomes above. 
Medical and scientific judgment should be exercised in deciding whether other situations 
should be considered serious reactions, such as important medical events that might not be 
immediately life threatening or result in death or hospitalization but might jeopardize the 
patient or might require intervention to prevent one of the other outcomes listed above. 
Examples of such events are intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization or 
development of dependency or abuse (please refer to Annex IV, ICH-E2D Guideline). 
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met. 


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Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All reports of intentional misuse and abuse of the products are also considered serious adverse 
event irrespective if a clinical event has occurred. 
7.1.3 
SAE reporting 
Randomized patients 
To ensure patient safety, every SAE, regardless of causality, occurring after the patient has 
provided informed consent until 20 weeks after the patient has discontinued or stopped study 
treatment (i.e. stopped secukinumab or placebo) must be reported to Novartis safety within 
24 hours of learning of its occurrence. Detailed instructions regarding the submission process 
and requirements are to be found in the investigator folder provided to each site. 
Screen failures 
SAEs occurring after the patient has provided informed consent until the time the patient 
is deemed a Screen Failure must be reported to Novartis. 
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
within 24 hours of the investigator receiving the follow-up information. An SAE occurring at 
a different time interval or otherwise considered completely unrelated to a previously reported 
one must be reported separately as a new event. 
Information about all SAEs is collected and recorded on the SAE Report Form (this may be a 
paper or electronic SAE CRF); all applicable sections of the form must be completed in order 
to provide a clinically thorough report. The investigator must assess the relationship of each 
SAE to each specific component of study treatment, (if study treatment consists of several 
components) complete the SAE Report Form in English, and submit the completed form 
within 24 hours to Novartis. Detailed instructions regarding the submission process and 
requirements for signature are to be found in the investigator folder provided to each site.  
Follow-up information is submitted as instructed in the investigator folder. Each 
re-occurrence, complication, or progression of the original event must be reported as a follow-
up to that event regardless of when it occurs. The follow-up information should describe 
whether the event has resolved or continues, if and how it was treated, whether the blind was 
broken or not, and whether the patient continued or withdrew from study participation. 
If the SAE is not previously documented in the IB or Package Insert (new occurrence) and is 
thought to be related to the study treatment, a Chief Medical Office and Patient Safety 
(CMO&PS) Department associate may urgently require further information from the 
investigator for health authority reporting. Novartis may need to issue an Investigator 
Notification (IN) to inform all investigators involved in any study with the same study 
treatment that this SAE has been reported.  


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Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with EU Guidance 
2011/C 172/01 or as per national regulatory requirements in participating countries. 
Any SAEs experienced after the period of 20 weeks after last administration of study drug 
should only be reported to Novartis Safety if the investigator suspects a causal relationship to 
study treatment.  
7.1.4 
Pregnancy reporting 
To ensure patient safety, each pregnancy occurring after signing the informed consent must be 
reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications. 
Pregnancy should be recorded and reported by the investigator to the Novartis CMO&PS. 
Pregnancy follow-up (Birth, 1, 3 and 12 months after the expected delivery) should be 
recorded on the same form and should include an assessment of the possible relationship to 
the study treatment. Any SAE experienced during pregnancy must be reported. 
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form. 
7.1.5 
Reporting of study treatment errors including misuse/abuse 
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, patient or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately 
used not in accordance with the protocol. 
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be collected in 
the appropriate eCRF, irrespective of whether or not associated with an AE/SAE and reported 
to Safety only if associated with an SAE. Misuse or abuse will be collected and reported in the 
safety database irrespective of it being associated with an AE/SAE within 24 hours of 
investigator’s awareness. 
Table 7-1 
Guidance for capturing the study treatment errors including 
misuse/abuse 
Treatment error type 
Document in dosing 
CRF (Yes/No) 
Document in AE 
eCRF 
Complete SAE form 
Unintentional study 
treatment error 
Yes 
Only if associated 
with an AE 
Only if associated with an 
SAE 
Misuse/Abuse 
Yes 
Yes 
Yes, even if not associated 
with a SAE 


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For more information on AE and SAE definition and reporting requirements, please see the 
respective sections. 
7.2 
Additional safety monitoring 
7.2.1 
Liver safety monitoring 
There has been no safety signal for liver toxicity with secukinumab to date in 
approximately 13000 patients and healthy subjects exposed, and from a mechanism of 
action standpoint there is no known effect of blocking IL-17a on the liver. Standard liver 
function tests will be obtained at regular intervals, but special measures for liver safety 
monitoring are not planned. For further information on standard liver function tests, see 
Appendix 1. 
7.2.2 
Renal safety monitoring 
There has been no safety signal for nephrotoxicity with secukinumab to date in 
approximately 13000 patients and healthy subjects exposed, and from a mechanism of 
action standpoint there is no known effect of blocking IL-17a on the kidney. All patients 
with laboratory tests containing clinically significant abnormal values (see Appendix 1 for 
notable laboratory values) are to be followed until the values return to normal ranges or 
until a valid reason, other than treatment related AE, is defined. Standard renal function 
tests (BUN, serum creatinine) will be obtained at regular intervals, but special measures 
for renal safety monitoring are not planned. 
7.2.3 
Data monitoring committee 
This study will include a data monitoring committee (DMC) which will function 
independently of all other individuals associated with the conduct of this clinical trial, 
including the site investigators participating in the study. The DMC will assess at defined 
intervals the progress of a clinical trial, safety data, and critical efficacy variables and 
recommend to the sponsor whether to continue, modify or terminate the trial. 
Specific details regarding composition, responsibilities, data monitoring and meeting 
frequency, and documentation of DMC reports, minutes, and recommendations will be agreed 
between the sponsor and the DMC. 
8 
Data review and database management  
8.1 
Site monitoring 
Before study initiation, at a site initiation visit or at an investigator’s meeting, a Novartis 
representative will review the protocol and data capture requirements (i.e. eCRFs) with the 
investigators and their staff. During the study, Novartis employs several methods of ensuring 
protocol and GCP compliance and the quality/integrity of the sites’ data. The field monitor 
will visit the site to check the completeness of patient records, the accuracy of data capture / 
data entry, the adherence to the protocol and to Good Clinical Practice, the 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 


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during these visits.  Continuous remote monitoring of each site’s data may be performed by a 
centralized Novartis CRA organization. Additionally, a central analytics organization may 
analyze data and identify risks and trends for site operational parameters, and provide reports 
to Novartis Clinical Teams to assist with trial oversight. 
The investigator must maintain source documents for each patient in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, ECGs, 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 ICF signed by the patient (a signed copy is given to 
the patient). 
The investigator must give the monitor access to all relevant source documents to confirm 
their consistency with the data capture and/or data entry. Novartis monitoring standards 
require full verification for the presence of informed consent, adherence to the 
inclusion/exclusion criteria, documentation of SAEs, and of data that will be used for all 
primary variables. Additional checks of the consistency of the source data with the 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  
Data not requiring a separate written record will be defined in the protocol and the assessment 
schedule and can be recorded directly on the eCRFs. All other data captured for this study will 
have an external originating source (either written or electronic) with the eCRF not being 
considered as source 
Designated investigator staff will enter the data required by the protocol into the eCRFs using 
fully validated secure web-enabled software that conforms to FDA  requirements. Designated 
investigator site staff will not be given access to the system until they have been trained. 
Automatic validation programs check for data discrepancies in the eCRFs, allow modification 
and/or verification of the entered data by the investigator staff. 
The investigator/designee is responsible for assuring that the data (entered into eCRF) is 
complete, accurate, and that entry and updates are performed in a timely manner. The 
Investigator must certify that the data entered are complete and accurate 
After final database lock, the investigator will receive copies of the patient data for archiving 
at the investigational site. 
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification. 
8.3 
Database management and quality control 
Novartis personnel (or designated contract research organization (CRO)) will review the data 
entered by investigational staff for completeness and accuracy. Electronic data queries stating 
the nature of the problem and requesting clarification will be created for discrepancies and 
missing values and sent to the investigational site via the EDC system. Designated 


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investigator site staff are required to respond promptly to queries and to make any necessary 
changes to the data. 
Concomitant treatments and prior medications entered into the database will be coded using 
the World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions and 
AEs will be coded using the Medical dictionary for regulatory activities (MedDRA) 
terminology. 
Randomization codes and data about all study drug dispensed to the patient and all dosage 
changes will be tracked using eCRFs.  
 
 
  
An independent unblinded study team will perform all interim analyses. Details will be 
specified in an Interim Analysis Charter. 
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 
locked and the treatment codes will be unblinded and made available for final data analysis. 
Any changes to the database after that time can only be made after written agreement by 
Novartis Development management. 
9 
Data analysis  
The data will be analyzed by Novartis and/or a designated CRO. Any data analysis carried out 
independently by the investigator should be submitted to Novartis before publication or 
presentation.  
It is planned that the data from all centers that participate in this protocol will be used, so that 
an adequate number of patients will be available for analysis. 
Data analyses will be presented by treatment regimen. Efficacy and safety data will be 
presented by the following treatment groups: 
• Secukinumab 300 mg s.c. in combination with 26-week prednisolone taper regimen 
• Placebo in combination with 26-week prednisolone taper regimen 
The analysis will be conducted on all patient data at the time the trial ends. Any data analysis 
carried out independently by the investigator should be submitted to Novartis before 
publication or presentation. 
9.1 
Analysis sets  
The Randomized Analysis Set (RAS) consists of all randomized patients. Unless otherwise 
specified, mis-randomized patients will be excluded from the randomized set. 
 (Misrandomized patients are defined as cases where subjects were mistakenly randomized by 
the investigator/qualified site staff either prematurely or inappropriately prior to confirmation 
of the subject’s final randomization eligibility and double-blind treatment was not 


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administered to the subject. If subjects were re-screened and successfully randomized they 
will be included in the RAS according to the treatment assigned in the last randomization.) 
The Full Analysis Set (FAS) comprises all patients to whom study treatment has been 
assigned by randomization and who received at least one dose of randomized study treatment 
(secukinumab or placebo). According to the intent to treat principle, patients will be analyzed 
according to the treatment assigned to at randomization procedure. 
The Safety Set includes all patients who received at least one dose of study treatment 
(secukinumab or placebo). Patients will be analyzed according to the study treatment 
received, where treatment received is defined as the treatment the patient received on the first 
day of study treatment. 
9.2 
Patient demographics and other baseline characteristics  
Demographic and other Baseline data including disease characteristics will be listed and 
summarized descriptively overall and by treatment group for the RAS. 
Categorical data will be presented as frequencies and percentages. For continuous data, mean, 
standard deviation, median, minimum, and maximum will be presented. For selected 
parameters, 25th and 75th percentiles will also be presented. 
Relevant medical histories and current medical conditions at Baseline will be summarized 
combined by system organ class and preferred term, by treatment group. 
9.3 
Treatments 
The Safety Set will be used for the analyses below. Categorical data will be summarized as 
frequencies and percentages. For continuous data, mean, standard deviation, median, 25th and 
75th percentiles, minimum, and maximum will be presented. 
The number of secukinumab and placebo injections received will be presented by treatment 
group. 
The duration of exposure in weeks to secukinumab and placebo, actual cumulative dose and 
dose intensity (computed as the ratio of actual cumulative dose received and actual duration of 
exposure) will be summarized by means of descriptive statistics using the Safety Set. 
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. 
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be listed and summarized according to the Anatomical Therapeutic 
Chemical (ATC) classification system, by treatment group. 


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9.4 
Analysis of the primary variable 
9.4.1 
Primary variable 
The primary endpoint is the proportion of GCA patients who adhere to the prednisolone taper 
regimen and are in sustained remission until Week 28. 
The analysis of the primary variable will be based on the following estimand: 
• Analysis set: FAS 
• Variable of interest: Proportion of GCA patients who adhere to the prednisolone taper 
regimen and are in sustained remission until Week 28 (refer to Table 2-1 for sustained 
remission definition)  
• Intervention effect: Effect between secukinumab versus placebo at Week 28 regardless of 
adherence to randomized treatment. 
• Summary measure: Odds ratio (OR) 
9.4.2 
Statistical model, hypothesis, and method of analysis 
A binomial distribution will be assumed for the observed data from this study. Due to the 
conjugate nature of the Beta distributions, the posterior distributions for the sustained 
remission response rates until Week 28 for secukinumab and placebo will also be Beta 
distributions.  
The response rate of the comparable placebo-arm of the GIACTA study (Stone et al 2017) 
will be used as the prior distribution for the placebo response rate for the primary endpoint in 
this study. The parameters of this Beta distribution are 10 and 43, i.e. Beta (10, 43). The prior 
distribution for the response rate on secukinumab will be a Beta distribution with parameters 
1/2 and 1/2, i.e. Beta (1/2, 1/2). This prior distribution was chosen because it has low weight 
to reflect the lack of current knowledge on the response rate on secukinumab in GCA. 
Posterior distributions for the estimate of the OR, risk-ratio (RR) and risk difference (RD) will 
be derived by sampling from the posterior distributions of the response rates of secukinumab 
and placebo. The associated median and 95% credibility interval will be presented. In addition 
the probability of the posterior distribution of the OR of the comparison of secukinumab 
versus placebo being greater than 1 will be provided. 
The posterior median OR will be calculated such that the OR is in favor of secukinumab. The 
probability of the posterior distribution of the OR of the comparison of secukinumab versus 
placebo being greater than 1 will be provided. 
Furthermore, the proportion of patients in sustained remission until Week 28 will be 
summarized descriptively by treatment group.  
9.4.3 
Handling of missing values/censoring/discontinuations 
Patients who (1) do not achieve remission within 12 weeks of Baseline; or (2) are in the 
“escape arm”; or (3) drop out from the study prior to/on Week 28, or (4) do not have 
information to evaluate sustained remission response at Week 28, will be classified as 
non-responders in the primary analysis. Patients receiving less than the full amount of 


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prednisolone as required by the taper, e.g. due to missing tablets, will not be classified as non-
responders.  
9.4.4 
Sensitivity analyses 
In order to assess the robustness of the primary endpoint, sensitivity analyses are planned. 
These may include, but are not limited to: 
• Using a non-informative prior, i.e. uniform prior Beta (1/2, 1/2), for both treatment groups 
• Evaluating the primary endpoint using a chi-square test to see if there is an association 
between the primary endpoint and treatment. In addition, the OR, RD, and RR will be 
presented. 
Furthermore, the primary analysis will be repeated based on only signs and symptoms of 
GCA (refer to Section 6.3.1.1 for definition) in order to mitigate against the possibility of 
biasing. 
9.4.5 
Subgroup analyses 
Subgroup analyses of the primary endpoint will be performed: 
• To investigate the difference between new-onset (diagnosed within 6 weeks of baseline) 
and refractory patients (diagnosed ≥ 6 weeks before baseline and previous treatment with 
≥ 25mg/day prednisolone for ≥ 2 consecutive weeks) given the homogenous nature of the 
disease. 
• To allow assessment of the benefit/risk of secukinumab in patients who need a higher 
(> 40 mg/day) versus lower (≤ 40 mg/day) initial dose of prednisone will also be provided.  
The posterior distributions for the estimate of the RD, OR, and RR will be derived and the 
associated median and 95% credibility interval will be presented. 
9.5 
Analysis of secondary variables 
9.5.1 
Efficacy variables 
The following secondary efficacy endpoints for this study will be analyzed for the FAS: 
• Remission rate at Week 12 
• Time to first GCA flare after remission (up to Week 52) 
• Total cumulative prednisolone dose over 28 Weeks and 52 Weeks 
• Proportion of GCA patients in sustained remission at Week 52 
- 
Definition of remission: absence of flare.  
- 
Definition of sustained remission: patients without flare until Week 52 and in 
adherence to the protocol prednisolone taper regimen + prednisolone-free phase 
from Week 27 onwards 
- 
Definition of flare: determined by the investigator and defined as the recurrence 
after remission of signs or symptoms of GCA and/or erythrocyte sedimentation 
rate (ESR) ≥ 30 mm/hr and/or CRP ≥ 10 mg/L attributable to GCA 
• Proportion of patients on prednisolone dose ≤ 5mg/day at Week 19, Week 28 and Week 
52 


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• Change from Baseline PGA at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 
• Change from Baseline PhGA at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 
• Change from Baseline FACIT-Fatigue at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 
• Change from Baseline SF-36 at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 
• Change from Baseline EQ-5D at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52 
• Change from Baseline CRP at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 
• Change from Baseline ESR at Week 4, 8, 12, 16, 20, 24, 28, 32, 36, 40, 44, 48 and 52 
Similar to the primary endpoint methodology, the posterior distributions for the estimate of 
the OR, RD, and RR will be derived by sampling from the posterior distributions of the 
remission response rates at Week 12 of secukinumab and placebo. The prior distribution for 
the remission response rates at Week 12 for both treatment groups will be a Beta distribution 
with parameters 1/2 and 1/2, i.e. Beta (1/2, 1/2). The associated median and 95% credibility 
interval will be presented. Patients that withdrew from the study or entered “escape” therapy 
will be classified as non-responders from the point of withdrawal/escape onwards. Patients 
with a missing remission status at a particular time point will be classified as non-responders 
at that time point. In addition, the proportion of patients in remission over time will be 
summarized descriptively by visit and by treatment group.  
The time to first GCA flare after remission (up to Week 52) will be summarized using Kaplan 
Meier curves. Patients who: 
• Withdraw from the study prior to Week 52 will be censored at the time of withdrawal 
• Do not have a flare up to Week 52 will be censored at Week 52 
Descriptive statistics will also be provided for time to first GCA flare after clinical remission 
(up to Week 52). 
Total cumulative prednisolone dose over 28 and 52 weeks will be summarized over time by 
treatment group. 
The proportion of GCA patients in sustained remission at Week 52 will be analyzed using the 
methods outlined in Section 9.4.2. Patients who (1) do not achieve remission within 12 weeks 
of Baseline; or (2) are in the “escape arm”; or (3) drop out from the study prior to/on Week 
52, or (4) do not have information to evaluate sustained remission response at Week 52, will 
be classified as non responders. Patients receiving less than the full amount of prednisolone as 
required by the taper, e.g. due to missing tablets, will not be classified as non-responders.  
The number (and percentage) of patients on prednisolone dose ≤5mg/day at Week 19, 28 and 
52 will be summarized by treatment group. 
The continuous secondary efficacy endpoints (actual value and change from baseline value) 
will be summarized descriptively by visit (where applicable) and by treatment group. 
 
 
 
For SF-36, the following variables will be evaluated: 
• SF-36 domain scores 


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• SF-36 domain score responders 
• Type I responders (improvement of ≥ 5 points in ≥ 6 domains) 
• Type II responders (improvement of ≥ 10 points in ≥ 3 domains) 
• SF-36 PCS and MCS scores 
• SF-36 PCS and MCS score responders  
• Type I responders (improvement of ≥ 2.5 points) 
• Type II responders (improvement of ≥ 5 points) 
The EQ-5D is a questionnaire with 5 questions (regarding mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression) each with three categories (no problem, moderate 
problem, severe problems) and a health state assessment from 0 (worst possible health state) 
to 100 (best possible health state) (see Section 6.5.2.1.4 for further details). The number and 
percentage of subjects in each of the three categories for each question will be presented by 
visit and treatment group. Summary statistics will be provided for the health state assessment 
by visit and treatment group. 
9.5.2 
Safety variables 
For all safety analyses, the Safety Set will be used. All listings and tables will be presented by 
treatment group. 
Safety summaries (tables, figures) include only data from the on-treatment period with the 
exception of Baseline data which will also be summarized where appropriate (e.g. change 
from Baseline summaries). In addition, a separate summary for death including on treatment 
and post treatment deaths will be provided. In particular, summary tables for AEs will 
summarize only on-treatment events, with a start date during the on-treatment period 
(treatment-emergent AEs). 
Treatment-emergent AEs are defined as events which start after the first dose of study 
medication or events present prior to the first dose of study medication but increase in severity 
after dosing based on preferred term and within last dose + 20 weeks. 
Adverse events 
All information obtained on AEs will be displayed by treatment group and patient. 
The number (and percentage) of patients with treatment-emergent AEs will be summarized in 
the following ways: 
• By treatment group, primary system organ class and preferred term. 
• By treatment group, primary system organ class, preferred term and maximum severity. 
Separate summaries will be provided for study medication related AEs, death, serious AEs, 
other significant AEs leading to discontinuation. 
A patient with multiple AEs within a primary system organ class is only counted once 
towards the total of the primary system organ class. 


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Vital signs 
All vital signs data will be listed by treatment group, patient, and visit/time and if ranges are 
available, abnormalities will be flagged.  
Summary statistics will be provided by visit and by treatment group. Change from baseline 
will only be summarized for patients with both baseline and post-baseline values. 
Clinical laboratory evaluations 
All laboratory data will be listed by treatment group, patient, and visit and if normal ranges 
are available abnormalities will be flagged.  
Summary statistics will be provided by treatment and visit. Change from baseline will only be 
summarized for patients with both baseline and post-baseline values. 
Shift tables using the low/normal/high/ (low and high) classification will be used to compare 
Baseline to the worst on-treatment value. 
Other safety evaluations 
Immunogenicity 
All immunogenicity results (Anti-AIN457 antibodies) will be listed by treatment group, 
patient and visit. 
QuantiFERON TB-Plus test 
All QuantiFERON TB-Plus test results will be listed by treatment group, patient and visit. 
9.5.3 
Resource utilization 
Not applicable. 
 
  
 
 
  
 
 
 
 
  
 
 
 
 
 


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9.5.6 
Biomarkers 
Not applicable. 
 
  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 


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9.8 
Sample size calculation 
Based on the observed response rates in the GIACTA study (Stone et al 2017), there were 56 
out of 100 patients on tocilizumab every other week (56%) in combination with 26-week 
prednisolone taper regimen and 9 out of 51 patients treated with placebo (18%) in 
combination with 52-week prednisolone taper regimen. The expected observed responders in 
a sample size of 25 patients per treatment group is then 25*(56/100) = 14 and 25*(9/51) = 4.  
The posterior distribution of the expected difference in proportions was investigated for the 
sample size of 25 patients per treatment group.  
Using an uninformative prior Beta (1, 1) for the secukinumab group and an informative prior 
for the expected observed responders in the placebo group of Beta (10, 43), 10000 Monte 
Carlo simulations of each posterior density was then computed and the posterior distribution 
of the difference then described using the 2.5, 50 (median) and 97.5 percentiles (Table 9-1). 
Other plausible outcomes have been investigated if the observed response rates are different 
from expected (refer to Table 9-1). 
Table 9-1 
Sensitivity to changes in assumptions in observed response rates 
Observed response rate 
Posterior quantiles 
Posterior 
Prob(p1 > p2) 
Secukinumab (p1) 
Placebo (p2) 
2.5% 
Median 
97.5% 
0.56 
0.16 
0.19 
0.38 
0.56 
0.99 
0.56 
0.20 
0.16 
0.36 
0.55 
0.99 
0.56 
0.24 
0.15 
0.35 
0.55 
0.99 
0.56 
0.28 
0.13 
0.34 
0.54 
0.99 
0.52 
0.16 
0.14 
0.34 
0.53 
0.99 
0.48 
0.16 
0.11 
0.31 
0.51 
0.99 
10 
Ethical considerations 
10.1 
Regulatory and ethical compliance 
This clinical study was designed and shall be implemented, executed and reported in 
accordance with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with 
applicable local regulations (including European Directive 2001/20/EC, US CFR 21, and 
Japanese Ministry of Health, Labor, and Welfare), and with the ethical principles laid down in 
the Declaration of Helsinki. 


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10.2 
Informed consent procedures 
Eligible patients may only be included in the study after providing (witnessed, where required 
by law or regulation), IRB/IEC-approved informed consent. Informed consent must be 
obtained before conducting any study-specific procedures (e.g. all of the procedures described 
in the protocol). The process of obtaining informed consent must be documented in the patient 
source documents.  
Novartis will provide to investigators in a separate document a proposed ICF that complies 
with the ICH GCP guideline and regulatory requirements and is considered appropriate for 
this study. Any changes to the proposed consent form suggested by the investigator must be 
agreed to by Novartis before submission to the IRB/IEC, and a copy of the approved version 
must be provided to the Novartis monitor after IRB/IEC approval. 
Women of child bearing potential must be informed that taking the study treatment may 
involve unknown risks to the fetus if pregnancy were to occur during the study and agree that 
in order to participate in the study they must adhere to the contraception requirement for the 
duration of the study. If there is any question that the patient will not reliably comply, they 
must not be entered in the study. 
 
 
 
 
 
 
 
 
 
 
 
 
10.3 
Responsibilities of the investigator and IRB/IEC 
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion 
from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial 
protocol, informed consent form, consent form updates, patient recruitment procedures (e.g., 
advertisements) and any other written information to be provided to patients/patients. Prior to 
study start, the investigator is required to sign a protocol signature page confirming his/her 
agreement to conduct the study in accordance with these documents and all of the instructions 
and procedures found in this protocol and to give access to all relevant data and records to 
Novartis monitors, auditors, Novartis Quality Assurance representatives, designated agents of 
Novartis, IRBs/IECs, and regulatory authorities as required. If an inspection of the clinical site 
is requested by a regulatory authority, the investigator must inform Novartis immediately that 
this request has been made. 


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10.4 
Publication of study protocol and results 
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. 
10.5 
Quality Control and Quality Assurance 
Novartis maintains a robust Quality Management (QM) system that includes all activities 
involved in quality assurance and quality control, including the assignment of roles and 
responsibilities, the reporting of results, and the documentation of actions and escalation of 
issues identified during the review of quality metrics, incidents, audits and inspections. 
Audits of investigator sites, vendors, and Novartis systems are performed by Novartis Pharma 
Auditing and Compliance Quality Assurance, a group independent from those involved in 
conducting, monitoring or performing quality control of the clinical trial. The clinical audit 
process uses a knowledge/risk based approach. 
Audits are conducted to assess GCP compliance with global and local regulatory 
requirements, protocols and internal SOPs, and are performed according to written Novartis 
processes. 
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 including 
incidental collection is an investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction, data, information, observation 
would be incidentally collected, the investigator shall immediately disclose it to Novartis and 
not use it for any purpose other than the study, except for the appropriate monitoring on study 
participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be 
implemented.  
11.1 
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation. Only amendments that are intended to eliminate an apparent immediate 
hazard to patients may be implemented immediately provided the health authorities are 
subsequently notified by protocol amendment and the reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 


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expected to take any immediate action required for the safety of any patient included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 7 must be followed. 
12 
References 
References are available upon request 
Cella DF, Tulsky DS, Gray G, et al (1993) The Functional Assessment of Cancer Therapy 
(FACT) scale: Development and validation of the general measure. Journal of Clinical 
Oncology; 11(3):570-579. 
Ciccia F, Rizzo A, Ferrante A, et al (2017) New insights into the pathogenesis of giant cell 
arteritis. Autoimmunity Reviews;16(7):675-683. 
De Silvia M and Hazleman B (1986) Azathioprine in giant cell arteritis polymyalgia 
rheumatica: a double-blind study. Ann Rheum Dis;45(2):136-138. 
Espigol-Frigolé G, Corbera-Bellalta M, Planas-Rigol E, et al (2013) Increased IL17A 
expression in temporal artery lesions is a predictor of sustained response to glucocorticoid 
treatment in patients with giant-cell arteritis. Ann Rheum Dis;72(9):1481-1487. 
Hayat S (2008) Infliximab for Maintenance of Glucocorticosteroid-Induced Remission of 
Giant Cell Arteritis: A Randomized Trial. Yearbook of Medicine:38-39. 
Hoffmann G, Cid M, Hellmann D, et al (2002) A multicenter, randomized, double-blind, 
placebo-controlled trial of adjuvant methotrexate treatment for giant cell arteritis. Arthritis 
Rheum;46(5):1309-1318.  
ICH E2D (2004) Post Approval Safety Data Management: Note for guidance on definitions 
and standards for expedited reporting. Available from: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC5
00002807.pdf (Accessed on 29-May-2018) 
Jover J, Hernandez-Garcia C, Morado I, et al (2001) Combined treatment of giant-cell arteritis 
with methotrexate and prednisone. A randomized double-blind, placebo-controlled trial. Ann 
Intern Med;134(2):106-114. 
Koster M, Warrington J, Kermani T, et al (2016) Update on Epidemiology and Treatment of 
Giant Cell Arteritis. Current Treatment Options in Rheumatology;2(2):138-152. 
Marquez A, Hernandez-Rodriguez J, Cid M, et al (2014) Influence of the IL17A locus in 
giant cell arteritis susceptibility. Ann Rheum Dis;73(9):1742-1745. 
McClure N, Sayah F, Xie F, et al (2017) Instrument-Defined Estimates of the Minimally 
Important Difference for EQ-5D-5L Index Scores. Value Health;20(4):644-650.  
 
 
Miyabe C, Miyabe Y, Strle K, et al (2017) An expanded population of pathogenic regulatory 
T cells in giant cell arteritis is abrogated by IL-6 blockade therapy. Ann Rheum 
Dis;76:898-905. 


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Mukhtyar C, Guillevin, L, Cid M, et al (2009) EULAR recommendations for the management 
of large vessel vasculitis. Ann Rheum Dis;68:318–323. 
Ness T, Bley T, Schmidt W, et al (2013) The diagnosis and treatment of giant cell arteritis. 
Dtsch Arztebl Int;110(21):376-385. 
Petri H, Nevitt A, Sarsour K, et al (2014) Incidence of giant cell arteritis and characteristics of 
patients: data-driven analysis of cormorbidities. Arthritis Gare Res (Hoboken);67(3):390-395. 
Proven A, Gabriel SE, Orces C, et al (2003) Glucocorticoid therapy in giant cell arteritis: 
Duration and adverse outcomes. Arthritis & Rheumatism 2003;49(5):703-708. 
Reichenbach S, Adler S, Bonel H, et al (2018) Magnetic resonance angiography in giant cell 
arteritis: results of a randomized controlled trial of tocilizumab in giant cell arteresis. 
Rheumatology;1:57(6):982-986.  
Rotar Z, Tomsic M, Hocevar A, et al (2018) Secukinumab for the maintenance of 
glucocorticoid-free remission in a patient with giant cell arteritis and psoriatic arthritis. 
Rheumatology;57(5):934-936. 
Salvarani C, Cantini F, Boiardi L, et al (2004) Polymyalgia rheumatica. Best Pract Res Clin 
Rheumaol;18(5):705-722. 
Samson M, Audia S, Fraszczak J, et al (2012) Th1 and Th17 lympocytes expressing CD 16 
are implicated in giant cell arteritis and polymyalgia rheumatica pathogenesis. Arthritis 
Rheum;64(11):3788-3798. 
Samson M, Corbera-Bellalta M, Audia S, et al (2017) Recent advances in our understanding 
of giant cell arteritis pathogenesis. Autoimmunity Reviews;16(8):833-844. 
Sammut L, Litwic A, Smith R, et al (2018) 002 Biopsy proven giant cell arteritis in a patient 
with psoriatic arthritis on TNF-alpha inhibitor treated with high dose prednisolone and a 
switch to secukinumab (anti IL-17). Rheumatology, Volume 57, Issue suppl_3. Available at 
[https://doi.org/10.1093/rheumatology/key075.226] 
Stone J, Tuckwell K, Dimonaco S, et al (2017) Trial of Tocilizumab in Giant-Cell Arteritis. 
The New England Journal of Medicine. N Engl J Med;377:317-328.  
Tfelt-Hansen P, Pascual J, Ramadan N, et al [International Headache Society Clinical Trials 
Subcommittee members] (2012) Guidelines for controlled trials of drugs in migraine: Third 
edition. A guide for investigators. Cephalalgia;32(1):6-38. 
Ware J, Kosinki M, Gandeck B (1993) SF-36 Health Survey manual and interpretation guide. 
Boston: The Health Institute, New England Medical Center. 
Ware J, Kosinki M, Gandeck B (1994) SF-36 Health Survey manual and interpretation guide. 
Update. Boston: The Health Institute, New England Medical Center. 
Xu R, Insinga R, Golden W, et al (2011) EuroQol (EQ-5D) health utility scores for patients 
with migraine. Qual Life Res;20(4):601-8. 
Yellen SB, Cella DF, Webster K, et al (1997) Measuring Fatigue and Other Anemia-Related 
Symptoms with the Functional Assessment of Cancer Therapy (FACT) Measurement System. 
Journal of Pain and Symptom Management;13:63-74. 


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13 
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 
Laboratory Variable 
Notable Criteria 
Standard Units 
SI Units 
LIVER FUNCTION AND RELATED VARIABLES 
SGOT (AST) 
> 3 x ULN 
> 3 x ULN 
SGPT (ALT) 
> 3 x ULN 
> 3 x ULN 
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 
< 100 x 10E9/L 
White blood cell count 
< 0.8 x LLN 
Neutrophils 
< 0.9 x LLN 
 

SAP_001.pdf: 
Clinical Development 
AIN457/Secukinumab/Cosentyx® 
CAIN457ADE11C / NCT03765788
A randomized, parallel-group, double-blind, placebo controlled, 
multicenter phase 2 trial to investigate the safety and efficacy of 
secukinumab (AIN457) in patients with giant cell arteritis (TitAIN) 
Statistical Analysis Plan (SAP) Amendment 1  
Document type: 
SAP Documentation 
Document status: 
Final 
Release date: 
15-Jul-2021
Number of pages: 
53 
Property of Novartis 
For business use only 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 
Template Version 3.0, Effective from 01-Jul-2020 


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Document History 
Date 
Time 
point 
Reason for update 
Outcome for update 
Section and title 
impacted 
(Current) 
26-
Mar-
2021 
Prior 
to 
DB 
lock 
Creation of final version 
N/A - First version 
NA 
 
 
 
 
 
15-Jul-
2021 
Prior 
to 
DB 
lock 
Minor editorial changes 
Amendment 1 
 
 
 
Updated age categories to align 
with Clinical Disclosure Office 
reporting requirements; Added 
summary of the two subgroups 
of interest. 
 
Section 2.3.2 
Demographics 
and other 
baseline 
characteristics 
 
 
Clarified that the addition of 84 
days is only applicable to study 
treatment. 
 
Section 2.4.1 
Study treatment 
/ compliance 
 
 
Clarified that a patient is non-
adherent if the patient takes 
prednisolone 
treatment 
for 
GCA for < 80% of the 26-week 
prednisolone taper regimen 
period. 
 
Section 2.5.1 
Primary 
endpoint 
 
 
Clarified 
that 
prednisolone 
refers to prednisolone for 
GCA. 
Clarified that the prednisolone 
done will be regarded as 0 
mg/day 
if 
there 
are 
no 
prednisolone for GCA records 
and the patient is still in the 
study. 
 
Section 2.7.2 
Statistical 
hypothesis, 
model, and 
method of 
analysis 
 
 
Clarified that as blood pressure 
will be assessed for both arms, 
the average of the available 
blood pressure assessments 
will be summarized/listed. 
 
Section 2.8.4.1 
Vital signs 


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Date 
Time 
point 
Reason for update 
Outcome for update 
Section and title 
impacted 
(Current) 
 
 
Updated text to refer to 5 rather 
than 3 categories. 
 
Section 5.4.1 
EQ-5D 
 
 
Added a table to show the 
precoded item values. 
 
Section 5.4.3 
SF-36 
 


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Table of contents 
Table of contents ................................................................................................................. 4 
List of abbreviations ............................................................................................................ 6 
1 
Introduction ......................................................................................................................... 8 
1.1 
Study design ............................................................................................................ 8 
1.2 
Study objectives and endpoints ............................................................................... 9 
2 
Statistical methods ............................................................................................................. 11 
2.1 
Data analysis general information ......................................................................... 11 
2.1.1 
General definitions ................................................................................ 12 
2.2 
Analysis sets .......................................................................................................... 17 
2.2.1 
Subgroup of interest .............................................................................. 17 
2.3 
Patient disposition, demographics and other baseline characteristics ................... 18 
2.3.1 
Patient disposition ................................................................................. 18 
2.3.2 
Demographics and other baseline characteristics ................................. 18 
2.3.3 
Protocol deviations ................................................................................ 21 
2.4 
Treatments (study treatment, rescue medication, concomitant therapies, 
compliance)............................................................................................................ 22 
2.4.1 
Study treatment / compliance ................................................................ 22 
2.4.2 
Prior, concomitant and post therapies ................................................... 23 
2.4.3 
Signs and symptoms of GCA ................................................................ 24 
2.5 
Analysis of the primary objective .......................................................................... 24 
2.5.1 
Primary endpoint ................................................................................... 24 
2.5.2 
Statistical hypothesis, model, and method of analysis .......................... 25 
2.5.3 
Handling of missing values/censoring/discontinuations ....................... 27 
2.5.4 
Supportive analyses ............................................................................... 27 
2.6 
Analysis of the key secondary objective ............................................................... 27 
2.7 
Analysis of secondary efficacy objectives ............................................................. 28 
2.7.1 
Secondary endpoints ............................................................................. 28 
2.7.2 
Statistical hypothesis, model, and method of analysis .......................... 28 
2.7.3 
Handling of missing values/censoring/discontinuations ....................... 29 
2.8 
Safety analyses....................................................................................................... 30 
2.8.1 
Adverse events ...................................................................................... 30 
2.8.2 
Deaths .................................................................................................... 32 
2.8.3 
Laboratory data ..................................................................................... 32 
2.8.4 
Other safety data ................................................................................... 32 
 
 33 
2.10 
Patient-reported outcomes ..................................................................................... 33 


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2.11 
Biomarkers ............................................................................................................. 34 
 
 34 
2.13 
Interim analysis ...................................................................................................... 35 
3 
Sample size calculation ..................................................................................................... 35 
4 
Change to protocol specified analyses .............................................................................. 36 
5 
Appendix ........................................................................................................................... 36 
5.1 
Imputation rules ..................................................................................................... 36 
5.1.1 
Study drug ............................................................................................. 36 
5.1.2 
Adverse event date imputation .............................................................. 36 
5.1.3 
Concomitant medication date imputation ............................................. 38 
5.1.4 
Other imputations .................................................................................. 40 
5.2 
Adverse events coding/grading.............................................................................. 41 
5.3 
Laboratory parameters derivations ........................................................................ 41 
5.3.1 
Imputation rules .................................................................................... 41 
5.4 
Questionnaires ....................................................................................................... 41 
5.4.1 
EQ-5D ................................................................................................... 41 
5.4.2 
FACIT-Fatigue ...................................................................................... 43 
5.4.3 
SF-36 ..................................................................................................... 43 
 
 46 
5.5 
Statistical models ................................................................................................... 49 
Primary analysis .................................................................................................... 49 
Secondary analysis ................................................................................................ 50 
5.6 
Rule of exclusion criteria of analysis sets.............................................................. 52 
6 
References ......................................................................................................................... 52 


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List of abbreviations 
AE 
Adverse Event 
AESI 
Adverse event of special interest 
AIS 
Aggregate Improvement Score 
ATC 
Anatomical Therapeutic Classification 
BDRM 
Blind Data Review Meeting 
BMI 
Body Mass Index 
CDBL 
Clinical Database Lock 
CI 
Confidence Interval 
CRF 
Case Report Form 
CRO 
Contract Research Organization 
CRP 
C-reactive Protein 
CSR 
Clinical Study Report 
CTT 
Clinical Trial Team 
CV 
Coefficient of Variation 
CWS 
Cumulative Worsening Score 
DMC 
Data Monitoring Committee 
eCRF 
Electronic Case Report Form 
eCRS 
Electronic Case Retrieval Sheet 
EQ-5D 
EuroQol-5D  
ESR 
Erythrocyte Sedimentation Rate 
FACIT-Fatigue  
Functional Assessment of Chronic Illness Therapy Fatigue Score  
FAS 
Full Analysis Set 
GCA 
Giant Cell Arteritis 
 
 
IA 
Interim Analysis 
IA1 
First Interim Analysis 
IA2 
Second Interim Analysis 
IA3 
Third Interim Analysis 
LOQ 
Limit of quantitation 
MAP 
Master Analysis Plan 
MCS 
Mental Component Summary 
MedDRA 
Medical Dictionary for Drug Regulatory Affairs 
 
 
MTX 
Methotrexate 
OR 
Odds ratio 
PCS 
Physical Component Summary 
PD 
Pharmacodynamics 
PFS 
Prefilled syringe 
 
 
PGA 
Patient’s Global Assessment 
PhGA 
Physician’s Global Assessment 
 
 


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PMR 
Polymyalgia rheumatica 
PPS 
Per-Protocol Set 
PRO 
Patient-reported Outcomes 
PT 
Preferred term 
qd 
Qua’que di’e / once a day 
QoL 
Quality of Life 
RAP 
Report and Analysis Process 
RAS 
Randomized Analysis Set 
RD 
Risk difference 
RR 
Risk ratio 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
s.c. 
Subcutaneous 
SD 
Standard Deviation 
SF-36 
Short Form 36  
SOC 
System Organ Class 
SOP 
Standard Operating Procedure 
TEAE 
Treatment Emergent Adverse Event 
TFLs 
Tables, Figures, Listings 
VAS 
Visual Analog Scale  
WHO 
World Health Organization 
 


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1 
Introduction 
This Statistical Analysis Plan (SAP) describes the statistical analysis for the clinical study report 
(CSR) for CAIN457ADE11C according to Section 9 of the study protocol (version no. 3 
including Amendment 3) along with any additional analyses, specifications or deviations from 
this protocol planned before unmasking of the data. Determination of the sample size is 
specified in Section 3. 
This document is written in the future tense. The CSR results will be used to provide 
information to support a phase III program of secukinumab in patients with giant cell arteritis 
(GCA). 
The following documents were used to support the creation of this SAP: 
• Study protocol (version no. 3 including Amendment 3) 
• Case report forms (CRFs) (version 9) 
• AIN457 efficacy master analysis plan (MAP) M3 Amendment 5 
• AIN457 safety master analysis plan (MAP) M3 Amendment 5 
1.1 
Study design 
This is a randomized, parallel-group, double-blind, placebo-controlled, multicenter, phase II 
study designed to evaluate the efficacy of secukinumab compared to placebo in combination 
with a 26-week prednisolone taper regimen in terms of sustained remission in patients with 
newly diagnosed or relapsing GCA who are naïve to biological therapy. 
The study will consist of 6-week (maximum duration) screening period, a 52-week treatment 
period and an 8-week safety follow-up period (Figure 1-1).  
Figure 1-1 
Study design 
 


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Patients who do not achieve remission by Week 12, experience a flare after remission or cannot 
adhere to the prednisolone taper regimen will enter “escape”. Upon entering “escape”, patients 
will receive prednisolone at a dose determined by the physician’s clinical judgment and 
continue to receive secukinumab or placebo in a blinded manner. Patients in “escape” should 
continue to attend all subsequent scheduled visit assessments. 
As outlined in the protocol, most flares occurred within the first 6 months in the GiACTA trial 
(Stone et al 2017). Therefore, the time point for the primary analysis of this study is at Week 28, 
to evaluate the effect of secukinumab in patients who are on study treatment or placebo for 24 
weeks. 
At the randomization visit (Baseline) all eligible patients will be given a randomization number 
that assigns them to one of the following 2 arms in a 1:1 ratio: 
• Group 1: secukinumab 300 mg s.c. + 26-week prednisolone taper regimen 
• Group 2: placebo s.c. + 26-week prednisolone taper regimen 
The patient randomization list was produced by or under the responsibility of Novartis Biometry 
using a validated system ensuring assignment of treatment arms to randomization numbers in 
the specified ratio. The randomization scheme was reviewed and approved by a member or 
delegate of the Novartis Biometry Randomization Group. It is planned to randomize at least 
25 patients per treatment group. 
Patients will receive secukinumab/placebo at Baseline, Week 1, 2, 3, 4, then every 4 weeks 
thereafter through to Week 48 (last dose) at the study center. Assessments will be performed in 
accordance to the study schedule. Patients in both groups will follow the protocol-defined 
prednisolone taper regimen. 
In total, three interim analyses (IAs) will be conducted unless deemed unwarranted by the study 
team: 
• First interim analysis (IA1): after approximately 50% of patients reach Week 28 
• Second interim analysis (IA2): after approximately 50% of patients reach Week 52 
• Third interim analysis (IA3): 100% of patients reach Week 28 
The analyses for each of the aforementioned IAs are detailed in separate SAPs. 
1.2 
Study objectives and endpoints 
The following table (Table 1-1) is an overview of the study objectives and endpoints. 
Table 1-1 
Study objectives and endpoints 
 
Objective 
Endpoint 
Primary 
• 
To evaluate the efficacy of 
secukinumab compared to 
placebo, in combination with a 26-
week prednisolone taper regimen, 
based on the proportion of 
patients with GCA who have 
sustained remission. 
• 
Proportion of GCA patients in 
sustained remission at Week 28 


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Objective 
Endpoint 
Secondary 
• 
To evaluate the efficacy of 
secukinumab in combination with 
a 26-week prednisolone taper 
regimen versus placebo in patients 
with GCA, measured by the 
following: 
• 
Remission rate at Week 12 
• 
Time to first flare after 
remission 
• 
Remission rate at Week 12 
• 
Time to first GCA flare after Baseline 
(up to Week 52) 
 
• 
Cumulative corticosteroid dose up 
to Week 28 and up to Week 52 
• 
Total cumulative prednisolone dose 
over 28 weeks and 52 weeks 
 
• 
Proportion of patients with GCA 
who have sustained remission 
• 
Proportion of GCA patients in 
sustained remission at Week 52 
 
• 
Proportion of patients on 
prednisolone dose ≤ 5mg/day at 
Week 19, 28, 52 
• 
Proportion of patients on prednisolone 
dose ≤ 5mg/day at Week 19, 28 and 
52 
 
• 
Changes from baseline in disease 
activity and quality of life 
measures at Week 4, 8, 12, 16, 
20, 24, 28, 36, 44 and 52 for each 
of the following: 
• 
Changes from Baseline in disease 
activity and quality of life measures at 
Week 4, 8, 12, 16, 20, 24, 28, 36, 44 
and 52 for each of the following:  
 
• 
Physician’s Global Assessment 
(PhGA), Visual Analog Scale 
(VAS)  
• 
PhGA, VAS  
 
 
• 
Patient-reported outcomes (PROs) 
• 
Patient’s Global Assessment 
(PGA), VAS  
• 
Functional Assessment of 
Chronic Illness Therapy 
Fatigue Score 
(FACIT-Fatigue)  
• 
Short Form 36 (SF-36)  
• 
EuroQoL-5D (EQ-5D) 
• 
PROs 
• 
PGA, VAS  
• 
FACIT-Fatigue  
• 
SF-36  
• 
EQ-5D 
 
• 
Laboratory parameters 
(Baseline vs. Week 28 and 52): 
• 
C-reactive protein (CRP) 
• 
Erythrocyte sedimentation 
rate (ESR) 
• 
Change from Baseline in CRP and 
ESR at Week 4, 8, 12, 16, 20, 24, 28, 
32, 36, 40, 44, 48, 52 
 
• 
To evaluate the safety/ tolerability 
and immunogenicity of 
secukinumab in patients with 
newly diagnosed or relapsing GCA 
• 
Safety and tolerability assessments 
over time: incidence and severity of 
adverse events (AEs) and serious AEs 
(SAEs) 


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2 
Statistical methods 
2.1 
Data analysis general information 
This study will be conducted under the sponsorship of Novartis. The analysis will be performed 
by Novartis NBS CONEXTS or a designated contract research organization (CRO) (if 
applicable). 
All analyses will be performed using SAS® statistical software (Version 9.4 or a more recent 
version), unless otherwise noted.  
The independent statistical and statistical programming team will perform the unblinded 
statistical analyses. These analyses are detailed in the respective data monitoring committee 
(DMC) and IA SAPs. 
Data will be summarized with respect to demographic and other baseline characteristics along 
with safety observations. 
Descriptive statistics (the number of non-missing observations [n], mean, median, standard 
deviation [SD], minimum, and maximum values) will be presented for continuous variables. 
For categorical variables, the number and percentage of each category within a variable will be 
calculated for non-missing data. If a count of zero is obtained for categorical data, only the zero 
count will be displayed. If no treatment group satisfies a category, then the category will be 


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displayed, unless stated otherwise. A row (category) denoted ‘Missing’ will be included in 
count tabulations if a non-zero count of missing values is present. In addition, the corresponding 
percentage for this row will be displayed. 
All data will be listed by center and subject number, unless otherwise stated. 
It is planned that the data from all centers that participate in this study will be used so that an 
adequate number of patients will be available for analysis. 
2.1.1 
General definitions  
2.1.1.1 
Treatment 
Study treatment 
At Baseline, patients will be assigned to one of the following two arms in a 1:1 ratio: 
• Group 1: secukinumab 300 mg subcutaneous (s.c.) + 26-week prednisolone taper regimen 
• Group 2: placebo s.c. + 26-week prednisolone taper regimen 
The study treatment is secukinumab 300 mg supplied in prefilled syringes (PFS) each 
containing 150 mg of secukinumab, or placebo supplied in PFS to match secukinumab dose.  
Co-administered treatment 
The co-administered treatment refers to prednisolone tablets for tapered oral administration 
(taper regimen from a dose of 25 mg to 60 mg at Baseline to 0 mg at Week 28). Prednisolone 
will be supplied as 1 mg, 5 mg, 10 mg, 20 mg tablets. 
Note: Prednisolone may continue to be taken after the 26-week prednisolone taper regimen. 
2.1.1.2 
Date of first administration of treatment 
Date of first administration of study treatment 
The date of first administration of study treatment is defined as the first date when a non-zero 
dose of study treatment was administered and recorded on the “Dosage Administration 
Record-Investigational Product” electronic CRF (eCRF).  
Date of first administration of co-administered treatment 
The date of first administration of co-administered prednisolone treatment is defined as the first 
date when a non-missing dose of co-administered prednisolone treatment was administered and 
recorded on the “Dosage Administration Record-Prednisolone” eCRF.  
Note: A patient may have a “0” dose as part of the prednisolone dosing taper regimen. 


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2.1.1.3 
Date of last administration of treatment 
Date of last administration of study treatment 
The date of last administration of study treatment is defined as the last date when a non-zero 
dose of study treatment was administered and recorded on the “Dosage Administration 
Record-Investigational Product” eCRF.  
Date of last administration of co-administered treatment 
The date of last administration of co-administered prednisolone treatment is defined as the last 
date when a non-missing dose of co-administered prednisolone treatment was administered and 
recorded on the “Dosage Administration Record-Prednisolone” eCRF.  
Note: A patient may have a “0” dose as part of the prednisolone dosing taper regimen. 
2.1.1.4 
Safety observation period 
The safety observation period (days) for treated patients begins at the first administration of 
study treatment within this study (refer to Figure 1-1). It finishes at: 
• the date of the Month X visit for patients that attend it (for patients who have not 
discontinued study treatment or study prior to the Month X visit) 
• the latest day in the window for the Month X visit for patients who have not discontinued 
(study treatment or study) prior to the Month X visit but do not attend that visit 
• the date of the last visit (including the study discontinuation visit) for patients who have 
discontinued study treatment prior to the Month X visit 
where Month X is the last scheduled visit in the study. 
Safety observation period (days) is defined as:  
• (date of last administration of study treatment - date of first administration of study 
treatment) + 85 (i.e. 84 days after last administration of study treatment) 
2.1.1.5 
Study day 
The study day for a baseline or post-baseline scheduled or unscheduled visit is defined as: 
• Study day = (Date of visit) – (Baseline date) + 1 
For visits prior to baseline, the study day is defined as: 
• Study day = (Date of visit) – (Baseline date) 
2.1.1.6 
Baseline date 
Baseline date is referred to as Day 1 of the study. It is defined as the date of first administration 
of study treatment in this study for treated patients. If a patient is randomized but not treated 
then the baseline date is defined as the date of randomization. 
2.1.1.7 
Baseline and post-baseline definitions 
The baseline value for efficacy and safety variables is the last available, non-missing, 
(scheduled or unscheduled) value collected prior to first administration of study treatment.  


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Some baseline assessments may be recorded on the day of the Baseline visit (Visit 3/Week 0). 
However the time of each of these assessments may not be recorded in the eCRF. In this case, 
only the assessments which, according to the protocol, should have been conducted pre-dose 
on Day 1 will be assumed to have been done prior to administration of study treatment on Day 1 
when deriving baseline values recorded on the day of the Baseline visit (Visit 3/Week 0). 
All data collected after the Baseline date are defined as post-baseline. 
2.1.1.8 
Coefficient of variation 
The coefficient of variation (CV) will be calculated as: 
• (SD/mean)*100 
2.1.1.9 
Geometric coefficient of variation 
The geometric CV will be calculated as: 
• sqrt( exp(variance of log-transformed data)-1)*100 
2.1.1.10 Geometric mean 
The geometric mean will be calculated as: 
• exp( (sum of log transformed data) / number of non-missing data points after log 
transformation) 
2.1.1.11 Change from baseline and relative change from baseline definitions 
Change from baseline and relative change from baseline will only be summarized for patients 
with both baseline and post-baseline data for the relevant visit and will be calculated using the 
following formulae: 
• Change from baseline = Post-baseline value − baseline value 
• Relative change from baseline (%) = 100 × ([Post-baseline value − baseline value] ∕  baseline 
value) 
2.1.1.12 Visit windowing 
The study day for each visit will be derived; this day will then be used to determine the analysis 
visit based on the visit windows outlined in Table 2-1. In addition the study day associated with 
each week will also be derived as a supportive analysis (see Table 2-2). 
If more than one analysis visit occurs at a visit, only one will be selected for summary tables 
but all visits will be listed.  
For categorical variables, the closest to the target study day is chosen (if two assessments have 
the same distance, than the earlier one will be chosen). 
For continuous variables, the worst record is selected. It is noted that in the analyses performed, 
worst case is always well defined (e.g., for urine protein values “+” and “++”, the worst case is 
defined as “++”). 


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The analysis visit will be used for listing of visit and period. If a visit falls after the last visit 
window (i.e. after Day 435) it is not assigned an analysis visit and will be listed under the label 
“After last scheduled visit” (i.e. “After Week 60”). 
Table 2-1 
Visit windows 
Timepoint 
Analysis visit 
Target Study day 
Visit window 
(study days) 
 
Baseline 
1 
-42 to 1 
4 
Week 1 
8 
2 to 11 
5 
Week 2 
15 
12 to 18 
6 
Week 3 
22 
19 to 25 
7 
Week 4 
29 
26 to 43 
8 
Week 8 
57 
44 to 71 
9 
Week 12 
85 
72 to 99 
10 
Week 16 
113 
100 to 127 
11 
Week 20 
141 
128 to 155 
12 
Week 24 
169 
156 to 183 
13 
Week 28 
197 
184 to 211 
14 
Week 32 
225 
212 to 239 
15 
Week 36 
253 
240 to 267 
16 
Week 40 
281 
268 to 295 
17 
Week 44 
309 
296 to 323 
18 
Week 48 
337 
324 to 351 
19 
Week 52 
365 
352 to 379 
20 
Week 56 
393 
380 to 407 
21 
Week 60 
421 
408 to 435 
Table 2-2 
Weekly period for co-administered prednisolone treatment 
Timepoint 
Week 
Week definition 
3 
Week 0 
Study day 1 to Study day 7 
4 
Week 1 
Study day 8 to Study day 14 
5 
Week 2 
Study day 15 to Study day 21 
6 
Week 3 
Study day 22 to Study day 28 
7 
Week 4 
Study day 29 to Study day 35 
8 
Week 5 
Study day 36 to Study day 42 
9 
Week 6 
Study day 43 to Study day 49 
10 
Week 7 
Study day 50 to Study day 56 
11 
Week 8 
Study day 57 to Study day 63 
12 
Week 9 
Study day 64 to Study day 70 
13 
Week 10 
Study day 71 to Study day 77 
14 
Week 11 
Study day 78 to Study day 84 
15 
Week 12 
Study day 85 to Study day 91 
16 
Week 13 
Study day 92 to Study day 98 
17 
Week 14 
Study day 99 to Study day 105 


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Timepoint 
Week 
Week definition 
18 
Week 15 
Study day 106 to Study day 112 
19 
Week 16 
Study day 113 to Study day 119 
20 
Week 17 
Study day 120 to Study day 126 
21 
Week 18 
Study day 127 to Study day 133 
22 
Week 19 
Study day 134 to Study day 140 
23 
Week 20 
Study day 141 to Study day 147 
24 
Week 21 
Study day 148 to Study day 154 
25 
Week 22 
Study day 155 to Study day 161 
26 
Week 23 
Study day 162 to Study day 168 
27 
Week 24 
Study day 169 to Study day 175 
28 
Week 25 
Study day 176 to Study day 182 
29 
Week 26 
Study day 183 to Study day 189 
30 
Week 27 
Study day 190 to Study day 196 
31 
Week 28 
Study day 197 to Study day 203 
32 
Week 29 
Study day 204 to Study day 210 
33 
Week 30 
Study day 211 to Study day 217 
34 
Week 31 
Study day 218 to Study day 224 
35 
Week 32 
Study day 225 to Study day 231 
36 
Week 33 
Study day 232 to Study day 238 
37 
Week 34 
Study day 239 to Study day 245 
38 
Week 35 
Study day 246 to Study day 252 
39 
Week 36 
Study day 253 to Study day 259 
40 
Week 37 
Study day 260 to Study day 266 
41 
Week 38 
Study day 267 to Study day 273 
42 
Week 39 
Study day 274 to Study day 280 
43 
Week 40 
Study day 281 to Study day 287 
44 
Week 41 
Study day 288 to Study day 294 
45 
Week 42 
Study day 295 to Study day 301 
46 
Week 43 
Study day 302 to Study day 308 
47 
Week 44 
Study day 309 to Study day 315 
48 
Week 45 
Study day 316 to Study day 322 
49 
Week 46 
Study day 323 to Study day 329 
50 
Week 47 
Study day 330 to Study day 336 
51 
Week 48 
Study day 337 to Study day 343 
52 
Week 49 
Study day 344 to Study day 350 
53 
Week 50 
Study day 351 to Study day 357 
54 
Week 51 
Study day 358 to Study day 364 
55 
Week 52 
Study day 365 to Study day 371 
56 
Week 53 
Study day 372 to Study day 379 
57 
Week 54 
Study day 380 to Study day 386 
58 
Week 55 
Study day 387 to Study day 393 
59 
Week 56 
Study day 394 to Study day 400 


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Timepoint 
Week 
Week definition 
60 
Week 57 
Study day 401 to Study day 407 
61 
Week 58 
Study day 408 to Study day 414 
62 
Week 59 
Study day 415 to Study day 421 
63 
Week 60 
Study day 422 to Study day 429 
Note: Co-administered treatment refers to prednisolone taken for GCA. There should be a 
26-week prednisolone taper regimen however a patient may take additional prednisolone over 
the 52-week treatment period. 
2.2 
Analysis sets 
The following analysis sets will be used for the patients of interest: 
• The Randomized Analysis Set (RAS) consists of all randomized patients. Unless otherwise 
specified, mis-randomized patients will be excluded from the RAS. (Misrandomized 
patients are defined as cases where patients were mistakenly randomized by the 
investigator/qualified site staff either prematurely or inappropriately prior to confirmation 
of the patient’s final randomization eligibility and double-blind treatment was not 
administered to the patient. If patients were re-screened and successfully randomized they 
will be included in the RAS according to the treatment assigned in the last randomization.) 
• The Full Analysis Set (FAS) comprises all patients to whom study treatment has been 
assigned by randomization and who received at least one dose of randomized study 
treatment (secukinumab or placebo). According to the intent to treat principle, patients will 
be analyzed according to the treatment assigned to them at randomization. 
• The Safety Set includes all patients who received at least one dose of study treatment 
(secukinumab or placebo). Patients will be analyzed according to the study treatment 
received, where treatment received is defined as the treatment the patient received on the 
first day of study treatment. 
The number of patients within each of the analysis sets used in this study will be summarized 
by treatment group and overall (i.e. all patients).  
2.2.1 
Subgroup of interest 
The subgroups of interest for this study are: 
• GCA diagnosis 
• New onset GCA (defined as GCA diagnosis date within 6 weeks of Baseline visit date 
or there is a protocol deviation, in relation to inclusion criteria 5, regardless of protocol 
deviation discrepancy status) 
• Relapsing disease GCA (defined as GCA diagnosis date > 6 weeks from Baseline visit 
date) 
• Baseline co-administered prednisolone treatment 
• ≥ 40 mg/day 
• < 40 mg/day 


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2.3 
Patient disposition, demographics and other baseline 
characteristics 
Patient disposition, background and demographic characteristics will be reported for the RAS, 
unless otherwise specified.  
No inferential tests for differences in background and demographic characteristics will be 
performed. 
2.3.1 
Patient disposition 
Patient disposition will be summarized using: 
• Study treatment disposition 
• Study disposition 
Note: Patients may stop study treatment but continue to stay in the study hence there will be a 
differentiation between study treatment and study disposition. Patients will be analyzed 
according to the treatment assigned at the last randomization (see Section 2.2 for further details). 
The number and percentage of patients who completed study treatment, those who discontinued 
study treatment prematurely, along with the primary reason for study treatment discontinuation, 
will be presented for each treatment group and overall (i.e. all patients) for the RAS. 
A similar summary table will be presented for study disposition, i.e. the treatment disposition 
phase. 
All patient disposition data will be listed by treatment group, center, and subject number for the 
RAS. 
In additition, for the legal requirements of clinicaltrials.gov and EudraCT, the number and 
percentage of patients enrolled in each site will be provided. 
2.3.2 
Demographics and other baseline characteristics 
Demographics and other baseline characteristics data will be summarized for each treatment 
group and overall (i.e. all patients) for the FAS. Patients will be analyzed according to the  
treatment assigned at the last randomization (see Section 2.2 for further details). 
Descriptive statistics will be presented for the following continuous demographic and other 
baseline characteristics variables: 
• Age (years) 
• Height (cm) 
• Note: This will be presented for each treatment group and overall and in addition for 
each sex category in each treatment group and overall. 
• Weight (kg) 
• Note: This will be presented for each treatment group and overall and in addition for 
each sex category in each treatment group and overall. 
• Body mass index (BMI) (kg/m2) 
• Defined as: (body weight in kg) / (height in meters)2 


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For BMI, height and body weight used is the last value prior to first administration of 
study treatment. If there is no weight recorded prior to taking the study treatment, BMI 
will be missing. 
Note: This will be presented for each treatment group and overall and in addition for 
each sex category in each treatment group and overall. 
• Time since diagnosis of GCA (years) 
• Defined as: (date of Visit 1 - date of diagnosis of GCA) / 365.25 
For handling of missing or incomplete GCA diagnosis dates, refer to Section 5.1.4. 
• Time since first GCA symptom (years) 
• Defined as: (date of Visit 1 - date of first GCA symptom) / 365.25 
For handling of missing or incomplete first GCA symptom dates, refer to Section 5.1.4. 
• GCA diagnosis (New onset GCA, Relapsing disease GCA) 
• Baseline co-administered prednisolone treatment (≥ 40, < 40 mg/day) 
The number and percentage of patients in each category of the following categorical variables 
overall will be presented: 
• Weight group (< 70, ≥ 70 to < 90, ≥ 90 kg) 
• Current smoking status (Current, Former, Never) 
• Race (White, Black or African American, Asian)   
• Sex (Male, Female) 
All important demographics and other baseline characteristics data will be listed by treatment 
group, center, and subject number for the RAS. 
In addtion, for the legal requirements of clinicaltrials.gov and EudraCT, the following age 
categories will also be presented: 
• 18 to < 65 years 
• Note: Inclusion criteria 3 indicates that patients must be at least 50 years of age to be 
included in this study. Therefore for this study the subgroup category 18 to < 65 years 
is equivalent to 50 to < 65 years. 
• 65 to < 85 years 
• ≥ 85 years 
2.3.2.1 
Medical history 
Relevant medical histories and current medical conditions at the time of informed consent will 
be summarized for each treatment group and overall (i.e. all patients) for the FAS. 
Note: If there are COVID-19 infected patients in this study, descriptive summaries of medical 
history will be provided first by all patients of interest, then by COVID-19 infected patients and 
non-COVID-19 infected patients. 
The summaries will be presented by primary system organ class (SOC) and preferred term (PT). 
Medical histories will be coded using the most recent (i.e. latest version as per clinical database 
lock [CDBL]) Medical Dictionary for Regulatory Activities (MedDRA). The primary SOCs 


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will be presented in alphabetical order and the PTs will be presented by decreasing proportion 
in the overall group. 
2.3.2.2 
Cardiovascular medical history 
Cardiovascular medical history will be presented by treatment group and overall (i.e. all patients) 
for the Safety Set.  
Note: If there are COVID-19 infected patients in this study, descriptive summaries of medical 
history will be provided first by all patients of interest, then by COVID-19 infected patients and 
non-COVID-19 infected patients. 
The number and percentage of patients with an occurrence of the following events will be 
provided: 
• Type 1 diabetes 
• Type 2 diabetes 
• Hypertension 
• Dyslipidemia/Hyperlipidemia 
• Prior transient ischemic attack 
• Prior hemorrhagic stroke 
• Prior ischemic stroke 
• Prior stroke: unknown type 
• Myocardial infarction 
• Atrial fibrillation 
• Supraventricular tachycardia 
• Deep vein thrombosis 
• Pulmonary embolism 
• Peripheral arterial disease 
• Stable coronary artery disease 
• Gout 
In addition, the number and percentage of patients with an ongoing event at Baseline will be 
provided in a summary table by treatment group and overall (i.e. all patients) for the Safety Set. 
2.3.2.3 
GCA medical history 
GCA medical history will be presented by treatment group and overall (i.e. all patients) for the 
Safety Set.  
Note: If there are COVID-19 infected patients in this study, descriptive summaries of medical 
history will be provided first by all patients of interest, then by COVID-19 infected patients and 
non-COVID-19 infected patients. 
The number and percentage of patients with an occurrence of the following events will be 
provided: 
• Diplopia 


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• Blurring of vision 
• Transient partial visual loss (Amaurosis fugax) - Left eye 
• Transient partial visual loss (Amaurosis fugax) - Right eye 
• Visual field defect - Left eye 
• Visual field defect - Right eye 
• Loss of vision - Left Eye 
• Loss of vision - Right Eye 
• Relative afferent pupillary defect 
• Headache 
• Scalp tenderness 
• Claudication of jaw muscles 
• Temporal artery abnormality 
• Fever 
• Night sweat 
• Weight loss 
• Large vessel involvement 
• Polymyalgia rheumatica 
In addition, the number and percentage of patients with an ongoing event at Baseline will be 
provided in a summary table by treatment group and overall (i.e. all patients) for the Safety Set. 
Only the following GCA medical history events can be classified as ongoing or not at Baseline: 
• Diplopia 
• Blurring of vision 
• Transient partial visual loss (Amaurosis fugax) - Left eye 
• Transient partial visual loss (Amaurosis fugax) - Right eye 
• Relative afferent pupillary defect 
2.3.3 
Protocol deviations 
The number and percentages of patients with each important protocol deviation type will be 
tabulated by treatment group and overall (i.e. all patients) for the FAS. The results will be 
grouped using the broad categories defined in the current Standard Operating Procedure (SOP) 
which are: 
• Patient did not satisfy entry criteria 
• Patient received the wrong treatment or incorrect dose 
• Patient developed study/treatment withdrawal criteria during the study, but was not 
withdrawn 
• Patient took an excluded concomitant medication 
• Others 
All important protocol deviations will be listed by treatment group, center, and subject number 
for the FAS. 


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Note: There is no per protocol analysis set in this study. Therefore no protocol deviation will 
lead to exclusion from any of the analysis sets.  
In addition, pandemic related protocol deviations will be summarized by category and 
relationship. All COVID-19 related protocol deviations will also be listed for the FAS. 
2.4 
Treatments (study treatment, rescue medication, concomitant 
therapies, compliance) 
Summaries will be presented for the Safety Set. Patients will be analyzed according to treatment 
received (see Section 2.2 for further details). 
2.4.1 
Study treatment / compliance 
The number and percentage of study treatment injections will be summarized by treatment 
group by means of contingency tables.  
In case it cannot be identified from the data collected or assumed from the planned treatment 
whether an injection contained placebo or secukinumab, it will be assumed that the syringe 
contained secukinumab. 
The duration of exposure to study treatment will be summarized by treatment group. Duration 
of exposure to study treatment will be defined as the time from first dose of study treatment to 
the end of the treatment period. The end of treatment period will be defined as the last dose of 
the study treatment plus 84 days or last visit whichever occurs earlier. i.e., for patients who 
discontinued or have their last visit earlier than last dose of study treatment plus 84 days, the 
end of study treatment exposure will be the date of the last study visit in the corresponding 
treatment period. 
Duration of exposure (weeks) = (min(end of treatment period date, last dose of study treatment 
date + 84 days) - first dose of study treatment date + 1)/7 
The number of patients with exposure of the following time thresholds will be displayed: 
• any exposure 
• ≥ 1 week 
• ≥ 2 weeks  
• ≥ 3 weeks 
• ≥ 4 weeks 
• ≥ 8 weeks 
• ≥ 12 weeks 
• ≥ 16 weeks 
• ≥ 20 weeks 
• ≥ 24 weeks 
• ≥ 28 weeks 
• ≥ 32 weeks 
• ≥ 36 weeks 
• ≥ 40 weeks 


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• ≥ 44 weeks 
• ≥ 48 weeks 
Descriptive statistics will also be provided for the study treatment group for the following: 
• Actual cumulative dose  
Defined as: the sum of all doses of study treatment during the treatment disposition phase 
• Dose intensity 
Defined as: the ratio of actual cumulative dose of study treatment received and actual 
duration of exposure of study treatment (weeks) 
Note: Each study treatment injection is equivalent to 150 mg. Patients assigned to study 
treatment should take 2 injections (150 mg) weekly from Week 0 to Week 4 and then every 4 
weeks until Week 48. 
The duration of exposure to the co-administered prednisolone treatment will also be 
summarized by treatment group using the same logic and rules as the study treatment (with the 
exception that the addition of 84 days is only applicable to study treatment). In addition 
descriptive statistics of the average daily dose (mg/day) of co-administered prednisolone 
treatment overall during the study and at each week (refer to Table 2-2 for weekly visit 
windowing) during the 26-week prednisolone taper regimen will be presented for each 
treatment group. 
Furthermore descriptive statistics of the co-administered prednisolone treatment at the time of 
first flare post-baseline will also be provided. 
Co-administered prednisolone treatment data will be listed by treatment group, center, and 
subject number for the Safety Set. In addition, a co-administered prednisolone treatment data 
listing will also be provided for the subset of patients who did not adhere to the prednisolone 
taper regimen. 
2.4.2 
Prior, concomitant and post therapies 
Medications will be identified by Anatomical Therapeutic Chemical (ATC) class and PT 
according to the World Health Organization (WHO) Drug Reference List dictionary (version 
18.9 or a more recent version).  
Note: If there are COVID-19 infected patients in this study, descriptive summaries of prior and 
concomitant medications will be provided first by all patients of interest, then by COVID-19 
infected patients and non-COVID-19 infected patients. 
Summaries will be presented separately for prior and concomitant medications. Tables will 
show the number and percentage of patients receiving at least one dose of the therapy. 
Note: Methotrexate (MTX) will not be included in the aforementioned summaries for prior and 
concomitant medications. Separate summaries will be created for prior and concomitant use of 
MTX. 
Prior medications are defined as drugs taken and stopped prior to first dose of study treatment. 
Any medication given at least once between the day of first dose of randomized study treatment 


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and the last day of study visit will be a concomitant medication, including those which were 
started pre-baseline and continued into the treatment period. 
Prior or concomitant medication will be identified based on recorded or imputed start dates of 
medication taken in this study. The rules for imputing incomplete start dates are described in 
Section 5.1.3. All prior and concomitant medication data will be listed by treatment group, 
center, and subject number. 
In addition, medical procedures and significant non-drug therapies as coded in MedDRA will 
be summarized. 
2.4.3 
Signs and symptoms of GCA 
The number and percentage of patients who experienced flare due to GCA will be summarized 
by visit for each treatment group and overall (i.e. all patients). The summary table will also 
include the number and percentage of patients with each of the following individual signs and 
symptoms of GCA: 
• Fever (Yes, No) 
• Symptoms of polymyalgia rheumatica (PMR) (Yes, No) 
• Localized headache, temporal artery or scalp tenderness (Yes, No) 
• Acute or subacute vision loss due to arteritic anterior ischemic optic neuropathy(A-AION) 
(Yes, No) 
• Transient blurry vision (generally monocular or at least affecting one eye at a time, but 
potentially affecting both eyes) (Yes, No) 
• Jaw or mouth pain (Yes, No) 
• New or worsened extremity claudication (Yes, No) 
• Other features judged by both the clinician-investigator to be consistent with a GCA or PMR 
flare (Yes, No) 
Note: More than 1 sign and symptom of GCA may be selected. 
2.5 
Analysis of the primary objective 
Patients will be analyzed according to the treatment assigned at the last randomization (see 
Section 2.2 for further details). 
2.5.1 
Primary endpoint 
The primary endpoint is the proportion of GCA patients who are in sustained remission until 
Week 28. 
The analysis of the primary variable will be based on the following estimand: 
• Analysis set: FAS (for the patients of interest as outlined in Section 2.1) 
• Variable of interest: Proportion of GCA patients who are in sustained remission until 
Week 28 
• Sustained remission: Patients without flare until Week 28 and in adherence to the 
protocol prednisolone taper regimen.  


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• Note: Flare is determined by the investigator and defined as the recurrence after 
remission of signs or symptoms of GCA and/or ESR ≥ 30 mm/hr and/or 
CRP ≥ 10 mg/L attributable to GCA. 
• Adhere to prednisolone taper: Patients do not adhere to the prednisolone taper regimen 
if during the 26-week prednisolone taper regimen any of the following occur: 
• Patient does not take prednisolone medication for GCA for ≥ 6 consecutive days. 
• Patient takes prednisolone treatment for GCA for < 80% of the 26-week 
prednisolone taper regimen period. 
• Patient has received additional prednisolone for GCA to that stated in the taper 
regimen.  
Note: This criteria (receiving additional prednisolone) does not apply to those 
patients in the “escape arm”. 
This means a patient is classified as receiving an additional prednisolone for 
GCA to that stated in the taper regimen if in the timeframe: 
• [Week 0-Week 11] the patient’s weekly dose is 20% over the stated dosage of 
prednisolone, or 
• [Week 12-Week 26] the patient’s weekly dose is 30% over the stated dosage 
of prednisolone. 
• Patient received an additional corticosteroid to that stated in the taper regimen. 
Note: This will be based on the respective PD associated with this criteria. 
Note: The final decision on whether the patient is non-adherent to the prednisolone 
taper will be confirmed by the blinded medical team on a by-patient basis in a Blind 
Data Review Meeting (BDRM) prior to CDBL. This decision will be documented in 
the associated BDRM minutes. 
• Intervention effect: Effect between secukinumab versus placebo at Week 28 regardless of 
adherence to randomized treatment. 
• Measure of intervention effect: Odds ratio (OR). 
2.5.2 
Statistical hypothesis, model, and method of analysis  
The primary endpoint variable of interest is binary, hence a binomial distribution will be 
assumed for the observed data from this study. It is of interest to estimate a one-dimensional 
scalar parameter (the primary endpoint estimand Ɵ) using Bayesian inference.  
To perform this inference, a prior distribution for Ɵ must first be specified. The response rate 
of the comparable placebo arm of the GIACTA study (Stone et al 2017) will be used as the prior 
distribution for the placebo response rate for the primary endpoint in this study. The parameters 
of this Beta distribution are 10 and 43, i.e. Beta (10, 43). The prior distribution for the response 
rate on secukinumab will be a Beta distribution with parameters 0.5 and 0.5, i.e. Beta (0.5, 0.5). 
This prior distribution was chosen because it has low weight to reflect the lack of current 
knowledge on the response rate on secukinumab in GCA. 
The process of Bayesian inference involves passing from a prior distribution, p(Ɵ), to a 
posterior distribution, p(Ɵ|y) where y refers to the data of interest from this study. Due to the 
conjugate nature of the Beta distributions, the posterior distributions of the primary endpoint 


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estimand Ɵ will also be Beta distributions. As the Beta distribution has a closed form nature, 
descriptive statistics of the posterior distribution are also available in closed form. 
Using the prior distribution information and the study data, the Beta posterior distribution for 
each treatment group will be derived. 
Ɵ|𝑦𝑦 ~ 𝐵𝐵𝐵𝐵𝐵𝐵𝐵𝐵 (𝑦𝑦 + 𝑎𝑎, 𝑛𝑛 − 𝑦𝑦 +  𝑏𝑏) 
Note: y = study data (i.e. proportion of GCA patients who are in sustained remission until 
Week 28) for the treatment of interest; n = number of randomized patients for the treatment of 
interest; a, b = the shape parameters from the prior Beta distribution [Beta(a,b)] associated with 
the treatment of interest. 
One hundred thousand random draws from the Beta posterior distributions will then be taken 
based on the seed 190207. An estimate of the 95% posterior interval (i.e. the 95% credibility 
interval), using the the 2.5 and 97.5 percentiles as well as the median (50 percentile) will be 
obtained. The median and 95% credibility interval of the OR, risk difference (RD) and risk ratio 
(RR) will be presented.  
Note: Odds ratio is the ratio of odds of the primary endpoint in secukinumab to the odds of the 
event in placebo. The odds of an event refers to the number of events / the number of non-
events. Risk difference is the difference in proportions of the patients with the primary endpoint 
in secukinumab vs placebo. Risk ratio (also known as relative risk) is the ratio of risk of the 
primary endpoint in secukinumab to the risk of the primary endpoint in placebo. 
For this study, similar response rates to the GIACTA study (Stone et al 2017) for the primary 
endpoint are expected, i.e. 56% secukinumab response rate and 18% placebo response rate. If 
the secukinumab response rate was < 40% this may indicate that further trials in this indication 
would not be worthwhile. Therefore assuming the 18% placebo response rate is fixed, the  
treatment response rates would translate into a RD of: 
• 38% (expected effect, based on 56%-18%) 
• 22% (minimal effect, based on 40%-18%) 
This study would suggest to proceed with the development of secukinumab in this indication, 
if the following GO-criterium are satisfied: 
• the posterior probability of a relevant effect (RD > 0.22) is at least 50% (also written as 
prob(RD > 0.22 | y) ≥ 50%) 
and  
• the posterior probability of any effect (RD > 0) is at least 90% (also written as prob(RD > 0 
| y) ≥ 90%) 
The posterior probabilities for a relevant effect and for any effect will be determined to give 
guidance in deciding whether to proceed in the development of secukinumab in this indication.   
The posterior probability of the OR and the RR of the comparison of secukinumab versus 
placebo being greater than 1 will also be provided. Note: An OR or RR greater than 1 indicates 
a favourable outcome for secukinumab vs placebo in regard to the primary endpoint. 


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Furthermore, the proportion of patients in sustained remission until Week 28 (Yes, No) will be 
summarized descriptively by treatment group. This analysis does not take into account the prior 
information, it is only based on information from this study. 
In addition, all primary endpoint data will be listed by treatment group, center, and subject 
number for the FAS. 
2.5.3 
Handling of missing values/censoring/discontinuations 
Patients will be classified as non-responders if they fulful any of the following: 
• Do not achieve remission within 12 weeks of Baseline 
• Note: Remission refers to the absence of flare. 
• Are in the “escape arm” 
• Note: This refers to the patient entering escape between Baseline and Week 28. 
• Prematurely discontinue study treatment prior to Week 28 
• Note: Absence of flare is checked prior to study treatment administration. 
• Do not have information to evaluate sustained remission response until Week 28 
Patients receiving less than the full amount of prednisolone for GCA as required by the taper, 
e.g. due to missing tablets, will not be classified as non-responders with the exception of those 
who are classified as non-adherent to the prednisolone taper regimen (refer to Section 2.5.1 for 
definition of adherence to the prednisolone taper regimen). Note: The final decision on whether 
the patient is non-adherent to the prednisolone taper will be confirmed by the blinded medical 
team on a by-patient basis in a BDRM prior to CDBL. This decision will be documented in the 
associated BDRM minutes. 
2.5.4 
Supportive analyses 
In order to assess the robustness of the primary endpoint, the following analyses are planned: 
• Using a non-informative prior, i.e. uniform prior Beta (0.5, 0.5), for both treatment groups 
• A logistic regression model with treatment in the model. ORs along with the respective 
2-sided 80% confidence interval (CI) will be derived for the treatment comparison.  
Furthermore, the primary analysis will be repeated based on only signs and symptoms of GCA 
in order to mitigate against the possibility of biasing. 
In addition, the reasons why a patient is determined to be a responder or non-responder to the 
primary endpoint will be summarized. 
Subgroup analyses (see Section 2.2.1 for further details) will only be performed if at least 5 
patients are present in each subgroup. Some grouping of classes will be considered if there are 
too few patients in some subgroups.  
 
 
2.6 
Analysis of the key secondary objective 
There are no key secondary objectives in this study. 


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2.7 
Analysis of secondary efficacy objectives 
Patients will be analyzed according to the treatment assigned at the last randomization (see 
Section 2.2 for further details) for the FAS. 
The analyses of the secondary efficacy objectives will not take into account the prior 
information, it is based only on information from this study. 
2.7.1 
Secondary endpoints 
The following secondary endpoints will be analyzed: 
• Proportion of GCA patients who adhere to the prednisolone taper regimen and are in 
sustained remission at Week 52 
• Remission rate at Week 12 
• Time to first GCA flare after Baseline (up to and including Week 52) 
• Total cumulative prednisolone dose from start of co-administered treatment to Week 28, 52 
• Proportion of patients on prednisolone dose ≤ 5mg/day at Week 19, 28, 52  
• Change from Baseline in PhGA VAS at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52  
• Change from Baseline in PGA VAS at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52  
• Change from Baseline in FACIT-Fatigue at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52  
• Change from Baseline in SF-36 at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52  
• Change from Baseline in EQ-5D at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52  
• Change from Baseline in CRP (mg/L) at Week 4, 8, 12, 16, 20, 24, 28, 36, 40, 44, 48, 52 
• Change from Baseline in ESR (mm/hr) at Week 4, 8, 12, 16, 20, 24, 28, 36, 40, 44, 48, 52 
2.7.2 
Statistical hypothesis, model, and method of analysis 
The proportion of patients in sustained remission until Week 52 (Yes, No) will be summarized 
descriptively for each treatment group. Note: Sustained remission at Week 52 refers to patients 
without flare until Week 52 and in adherence to the protocol prednisolone taper regimen. Flare 
is determined by the investigator and defined as the recurrence after remission of signs or 
symptoms of GCA and/or ESR ≥ 30 mm/hr and/or CRP ≥ 10 mg/L attributable to GCA. In 
addition, the reasons why a patient is determined to be a responder or non-responder to patients 
in sustained remission until Week 52 will be summarized. 
The proportion of patients in remission (Yes, No) at each time point will be summarized 
descriptively for each treatment group. Note: Remission refers to the absence of flare. This 
summary table will only summarize remission information up to 4 weeks post last 
administration of study treatment. 
The time to first GCA flare after remission (up to and including Week 52) will be summarized 
using Kaplan Meier curves. Descriptive statistics will also be provided for time to first GCA 
flare after remission in days (up to and including Week 52). This will also include information 
on follow-up. Follow-up is defined as: 
• (Date of event or censoring – Baseline date) + 1 (regardless of censoring) 


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Total cumulative prednisolone dose from the first dose of co-administered prednisolone 
treatment to Weeks 26, Week 28, and 52 will be summarized over time by treatment group. 
Note: Prednisolone dose refers to prednisolone dose taken for GCA. 
The number and percentage of patients on prednisolone dose ≤ 5mg/day at Week 19, 28 and 52 
will be summarized by treatment group. Note:  
• Prednisolone dose refers to prednisolone dose taken for GCA. 
• Prednisolone dose refers to the average co-administered prednisolone treatment in the week 
of interest. 
• Prednisolone dose for GCA will be based on the information collected on the “Dosage 
Administration Record-Prednisolone” eCRF. However as the prednisolone taper regimen is 
planned to be 26-weeks in duration, the Investigator is not required to enter daily 
prednisolone records on the “Dosage Administration Record-Prednisolone” eCRF post 
Week 26 unless the patient has taken additional prednisolone for GCA. Therefore if the 
patient is still in the study at the post Week 26 week of interest and has no prednisolone 
information in the “Dosage Administration Record-Prednisolone” eCRF for that week of 
interest the patient will be regarded as having 0 mg/day at that week of interest. 
Descriptive summary statistics for the change as well as relative change from baseline of PhGA 
VAS to each study visit of interest will be presented for each treatment group. Change from 
baseline will only be summarized for patients with both baseline and post baseline values.  
The analysis of the PRO secondary endpoints is detailed in Section 2.10. 
Descriptive summary statistics for the change from baseline of CRP and ESR to each study visit 
of interest will be presented for each treatment group. Change from baseline will only be 
summarized for patients with both baseline and post baseline values. Further details are 
provided in Section 2.8.3. This analysis will also be presented for the following subgroups: 
• Sustained remission until Week 28 (Yes, No) 
• Sustained remission until Week 52 (Yes, No) 
2.7.3 
Handling of missing values/censoring/discontinuations 
For sustained remission until Week 52, patients will be classified as non-responders if they 
fulful any of the following: 
• Do not achieve remission within 12 weeks of Baseline 
• Note: Remission refers to the absence of flare. 
• Are in the “escape arm” 
• Note: This refers to the patient entering escape between Baseline and Week 52. 
• Prematurely discontinue study treatment prior to Week 52 
• Note: Absence of flare is checked prior to study treatment administration. 
• Do not have information to evaluate sustained remission response until Week 52 
Patients receiving less than the full amount of prednisolone for GCA as required by the taper, 
e.g. due to missing tablets, will not be classified as non-responders with the exception of those 
who are classified as non-adherent to the prednisolone taper regimen (refer to Section 2.5.1 for 
definition of adherence to the prednisolone taper regimen). Note: The final decision on whether 


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the patient is non-adherent to the prednisolone taper will be confirmed by the blinded medical 
team on a by-patient basis in a BDRM prior to CDBL. This decision will be documented in the 
associated BDRM minutes. 
For remission rate at Week 12, patients will be classified as non-responders if they fulfil any of 
the following: 
• Prematurely discontinue study treatment 
• Enter “escape” therapy 
Note: Patients will be classified as non-responders for the above two scenarios from the point 
of withdrawal/escape onwards. Patients with a missing remission status at Week 12 will be 
classified as non-responders. 
For time to first GCA flare after remission (up to and including Week 52), patients who: 
• Prematurely discontinue study treatment prior to Week 52 will be censored at the time of 
premature discontinuation 
• Complete treatment and do not have a flare will be censored at their last visit in the treatment 
phase 
2.8 
Safety analyses 
Patients will be analyzed according to treatment received (see Section 2.2 for further details) 
for the Safety Set. 
2.8.1 
Adverse events 
Adverse events will be coded by primary SOC and PT according to the MedDRA version 23.0 
or later and will be presented for the whole study period. Only treatment emergent AEs (TEAEs) 
will be summarized. 
Treatment emergent AEs are defined as events started after the first dose of study treatment or 
events present prior to the first dose of study treatment but increased in severity after dosing 
based on preferred term and within last dose + 84 days. For handling of missing or incomplete 
start and end dates, refer to Section 5.1.2. 
Treatment emergent AEs will be summarized for each treatment group by presenting the crude 
incidence of patients having any TEAE and having a TEAE by primary SOC and by PT. Patients 
who experienced multiple AEs for a PT will be counted once for that PT, similarly for patients 
with multiple AEs per primary SOC. For summaries of TEAEs by severity, if a patient reports 
more than one AE with the same PT, only the AE with the maximum severity will be counted. 
Similarly, if a patient reports more than one AE within the same primary SOC, the event with 
the maximum severity will be counted for the SOC level. If the severity of a particular AE is 
missing, this severity will be treated as missing in summaries and listed accordingly. 
The following TEAE information will be summarized separately by contingency tables: 
• Adverse events, regardless of relationship to study or co-administered prednisolone 
treatment, by primary SOC and PT 
• Adverse events, suspected to be related to study treatment, by primary SOC and PT 


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• Adverse events, suspected to be related to co-administered prednisolone treatment, by 
primary SOC and PT 
• Serious AEs, regardless of relationship to study or co-administered prednisolone treatment, 
by primary SOC and PT 
• Serious AEs, suspected to be related to study treatment, by primary SOC and PT 
• Serious AEs, suspected to be related to co-administered prednisolone treatment, by primary 
SOC and PT 
• Adverse events, regardless of relationship to study or co-administered prednisolone 
treatment, by primary SOC, PT and maximum severity (mild, moderate, severe) 
• Adverse events leading to study treatment discontinuation, regardless of relationship to 
study or co-administered prednisolone treatment, by primary SOC and PT 
• Adverse events leading to study treatment discontinuation, suspected to be related to study 
treatment, by primary SOC and PT 
• Adverse events leading to study treatment discontinuation, suspected to be related to 
co-administered prednisolone treatment, by primary SOC and PT 
• Adverse events requiring study dose adjustment/interruption, regardless of relationship to 
study or co-administered prednisolone treatment, by primary SOC and PT 
• Adverse events requiring additional therapy, regardless of relationship to study or 
co-administered prednisolone treatment, by primary SOC and PT 
In addition, for the legal requirements of clinicaltrials.gov and EudraCT, 2 required tables on 
TEAEs which are not SAEs with an incidence greater than 5% and on treatment emergent SAEs 
and SAEs suspected to be related to study treatment will be provided by primary SOC and PT. 
If for the same patient, several consecutive AEs (irrespective of study treatment causality, 
seriousness and severity) occurred with the same primary SOC and PT: 
• A single occurrence will be counted if there is  ≤ 1 day gap between the end date of the 
preceding AE and the start date of the consecutive AE 
• More than one occurrence will be counted if there is > 1 day gap between the end date of 
the preceding AE and the start date of the consecutive AE 
For occurrence, the presence of at least one SAE/SAE suspected to be related to study 
treatment/non-SAE has to be checked in a block e.g., among AEs in a ≤ 1 day gap block, if at 
least one SAE is occurring, then one occurrence is calculated for that SAE. 
2.8.1.1 
Adverse events of special interest / grouping of AEs 
Specific groupings of AEs of special interest (AESI) will be considered and the number of 
patients with at least one event in each grouping will be reported. Such groups consist of AEs 
for which there is a specific clinical interest in connection with secukinumab or AEs which are 
similar in nature (although not identical). Note that certain AEs may be reported within multiple 
groupings. These AESIs are updated on a regular basis at the secukinumab program level. The 
most recent version of the AESI search criteria form as described in the electronic Case 
Retrieval Sheet (eCRS) will be used for the reporting activity.  


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AESIs will be summarized regardless of study drug relationship, for each treatment group by 
grouping and PT.  
2.8.2 
Deaths 
The number and percentage of deaths resulting from SAEs suspected to be related to study 
treatment and SAEs irrespective of study treatment relationship will be provided for each 
treatment group by primary SOC and PT. 
2.8.3 
Laboratory data 
Only “on-treatment” laboratory data (i.e. all assessments in the the safety observation as defined 
in Section 2.1.1.4) will be summarized.  
The summary of laboratory evaluations will be presented for three groups of laboratory tests 
(hematology, clinical chemistry, and urinalysis). 
Descriptive summary statistics for the change from baseline to each study visit of interest will 
be presented. These descriptive summaries will be presented by laboratory test and treatment 
group. Change from baseline will only be summarized for patients with both baseline and post 
baseline values. In addition, shift tables using the low/normal/high/ (low and high) classification 
will be used to compare Baseline to the worst on-treatment value. 
For urinalysis, frequency tables will be presented. 
All laboratory data will be listed by center, subject number, and visit/time and if ranges are 
available, abnormalities will be flagged.  
2.8.4 
Other safety data 
2.8.4.1 
Vital signs 
Only “on-treatment” vital signs data (i.e. all assessments in the the safety observation as defined 
in Section 2.1.1.4) will be summarized.  
Descriptive summary statistics for the change from baseline to each study visit of interest will 
be presented. These descriptive summaries will be presented by vital sign parameter and 
treatment group. Change from baseline will only be summarized for patients with both baseline 
and post baseline values. Note: As blood pressure will be assessed for both arms, the average 
of the available blood pressure assessments will be summarized/listed. 
All vital signs data will be listed by center, subject number, and visit/time and if ranges are 
available, abnormalities will be flagged.  
2.8.4.2 
Immunogenicity 
The number and percentage of patients without immunogenicity and with positive 
immunogenicity will be provided. The number and percentage of patients with neutralizing 
antibodies will be presented as well.  
All immunogenicity results (anti-AIN457 antibodies) will be listed by treatment group, center, 
subject number, and study visit. 


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2.8.4.3 
QuantiFERON TB-Plus test  
All QuantiFERON TB-Plus test results will be listed by treatment group, center, subject number, 
and study visit. 
 
   
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
2.10 
Patient-reported outcomes 
The following secondary PRO endpoints will be analyzed according to treatment received (see 
Section 2.2 for further details) for the FAS: 
• Change from Baseline in PGA VAS at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52  
• Change from Baseline in FACIT-Fatigue at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52  
• Change from Baseline in SF-36 at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52  
• Change from Baseline in EQ-5D at Week 4, 8, 12, 16, 20, 24, 28, 36, 44 and 52  
Descriptive summary statistics for the change as well as relative change from baseline of PGA 
VAS to each study visit of interest will be presented for each treatment group. Change from 
baseline will only be summarized for patients with both baseline and post baseline values.  
Descriptive summary statistics for the change as well as relative change from baseline of 
FACIT-Fatigue to each study visit of interest will be presented for each treatment group. 
Change from baseline will only be summarized for patients with both baseline and post baseline 
values.  
For SF-36, the following variables will be evaluated:  
• SF-36 domain scores 


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• SF-36 domain score responders  
• Type I responders (improvement of ≥ 5 points in ≥ 6 domains)  
• Type II responders (improvement of ≥ 10 points in ≥ 3 domains)  
• SF-36 Physical Component Summary (PCS) and Mental Component Summary (MCS) 
scores (norm-based scores) 
• SF-36 PCS and MCS score responders  
• Type I responders (improvement of ≥ 2.5 points)  
• Type II responders (improvement of ≥ 5 points)  
Descriptive summary statistics for the change as well as relative change from baseline of SF-36 
domain and summary scores to each study visit of interest will be presented for each treatment 
group. Change from baseline will only be summarized for patients with both baseline and post 
baseline values. The proportion of responders at each time point will be summarized 
descriptively for each treatment group. 
The EQ-5D is a questionnaire with 5 questions (regarding mobility, self-care, usual activities, 
pain/discomfort, and anxiety/depression) each with 5 categories and a health state assessment 
from 0 (worst possible health state) to 100 (best possible health state). The number and 
percentage of patients in each of the 5 categories for each question will be presented by study 
visit and treatment group. Descriptive summary statistics will be provided for the change from 
baseline of health state assessment (known as EQ-5D-5L VAS) and EQ-5D-5L utility index 
(see Section 5.4.1 for further details) by study visit and treatment group. 
2.11 
Biomarkers 
Not applicable. 
 
 
 
 
 
 
  
 
 
  
 
 
 
 
 
 
 
 
 
 
 


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2.13 
Interim analysis 
In total, 3 IAs will be conducted: 
• IA1 – after approx. 50% of patients reach Week 28  
• IA2 – after approx. 50% of patients reach Week 52  
• IA3 - 100% of patients reach Week 28 
The analyses for each of the aforementioned IAs are detailed in separate SAPs. 
Prior to the protocol amendment version no. 2 including Amendment 2, the analyses of the 
primary endpoint and all other data at Week 28 were intended to be the final analysis of this 
study. As the blinded treatment period was extended until Week 52, this formerly final analysis 
will be conducted as IA3. 
All IAs, in particular IA2 on Week 52 data will be informative to the planning of a Phase 3 
program of secukinumab in GCA. There will be no multiplicity adjustment.  
An independent unblinded study team will perform all interim analyses. Details will be 
specified in the Interim Analyses Charter.  
3 
Sample size calculation 
Based on the observed response rates in the GIACTA study (Stone et al 2017), there were 56 out 
of 100 patients on tocilizumab every other week (56%) in combination with 26-week 
prednisolone taper regimen and 9 out of 51 patients treated with placebo (18%) in combination 
with 52-week prednisolone taper regimen. The expected observed responders in a sample size 
of 25 patients per treatment group is then 25*(56/100) = 14 and 25*(9/51) = 4.  The posterior 
distribution of the expected difference in proportions was investigated for the sample size of 
25 patients per treatment group.  
Using an uninformative prior Beta (1, 1) for the secukinumab group and an informative prior 
for the expected observed responders in the placebo group of Beta (10, 43), 10000 Monte Carlo 
simulations of each posterior density was then computed and the posterior distribution of the 
difference then described using the 2.5, 50 (median) and 97.5 percentiles (Table 3-1). 
Other plausible outcomes have been investigated if the observed response rates are different 
from expected (refer to Table 3-1). 
Table 3-1 
Sensitivity to changes in assumptions in observed response rates 
Observed response rate 
Posterior quantiles for p1 – p2 
Posterior 
Prob(p1 > p2) 
Secukinumab (p1) 
Placebo (p2) 
2.5% 
Median 
97.5% 
0.56 
0.16 
0.19 
0.38 
0.56 
0.99 
0.56 
0.20 
0.16 
0.36 
0.55 
0.99 
0.56 
0.24 
0.15 
0.35 
0.55 
0.99 


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Observed response rate 
Posterior quantiles for p1 – p2 
Posterior 
Prob(p1 > p2) 
Secukinumab (p1) 
Placebo (p2) 
2.5% 
Median 
97.5% 
0.56 
0.28 
0.13 
0.34 
0.54 
0.99 
0.52 
0.16 
0.14 
0.34 
0.53 
0.99 
0.48 
0.16 
0.11 
0.31 
0.51 
0.99 
4 
Change to protocol specified analyses 
  
The baseline prednisolone dose subgroup categories have been updated from > 40 mg/day and 
≤ 40 mg/day to ≥ 40 mg/day and < 40 mg/day to align with the planned prednisolone taper 
regimen. 
Sustained remission at a timepoint refers to patients being without flare until that timepoint and 
in adherence to the protocol prednisolone taper regimen. As adherence to the protocol 
prednisolone taper regimen is a component of the sustained remission definition already; any 
redundant mention of adherence to prednisolone taper regimen has been removed throughout 
this document.  
Any reference to the time point after clinical remission has been updated to be after Baseline; 
this aligns more clearly with what was planned to be analyzed. 
5 
Appendix 
5.1 
Imputation rules 
5.1.1 
Study drug 
Any partial dates will be imputed as follows: 
• Take the earlier day of: 
• The last day in the month and 
• The end day of the corresponding epoch 
5.1.2 
Adverse event date imputation 
5.1.2.1 
Adverse event end date 
For the purpose of date imputation, the study treatment follow-up period date is defined as the 
last available visit date, i.e. including unscheduled visits after the end of study visit. 
1. If the AE end date month is missing, the imputed end date should be set to the earliest of 
the (study treatment follow-up period date, 31DECYYYY, date of death). 
2. If the AE end date day is missing, the imputed end date should be set to the earliest of the 
(study treatment follow-up period date, last day of the month, date of death). 
3. If AE year is missing or AE is ongoing, the end date will not be imputed. 


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If the imputed AE end date is less than the existing AE start date then use AE start date as AE 
end date. 
5.1.2.2 
Adverse event start date 
Adverse events with completely missing onset dates will be considered to be treatment 
emergent.  AEs with partially missing onset dates will also be included as treatment emergent 
when the month (if it exists) and the year occur on or later than the month and year of first 
administration of study treatment within this study. 
Partial AE start dates are imputed with reference to the first administration of study treatment 
within this study as outlined in the table below.  
The date value is split into day, month, year sections and referenced in the imputation table as 
outlined below. 
 
Day 
Month 
Year 
Partial AE Start Date  
Not used  
MON  
YYYY 
Treatment Start Date 
Not used  
TRTM 
TRTY 
The following matrix explains the logic behind the imputation.  
Comparison of 
month section 
MON missing 
MON<TRTM 
MON=TRTM 
MON>TRTM 
YYYY missing 
NC 
NC 
NC 
NC 
YYYY<TRTM 
(D) = 
01JULYYYY 
Before Treatment 
Start 
(C) = 
15MONYYYY 
Before Treatment 
Start 
(C) = 
15MONYYYY 
Before Treatment 
Start 
(C) = 
15MONYYYY 
Before Treatment 
Start 
YYYY=TRTY 
(B) = 
TRTSTD+1 
Uncertain 
(C) = 
15MONYYYY 
Before Treatment 
Start 
(A) 
= TRTSTD+1 
Uncertain 
(A) 
= 01MONYYYY 
After Treatment 
Start 
YYYY>TRTY 
(E) = 
01JANYYYY 
After Treatment 
Start 
(A) 
= 01MONYYYY 
After Treatment 
Start 
(A) 
= 01MONYYYY 
After Treatment 
Start 
(A) 
= 01MONYYYY 
After Treatment 
Start 
The following table is the legend to the logic matrix. 
Relationship 
Before Treatment start 
Partial date indicates AE start date prior to Treatment 
Start Date in this study 
After Treatment start 
Partial date indicates AE start date after Treatment 
Start Date in this study 
Uncertain 
Partial date insufficient to determine relationship of AE 
start date to Treatment Start Date in this study 
Imputation calculation 
NC/Blank Uncertain 
No convention 
(A) After Treatment Start or Uncertain  
MAX( 01MONYYYY, TRTSTD+1 ) 
(A) After Treatment Start or Uncertain  
MAX( 01MONYYYY, Treatment Start +1 ) 
(C) Before Treatment Start 
15MONYYYY 


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Relationship 
Before Treatment start 
Partial date indicates AE start date prior to Treatment 
Start Date in this study 
(D) Before Treatment Start 
01JULYYYY 
(E) After Treatment Start 
01JANYYYY 
Before imputing the AE start date, find the AE start reference date. 
• If the AE end date is complete and the (imputed) AE end date < Treatment Start Date then 
AE start reference date = min (study informed consent date, earliest visit date). 
• Else AE start reference date = Treatment Start Date 
To impute AE start date: 
1. If the AE start date year value is missing, the date uncertainty is too high to impute a rational 
date. Therefore, if the AE year value is missing, the imputed AE start date is set to NULL. 
2. If the AE start date year value is less than the study treatment start date year value, the AE 
started before study treatment. Therefore: 
a. If AE month is missing, the imputed AE start date is set to the mid-year point 
(01JULYYYY). 
b. Else if AE month is not missing, the imputed AE start date is set to the mid-month point 
(15MONYYYY).  
3. If the AE start date year value is greater than the study treatment start date year value, the 
AE started after study treatment. Therefore: 
a. If the AE month is missing, the imputed AE start date is set to the year start point 
(01JANYYYY). 
b. Else if the AE month is not missing, the imputed AE start date is set to the later of 
(month start point (01MONYYYY), AE start reference date + 1 day). 
4. If the AE start date year value is equal to the study treatment start date year value: 
a. And the AE month is missing the imputed AE start date is set to the AE reference start 
date + 1 day. 
b. Else if the AE month is less than the study treatment start month, the imputed AE start 
date is set to the mid-month point (15MONYYYY). 
c. Else if the AE month is equal to the study treatment start date month or greater than the 
study treatment start date month, the imputed AE start date is set to the later of (month 
start point (01MONYYYY), AE start reference date + 1 day). 
If complete (imputed) AE end date is available and the imputed AE start date is greater than the 
(imputed) AE end date, then imputed AE start date should be set to the (imputed) AE end date. 
5.1.3 
Concomitant medication date imputation 
5.1.3.1 
Concomitant medication end date 
To impute concomitant end date: 


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1. If the concomitant end date year value is missing, the date uncertainty is too high to impute 
a rational date. Therefore, if the concomitant end year value is missing or ongoing, the 
imputed concomitant end date is set to NULL. 
2. Else, if the concomitant end date month is missing, the imputed end date should be set to 
the earliest of the (study treatment follow-up period date, 31DECYYYY, date of death). 
3. If the concomitant end date day is missing, the imputed end date should be set to the earliest 
of the (study treatment follow-up period date, last day of the month, date of death). 
If the imputed concomitant end date is less than the existing concomitant start date, use the 
concomitant start date as the imputed concomitant end date. 
5.1.3.2 
Concomitant medication start date 
Concomitant treatments with partial start dates will have the date or dates imputed. Partial 
concomitant treatment start dates are imputed with reference to the first administration of study 
treatment within this study in accordance with the rules outlined below. 
 
Day 
Month 
Year 
Partial Concomitant medication (CMD) 
Start Date  
Not used  
MON  
YYYY 
Treatment Start Date 
Not used  
TRTM 
TRTY 
The following matrix explains the logic behind the imputation.  
Comparison of 
month section 
MON missing 
MON<TRTM 
MON=TRTM 
MON>TRTM 
YYYY missing 
(C) 
Uncertain 
(C) 
Uncertain 
(C) 
Uncertain 
(C) 
Uncertain 
YYYY<TRTM 
(D) = 
01JULYYYY 
Before Treatment 
Start 
(A) = 
15MONYYYY 
Before Treatment 
Start 
(A) = 
15MONYYYY 
Before Treatment 
Start 
(A) = 
15MONYYYY 
Before Treatment 
Start 
YYYY=TRTY 
(C) 
Uncertain 
(A) = 
15MONYYYY 
Before Treatment 
Start 
(C) 
Uncertain 
(B) = 
01MONYYYY 
After Treatment 
Start 
YYYY>TRTY 
(E) = 
01JANYYYY 
After Treatment 
Start 
(B) = 
01MONYYYY 
After Treatment 
Start 
(B) = 
01MONYYYY 
After Treatment 
Start 
(B) = 
01MONYYYY 
After Treatment 
Start 
The following table is the legend to the logic matrix. 
Relationship 
Before Treatment start 
Partial date indicates CMD start date prior to 
Treatment Start Date in this study 
After Treatment start 
Partial date indicates CMD start date after Treatment 
Start Date in this study 
Uncertain 
Partial date insufficient to determine relationship of    
CMD start date to Treatment Start Date in this study 
Imputation calculation 


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Relationship 
NC/Blank Uncertain 
No convention 
(A) Before Treatment Start 
15MONYYYY 
(B) After Treatment Start 
MAX( 01MONYYYY, Treatment Start Date +1 ) 
(C) Uncertain 
IF CMDTYP IN (1, 3) THEN Treatment Start Date -1 
ELSE IF CMDTYP IN (. 2) THEN Treatment Start Date 
+1 
(D) Before Treatment Start 
01JULYYYY 
(E) After Treatment Start 
01JANYYYY 
To compute concomitant start date: 
1. If the concomitant  start date year value is missing, the imputed concomitant start date is set 
to one day prior to study treatment start date. 
2. If the concomitant start date year value is less than the study treatment start date year value, 
the concomitant medication started before study treatment. Therefore:  
a. If the concomitant month is missing, the imputed concomitant start date is set to the 
mid-year point (01JULYYYY). 
b. Else if the concomitant month is not missing, the imputed concomitant start date is set 
to the mid-month point (15MONYYYY). 
3. If the concomitant start date year value is greater than the study treatment start date year 
value, the concomitant started after study treatment. Therefore:  
a. If the concomitant month is missing, the imputed concomitant start date is set to the 
year start point (01JANYYYY).  
b. Else if the concomitant month is not missing, the imputed concomitant start date is set 
to the month start point (01MONYYYY). 
4. If the concomitant start date year value is equal to the study treatment start date year value: 
a. And the concomitant month is missing or the concomitant month is equal to the study 
treatment start date month, then the imputed concomitant start date is set to one day 
prior to study treatment start date. 
b. Else if the concomitant month is less than the study treatment start date month, the 
imputed concomitant start date is set to the mid-month point (15MONYYYY). 
c. Else if the concomitant month is greater than the study treatment start date month, the 
imputed concomitant concomitant start date is set to the month start point 
(01MONYYYY). 
If complete (imputed) concomitant end date is available and the imputed concomitant start date 
is greater than the (imputed) concomitant end date, then imputed concomitant start date should 
be set to the (imputed) concomitant end date.  
5.1.4 
Other imputations 
5.1.4.1 
Medical history date of diagnosis imputation 
Completely missing dates and partially missing end dates will not be imputed. Partial dates of 
diagnosis will be compared to the treatment start date. 


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• If diagnosis year < study treatment start date year and diagnosis month is missing, the 
imputed diagnosis date is set to the mid-year point (01JULYYYY) 
• Else if diagnosis month is not missing, the imputed diagnosis date is set to the mid-month 
point (15MONYYYY) 
• If diagnosis year = study treatment start date year and (diagnosis month is missing OR 
diagnosis month is equal to study treatment start month), the imputed diagnosis date is set 
to one day before study treatment start date 
5.2 
Adverse events coding/grading 
Reporting of AEs will be based on MedDRA version 23.0 or higher. For the analysis purpose, 
the latest version of MedDRA available at CDBL will be used for reporting activity. 
5.3 
Laboratory parameters derivations 
All laboratory parameters were analyzed at a central laboratory with the exception of the 
following which were analyzed locally: 
• ESR  
• Urinalysis 
• Urine pregnancy test 
If the statistics and statistical programming team receive any laboratory data in conventional 
rather than SI units, these will be converted to SI units using the global conversion library in 
GPS.  
5.3.1 
Imputation rules 
If laboratory values are provided as “<X” (i.e. below limit of detection) or “>X”, prior to 
conversion of laboratory values to SI unit, these numeric values are set to X. 
The following rules will be applied to derive the WBC differential counts when only 
percentages are available for a xxx differential: 
• xxx count = (WBC count) * (xxx %value / 100) 
5.4 
Questionnaires 
5.4.1 
EQ-5D 
This questionnaire is used to assess the health status in adults. The measure is divided into 2 
distinct sections.  
The first section includes one item addressing each of 5 dimensions:  
• mobility 
• self-care 
• usual activity 
• pain/discomfort 
• anxiety/depression 


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Patients rate each of these items from "no problems", "slight problems", "moderate problems", 
"severe problems", or "extreme problems". A composite health index is then defined by 
combining the levels for each dimension.  
The second section measures self-rated (global) health status utilizing a vertically oriented VAS 
where 100 represents the "best possible health state" and 0 represents the "worst possible health 
state." Respondents are asked to rate their current health by placing a mark along this continuum. 
The recall period is "today”. 
Computing EQ-5D-5L utility index values 
The following derivation is based on the SPSS value set - Germany - EQ-5D-5L using the 
German (GER) Ludwig value set version 1.1 (last updated 17FEB2020). 
 
****************************************************************** 
*SPSS syntax code for the computation of index* 
*values with the GER TTO value set* 
******************************************************************; 
 
IF (mobility=1) disut_mo=0. 
IF (mobility=2) disut_mo=0.026. 
IF (mobility=3) disut_mo=0.042.  
IF (mobility=4) disut_mo=0.139. 
IF (mobility=5) disut_mo=0.224. 
 
IF (selfcare=1) disut_sc=0. 
IF (selfcare=2) disut_sc=0.050. 
IF (selfcare=3) disut_sc=0.056. 
IF (selfcare=4) disut_sc=0.169. 
IF (selfcare=5) disut_sc=0.260. 
 
IF (activity=1) disut_sc=0. 
IF (activity=2) disut_sc=0.036. 
IF (activity=3) disut_sc=0.049. 
IF (activity=4) disut_sc=0.129. 
IF (activity=5) disut_sc=0.209. 
 
IF (pain=1) disut_sc=0. 
IF (pain=2) disut_sc=0.057. 
IF (pain=3) disut_sc=0.109. 
IF (pain=4) disut_sc=0.404. 
IF (pain=5) disut_sc=0.612. 
 
 
IF (anxiety=1) disut_sc=0. 
IF (anxiety=2) disut_sc=0.030. 
IF (anxiety=3) disut_sc=0.082. 
IF (anxiety=4) disut_sc=0.244. 
IF (anxiety=5) disut_sc=0.356. 
 
Compute disut_total= disut_mo +disut_sc +disut_ua +disut_pd +disut_ad. 
 
Compute EQindex = 1-disut_total. 
execute. 


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5.4.2 
FACIT-Fatigue 
The questionnaire is a 13-item questionnaire that assesses self-reported fatigue and its impact 
upon daily activities and function. 
Patients respond to each item on a 5-point Likert-type scale: 
• 0 = not at all 
• 1 = a little bit 
• 2 = somewhat 
• 3 = quite a bit 
• 4 = very much 
based on their experience of fatigue during the past 2 weeks.  
The scale score is computed by summing the item scores, after reversing those items that are 
worded in the negative direction. It should be noted that numbering the questions from 1 to 13, 
it is evident that questions 7 and 8 are worded in the positive direction (4 indicates a desirable 
response) and all other questions are worded in the negative directions (4 indicates an 
undesirable response). Thus, it is necessary to reverse the responses for all but questions 7 and 
8 (i.e. original response of 0 gets mapped to 4, 1=3, 2=2, 3=1, and 4=0) for scoring purposes. 
When there are missing item scores, the subscale score was computed by summing the 
non-missing item scores, multiplying by 13 (the total number of items in the scale) and dividing 
by the number of non-missing items (i.e. normalizing the results). The latter rule applied only 
when at least half of the items (seven or more) are non-missing. 
FACIT-Fatigue subscale scores range from 0 to 52, where higher scores represent less fatigue. 
5.4.3 
SF-36 
The Standard SF-36 v2 survey is used to measure health-related quality of life among healthy 
patients and patients with acute and chronic conditions. It consists of eight scales that can be 
scored individually (Maruish 2011). Note: Self-Evaluated Transition is not regarded as a scale. 
Table 5-1 
SF-36 domains 
Domain 
Total no. of items 
Item 
Physical Functioning 
10 
3a, 3b, 3c, 3d, 3e, 3f, 3g, 3h, 3i, 3j 
Role-Physical 
4 
4a, 4b, 4c, 4d 
Bodily Pain 
2 
7, 8 
General Health 
5 
1, 11a, 11b, 11c, 11d 
Vitality 
4 
9a, 9e, 9g, 9i 
Social Functioning 
2 
6, 10 
Role-Emotional 
3 
5a, 5b, 5c 
Mental Health 
5 
9b, 9c, 9d, 9f, 9h 
Self-Evaluated Transition 
1 
2 
Each item will have a precoded item value as outlined in the table below. 


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Table 5-2 
Precoded item values 
Domain 
Item 
Response Choice 
Precoded 
value 
Physical 
Functioning 
3a, 3b, 3c, 3d, 3e, 3f, 3g, 
3h, 3i, 3j 
Yes, limited a lot 
1 
Yes, limited a little 
2 
No, not limited at all 
3 
 
 
 
 
Role-
Physical 
4a, 4b, 4c, 4d 
All of the time 
1 
Most of the time 
2 
Some of the time 
3 
A little of the time 
4 
None of the time 
5 
 
 
 
 
Bodily Pain 
7 
None 
1 
Very mild 
2 
Mild 
3 
Moderate 
4 
Severe 
5 
Very severe 
6 
 
 
 
8 (if both Items 7 and 8 
are answered) 
Not at all (and Item 7 Precoded value=1) 
1 
Not at all (and Item 7 Precoded value=2 
through 6) 
1 
A little bit (and Item 7 Precoded value=1 
through 6) 
2 
Moderately (and Item 7 Precoded 
value=1 through 6) 
3 
Quite a bit (and Item 7 Precoded value=1 
through 6) 
4 
Extremely (and Item 7 Precoded value=1 
through 6) 
5 
 
 
 
8 (if Item 7 is not 
answered) 
Not at all 
1 
A little bit 
2 
Moderately 
3 
Quite a bit 
4 
Extremely 
5 
 
 
 
 
General 
Health 
1 
Excellent 
1 
Very good 
2 
Good 
3 
Fair 
4 
Poor 
5 


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Domain 
Item 
Response Choice 
Precoded 
value 
 
 
 
11a, 11c 
Definitely True 
1 
Mostly True 
2 
Don’t Know 
3 
Mostly False 
4 
Definitely False 
5 
 
 
 
11b, 11d 
Definitely True 
1 
Mostly True 
2 
Don’t Know 
3 
Mostly False 
4 
Definitely False 
5 
 
 
 
 
Vitality 
9a, 9e 
All of the time 
1 
Most of the time 
2 
Some of the time 
3 
A little of the time 
4 
None of the time 
5 
 
 
 
9g, 9i 
All of the time 
1 
Most of the time 
2 
Some of the time 
3 
A little of the time 
4 
None of the time 
5 
 
 
 
 
Social 
Functioning 
6 
Not at all 
1 
Slightly 
2 
Moderately 
3 
Quite a bit 
4 
Extremely 
5 
 
 
 
10 
All of the time 
1 
Most of the time 
2 
Some of the time 
3 
A little of the time 
4 
None of the time 
5 
 
 
 
 
Role-
Emotional 
5a, 5b, 5c 
All of the time 
1 
Most of the time 
2 
Some of the time 
3 


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Domain 
Item 
Response Choice 
Precoded 
value 
A little of the time 
4 
None of the time 
5 
 
 
 
 
Mental 
Health 
9b, 9c, 9f 
All of the time 
1 
Most of the time 
2 
Some of the time 
3 
A little of the time 
4 
None of the time 
5 
 
 
 
9d, 9h 
All of the time 
1 
Most of the time 
2 
Some of the time 
3 
A little of the time 
4 
None of the time 
5 
 
 
 
 
Self-
Evaluated 
Transition 
2 
Much better now than one year ago 
1 
Somewhat better now than one year ago 
2 
About the same as one year ago 
3 
Somewhat worse now than one year ago 
4 
Much worse now than one year ago 
5 
The source SF-36 data will be provided to the third party vendor Quality Metric via a secure 
data exchange. The vendor will complete the required derivations and provide a dataset to the 
Novartis study team containing: 
• the scale scores transformed to 0 to 100 scores for each domain 
• norm-based scores for each domain 
Note: These are the scores normed to the US population to have a mean of 50 and standard 
deviation of 10 
• component summary scores (PCS, MCS) 


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5.5 
Statistical models  
Primary analysis 
SAS Code for Bayesian Analysis 
The Bayesian analysis will be performed using SAS.  
Note that for this illustrative example: 
• the data are stored in the file data_set 
• response1 = number of patients in the secukinumab treatment group who fulfil the primary 
endpoint 


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• number1 = number of patients in the secukinumab treatment group in the population of 
interest 
• a1, b1 = the shape parameters from the prior Beta distribution [Beta(a,b)] associated with 
the secukinumab treatment group 
• response2 = number of patients in the placebo treatment group who fulfil the primary 
endpoint 
• number2 = number of patients in the placebo treatment group in the population of interest 
• a2, b2 = the shape parameters from the prior Beta distribution [Beta(a,b)] associated with 
the placebo treatment group 
 
data <data_set>; 
*** set the seed; 
call streaminit(190207);  
  *** one hundred thousand draws from the Beta posterior distributions; 
  do draw=1 to 100000; 
    ***secukinumb treatment group; 
    post_resp1=RAND('BETA',<a1>+<response1>,<number1>+<b1><response1>); 
    ***placebo treatment group; 
    post_resp2=RAND('BETA',<a2>+<response2>,<number2>+<b2>-<response2>); 
    ***risk difference; 
    rd=post_resp1 - post_resp2; 
    ***risk ratio; 
    rr=post_resp1/post_resp2; 
    ***odds ratio; 
    or=(post_resp1/(1 - post_resp1))/(post_resp2/(1 - post_resp2)); 
    output; 
  end; 
run; 
 
***obtain percentiles of interest to determine median and 95% 
credibility interval; 
proc univariate data=<data_set>; 
  var post_resp1 post_resp2 rd rr or; 
  output out=percentiles1 pctlpts=2.5 25 50 75 97.5 pctlpre=post1_ 
post2_rd_ rr_ or_; 
run; 
 
***determine probabilities of interest; 
proc sql; 
  create table prob1 as 
  select mean(or gt 1) as probnor1, 
         mean(rd gt 0.22) as probnrd1, 
         mean(rd gt 0.38) as probnrd2, 
      mean(rd gt 0) as probnrd3, 
         mean(rr gt 1) as probnrr1 
  from <data_set>; 
quit; 
Secondary analysis  
SAS Code for Kaplan-Meier Plot 


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The time to event analysis will be performed using the SAS procedure PROC LIFETEST.  
Note that for this illustrative example: 
• the data are stored in the file data_set 
• timevar = survival time 
• censorvar = censoring variable (Note: 1 indicates a censored time) 
• stratavar = stratification variable  
 
ODS GRAPHICS ON; 
PROC LIFETEST DATA=<data_set> PLOTS=survival (failure test at 
risk(outside(0.15))=0 to 360 by 30); 
TIME <timevar> * <censorvar> (1); 
 
STRATA <stratavar>; 
RUN; 
The option OUTSIDE(0.15) reserves 15% of the vertical graph window for the at-risk table. It 
can be adjusted. 
SAS Codes for Kaplan-Meier Table 
The summary statistics for time to event analysis will be performed using SAS procedure PROC 
LIFETEST. 
Note that for this illustrative example: 
• the data are stored in the file data_set 
• timevar = survival time 
• censorvar = censoring variable (Note: 1 indicates a censored time) 
• stratavar = stratification variable  
 
PROC LIFETEST DATA = <data_set> method=km 
                               conftype=linear; 
TIME <timevar> * <censorvar> (1); 
 
STRATA <stratavar>; 
RUN; 
SAS code for logistic regression 
For the appropriate treatment difference, the treatment cohorts should be sorted or coded 
appropriately before using this model. 
The analysis will be performed using SAS procedure PROC GENMOD as below. Note that for 
this illustrative example: 
• the data are stored in the file data_set 
• treatmentvar = treatment cohort variable 
• responsevar = dependent variable 
• catvar = categorical variable of interest 


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• contvar = continuous variable of interest 
 
PROC GENMOD DATA = <data_set>; 
CLASS <treatmentvar> <catvar> 
TABLES <responsevar> = <treatmentvar> <catvar> <contvar> / DIST=BINOMIAL 
LINK=LOGIT; 
LSMEANS <treatmentvar> / PDIFF CL;  
RUN; 
5.6 
Rule of exclusion criteria of analysis sets  
Table 5-4 
Protocol deviation categories used 
PD Category 
PD Code 
Eligibility 
INCL or EXCL 
Discontinuation of treatment/ study 
WITH 
Prohibited Concomitant Medication 
COMD 
Study drug (incorrect dose, wrong treatment) 
TRT 
Other 
OTH 
The full list of protocol deviations are defined in the edit check specifications which is located 
in the document management system in the following folder: 
• ‘CREDI Projects/A/AIN457A/CREDI Studies/AIN457ADE11C/Administrative Files 
(study level)/Validation and Planning documents’ 
Table 5-5 
Patient classification 
Analysis Set 
PD ID that 
    
cause patients to be excluded 
Non-PD criteria that cause  
patients to be excluded 
RAS 
OTH03 
No informed consent; 
Not randomized 
FAS 
OTH03 
No informed consent; 
Not randomized; 
No study drug taken during the study 
Safety Set 
OTH03 
No informed consent;  
No study drug taken during the study 
6 
References 
CAIN457 Project Master Analysis Plan (MAP) 
• [CREDI 
Projects/A/AIN457A/Administrative 
files/CIS 
(Clinical 
Information 
Sciences)/Biostatistics – AIN457 safety MAP M3 Amendment 5] 
• [CREDI 
Projects/A/AIN457A/Administrative 
files/CIS 
(Clinical 
Information 
Sciences)/Biostatistics – AIN457A efficacy MAP M3 Amendment 5] 
CAIN457ADE11C Protocol 
• [CREDI Projects/A/AIN457A/CREDI Studies/AIN457ADE11C/CSP (Clinical Study 
Protocol) – CAIN457ADE11C_Protocol_V02_Final_13052019_clean.pdf] 


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[Novartis (2020) COVID-19 (Coronavirus) Guidance Start and End Dates by Region for 
Sensitivity Analyses; Version 3.0 28-Oct-2020.]  
 
 
 
Maruish, M. E. (Ed.). User’s manual for the SF-36v2 Health Survey (3rd ed.). Lincoln, RI: 
QualityMetric Incorporated. 
Stone J, Tuckwell K, Dimonaco S, et al (2017) Trial of Tocilizumab in Giant-Cell Arteritis. The 
New England Journal of Medicine. N Engl J Med;377:317-328.