A Randomized, Double-blind, Placebo-controlled, Parallel Group, Phase II, 24-week Study Investigating the Efficacy, Safety and Tolerability of AIN457 in Patients With Active Overuse Tendinopathy Refractory to Oral NSAIDs/Acetaminophen, Physiotherapy or Corticosteroid Injections
Phase: PHASE2
Conditions: Tendinopathy
Sponsor: Novartis Pharmaceuticals

Novartis Institutes for BioMedical Research
AIN457 / Secukinumab
Clinical Trial Protocol CAIN457X2201
A randomized, double-blind, placebo-controlled, 
parallel group, Phase II, 24-week study investigating the 
efficacy, safety and tolerability of AIN457 in patients with 
active overuse tendinopathy refractory to oral 
NSAIDs/acetaminophen, physiotherapy or 
corticosteroid injections
Document type:
Amended Protocol Version
EUDRACT number:
2017-003099-30
Version number:
v02 Clean (incorporating Amendment 02)
Clinical Trial Phase:
II
Release date:
13-Mar-2018
Property of Novartis
Confidential
May not be used, divulged, published or otherwise disclosed
without the consent of Novartis

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Site Operations Manual (SOM)
A Site Operations Manual (SOM) accompanies this protocol, providing the operational details 
for study conduct. Note: The SOM will not form part of the Clinical Study Report.
Notification of serious adverse events
Dear Investigator,
You must report a serious adverse event (SAE) (initial or follow-up) to Novartis as 
summarized below. Refer to Section 9.2 of the Clinical Trial Protocol for SAE criteria and 
additional requirements. See also page 2 of the Site Operations Manual for further details on 
the method of reporting a SAE.

Complete SAE report 

Submit SAE report to Novartis Chief Medical Office and Patient Safety (CMO & 
PS) within 24 hours after awareness of the SAE 

Notify the Novartis Medical Lead

The fax number(s) and email addresses are located in the Site Operations Manual. 

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Table of contents
Site Operations Manual (SOM)...........................................................................................2
Notification of serious adverse events.................................................................................2
Table of contents .................................................................................................................3
List of tables ........................................................................................................................7
List of figures ......................................................................................................................7
List of abbreviations............................................................................................................8
Pharmacokinetic definitions and symbols.........................................................................11
Glossary of terms...............................................................................................................12
Amendment 2 (March 2018) .............................................................................................14
Amendment 1 (October 2017)...........................................................................................15
Protocol summary..............................................................................................................16
1
Introduction .......................................................................................................................21
1.1
Background............................................................................................................21
1.2
Nonclinical safety data ..........................................................................................23
1.3
Clinical data...........................................................................................................23
1.3.1
Human safety and tolerability data .......................................................23
1.3.2
Human pharmacokinetic data................................................................24
1.4
Study purpose ........................................................................................................24
2
Objectives and endpoints...................................................................................................25
2.1
Primary objective(s)...............................................................................................25
2.2
Secondary objective(s)...........................................................................................25
2.3
Exploratory objective(s) ........................................................................................26
3
Investigational plan ...........................................................................................................27
3.1
Study design...........................................................................................................27
3.2
Rationale for study design .....................................................................................28
3.3
Rationale for dose/regimen, route of administration and duration of treatment....30
3.4
Rationale for choice of comparator .......................................................................31
3.5
Rationale for choice of background therapy..........................................................31
3.6
Purpose and timing of interim analyses/design adaptations..................................32
3.7
Risks and benefits..................................................................................................32
3.7.1
Blood sample volumes..........................................................................33
4
Population..........................................................................................................................34
4.1
Inclusion criteria ....................................................................................................34
4.2
Exclusion criteria...................................................................................................35
5
Restrictions for study subjects...........................................................................................39

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5.1
Prohibited treatment...............................................................................................39
6
Treatment...........................................................................................................................40
6.1
Study treatment......................................................................................................40
6.1.1
Investigational and control drug(s) .......................................................40
6.1.2
Additional study treatment....................................................................40
6.2
Treatment arms......................................................................................................41
6.3
Treatment assignment and randomization.............................................................41
6.4
Treatment blinding.................................................................................................42
6.5
Treating the subject................................................................................................43
6.5.1
Instructions for prescribing and taking study treatment........................43
6.6
Emergency breaking of assigned treatment code ..................................................44
6.7
Treatment exposure and compliance .....................................................................44
6.8
Recommended treatment of adverse events ..........................................................44
6.9
Rescue medication.................................................................................................45
6.10
Concomitant treatment...........................................................................................45
6.10.1
Physiotherapy........................................................................................45
7
Study completion and discontinuation ..............................................................................46
7.1
Study completion and post-study treatment ..........................................................46
7.2
Discontinuation of study treatment........................................................................46
7.3
Withdrawal of informed consent ...........................................................................47
7.4
Lost to follow-up ...................................................................................................48
7.5
Early study termination by the sponsor .................................................................48
8
Procedures and assessments ..............................................................................................49
8.1
Assessment schedule .............................................................................................49
8.2
Informed consent procedures.................................................................................52
8.3
Patient screening....................................................................................................53
8.4
Information to be collected on screening failures..................................................53
8.5
Patient demographics/other baseline characteristics .............................................53
8.5.1
Hepatitis screen, HIV screen.................................................................53
8.5.2
Alcohol test, drug screen.......................................................................54
8.5.3
X-ray of the shoulder ............................................................................54
8.5.4
Treatment exposure and compliance.....................................................54
8.6
Efficacy..................................................................................................................54
8.6.1
The PRO efficacy measures, primary and secondary objectives:.........54
8.6.2
Clinician reported outcome (CRO) efficacy measures collected in 
the trial for secondary objectives ..........................................................57

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8.6.3
Imaging efficacy measures collected in the trial for secondary and 
exploratory objectives are: ....................................................................57
8.7
Safety.....................................................................................................................58
8.7.1
Physical examination ............................................................................59
8.7.2
Vital signs..............................................................................................59
8.7.3
Height and weight .................................................................................59
8.7.4
ECG.......................................................................................................59
8.7.5
Tuberculosis screening..........................................................................60
8.7.6
Ultrasound of the shoulder....................................................................60
8.7.7
Chest X-ray ...........................................................................................61
8.7.8
Tolerability of investigational treatments .............................................61
8.7.9
Laboratory evaluations..........................................................................61
8.7.10
Pregnancy and assessments of fertility .................................................62
8.7.11
Additional parameters...........................................................................63
8.8
Pharmacokinetics...................................................................................................63
8.9
Other assessments..................................................................................................64
8.9.3
Immunogenicity ....................................................................................64
9
Safety monitoring..............................................................................................................66
9.1
Adverse events.......................................................................................................66
9.2
Serious adverse event reporting.............................................................................67
9.2.1
Definition of SAE .................................................................................67
9.2.2
SAE reporting........................................................................................68
9.3
Liver safety monitoring .........................................................................................69
9.4
Renal safety monitoring.........................................................................................70
9.5
Reporting of study treatment errors including misuse/abuse ................................70
9.6
Pregnancy reporting...............................................................................................71
10 Data review and database management.............................................................................71
10.1
Site monitoring ......................................................................................................71
10.2
Data collection.......................................................................................................72
10.3
Database management and quality control............................................................72
10.4
Data Monitoring Committee..................................................................................73
10.5
Adjudication committee.........................................................................................73
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11 Data analysis......................................................................................................................73
11.1
Analysis sets ..........................................................................................................73
11.2
Subject demographics and other baseline characteristics......................................74
11.3
Treatments .............................................................................................................74
11.4
Analysis of the primary variable(s) .......................................................................74
11.4.1
Primary Variable(s)...............................................................................74
11.4.2
Statistical model, hypothesis, and method of analysis..........................74
11.4.3
Handling of missing values/censoring/discontinuations.......................74
11.4.4
Summary statistics of safety..................................................................75
11.4.5
Sensitivity analyses ...............................................................................75
11.5
Analysis of secondary variable(s)..........................................................................75
11.5.1
Efficacy / Pharmacodynamics...............................................................76
11.5.2
Safety.....................................................................................................76
11.5.3
Pharmacokinetics ..................................................................................76
11.5.4
Pharmacokinetic / pharmacodynamic correlation analysis...................76
11.5.5
Other assessments .................................................................................77
11.6
Analysis of exploratory variables ..........................................................................77
11.7
Sample size calculation..........................................................................................77
11.8
Power for analysis of key secondary variables......................................................77
11.9
Interim analyses.....................................................................................................78
12 Ethical considerations........................................................................................................78
12.1
Regulatory and ethical compliance........................................................................78
12.2
Responsibilities of the investigator and IRB/IEC..................................................78
12.3
Publication of study protocol and results...............................................................79
12.4
Quality control and quality assurance....................................................................79
13 Protocol adherence ............................................................................................................79
13.1
Protocol amendments.............................................................................................79
14 References .........................................................................................................................80
15 Appendix 1: Clinically notable laboratory values and vital signs.....................................83
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List of tables
Table 5-1
Prohibited medications..........................................................................39
Table 6-1
Overview of study medication ..............................................................40
Table 6-2
Blinding and unblinding plan................................................................43
Table 8-1
Assessment schedule.............................................................................49
Table 9-1
Guidance for capturing study treatment errors......................................70
Table 15-1
Safety Analyses: Expanded Limits and Notable Criteria......................83
List of figures
Figure 3-1
Study design..........................................................................................28

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List of abbreviations
AE
Adverse event
ALT
Alanine aminotransferase
ALP
Alkaline phosphatase
anti-CCP
Anti-cyclic citrullinated peptide 
AP
Anterior-posterior
AS
Ankylosing spondylitis
ASES
American shoulder and elbow surgeons shoulder score
AST
Aspartate aminotransferase
BUN
Blood urea nitrogen
CK
Creatinine kinase
CMO & PS
Chief Medical Office & patient safety
CRF
Case report/record form (paper or electronic)
CRO
Contract research organization
CSR
Clinical study report
CT
Computerized tomography
CTC
Common toxicity criteria
CV
Coefficient of variation
ECG
Electrocardiogram
EDC
Electronic data capture
ELISA
Enzyme-linked immunosorbent assay
EoS
End of the Study
eSource
Electronic source
EQ5D
EuroQol-5D
EU
Europe
FDA
Food and Drug Administration
GCP
Good Clinical Practice
GGT
Gamma-glutamyl transferase
h
Hour
HAQ-DI
Health assessment questionnaire disability index
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HBsAg
Hepatitis B surface antigen
HBV
Hepatitis B virus
hCG
Human chorionic gonadotropin
HCV
Hepatitis C virus
HIV
Human immunodeficiency virus
IB
Investigators brochure
ICF
Informed consent form
ICH
International Conference on Harmonization of Technical Requirements for 
Registration of Pharmaceuticals for Human Use
IEC
Independent Ethics Committee
IGA
Investigator’s global assessment
IL
Interleukin
IL-17/IL-17A
Interleukin 17 and interleukin-17A
IRB
Institutional review board
IRT
Interactive response technology
i.v.
Intravenous
LFT
Liver function test
MedDRA
Medical dictionary for regulatory activities 
Sv
MicroSievert
mSv
MilliSievert
MRI
Magnetic resonance imaging
NSAIDs
Non-steroidal anti-inflammatory drugs
PASI
Psoriasis area and severity index
PCR
Polymerase chain reaction
PD
Pharmaco-dynamic(s)
PFS
Prefilled syringe
PGA
Patient global assessment
PhGA
Physician global assessment
PK
Pharmacokinetic(s)
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PPD
Purified protein derivative
PRO
Patient reported outcome
PRP
Platelet rich plasma
PsA
Psoriatic arthritis
RA
Rheumatoid arthritis
RBC
Red blood cell(s)
RC
Rotator cuff
RF
Rheumatoid factor 
RNA
Ribonucleic acid
SAE
Serious adverse event
s.c.
Subcutaneous
sCR
Serum creatinine
SGOT
Serum glutamic oxaloacetic transaminase
SGPT
Serum glutamic pyruvic transaminase
SD
Standard deviation
SOM
Site operations manual
SpA
Spondylarthritides
SUSAR
Suspected unexpected serious adverse reactions
TB
Tuberculosis
TBL
Total bilirubin
Tmax
Time to maximum concentration
TNF
Tumor necrosis factor-α inhibitor
TNF-IR
Tumor necrosis factor-α inhibitor incomplete responders
ULN
Upper limit of normal
VAS
Visual analog scale
WBC
White blood cell(s)
WHO
World health organization
WoC
Withdrawal of consent
WORC
Western Ontario rotator cuff (score)
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Pharmacokinetic definitions and symbols
Cmin
The lowest serum concentration observed during a dosing interval [mass / 
volume]

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Glossary of terms
Assessment
A procedure used to generate data required by the study
Cohort
A specific group of subjects fulfilling certain criteria
Control drug
Any drug(s) (an active drug or an inactive drug, such as a 
placebo) which is used as a comparator to the investigational 
drug being tested in the trial
Dosage
Dose of the study treatment given to the subject in a time unit 
(e.g. 100 mg once a day, 75 mg twice 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.
Enrollment
Point/time of subject entry into the study at which informed 
consent must be obtained (i.e. prior to starting any of the 
procedures described in the protocol)
Epoch
Interval of time in the planned conduct of a study. An epoch is 
associated with a purpose (e.g. screening, randomization, 
treatment, follow-up) which applies across all arms of a study.
eSource
eSource Direct Data Entry (DDE) refers to the capture of 
clinical study data electronically, at the point of care. eSource 
combines source documents and case report forms (eCRFs) into 
one application, allowing for the real time collection of clinical 
trial information to sponsors and other oversight authorities, as 
appropriate.
Investigational drug
The study drug whose properties are being tested in the study; 
this definition is consistent with US CFR 21 Section 312.3 and 
Directive 2001/20/EC and is synonymous with “investigational 
new drug,” "Investigational Medicinal Product," or “test 
substance”
Medication pack number
A unique identifier on the label of each drug package in studies 
that dispense study treatment using an IRT system
Patient
An individual with the condition of interest

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Randomization number
A unique identifier assigned to each randomized subject, 
corresponding to a specific treatment arm assignment
Run in failure
A subject who is screened but not randomized/treated after the 
run-in period (where run-in period requires adjustment to 
subject’s medications or other intervention) 
Screen failure
A subject who is screened but is not treated or randomized 
Subject
A trial participant (can be a healthy volunteer or a patient)
Subject number
A unique number assigned to each subject upon signing the 
informed consent. This number is the definitive, unique
identifier for the subject and should be used to identify the 
subject throughout the study for all data collected, sample 
labels, etc.
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.
Study treatment
Any drug or combination of drugs administered to the study 
participants as part of the required study procedures; includes 
investigational drug(s), control(s) or background therapy 
Study treatment 
discontinuation
When the subject permanently stops taking study treatment prior 
to the defined study treatment completion date
Variable
A measured value or assessed response that is determined in 
specific assessments and used in data analysis to evaluate the 
drug being tested in the study 
Withdrawal of consent 
(WoC)
Withdrawal of consent from the study is defined as when a 
subject does not want to participate in the study any longer, and
does not want any further visits or assessments, and does not 
want any further study related contact, and does not allow 
analysis of already obtained biologic material

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Protocol No. CAIN457X2201
Protocol summary
Protocol number
CAIN457X2201
Full Title
A randomized, double-blind, placebo-controlled, parallel group, Phase II, 
24-week study investigating the efficacy, safety and tolerability of AIN457 in
patients 
with 
active 
overuse 
tendinopathy 
refractory 
to 
oral
NSAIDs/acetaminophen, physiotherapy or corticosteroid injections
Brief title
Study of efficacy, safety and tolerability of AIN457 in patients with active 
overuse tendinopathy
Sponsor and Clinical 
Trial Phase
Novartis 
Phase II
Intervention type
Biologic
Study type
Interventional 
Purpose and 
rationale
Cosentyx is an anti-IL-17 antibody, approved for the treatment of PsA and 
AS, and there is a plenitude of evidence of efficacy in treating the enthesitis 
in patients with these symptoms in both these indications.
Recent 
musculoskeletal 
scientific 
attention 
has 
focused 
on
the 
immunobiology of the enthesis, the connective tissue between tendon or 
ligament and bone. This area has been considered analogous to 
tendinopathy as both enthesis and tendon are sites of high mechanical 
stress.
Millar et al (2017)
has provided recent evidence indicating
that 
IL-17-expressing tendon-resident immune cells are present in human overuse 
tendinopathy and IL-17 mRNA and protein expression levels are increased in 
early human tendinopathic samples. IL-17, being a mediator of tendon 
inflammation, disrepair of tendon matrix and tenocyte apoptosis is thus 
considered to be a key player in the pathogenesis of overuse tendinopathy. 
The study design addresses the primary objective of determining the efficacy 
of secukinumab in improving signs, symptoms and structure in patients with 
overuse rotator cuff tendinopathy. 
Primary Objective(s)
To assess the efficacy of secukinumab 300 mg s.c. vs. placebo in patients 
with overuse rotator cuff tendinopathy in relieving clinical symptoms at week 
14
Secondary 
Objectives
To assess the efficacy of secukinumab 300 mg s.c. vs. placebo in patients 
with overuse rotator cuff tendinopathy in relieving symptoms over time
To assess the structural changes in the rotator cuff tendinopathy over time
To assess PK/immunogenicity in secukinumab treated patients
To confirm the safety and tolerability of AIN457 in overuse rotator cuff 
tendinopathy over time

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Study design
This is a randomized, double-blind, placebo-controlled, multi-center, Phase II 
study of s.c. secukinumab 300 mg in approximately 100 randomized patients 
with overuse rotator-cuff tendinopathy without systemic inflammatory disease 
and refractory to NSAIDs/acetaminophen, physiotherapy or corticosteroids. 
The patient and investigator will be blinded throughout the study, while the 
sponsor will be blinded until after the analysis of the primary endpoint. 
The study consists of a 4-week screening period, a 2-week run-in period, a 
12-week treatment period and a 12-week follow-up period after last treatment
(Figure 3-1).
The population will consist of patients with MRI-positive unilateral overuse 
(non-systemic inflammatory) shoulder tendinopathy, 18 - 65 years of age. 
The screening period will be used to assess eligibility and to start/continue 
patients on physiotherapy. In the run-in period the patient should have 
2 weeks 
of 
stable 
NSAID/acetaminophen 
intake 
and 
standardized 
physiotherapy (defined in the SOM). Patients who meet the eligibility criteria 
at screening after the run-in period will go through baseline evaluations.
Eligible subjects as per inclusion/exclusion criteria will be randomized to one 
of the two treatment arms: 7 s.c. injections of secukinumab 300 mg or 
placebo in a 12-week treatment period, followed by a 12-week follow-up 
period. Randomization will be stratified by the following 2 factors: 
Partial tear/no tear and previous steroid injection (yes/no), in order to achieve 
approximate balance between these factors in the treatment groups. 
The assessments to address the primary endpoint will be performed at 
14 weeks (2 weeks after the last injection).
Patients will come to the out-patient clinic approximately 2-4 hours prior to 
dosing for the evaluations. Dosing will be on-site, except for injections at 1 
and 3 weeks, that can be done either on site or by a nurse at the patient’s 
home. 
Safety assessments will include physical examinations, ECGs, vital signs, 
standard clinical laboratory evaluations (hematology, blood chemistry, and 
urinalysis), adverse event and serious adverse event monitoring.
Population
The population will consist of male and female patients at least 18 years of 
age, but under or equal to 65 years of age at the time point of randomization 
with a MRI-positive diagnosis of overuse (non-systemic inflammatory) 
unilateral shoulder tendinopathy with symptoms present for at least 6 weeks 
but not more than 12 months.

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Key Inclusion 
criteria
Patients eligible for inclusion in this study must fulfill all of the following 
criteria:

Written informed consent obtained prior to all study specific screening
procedures, as close to the start of the screening period as possible

Male or non-pregnant, non-lactating female patients 18 to 65 years of
age at randomization

Presence of unilateral rotator cuff tendinopathy with:
a. Symptoms present ≥6 weeks, but <12 months prior to randomization
b.
Tendinopathy with no more than a 50% tear as established by
ultrasound at screening and MRI at baseline: Sein MRI tendinopathy
scoring system grade I-III; with no tear or partial tear [maximum 50%
tendon thickness (Bauer tendon thickness score maximum 2);
AP length maximum 10 mm (Bauer tendon length score max 2)].
Maximum 50% of patients with partial tear
c.
Pain in the affected shoulder (at rest or on movement) on at least
3 days out of 7 days in the past week prior to baseline and a score of
≥4 out of 10 on a VAS pain scale
d.
Positive “Painful Arc Test” on examination and/or nightly pain in the
affected shoulder on at least 4 out of 7 days in the past week prior to
baseline

The rotator-cuff tendinopathy must have been refractory to standard
treatment defined as:

NSAIDs / acetaminophen

In the run-in period patients should be on a stable dose of
NSAIDs and/or acetaminophen for at least 2 weeks prior to
randomization, not exceeding – e.g.: Ibuprofen 1600 mg/d,
naproxen 1000 mg, diclofenac 105 mg/d, or diclofenac sodium
enteric-coated tablets 150 mg/d, or equivalent.

If patients cannot tolerate these doses, the maximal tolerable
dose should be used, and may be augmented with
acetaminophen/paracetamol, at doses not exceed local
guidelines or 4 g/day, whichever is lower. This medication should
also be at a stable dose for at least 2 weeks.

If patients have contraindications to NSAIDs or to
acetaminophen, these treatments can be omitted
(contraindication, drug and dose must be specified in the eCRF).

If patients were refractory to at least 2 weeks of previous
treatment as specified in 4 i/ii, NSAIDs or acetaminophen
treatment can be omitted.

Physiotherapy

In the run in period patients should have had 2 weeks of a
standardized physiotherapy treatment before randomization.
In Czech Republic, patients should have had at least 6 weeks of
physiotherapy prior to randomization. This includes the 2 weeks
of standardized physiotherapy in run in phase.

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Key Exclusion 
criteria

History of hypersensitivity to any of the study treatments or excipients or
to drugs of similar chemical classes

Rheumatologic, inflammatory diseases, including but not limited to: PsA,
AS and RA

Previous shoulder surgery in affected shoulder

History of adhesive capsulitis/frozen shoulder or calcification in the
tendon (in affected or contralateral shoulder) confirmed by X-Ray, historic
X-Rays can be used if performed within 3 months of baseline

Symptomatic osteoarthritis of the shoulder (gleno-humeral,
acromioclavicular) (in affected or contralateral shoulder confirmed by
X-Ray, historic X-Rays can be used if performed within 3 months of
baseline

Neck conditions, including but not limited to cervical spine syndrome,
which in the opinion of the investigator, may explain the patient’s
symptoms

Previous platelet rich plasma injections within the last 12 months prior to
randomization
Study treatment

Group 1: Secukinumab 300 mg s.c. (2 x 150 mg)

Group 2: Placebo s.c. (2 injections)
Pharmacokinetic 
assessments

PK/immunogenicity assessment
Efficacy/PD 
assessments
Patient Reported Outcomes (PROs)

The WORC score

The QuickDASH score

The ASES score

The EQ5D-5L score

Patient’s global assessment of disease activity
Clinician Reported outcome

Physician’s global assessment of disease activity
Imaging

Shoulder MRI
Key safety 
assessments
Key safety assessments:

Evaluation of AE/ SAE’s

Physical examination

Vital signs

Height and weight

Tuberculosis screening: QuantiFERON TB-Gold test or PPD skin test

Chest X-Ray

Electrocardiogram

Local tolerability (Injection site reactions)

Laboratory evaluations (Hematology, Clinical Chemistry, Lipid Panel,
Urinalysis)

Pregnancy and assessment of fertility

Immunogenicity
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Other assessments
Data analysis
The primary end-point (change from baseline in WORC score at Week 14) 
will be analyzed by repeated measures analysis of covariance including all 
WORC scores available. Change at Week 14 will be compared between 
treatments to address the primary objective. The baseline WORC score will 
be included as a covariate. The stratification factors partial tear/no tear and 
previous steroid injection (yes/no) will be included in the model as fixed 
effects. A 95% one-sided (90% two-sided) confidence interval for the 
treatment effect at Week 14 will be reported. Missing variables will be 
considered missing at random.
Initially, models with an unstructured within-subject covariance and a 
separate mean for each treatment and time point will be fitted. These models 
may be reduced in number of covariance and mean parameters by model 
comparison using tools such as the BIC criterion for model fit.
Key words
Overuse tendinopathy, shoulder, rotator cuff, IL-17A-Ab
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1
Introduction
1.1
Background
Overuse tendinopathy is a complex multi-faceted disease of the tendon, clinically diagnosed 
after gradual onset of activity-related pain, decreased function and sometimes with localized 
swelling of the tendon (Riley 2005, Riley 2008). Historically the terms ‘tendinitis’ and 
‘tendinosis’ have interchanged with the term ‘tendinopathy’, however, these definitions are 
now included in the spectrum of human tendon disorders (‘tendinopathy’). Tendinopathy is a 
common overuse injury in the athletic and working populations; it is the most common reason 
for consultation for a musculoskeletal complaint, corresponding to around 30% of all such 
consultations with a general practitioner (Forde et al 2005; Riley 2008).
The exact incidence of overuse tendon injuries is not known, but in sports medicine, they 
account for 30% to 50% of all injuries (Scott and Ashe 2006). Generally, for physical workers, 
the prevalence of musculoskeletal symptoms increases with duration of employment 
(Forde et al 2005).
Upper limb tendinopathy
A systematic review showed that the incidence of rotator cuff tendinopathy ranges from 0.3% 
to 5.5% per year and the annual prevalence from 0.5% to 7.4% (Littlewood et al 2013). 
The incidence is higher in physical workers and athletes (15-20%) and in the wheelchair 
populations (31-73%). It is typically seen in swimmers, baseball-, tennis-, volleyball players
(Kaux et al 2011).
Tennis elbow (lateral epicondylitis) is another frequent tendinopathy and is common in 
athletes of all ages participating in sports involving overhead or repetitive arm actions 
(Hume et al 2006). Its incidence in tennis players is as high as 9% to 40% (Maffulli et al 2003; 
Scott and Ashe 2006). The condition affects approximately 1 to 3% of the general population. 
Another elbow tendinopathy is the golfer’s elbow (medial epicondylitis), which is a typical 
complaint in javelin throwing, baseball and golf (Maffulli et al 2003; Scott and Ashe 2006). 
Lower limb tendinopathy
Achilles tendinopathy is the most prevalent lower extremity tendinopathy, with a 
5.9% frequency in sedentary people and around a 50% frequency in elite endurance athletes 
(Scott and Ashe 2006; Fredberg and Stengaard-Pedersen 2008).
About one third of sports injuries treated in sports clinics concern the knees and one quarter of 
athletes treated for a knee injury are diagnosed with tendinopathy (Maffulli et al 2003). The most 
common knee disorder is jumper’s knee (insertional patellar tendonitis), and its incidence is reported 
to be in the range of 7% to 40% (Fredberg and Stengaard-Pedersen 2008; Scott and Ashe 2006). 

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Treatments
Current treatments for tendinopathy are rest, icepacks and physiotherapy (including 
therapeutic ultrasound, laser therapy, hyperthermia and extra corporeal shockwave therapy). 
Evidence to support the widespread use of these therapies in tendinopathies remains 
inconsistent (Alfredson and Cook 2007). Non-steroidal anti-inflammatory drugs (NSAIDS), 
or local corticosteroid injections can give transient pain relief, but the long term benefit is 
questionable (Mohamadi et al 2017; Coombes et al 2010). Even more, it has been shown that 
repetitive steroid injections have the potential to accelerate tendon degeneration increasing the 
risk of tendon rupture (Mohamadi et al 2017; Coombes et al 2010).  Autologous platelet rich 
plasma (PRP) injections are being used, however the evidence for long term efficacy is weak, 
thus the benefits of PRP for tendinopathy remain controversial, with several trials showing no 
efficacy compared with saline (Krogh et al 2013; de Vos et al 2010). 
Overall, overuse tendinopathy is a disease with high medical need without adequate treatment 
options.
Secukinumab (AIN457, Cosentyx®), interleukin-17A (IL-17A) neutralization
IL-17A is a central cytokine in multiple autoimmune and inflammatory processes. 
Recent evidence indicates that IL-17-expressing tendon-resident immune cells are present in 
human overuse tendinopathy and IL-17 mRNA and protein expression levels are increased in 
early human tendinopathic samples. In human tenocytes, IL-17 regulates pro-inflammatory 
cytokines, key apoptotic mediators and tendon matrix changes towards a mechanically 
inferior type III collagen phenotype. IL-17 being a mediator of tendon inflammation, disrepair 
of tendon matrix and tenocyte apoptosis is thus considered to be a key player in the 
pathogenesis of overuse tendinopathy (Millar 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 postular psoriasis (Japan only); 2) adults 
with active psoriatic arthritis (PsA); 3) adults with active ankylosing spondylitis (AS) 
(Cosentyx prescribing information 2016). 
Enthesitis is the term used to describe inflammation at tendon, ligament or joint capsule 
insertions. It applies to diseases associated with the spondylarthritides (SpA) including AS 
and PsA. Enthesitis can be inflammatory or mechanically induced; the two may share 
common features (McGonagle and Benjamin 2009). Neutralization of IL-17 has proven 
efficacy in inflammatory enthesitis in PsA and AS, as seen in studies with secukinumab: 
CAIN457F- 2305, 2306, 2310, and 2312. In study CAIN457F2312, enthesitis was evaluated 
in the subset of patients who had disease activity at baseline. In this patient population 
secukinumab significantly increased the percentage of patients with resolution of enthesitis 
compared with placebo (CAIN457F2312 CSR). Overall, the percentage of patients without 
resolution of enthesitis at Week 24 was 67.6%, 57.8%, 51.8%, 59.6%, and 78.5% for 
secukinumab 75 mg, 150 mg, 300 mg, secukinumab pooled, and placebo groups, respectively. 
These differences vs. placebo were also greater for the 150 mg and 300 mg dose groups vs 
placebo (p=0.0108 and p=0.0025, respectively), while 75 mg vs was similar (p=0.1678) to 
placebo. 

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Neutralization of IL-17 with secukinumab is thought to reduce tendon inflammation and to 
stop tendon matrix disrepair and degeneration. Secukinumab will therefore be tested as a 
disease-modifying therapy for overuse tendinopathy.
The most relevant data for the present study are summarized in the sections below. 
For detailed information, please refer to the Investigator's Brochure or Core Data Sheet.
Data from this study are aimed at supporting the planning and design of the Phase III studies 
for global submission of secukinumab as a treatment option for patients with active 
tendinopathy.
1.2
Nonclinical safety data
1.3
Clinical data
1.3.1
Human safety and tolerability data
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1.3.2
Human pharmacokinetic data
1.4
Study purpose
The purpose of this Phase II study is to determine the efficacy of secukinumab in treating 
patients with a diagnosis of overuse, non-systemic inflammatory rotator cuff tendinopathy and 
to confirm the safety and tolerability profile of secukinumab in a dose of 300 mg s.c. given at 
day 1 and weekly until and including week 4, thereafter additional injections at weeks 8 
and 12. 
. Patients will be followed up without treatment from week 12 to week 24 to 
investigate long-term safety.
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2
Objectives and endpoints
2.1
Primary objective(s)
Objective
Endpoint

To assess the efficacy of secukinumab
300 mg s.c. vs. placebo in patients with
overuse rotator cuff tendinopathy in
relieving clinical symptoms at week 14

The 
Western 
Ontario 
Rotator 
Cuff
(WORC) patient reported outcome (PRO)
score at week 14
2.2
Secondary objective(s)
Objective
Endpoint

To assess the efficacy of secukinumab
300 mg s.c. vs. placebo in patients with
overuse rotator cuff tendinopathy in
relieving symptoms over time

WORC score at Weeks 2, 4, 8, 12, 18 and 24

Disability of Arm, Shoulder and Hand
Questionnaire (QuickDASH) score at
Weeks 2, 4, 8, 12, 14, 18 and 24

American Shoulder and Elbow Surgeons
Shoulder Evaluation Form (ASES) score at
Weeks 2, 4, 8, 12, 14, 18 and 24

EQ5D-5L score at Weeks 2, 4, 8, 12, 14, 18
and 24

Pain score using a VAS scale (considering
the last 24 hours) at Weeks 2, 4, 8, 12, 14, 18
and 24

Patient global assessment (PGA) score using
a VAS scale (considering the last 24 hours),
at Weeks 2, 4, 8, 12, 14, 18 and 24

Physician global assessment (PhGA) score
using a VAS scale (considering the last
24hours), at Weeks 2, 4, 8, 12, 14, 18 and 24

To assess the structural changes in the
rotator cuff tendinopathy over time

MRI Sein score at Weeks 8, 14 and 24

To assess PK/immunogenicity in
secukinumab treated patients

PK/immunogenicity assessment at Day 1,
Weeks 4, 12, 24

To confirm the safety and tolerability
of AIN457 in patients with overuse
rotator cuff tendinopathy over time

Safety and tolerability assessments over
time: Incidence and severity of AEs and
SAEs; routine safety laboratory parameters

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2.3
Exploratory objective(s)
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3
Investigational plan
3.1
Study design
This is a randomized, double-blind, placebo-controlled, multi-center, Phase II study of s.c. 
secukinumab 300 mg in approximately 100 randomized patients with overuse rotator-cuff 
tendinopathy 
without 
systemic 
inflammatory 
disease 
and 
refractory 
to 
NSAIDs/acetaminophen, physiotherapy or corticosteroids. The patient and investigator will 
be blinded throughout the study, while the sponsor will be blinded until after the analysis of 
the primary endpoint. The study consists of a 4-week screening period, a 2-week run-in period, 
a 12-week treatment period and a 12-week follow-up period after last treatment (Figure 3-1).
The population will consist of patients with MRI-positive unilateral overuse (non-systemic 
inflammatory) shoulder tendinopathy, 18 - 65 years of age. Symptoms should have been 
present for at least 6 weeks but not more than 12 months. The tendinopathy must have been 
refractory to NSAIDS/acetaminophen as defined in the inclusion criteria. On MRI, patients 
may have no tendon tear or a partial tendon tear (up to 50% thickness, in max. 50% of 
patients). The patients should also have had at least 2 weeks of a standardized physiotherapy 
treatment.
The screening period will be used to assess eligibility and to start/continue patients on 
physiotherapy. In the run-in period the patient should have 2 weeks of stable 
NSAID/acetaminophen intake and standardized physiotherapy (defined in the SOM). 
Patients who meet the eligibility criteria at screening after the run-in period will go through 
baseline evaluations.
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Eligible subjects as per inclusion/exclusion criteria will be randomized to one of the two 
treatment arms: 7 s.c. injections of secukinumab 300 mg or placebo in a 12-week treatment 
period, followed by a 12-week follow-up period. Randomization will be stratified by the 
following 2 factors: Partial tear/no tear and previous steroid injection (yes/no), in order to 
achieve approximate balance between these factors in the treatment groups. The assessments 
to address the primary endpoint will be performed at 14 weeks (2 weeks after the last 
injection).
Patients will come to the out-patient clinic approximately 2-4 hours prior to dosing for the 
evaluations. Dosing will be on-site, except for injections at 1 and 3 weeks, that can be done
either on site or by a nurse at the patient’s home. 
Safety assessments will include physical examinations, ECGs, vital signs, standard clinical 
laboratory evaluations (hematology, blood chemistry, and urinalysis), adverse event and 
serious adverse event monitoring.
Figure 3-1
Study design
3.2
Rationale for study design
The study design addresses the primary objective of determining the efficacy of secukinumab
in improving signs, symptoms and structure in patients with overuse rotator cuff tendinopathy. 
The study will enroll patients with inadequate response (determined by a VAS pain score ≥4) 
to physiotherapy or NSAIDs/acetaminophen or intolerance to NSAIDs/acetaminophen, using 
a double-blinded, randomized, parallel group design to minimize bias. At the time of inclusion, 
patients can be steroid-naïve or have inadequate response or intolerance to local steroid 
injection in the tendon, but last steroid therapy must have been >8 weeks prior to 
randomization. Patients must be naïve to IL-17 inhibition therapy.
The patient population with rotator cuff tendinopathy was chosen, as this is one of the most 
frequent tendinopathies. Moreover, the clinical evidence for an IL-17 connection has so far 
only been shown for rotator cuff tendinopathy and has not been investigated for other 
tendinopathies (Millar et al 2017).

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Currently, no Health Authority guideline exists for developing drugs for the overuse 
tendinopathy indication. The 14-week endpoint is chosen to allow the last injection at 
12 weeks to take effect.
The study uses validated Patient Reported Outcome (PRO) questionnaires including indices of 
signs, symptoms and physical function. The PROs used have been chosen based on their validity, 
reliability and specificity. The different PROs have different recall times, 1 week, 24 hours, and a 
moment in time. One is specific for rotator cuff; two others are for arm and shoulder.
During the 2-week run-in period patients should take NSAIDs/acetaminophen at a stable and 
adequate (or maximally tolerable) dose, and still have inadequate control of symptoms at 
randomization. Alternatively NSAID should have been stopped due to intolerance. 
Patients who tolerate it will continue taking the NSAID regimen from the run-in period. 
Patients should not increase the NSAID/acetaminophen dose, but can choose to decrease the 
dose at any time. Dose adjustments are allowed after the primary endpoint at 14 weeks. 
During first 14 weeks of the study local steroid injection is not allowed. After assessment of 
the primary endpoint at week 14 patients may have 1 steroid injection during the last 
10 weeks observation period. The stable NSAID dosing and avoidance of steroid injections 
are required in order not to have other variables than AIN457 influencing the effect on the 
tendinopathy.
The rationale for key design elements in this study include:
Randomization: This decreases the chance of an imbalance in subject characteristics between 
groups, thereby facilitating a valid basis for the treatment comparison.
Double-blind: Blinding of subjects, investigators and sponsor up to the point of week 14, the 
primary endpoint, allows for an unbiased assessment of subjective readouts such as the 
efficacy parameters, especially the PROs and as well for adverse events evaluation. 
The blinding is maintained for patient and investigator beyond the primary endpoint until the 
end of the study to ensure reliable efficacy and safety measures. The sponsor will be 
unblinded after the primary endpoint analysis. 
Placebo-controlled: A placebo arm is included in this study because it is not known whether 
secukinumab can improve tendinopathy, and because there is no disease modifying therapy 
available. However, standard of care with NSAIDs and physiotherapy will be given to both 
treatment groups throughout the study, and if required a steroid injected into the tendon can be 
given also in both groups. 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 adverse events to secukinumab.

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3.3
Rationale for dose/regimen, route of administration and duration 
of treatment
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.
Furthermore, recent musculoskeletal scientific attention has focused on the immunobiology of the 
enthesis, the connective tissue between tendon or ligament and bone. This area has been considered 
analogous to tendinopathy as both enthesis and tendon are sites of high mechanical stress.
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 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% body surface area (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).
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. 
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.

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In study CAIN457F2312 the presence of enthesitis was assessed by using Leeds enthesitis 
score. Overall, the percentage of patients without resolution of enthesitis at Week 24 were 
67.6%, 57.8% and 51.8% in the 75 mg, 150 mg and 300 mg s.c. groups, whereas it was 78.5% 
in the placebo group. At Week 24, these differences vs placebo were greater for the 150 mg 
and 300 mg dose groups vs placebo (p=0.0108 and p=0.0025, respectively), while 75 mg vs 
placebo was similar (p=0.17).
Treatment duration: The 12 weeks treatment duration was chosen as this is considered the 
maximum acceptable duration for resolution or partial resolution in subacute tendinopathy. 
The 12 weeks follow-up 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 this indication.
3.4
Rationale for choice of comparator
A placebo arm is included in this study for the duration of the 12 weeks of treatment (7 doses), 
the placebo group will continue without treatment until week 24. Due to the nature of the 
disease and the primary and secondary outcome measures used (PROs), a placebo arm is 
necessary to obtain reliable efficacy measurements. Adjustment of NSAID dosing is allowed, 
and one local steroid injection is permitted. 
The regular assessments of disease activity ensures that subjects experiencing worsening of 
their disease in any of the treatment groups can exit the study upon their own wish or based on 
the advice of the investigator at any time. In addition, the inclusion of a placebo group is in 
accordance with health authority guidelines, including (FDA 1999; EMA 2009), and the 
parallel-group, placebo controlled design is in alignment with Phase II/III trials of other 
biologics in a related therapeutic domain (PsA) as outlined in EMA guidelines (EMA 2009). 
3.5
Rationale for choice of background therapy
Patients should have taken NSAIDs or acetaminophen at a stable dose for at least 2 weeks 
prior to randomization with inadequate control of symptoms or at least one dose if stopped 
due to intolerance to NSAIDs or acetaminophen. Patients should continue on their 
NSAIDs/acetaminophen regimen at time of randomization. The dose of NSAID should
remain stable until the timing of the primary endpoint at 14 weeks, however, dose reduction is 
allowed. After Week 14 dose adjustments are allowed. Local steroid injection will only be 
allowed after the primary endpoint, and only as one injection during the last 12 weeks 
observation period.

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3.6
Purpose and timing of interim analyses/design adaptations
3.7
Risks and benefits
It is anticipated that secukinumab will have a beneficial effect on the symptoms of rotator cuff 
tendinopathy, by inhibiting the IL-17 driven inflammation and thereby decreasing pain and 
improving mobility
. Ultimately, this should result in few cases of tendinopathy 
progressing to a tear and therefor lessen the need for surgery. 
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 subjects 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).
The risks of secukinumab treatment identified from the clinical experience described in 
Section 1.3.1 are:
a)
Infections, which are primarily upper respiratory tract infections (non-serious, mild to
moderate in severity and did not lead to treatment discontinuation), oral candidiasis, and
other forms of mucosal and cutaneous candidiasis are uncommon.
b)
Neutropenia, mostly non-serious, transient, spontaneously reversible, grade 1-2, seldom
associated with infections and did not lead to treatment discontinuation.
c) Hypersensitivity, primarily non-serious, mild to moderate urticaria, eczema or dermatitis.
The safety profile of secukinumab remains unchanged since the launch in 2015.
Please refer to the IB for a more detailed review of the pre-clinical and clinical information on 
secukinumab.
Taking into account the individual risks, the expected risk profile of secukinumab from a 
mechanism of action perspective in tendinopathy is anticipated to be similar or less (shorter 
duration of treatment) to that of the approved indications.
From the standpoint of the overall risk benefit assessment, the current trial with secukinumab 
is justified.
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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 the Section 4.2 (Exclusion Criteria). If there is any question that the subject will not reliably 
comply, they should not be entered or continue in the study.
Risks of imaging procedures
For screening purposes, the patient should have a chest x-ray that is less than 3 months old. 
If they do not have this (or a historic CT scan or chest MRI), then a new chest x-ray must be 
performed in the posterior-anterior plane; the lateral plane is only done if acceptable per local 
practice and regulations. The amount of exposure for a patient chest X-ray is 100 μSv
(https://www.radiologyinfo.org/en/pdf/safety-xray.pdf).
For screening purposes, a shoulder x-ray will be performed in anterior-posterior and lateral 
plane. This is often performed during the routine evaluation of patients with shoulder pain, but 
not always. Consequently, in some patients the x-rays may be obtained only for research 
purposes. The total amount of radiation exposure per patient from these X-rays will be about 
100 μSv. The 200 μSv of radiation from both x-rays is equivalent to approximately 28 days of 
background exposure (approx. 0.3 μSv per hour at sea level). For effective radiation doses 
under 3 mSv, the risk is considered to be "minimal".
Therefore, the radiation exposure in this study involves minimal risk and is necessary to
ensure eligibility of patients. 
The only imaging technique used in this study for follow-up purposes is MRI
. MRI is a noninvasive radiology technique that has no x-ray radiation exposure. 
No MRI contrast agent will be administered in this study. Thus in principle, MRI scans can be 
repeated in the same patient as often as necessary. The MRI scanning equipment may cause a 
feeling of claustrophobia in susceptible persons. The presence of metal in the body may also 
be a safety hazard or affect a MRI image quality. For more information, see Section 4.2
exclusion criterion 11.
There may be unknown risks of AIN457 which may be serious.
3.7.1
Blood sample volumes
A maximum of 500 mL of blood will be collected over a period of 24 weeks, from each 
subject as part of the study. Additional samples may be required for safety monitoring.
Timings of blood sample collection are outlined in the Assessment schedule (Section 8.1).
A summary blood log is provided in the Site Operations Manual. Instructions for all sample 
collection, processing, storage and shipment information is also available in the SOM and 
central Laboratory Manual.
See Section 8.9.5 regarding the potential use of residual samples. 
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4
Population
The population will consist of male and female patients at least 18 years of age, but under or 
equal to 65 years of age at the time point of randomization with a MRI-positive diagnosis of 
overuse (non-systemic inflammatory) unilateral shoulder tendinopathy with symptoms present 
for at least 6 weeks but not more than 12 months. 
The tendinopathy must have been refractory to NSAIDs and/or acetaminophen as defined in 
the inclusion criteria.  The patients should also have had at least 2 weeks of a standardized 
physiotherapy treatment. 
The tendinopathy must be MRI-positive, as indicated by a Sein MRI tendinopathy scoring 
system grade I-III, with no tear or partial tear (maximum 50% tendon thickness = Bauer 
tendon thickness score maximum 2; AP length maximum 10 mm, Bauer tendon length score 
maximum 2. Up to 50% of enrolled patients may have a partial tear. Patients will be stratified 
to four strata: Patients with or without a tendon tear and patients with or without previous 
local steroid treatment to the affected shoulder. Randomization will occur within these four 
strata.
The investigator must ensure that all patients being considered for the study meet the 
following eligibility criteria. No additional criteria should be applied by the investigator, in 
order that the study population will be representative of all eligible subjects.
Unless specified otherwise in the inclusion/exclusion criteria, subject selection is to be 
established by checking through all eligibility criteria at both screening and baseline, except 
for assessments that according to the Assessment schedule are performed at only one of these 
visits. In this case, it is acceptable to include the patient based on only screening or only 
baseline results. 
A relevant record (e.g., checklist) of the eligibility criteria must be stored with the source 
documentation at the study site. Deviation from any entry criterion excludes a patient from 
enrollment into the study.
4.1
Inclusion criteria
Patients eligible for inclusion in this study must fulfill all of the following criteria:
1. Written informed consent obtained prior to all study specific screening procedures, as 
close to the start of the screening period as possible
2. Male or non-pregnant, non-lactating female patients 18 to 65 years of age at 
randomization
3. Presence of unilateral rotator cuff tendinopathy with:
a.
Symptoms present ≥6 weeks, but <12 months prior to randomization
b. Tendinopathy with no more than a 50% tear as established by ultrasound at screening
(historic data acceptable if not older than 3 months) and MRI at baseline: Sein MRI 
tendinopathy scoring system grade I-III; with no tear or partial tear [maximum 50% 
tendon thickness (Bauer tendon thickness score maximum 2); AP length maximum
10 mm (Bauer tendon length score max 2)]. Maximum 50% of patients with partial 
tear

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c.
Pain in the affected shoulder (at rest or on movement) on at least 3 days out of 7 days 
in the past week prior to baseline and a score of ≥4 out of 10 on a VAS pain scale  
d.
Positive “Painful Arc Test” on examination and/or nightly pain in the affected 
shoulder on at least 4 out of 7 days in the past week prior to baseline
4. The rotator-cuff tendinopathy must have been refractory to standard treatment defined as:
a. NSAIDs / acetaminophen
i.
In the run-in period patients should be on a stable dose of NSAIDs and/or 
acetaminophen for at least 2 weeks prior to randomization, not exceeding – e.g.:
Ibuprofen 1600 mg/d, naproxen 1000 mg, diclofenac 105 mg/d, or diclofenac 
sodium enteric-coated tablets 150 mg/d, or equivalent. 
ii.
If patients cannot tolerate these doses, the maximal tolerable dose should be 
used, and may be augmented with acetaminophen/paracetamol, at doses not 
exceed local guidelines or 4 g/day, whichever is lower. This medication should 
also be at a stable dose for at least 2 weeks. 
iii.
If patients have contraindications to NSAIDs or to acetaminophen, these 
treatments can be omitted (contraindication, drug and dose must be specified in 
the eCRF).  
iv.
If patients were refractory to at least 2 weeks of previous treatment as specified 
in 4 i/ii, NSAIDs or acetaminophen treatment can be omitted.
b. Physiotherapy
i.
In the run-in and baseline period, patients should have had at least 2 weeks of a 
standardized physiotherapy treatment. In Czech Republic, patients should have 
had at least 6 weeks of physiotherapy prior to randomization. This includes the 
2 weeks of standardized physiotherapy in run in phase.
5. If the patient had previous steroid treatment, it must be ≥8 weeks prior to randomization 
and ≤3 injections
6. If the patient had previous shock-wave therapy, it must be ≥8 weeks prior to 
randomization
7. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies must 
be negative at Screening
4.2
Exclusion criteria
Patients fulfilling any of the following criteria are not eligible for inclusion in this study. 
No additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients.
1. Use of other investigational drugs at the time of enrollment, or within 5 half-lives of 
enrollment, or within 30 days for small molecules/until the expected PD effect has 
returned to baseline for biologics, whichever is longer; or longer if required by local 
regulations.
2. History of hypersensitivity to any of the study treatments or excipients or to drugs of 
similar chemical classes
3. Rheumatologic, inflammatory diseases, including but not limited to: PsA, AS and RA
4. Previous shoulder surgery in affected shoulder

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5. History of adhesive capsulitis/frozen shoulder or calcification in the tendon (in affected or 
contralateral shoulder) confirmed by X-Ray, historic X-Rays can be used if performed 
within 3 months of baseline
6. Symptomatic osteoarthritis of the shoulder (gleno-humeral, acromioclavicular) (in 
affected or contralateral shoulder confirmed by X-Ray, historic X-Rays can be used if 
performed within 3 months of baseline
7. Neck conditions, including but not limited to cervical spine syndrome, which in the 
opinion of the investigator, may explain the patient’s symptoms
8. Previous platelet rich plasma injections within the last 12 months prior to randomization
9. Previous treatment with any cell-depleting therapies including but not limited to anti-
CD20, investigational agents (e.g. Campath, anti-CD4, anti-CD5, anti-CD3, anti-CD19)
10. Previous exposure to any biologic immunomodulating agents, including but not limited to 
TNFalpha inhibitors (including, but not limited to adalimumab, infliximab), or biologics 
targeting IL-17 (including, but not limited to secukinumab, ixekizumab or brodalumab) or 
the IL-17 receptor within the last 12 months prior to baseline
11. Patients taking high-potency opioid analgesics, including but not limited to, methadone, 
hydromorphone, and morphine
12. Any intraarticular/subacromial corticosteroid treatment within 8 weeks prior to 
randomization and more than 3 injections for the current tendinopathy. Oral, intramuscular 
or i.v. corticosteroid treatment within the last 12 months prior to randomization
13. Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a 
female after conception and until the termination of gestation, confirmed by a positive 
human chorionic gonadotropin (hCG) laboratory test.
14. Women of 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 minimum 16 weeks after the last dose, or longer, if local 
regulations require it (e.g. 20 weeks in EU). Effective contraception methods include:
a. 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
b. Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy), total hysterectomy or tubal ligation at least six 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
c. Male sterilization (at least 6 months prior to screening). For female patients on the 
study, the vasectomized male partner should be the sole partner of that patient
d. Barrier methods of contraception: Condom or occlusive cap (diaphragm or 
cervical/vault caps. For UK: with spermicidal foam/gel/film/cream/vaginal 
suppository

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e. Use of oral, (estrogen and progesterone), injected or implanted hormonal methods
of contraception or other forms of hormonal contraception that have comparable
efficacy (failure rate <1%), for example hormone vaginal ring or transdermal
hormone contraception or placement of an intrauterine device (IUD) or intrauterine
system (IUS)
f.
In case of use of oral contraception, women should have been stable on the same
pill for a minimum of 3 months before taking investigational drug
g. In case local regulations deviate from the methods listed, local regulations apply
and will be described in the ICF
h. 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 six weeks ago. In the case of oophorectomy
alone, only when the reproductive status of the woman has been confirmed by
follow up hormone level assessment is she considered not of child bearing
potential
15. Chest X-ray, CT or MRI scan with evidence of ongoing infectious or malignant process
obtained at screening  or within 3 months prior to screening and evaluated by a qualified
physician
16. Underlying metabolic, hematologic, renal, hepatic, pulmonary, neurologic, endocrine,
cardiac, infectious or gastrointestinal conditions which in the opinion of the investigator
immune-compromises the patient and/or places the patient at unacceptable risk for
participation in an immunomodulatory therapy
17. Significant medical problems or diseases, including but not limited to the following:
uncontrolled hypertension (≥160/95 mmHg), congestive heart failure (New York Heart
Association status of class III or IV) and uncontrolled diabetes
18. Evidence of hypomagnesemia or other reason associated with risk of reduced activity of
matrix metalloproteinases. Treatment with fluorquinolone antibiotics (mainly
ciprofloxacin, moxifloxacin or similar drugs) associated with risk of magnesium chelation
and reduced activity of matrix metalloproteinases.
19. History of clinically significant liver disease or liver injury as indicated by abnormal liver
function tests (LFTs) such as aspartate aminotransferase/serum glutamic oxaloacetic
transaminase (AST/SGOT), alanine aminotransferase/ serum glutamic pyruvic
transaminase (ALT/SGPT) alkaline phosphatase or serum bilirubin. The investigator
should be guided by the following criteria:
a. Any single parameter may not exceed 3 x upper limit of normal (ULN). A single
parameter elevated up to and including 3 x ULN should be re-checked once more as
soon as possible and in all cases, at least prior to enrollment/randomization, to rule out
any possible laboratory error
b. If the total bilirubin concentration is increased above 2 x ULN, total bilirubin should be
differentiated into the direct and indirect reacting bilirubin
20. History of renal trauma, glomerulonephritis, or patients with one kidney only, or a serum
creatinine level exceeding 1.5 mg/dL (132.6 µmol/L).

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21. Screening/baseline total white blood cell (WBC) count <3,000/µL, or platelets 
<100,000/µL or neutrophils <1,500/µL or hemoglobin <8.5 g/dL (85 g/L).
22. Active systemic infections during the last two weeks (exception: common cold) prior to 
randomization.
23. 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 
test. Patients with a positive test may participate in the study if further work up (according 
to local practice/guidelines) establishes conclusively that the patient has no evidence of 
active tuberculosis. If presence of latent tuberculosis is established then treatment 
according to local country guidelines must have been initiated prior to enrollment.
24. Known infection with human immunodeficiency virus (HIV) Hepatitis B (HBV) or 
Hepatitis C (HCV) at screening or randomization.  
25. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system (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), treated or 
untreated within the past 5 years prior to baseline regardless of whether there is evidence 
of local recurrence or metastases.
26. Current severe progressive or uncontrolled disease which in the judgment of the clinical 
investigator renders the patient unsuitable for the trial.
27. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor 
tolerability or lack of access to veins).
28. Any medical or psychiatric condition which, in the investigator’s opinion, would preclude 
the participant from adhering to the protocol or completing the study per protocol.
29. Donation or loss of 400 mL or more of blood within 8 weeks before randomization.
30. History or evidence of ongoing alcohol or drug abuse, within the last six months before 
randomization.
31. Plans for administration of live vaccines during the study period or within 6 weeks prior to 
randomization.
32. Inability or unwillingness to undergo MRI of the shoulder (e.g., patients with pacemakers, 
or metal fragments / foreign objects in the body that are not compatible with performing a 
MRI.
In the case where a safety laboratory assessment at screening and/or initial baseline is outside 
of the range specified in the exclusion criteria, the assessment may be repeated once prior to 
randomization. If the repeat value remains outside of the specified ranges, the subject must be 
excluded from the study.
Refer to Section 8.3 (Patient Screening) for information regarding re-screening. 
No additional exclusions may be applied by the investigator, in order to ensure that the study 
population will be representative of all eligible patients.

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5
Restrictions for study subjects
For the duration of the study, the subjects should be informed and reminded of the restrictions 
outlined in this section.
5.1
Prohibited treatment
Use of the treatments displayed in Table 5-1 is NOT allowed after the start of the washout 
period unless specified otherwise below.
Live vaccines should not be given until 12 weeks after last study treatment administration.
Table 5-1
Prohibited medications
Prohibited treatments
Prohibition1
/Washout period before 
randomization2
Action to be taken
Any immunomodulating biologic drugs, 
including but not limited to TNFalpha 
inhibitors or other biologic drugs 
targeting IL-17 or IL-17 receptor*
Never
Discontinue study medication
Any cell-depleting therapies including but 
not limited to anti-CD20 or 
investigational agents*
Never
Discontinue study medication
cDMARD (e.g. MTX) including apremilast, 
tofacitinib*
Never
Discontinue study medication
Any investigational treatment other than 
study medication or participation in any 
interventional trial
4 weeks or 5 half-lives 
(whichever is longer)
Discontinue study medication
Unstable dose of NSAIDs (including 
selective COX-2 inhibitors) and/or
paracetamol/acetaminophen
2 weeks
Reduce dose as soon as possible, 
back to baseline dose.  
Dose decreases after randomization 
are allowed within the first 14 weeks
Dose increases are only allowed 
after Week 14. All dose changes
must be recorded
Analgesics other than NSAIDs, 
paracetamol/acetaminophen and low 
strength opioids PRN
2 weeks
Discontinue the forbidden
medication. All medications must be 
recorded
High potency opioids
12 weeks
Discontinue study medication
Systemic corticosteroids 
12 months
Discontinue study medication
Local steroid injections in the shoulder 
(until Week 14)
8 weeks and not more than 3 
injections
Discontinue study medication
Intramuscular steroid injection
8 weeks
Discontinue study medication
Fluoroquinolone
8 weeks
Discontinue study medication

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Prohibited treatments
Prohibition1
/Washout period before 
randomization2
Action to be taken
Shock wave therapy
8 weeks
Discontinue study medication
Live vaccinations
6 weeks
Discontinue study medication
Platelet rich plasma injections
12 months
Discontinue study medication
Oral or topical retinoids
12 weeks
Discontinue study medication
* These agents fall under the category of biologic immunomodulators and are prohibited medications.
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.
6
Treatment
6.1
Study treatment
Details on the requirements for storage and management of study treatment, and instructions 
to be followed for subject numbering, prescribing/dispensing and taking study treatment are 
outlined in the SOM.
6.1.1
Investigational and control drug(s)
Table 6-1
Overview of study medication
Study drug name
Formulation
Unit dose
Packaging
Provided by
Secukinumab 300 mg
(2 injections of 150 mg)
2 x 1 mL PFS 
1 mL (150 mg) Single -blind supply
Novartis
Placebo, 2 injections
2 x 1 mL PFS
Single-blind supply
Novartis
Patients will be given the injections by the site staff on site, except for injections at weeks 1
and 3, which will be given by a study nurse on site or at home, whichever is most convenient 
for the patient, in agreement with the investigator.
The PFSs are packed in a single blinded fashion and do not need to be prepared. The study 
treatments will be labeled as follows:

Single blind secukinumab and placebo pre-filled syringe (PFS) will be labeled AIN457
150 mg/1 ml/Placebo for dosing up to and including Week 12.
For detailed instructions on storage of the investigational treatments, please refer to the SOM.
6.1.2
Additional study treatment
No additional treatment beyond investigational drug and control drug are included in this trial.

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6.2
Treatment arms
Patients will be assigned to one of the following 2 treatment arms in a 1:1 ratio, with 
approximately 50 patients per arm. 

Group 1: Secukinumab 300 mg s.c. (2 x 150 mg)

Group 2: Placebo s.c. (2 injections)
Treatment is administered at Day 1 (randomization visit), and Weeks 1, 2, 3, 4, 8 and 12.
Subjects who complete the assessments associated with Week 14 visit should continue the 
study in a (treatment free) follow up period of 10 weeks up to 24 weeks.
6.3
Treatment assignment and randomization
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from subjects and investigator staff. 
A subject randomization list will be produced by the Interactive Response Technology (IRT) 
provider using a validated system that automates the random assignment of subject numbers 
to randomization numbers. These randomization numbers are linked to the different treatment 
arms, which in turn are linked to medication numbers. A separate medication list will be 
produced by or under the responsibility of Novartis Drug Supply Management using a 
validated system that automates the random assignment of medication numbers to packs 
containing the investigational drug(s).
The randomization number is only used to identify which treatment the subjects have been 
randomized to receive.  The Subject number assigned to a subject at screening remains the 
unique identifier for the subject throughout the study.  For information on subject numbering, 
please see ‘Subject numbering’ section in the SOM.
Randomization will be stratified on the basis of 

Tendinopathy without tear / tendinopathy with partial tear.

Steroid-naïve for the current RC injury / local steroid treatment for the current RC 
injury.  
The stratification occurs in order to make sure that these two potential factors, which may 
impact response to treatment, are evenly distributed in the treatment groups.
The randomization scheme for subjects will be reviewed and approved by a member of the 
Randomization Office.
Follow the details outlined in the Site Operations Manual regarding the process and timing of 
treatment assignment and randomization of subjects.

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6.4
Treatment blinding
This is a subject, investigator and sponsor-blinded study. Subjects, investigators and sponsor 
will remain blinded to study treatment throughout the study, except where indicated below. 
The identity of the treatments will be concealed by the use of study drugs that are all identical 
in packaging, labeling, schedule of administration, appearance, and odor.
Site staff
All site staff (including study investigator and study nurse), except the unblinded pharmacist,
will be blinded to study treatment throughout the study.
Unblinding a single subject at site for safety reasons (necessary for subject management) will 
occur via an emergency system in place at the site (see Section 6.6).
Sponsor staff
All other sponsor staff (study statistician, study programmer, biomarker expert, clinical trial 
team, decision boards etc.) will stay blinded to treatment assignments (except in the case of a 
safety event necessitating unblinding) until after database lock for the analysis of the primary 
endpoint at Week 14. Study monitors will remain blinded throughout the study.
All unblinded personnel will otherwise keep randomization lists and data or information that 
could unblind other study team members confidential and secure until database lock for the 
primary endpoint at Week 14. 
Following final database lock all roles may be considered unblinded.  See Table 6-2 for an 
overview of the blinding/unblinding plan.
The sample analysts will receive a copy of the randomization schedule (via request to the 
Randomization Office), to facilitate analysis of the samples. The sample analysts will provide 
the sample data to the study team under blinded conditions unless otherwise allowed.
The study statistician will be able to access the randomization list for interim analyses and is 
allowed to share unblinded information with the rest of the clinical team as appropriate for 
internal decision purposes, as outlined in Table 6-2. For example, unblinded summaries and 
unblinded individual data can be shared with the team for after the primary endpoint analysis 
at Week 14.
Study programmers and other personnel involved in study data analysis (e.g. biomarker expert) 
are allowed to access treatment assignment information for the purpose of conducting the 
primary endpoint analysis.
The clinical trial team is allowed to share unblinded results with other sponsor staff 
(e.g. decision boards) as required for internal decision making on the study or the project at 
the time of interim analyses while the study is ongoing.

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Table 6-2
Blinding and unblinding plan
Time or Event
Role
Randomization 
list generated
Treatment 
allocation & 
dosing
Safety event 
(single subject 
unblinded)
Primary 
analysis at 
Week 14
Subjects/Patients
B
B
UI
B
Site staff
B
B
UI
B
Unblinded pharmacist
B
UI
UI
UI
Drug Supply and Randomization 
Office
UI
UI
UI
UI
Statistician/statistical programmer/ 
data analysts (e.g. biomarker, PK)
UI
UI
UI
UI
Unblinded monitor
B
UI
UI
UI
All other sponsor staff not 
identified above (trial team, project 
team, management & decision 
boards, support functions)
B
B
UI
UI
Key:
UI:Allowed to be unblinded on individual patient level 
B: Remains blinded
NA: Not applicable to this study
6.5
Treating the subject 
AIN457 will be administered to the subject via the s.c. route of administration. Patients will 
be given the injections by the site staff on site, except for injections at weeks 1 and 3, which 
will be given by a study nurse on site or by a study nurse at home, whichever is most 
convenient for the patient. See the Site Operations Manual for further details.
Sponsor qualified medical personnel will be readily available to advise on trial related 
medical questions or problems.
6.5.1
Instructions for prescribing and taking study treatment
Study treatment (2 x 150 mg s.c. secukinumab or matching placebo) will be administered by 
PFSs throughout the study. 
S.c. administration with pre-filled syringes
Secukinumab solution for s.c. injection (150 mg in 1.0 mL active/placebo) will be provided in 
PFSs. Details of the injection is provided in the SOM. Permitted dose adjustments and 
interruptions of study treatment
Study treatment interruption should be avoided with the following exceptions:

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Study treatment interruption is only permitted if, in the opinion of the investigator, a subject 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 eCRF page.
6.6
Emergency breaking of assigned treatment code
Emergency code breaks must only be undertaken when it is required to in order to treat the 
subject safely. Most often, study treatment discontinuation and knowledge of the possible 
treatment assignments are sufficient to treat a study subject who presents with an emergency 
condition. Emergency treatment code breaks are performed using the IRT. When the 
investigator contacts the system to break a treatment code for a subject, he/she must provide 
the requested subject identifying information and confirm the necessity to break the treatment 
code for the subject. The investigator will then receive details of the investigational drug 
treatment for the specified subject and a fax or email confirming this information. The system 
will automatically inform the study monitor for the site and the Study Team that the code has 
been broken.
It is the investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT at any time in case of emergency.   The investigator will need to 
provide:  

Protocol number

Study drug name (if available)

Subject number. 
In addition, the investigator must provide oral and written information to inform the subject 
how to contact his/her backup in cases of emergency when he/she is unavailable to ensure that 
un-blinding can be performed at any time.
6.7
Treatment exposure and compliance
Pharmacokinetic parameters (measures of treatment exposure) will be determined in all 
subjects treated with AIN457, as detailed in Section 8.8.
Compliance to the treatment regimen is ensured by administration of the AIN457 at the study 
site at all visits as per Assessment schedule except for visits at weeks 1 and 3, when AIN457
will be administrated by a nurse at the patients’ home. Information on the study treatment 
administration or any deviation from the dose regimen must be recorded in the Case Report 
Form (CRF).  All study treatment dispensed and returned must be recorded in the Drug 
Accountability Log.
6.8
Recommended treatment of adverse events
Medication used to treat AEs must be recorded on the Concomitant medications/Significant 
non-drug therapies CRF.

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6.9
Rescue medication
Rescue medication is defined as any new therapeutic intervention or a significant change to 
ongoing therapy made because a subject is experiencing either no benefit from participation in 
the trial or worsening / exacerbation of their disease.
Rescue medication must not be used before completion of Week 14 assessments as outlined in 
Section 3.1.
Efficacy and safety will be assessed in detail at every study visit, and patients who are deemed 
not to be benefiting from the study treatment based upon safety and efficacy assessments by 
the investigator or for any reason on their own accord will be free to discontinue participation 
in the study at any time.
Changes in NSAIDs concomitant therapy is permitted after Week 14 assessments as per 
investigator’s clinical judgment.
6.10
Concomitant treatment
The investigator must instruct the subject to notify the study site about any new medications 
he/she takes after the subject has been enrolled into the study. 
All prescription medications, over-the-counter drugs and significant non-drug therapies
(including physical therapy and blood transfusions) administered or taken within the 
timeframe defined in the entry criteria prior to the start of the study and during the study, must 
be recorded on the Concomitant medications/Significant non-drug therapies CRF.
Medication entries should be specific to trade name, the single dose and unit, the frequency 
and route of administration, the start and discontinuation date and the reason for therapy.
Each concomitant drug must be individually assessed against all exclusion criteria/prohibited 
medication. If in doubt, the investigator should contact Novartis before randomizing a subject 
or, if the subject is already enrolled, to determine if the subject should continue participation 
in the study.
6.10.1
Physiotherapy
Patients should be on the standard home-base physiotherapy for at least 2 weeks prior to 
randomization until study Week 14. Please refer for the details in provided separately 
Exercise Manual for patients. 

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7
Study completion and discontinuation 
7.1
Study completion and post-study treatment
Each subject will be required to complete the study in its entirety; no further study treatment 
will be made available after Week 14. 
Study completion is defined as when the last subject completes their End of Study (EoS) 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 subjects should have a safety follow-up call 
conducted 60 days after last administration of study treatment; however the 60 days falls 
within the study 12-week follow-up period, where no treatment is given, therefore the safety 
follow up is part of the EoS. 
All SAEs reported during this time period must be reported as described in Section 9.2 and 
the Site Operations Manual. 
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 
subjects who prematurely withdraw from the study, or must refer them for appropriate 
ongoing care.
7.2
Discontinuation of study treatment
Discontinuation of study treatment for a subject occurs when study treatment is stopped 
earlier than the protocol planned duration. Discontinuation of study treatment can be decided 
by either the subject or the investigator.
Study treatment must be discontinued under the following circumstances:

Subject/guardian decision - subjects may choose to discontinue study treatment for any 
reason at any time.

The investigator believes that continuation would negatively impact the safety of the 
subject or the risk/benefit ratio of trial participation.

Emergence of the following adverse events:
- Any severe or serious adverse event that is not compatible with administration of study 
medication, including adverse events that require treatment with an unacceptable co-
medication
- Life-threatening infection

Any protocol deviation that results in a significant risk to the subject’s safety.

Pregnancy (see Section 8.6 (Safety) and Section 9.6 (Pregnancy reporting))

Use of prohibited treatment as per recommendations in Table 5-1.

Adverse events, abnormal laboratory values or abnormal test results that indicate a safety 
risk to the subject.

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
Any laboratory abnormalities that in the judgment of the investigator, taking into
consideration the subject’s overall status, prevents the subject from continuing
participation in the study.

The following deviations from the prescribed dose regimen for the study drug:
- Missed 2 doses or more
The appropriate personnel from the site and Novartis will assess whether investigational drug 
treatment should be discontinued for any subject whose treatment code has been broken 
inadvertently for any reason.
If discontinuation of study treatment occurs, investigator must determine the primary reason 
for the subject’s premature discontinuation of study treatment and record this information on 
the Dosage Administration CRF. 
Subjects who discontinue study treatment or who decide they do not wish to participate in the 
study further should NOT be considered withdrawn from the study UNLESS they withdraw 
their consent (see Section 7.3, Withdraw of Informed Consent).The patients who discontinue 
the treatment should return to the clinic as soon as possible, after discontinuation of study 
drug, for EoS visit. At a minimum, in abbreviated visits, the following data should be 
collected at clinic visits or via telephone/email contact: 

New / concomitant treatments

Adverse events/Serious Adverse Events
If they fail to return for the EOS visit for unknown reasons, every effort (e.g., telephone,
e-mail, letter) should be made to contact the subject/pre-designated contact as specified
in Section 7.4 (Lost to follow-up). This contact should preferably be done according to the
study visit schedule.
7.3
Withdrawal of informed consent
Subjects may voluntarily withdraw consent to participate in the study for any reason at any 
time.
Withdrawal of consent from the study is defined as when a subject:

Does not want to participate in the study anymore and

Does not want any further visits or assessments and

Does not want any further study related contacts and

Does not allow analysis of already obtained biologic material.
In this situation, the investigator must make every effort (e.g. telephone, e-mail, letter) to 
determine the primary reason for the subject’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 subject are not allowed unless safety findings require 
communicating or follow-up.

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7.4
Lost to follow-up
For subjects whose status is unclear because they fail to appear for study visits without stating 
an intention to discontinue or withdraw, the investigator should show "due diligence" by 
documenting in the source documents steps taken to contact the subject, e.g. dates of 
telephone calls, registered letters, etc. A subject cannot be formally considered lost to follow-
up until his/her scheduled end of study visit would have occurred.
7.5
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 
(including slow enrollment), or for regulatory or medical reasons. Should this be necessary, 
subjects must be seen as soon as possible and treated as a prematurely discontinued subject. 
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 subject’s interests. 
The investigator will be responsible for informing IRBs/IECs of the early termination of the 
trial.

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8
Procedures and assessments
8.1
Assessment schedule
Subjects should be seen for all visits/assessments as outlined in the assessment schedule, Table 8-1, or as close to the designated day/time as 
possible.
Missed or rescheduled visits should not lead to automatic discontinuation. Subjects who prematurely discontinue the study for any reason 
should be scheduled for a visit as soon as possible, at which time all of the assessments listed for the final visit will be performed. At this 
final visit, all dispensed investigational product should be reconciled, and the adverse event and concomitant medications recorded on the 
CRF.
Table 8-1
Assessment schedule
Epoch
Screening
Treatment
Follow-up
Visit Name
Screening
Run-in2
Baseline
Treatment
Follow-up
EOS
Visit Numbers1
1
2
3
101
102
103
104
105
106
107
199
201
299
Days
-49 to -22
-21 to -8
-7 to -1
1
8
15
22
±1
29
±1
57
±2
85
±2
99
±2
127
±7
169
±7
Weeks of dosing
-
-
-
0
1
2
3
4
8
12
14
18
24
Informed consent
X
Inclusion / Exclusion criteria
S
S
Medical history/current medical conditions
X
Prior medication for tendinopathy
X
Hepatitis B, C or HIV serology (only in countries where 
required)
S
S
Tuberculosis test11
S
Demography
X
Pregnancy and assessments of fertility3
X
X
X
X
X
X
X
Alcohol Test, Drug Screen 
S
T3, T4, TSH
X
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Epoch
Screening
Treatment
Follow-up
Visit Name
Screening
Run-in2
Baseline
Treatment
Follow-up
EOS
Visit Numbers1
1
2
3
101
102
103
104
105
106
107
199
201
299
Days
-49 to -22
-21 to -8
-7 to -1
1
8
15
22
±1
29
±1
57
±2
85
±2
99
±2
127
±7
169
±7
Weeks of dosing
-
-
-
0
1
2
3
4
8
12
14
18
24
Chest X-Ray7
S
Randomization
X
Study drug administration4
X
X
X
X
X
X
X
Physiotherapy
S13
S
Physical Examination5
S
S
S
Body Height5
X
Body Weight5
X
X
X
Body Temperature5
X
X
X
X
X
X
X
X
X
Blood Pressure and Pulse Rate5
X
X
X
X
X
X
X
X
X
Electrocardiogram (ECG) 5
S
S
S
S
Hematology5
X
X
X
X
X
Clinical Chemistry 5
X
X
X
X
X
Urinalysis5
X
X
X
X
Lipid panel and glucose5
X
X
Shoulder X-Ray6, 12
S
Shoulder US
S
Shoulder MRI
X12
X
X
X
Patient pain & NSAIDs diary
X
Patient reported outcomes5
X
X
X
X
X
X
X
X
X
Pain VAS
X
X
X
Clinician reported outcome (PhGA)5
X
X
X
X
X
X
X
X
X
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Epoch
Screening
Treatment
Follow-up
Visit Name
Screening
Run-in2
Baseline
Treatment
Follow-up
EOS
Visit Numbers1
1
2
3
101
102
103
104
105
106
107
199
201
299
Days
-49 to -22
-21 to -8
-7 to -1
1
8
15
22
±1
29
±1
57
±2
85
±2
99
±2
127
±7
169
±7
Weeks of dosing
-
-
-
0
1
2
3
4
8
12
14
18
24
PD blood (IL-17A)5
X
X
X
X
PK blood collection5
X
X
X
X
Immunogenicity5
X
X
X
Concomitant medications
X
Adverse Events
X
Comments
X
Study completion information
X
1 Visit structure given for internal programming purpose only
2 Run-in to standardize physiotherapy and stabilize NSAIDS, no site visit required
3 Serum pregnancy test required as Screening and EOS, for remaining visits: urine test
4 At study days 8 and 22 study medication can be administered by study nurse at patients home
5 Collected pre-dose if applicable
6 Historic data accepted if obtained ≤3 months before baseline
7 A chest X-ray (can be replaced by historic CT or MRI) is required if it was not performed and evaluated within 3 months prior to screening. The X-ray should be 
performed after it is certain the subject meets other inclusion/exclusion criteria in order to minimize unnecessary exposure to radiation. 
8 To be done the night before and the night after each visit (except for EOS when it is done only before the visit).
9
10
11 The PPD skin test can be performed at any time during the screening period, but it must be read within 72 hours and before randomization
12 Assessments to be performed maximum 14 days before study Day 1
13 Duration of the standardized physiotherapy might be prolonged if required by local regulations
S: collected as source data only
For all subjects who discontinue from the study, the investigator should ensure that the subject completes the end of treatment visit (EOS) 4 weeks after last study 
treatment of secukinumab.  Every attempt should be made to obtain MRI images at the final visit, unless the MRI was taken within 8 weeks before discontinuation.
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8.2
Informed consent procedures
Eligible patients may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent. 
If applicable, in cases where the patient’s representative gives consent (if allowed according 
to local requirements), the patient must be informed about the study to the extent possible 
given his/her understanding. If the patient is capable of doing so, he/she must indicate assent 
by personally signing and dating the written informed consent document or a separate assent 
form. 
Informed consent must be obtained before conducting any study-specific procedures (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 a proposed informed consent form that complies with 
the ICHE6 GCP guideline and regulatory requirements and is considered appropriate for this 
study. The informed consent form will also include a section related to optional future 
research which will require a separate signature if the patient agrees to future research.  
The procedures set out in the main consent form concerning the storage, maintenance of 
privacy, and release of the data or specimens for the main study will also be adhered to for 
any future research. Any changes to the proposed consent form suggested by the investigator 
must be agreed to by Novartis before submission to the IRB/IEC.
Information about common side effects already known about the investigational drug can be 
found in the IB. This information will be included in the patient informed consent and should 
be discussed with the patient during the study as needed. Any new information regarding the 
safety profile of the investigational drug that is identified between IB updates will be 
communicated as appropriate, for example, via an Investigator Notification or an Aggregate 
Safety Finding. New information might require an update to the informed consent and then 
must be discussed with the subject.
Ensure patients are informed of the contraception requirements outlined in the Section 4.2
(Exclusion criteria).
A copy of the approved version of all consent forms must be provided to the Novartis monitor 
after IRB/IEC approval.
Refer to the SOM for a complete list of Informed Consent Forms included in this study.
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8.3
Patient screening
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. 
8.4
Information to be collected on screening failures
Subjects who discontinue from the study prior to randomization are considered screen failures. 
The reason for not being randomized and demographics will be entered in the CRF. The CRF 
for adverse events (AEs) should be completed for any Serious Adverse Events (SAEs) that 
occurred during the screening period. Adverse events that are not SAEs will be followed by 
the investigator and collected only in the source data. 
All subjects who have signed informed consent and are randomized into the Treatment Period 
of the study will have all AEs occurring after informed consent is signed recorded on the 
CRF capturing AEs, and SAEs if applicable, i.e. when SAE criteria are met.
Investigators will have the discretion to record abnormal test findings on the medical history 
CRF whenever in their judgement, the test abnormality occurred prior to the informed consent 
signature. 
8.5
Patient demographics/other baseline characteristics
Subject demographic and baseline characteristic data to be collected on all patients and 
recorded in the eCRF include: 

Date of birth, age, sex, race, ethnicity

Relevant tendinopathy and general medical history/current medical condition data until
the start of study treatment, such as date of diagnosis of tendinopathy, previous
tendinopathy therapies, especially pain medication and physiotherapy

Potential corticoid steroid treatment and information on potential tear on MRI will be
recorded to assess patients for eligibility and to stratify patients
Whenever possible, diagnoses and not symptoms will be recorded. Further details are outlined
in the SOM.
Investigators have the discretion to record abnormal test findings on the medical history CRF, 
if in their judgment, the test abnormality occurred prior to the informed consent signature.
8.5.1
Hepatitis screen, HIV screen
Hepatitis B and/or hepatitis C and/or HIV serology testing are to be performed during 
screening period, only if required per local medical practice or local regulations prior to 
initiation of therapy.
If HIV test is seropositive, it should be confirmed by a second technique available at the 
laboratory site, e.g., Western blot.  Appropriate counseling will be made available by the 
Investigator in the event of a positive finding. Notification of state and federal authorities, as 
required by law, will be the responsibility of the Investigator.

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Results for Hepatitis and HIV tests will be available as source data at the study site and will 
not be recorded within the CRF.
8.5.2
Alcohol test, drug screen 
All subjects will be screened for substances of abuse. These assessments will be documented 
in source records only and will not be entered into the CRF.
See the SOM for details.
8.5.3
X-ray of the shoulder
An X-ray of the shoulders will be taken at screening, if one was not taken within the last 
3 months. It is recommended that shoulders X-ray is performed in anterior-posterior and 
lateral planes in order to evaluate patient’s eligibility.
8.5.4
Treatment exposure and compliance
All dates and times of study treatment administration will be recorded on the appropriate 
Dosage Administration Record eCRF page.
Drugs administered prior to start of treatment and other drugs continuing or started during the 
study treatment period will be entered in the “Prior/Concomitant medications” or “Significant 
non-drug therapies” eCRF page. 
Compliance is expected to be 100%, unless temporary interruption is needed for safety 
reasons. Compliance will also be assessed by a Novartis monitor using information provided 
by the authorized site personnel.
8.6
Efficacy
8.6.1
The PRO efficacy measures, primary and secondary objectives:
The impact of tendinopathy on various aspects of patient’s health-related quality of life (QoL) 
will be assessed by the following instruments:

The WORC score

The QuickDASH score (in case available in local language/dialect)

The ASES score

The EQ5D-5L score

Patient’s global assessment of disease activity (VAS)

Patient’s assessment of tendinopathy pain intensity (VAS)
Daily assessments of pain intensity, as well as any changes in concomitant pain medication
will be recorded in the patient diary.
All questionnaires will be available, in the local languages of the participating countries.
The patients will be asked to fill in these PROs at the clinic at the visits specified in the
Assessment schedule.

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Subjects should be given sufficient instruction, space, time and privacy to complete all study 
PROs. The study coordinator should check the responses to the questionnaire for 
completeness and encourage the subject to complete any missing responses. If subjects 
experience any difficulties with submission after they complete the PROs, the study staff 
should assist them with submitting their PRO responses. Attempts should be made to collect 
responses to all PROs for all subjects, including patients who prematurely discontinue prior to 
the study evaluation completion visit. However, if subjects refuse to complete PROs, this 
should be documented in study source records. Subject’s refusal to complete study PROs are 
not protocol deviations. 
Guidelines for administering the PRO questionnaires can be found in SOM. 
Completed questionnaires and patient diaries will be reviewed and examined by the 
investigator, before the clinical examination, for responses that may indicate potential AEs or 
SAEs. The investigator should review not only the responses to the questions in the 
questionnaires but also for any unsolicited comments written by the subject. If AEs or SAEs 
are confirmed, then the physician must record the events as per instructions given in 
Section 9.1 and Section 9.2 of the protocol. Investigators should not encourage the subjects to 
change the responses reported in the completed questionnaires.
8.6.1.1
The WORC score
The WORC score is a patient reported outcome tool, uniquely developed for the rotator cuff
diseases by Kirkley and co-workers (Kirkley et al 2003). The WORC is self-administered and 
consists of 21 items divided into five domains: Physical Symptoms (6 items); 
Sport/Recreation (4 items); Work Function (4 items); Lifestyle Function (4 items) and 
Emotional Function (3 Items). Items are scored by a 10 cm VAS so the best possible result is 
0 (asymptomatic patient) while the worst possible result is 2100 (highly symptomatic).
The WORC Index has a recall period of 1 week and is filled in by the patient at the clinic at 
visits specified in the Assessment schedule.
Details of the WORC are outlined in the SOM.  
8.6.1.2
The QuickDASH score
Quick DASH should be performed in all countries for which local language/dialect is 
available. The Quick DASH is an abbreviated form of the DASH a patient reported outcome 
tool, which has been developed by the American Academy of Orthopedic Surgeons along 
with 
the 
Institute 
for 
Work 
&
Health 
(Toronto, 
Ontario, 
Canada)
(http://www.dash.iwh.on.ca/scoring). The Quick DASH Index is self-administered and uses 
11 items to measure physical function and symptoms in patients with any or multiple 
musculoskeletal disorders of the upper limb. Each item of the QuickDASH has five response 
options. The total score is reported on a 100-point scale, with 100 indicating the most 
disability. It has a recall period of 1 week. The tool is filled in by the patient at visits specified 
in the Assessment schedule.
Details of the Quick DASH are outlined in the SOM.  

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8.6.1.3
The ASES score
The ASES score is developed by the Society of the American Shoulder and Elbow Surgeons 
for the assessment of shoulder function (Richards et al 1994). The ASES score is 
self-administered and has 17 questions in the areas of symptoms and functions. The severity 
of pain is graded on a 10 cm visual analog scale that ranges from 0 (no pain at all) to 10 
(pain as bad as it can be). The recall period is the current point in time. The tool is filled in by 
the patient at visits specified in the Assessment schedule.
Details of the ASES are outlined in the SOM.
8.6.1.4
EuroQuol 5D (EQ-5D-5L)
The EQ-5D-5L is a widely used, self-administered questionnaire designed to assess health 
status in adults. 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 two distinct sections. The first section 
includes one item addressing each of five dimensions (mobility, self-care, usual activity, 
pain/discomfort, and anxiety/depression). Subjects 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 six 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 subject of particular health states and the generation of subject 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 Day 1 prior to drug administration and at 
visits specified in the Assessment schedule.
Details of the EQ5D are outlined in the SOM.
8.6.1.5
Patient’s assessment of tendinopathy pain intensity and change in 
pain medication
The patient will assess his/her pain in a PRO diary once per day rating the pain during the 
previous 24 hours. The patient’s assessment of pain will be performed using 100 mm visual 
analog scale (VAS) ranging from “no pain” to “worst possible pain” after the question 
“Please rate the severity of your pain at its worst during the last 24 hours by marking an X on 
the line below”.
Similarly, 
the 
patient 
should 
note 
down 
whenever 
he/she 
has 
changed
the 
NSAID/acetaminophen intake.

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8.6.1.6
Patient’s global assessment of disease activity
The patient’s global assessment of disease activity will be performed using 100 mm VAS 
ranging from ”no activity” to ”most active”, after the question " Please indicate with a 
vertical mark ( | ) through the horizontal line the global activity of your disease in the last 
24 hours”. 
The patient’s global assessment of disease activity is filled in by the patient at Day 1 prior to 
drug administration and at visits specified in the Assessment schedule.
8.6.2
Clinician reported outcome (CRO) efficacy measures collected in the 
trial for secondary objectives
Physician’s global assessment of disease activity
The physician’s global assessment of disease activity will be performed using 100 mm VAS 
ranging from no disease activity to maximal disease activity, after the question " Considering 
all the ways the tendinopathy affects your patient, please 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, 
when performing his own assessment on that subject.
The physician’s global assessment of disease activity is filled in by the investigator at Day 1 
prior to drug administration and at visits specified in the Assessment schedule.
8.6.3
Imaging efficacy measures collected in the trial for secondary and 
exploratory objectives are:
8.6.3.1
MRI of the shoulder, Sein score and Bauer score
The MRI Sein score will be used primarily to grade supraspinatus tendinosis at screening 
using a modified 4-point scale (Sein et al 2007), and monitor changes in this grading over 
time as a treatment outcome (secondary objective). Tendinopathy will be characterized by 
thickened inhomogeneous rotator cuff tendon with increased signal intensity on all pulse MRI 
sequences, yet not as bright as the fluid on typical T2-weighted images. Since tendonisis and 
partial thickness cuff injuries are prevalent in sporting activity and in middle age, another 
grading system, the Bauer score, will be used as an exploratory endpoint for a differentiated 
assessment of supraspinatus partial tears and tendonosis (Bauer et al 2014). A 9-point 
tendinopathy grade will be generated out of this approach, including sub-scores for tendonisis 
(0-2), tear thickness (0-4) and AP tear size (0-3). Finally these images will also be used to 
measure thickness of the rotator cuff tendon and assess for presence of bursitis in the area of 
the rotator cuff.
Enhancement of the subacromial bursa will be assessed. Images will be scored on a scale of 
0–2 depending on the maximum thickness of enhancing tissue: 0: no abnormal enhancement; 
1: up to 3 mm thickness of enhancing tissue; 2: 3 mm or more enhancing tissue
(Hodgson et al 2012).

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MR images will be acquired at 3T in multiple planes by using an imaging sequences 
optimized for tendon/surrounding tissue separation and adapted to the MRI system 
capabilities. All MRI scans will be sent for central reading and all results obtained post 
Baseline visit will remain blinded to the investigator, patient and sponsor until after the 
primary endpoint analysis at week 14. Detailed information can be located in the imaging 
manual. The coded MRI medical images will be used primarily for analysis as described in 
this protocol; however, the images may also be used for the development and evaluation of 
new analysis methods directly related to the area of research that this study covers.
8.7
Safety
All blood draws and safety assessments should be done prior to study treatment 
administration. Appropriate safety assessments (e.g. evaluation of AEs and SAEs including 
injection site reactions) should be repeated after the dose is administered. Assessments done 
as a part of the safety evaluation include:

Evaluation of AE/ SAE’s

Physical examination

Vital signs

Height and weight

Tuberculosis screening: QuantiFERON TB-Gold test or PPD skin test

Chest X-Ray

Electrocardiogram

Local tolerability (Injection site reactions)

Laboratory evaluations (Hematology, Clinical Chemistry, Lipid Panel, Urinalysis)
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
Pregnancy and assessment of fertility

Tolerability of secukinumab

Immunogenicity
8.7.1
Physical examination
The physical examination will include the examination of general appearance, skin, neck, 
eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, vascular and 
neurological system.
Information for all physical examinations must be included in the source documentation at the 
study site. Significant findings that are present before signing the ICF must be included in the 
relevant medical history eCRF. Significant findings made after signing the ICF which meet 
the definition of an AE must be recorded in the Adverse Event eCRF.
8.7.2
Vital signs
This will include body temperature, BP and pulse rate measurements after 5 minutes rest in 
sitting position.
Clinically notable vital signs are defined in Appendix 1.
8.7.3
Height and weight
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram [kg] in indoor 
clothing) (both without shoes) will be measured.
If possible, body weight assessments should be performed by the same study site staff 
member using the same scale throughout the study. 
8.7.4
ECG
In this study, local ECG will be used. 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, subject initials, subject 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 9).

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8.7.5
Tuberculosis screening
Either a central laboratory immunological test (QuantiFERON TB-Gold) or a locally 
performed skin test must be performed at the screening visit to screen the subject population 
for latent tuberculosis infection. The results must be known prior to randomization to 
determine the subject’s eligibility for the study. 
Subjects with a positive test may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that 

the subject has no evidence of active tuberculosis

if presence of latent tuberculosis is established then treatment according to local country
guidelines must have been initiated.
Central laboratory test for Tuberculosis screening
The QuantiFERON TB-Gold 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.
Local skin test for Tuberculosis screening
A PPD skin test is to be performed at screening and read before randomization to determine 
the subject’s eligibility for the study. The test dose is bioequivalent to 5 tuberculin units of 
standard PPD injected intradermally, usually into the volar surface of the forearm. The site is 
cleaned and the PPD extract is then injected into the most superficial layer under the skin. 
If given correctly, the injection should raise a small wheal of about 5 mm, which resolves 
within 10-15 minutes.
Because the reaction (induration) will take 48-72 hours to develop, the subjects must return to 
the investigators’ site within that time for a proper evaluation of the injection site. This will 
determine whether the subject has had a significant reaction to the PPD test. A reaction is 
measured in millimeters of induration (hard swelling) at the site. A PPD skin induration 
≥5 mm (or according to local practice/guidelines
Either a QuantiFERON TB-Gold test or a PPD skin test must be performed at screening. 
Subjects with a positive test may participate in the study if further work up (according to local 
practice/guidelines) establishes conclusively that the subject has no evidence of active 
tuberculosis, or if presence of latent tuberculosis is established then treatment according to 
local country guidelines must have been initiated.
8.7.6
Ultrasound of the shoulder
Ultrasound of the shoulder is done at screening, in order to assess eligibility unless US or 
MRI are available from within previous 3 month and clinical symptoms stabile, these 
examinations can be used for source data. B-mode US is utilized to rule out major structural 
damage to the tendon (i.e. more than 50% tear) or other shoulder pathologies 

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8.7.7
Chest X-ray 
A chest x-ray (posterior-anterior plane) is required if it was not performed and evaluated 
within 3 months prior to screening. An additional x-ray in the lateral plane is only done if 
acceptable per local practice and regulations. Lateral plane x-ray will not be permitted in the 
UK for this study. The X-ray should be performed after it is certain the subject 
meets inclusion/exclusion criteria in order to minimize unnecessary exposure to radiation. 
The X-Ray might be replaced by historic CT or MRI scan if performed within 3 months prior 
to screening.
8.7.8
Tolerability of investigational treatments
Tolerability will be assessed by adverse events, 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 CRF capturing AEs, including the severity (mild, 
moderate, severe) and the duration of the adverse reaction.
8.7.9
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 adverse event 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.
8.7.9.1
Hematology
Hemoglobin, hematocrit, red blood cell (RBC) count, white blood cell (WBC) count with 
differentials and platelet count will be measured. 
8.7.9.2
Clinical chemistry
Serum chemistries will include sodium, potassium, BUN/urea, bicarbonate, calcium, 
phosphorous, total protein, calcium, albumin, uric acid, creatinine, CK, total bilirubin, AST 
(SGOT), ALT (SGPT), GGT and alkaline phosphatase; at all timepoints specified in the 
Assessment schedule. 
If the total bilirubin concentration is increased above 1.5 times the upper limit of normal, 
direct and indirect reacting bilirubin should be differentiated.
Triiodothyronine 
(T3), 
thyroxine 
(T4), 
thyroid-stimulating
hormone
(TSH), 
Rheumatoid factor (RF), anti-cyclic citrullinated peptide (anti-CCP) antibodies, and 
interferon-gamma release test done only at screening. FSH is only done at screening and only 
in patients who are reported post-menopausal at screening

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8.7.9.3
Lipid panel and glucose
A lipid profile including High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), 
cholesterol, triglycerides and glucose will be measured from a fasting blood sample.
8.7.9.6
Urinalysis
Dipstick measurements for protein, blood, and WBC/leukocytes will be performed at site ad 
documented as source data. 
If dipstick measurement results are positive (abnormal), results will be captured in the CRF.
Microscopy must be assessed following an abnormal dipstick test with results captured in the CRF.
8.7.10
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 1 (screening). All women who 
are not surgically sterile at screening will have local urine pregnancy tests as indicated in
Table 8-1. 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 subject must be 
discontinued from the trial. Additional pregnancy testing might be performed if requested per 
local requirements.  Refer to Section 9.6
for details
on Reporting Pregnancy.
Pregnancy testing results are kept in the source data documentation.
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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 
subject who states that they are of non-child bearing potential, regardless of reported 
reproductive/menopausal status at screening/baseline
8.7.11
Additional parameters
Blood will be obtained at the first screening visit (Visit 1) for anti-CCP antibodies and the 
Rheumatoid Factor (RF)
8.8
Pharmacokinetics
PK samples will be collected at the timepoints defined in the Assessment schedule
(Section 8.1). Follow instructions outlined in the Site Operations Manual regarding sample 
collection, numbering, processing and shipment. See Section 8.9.5 regarding the potential use 
of residual samples. 
For standard pharmacokinetic abbreviations and definitions see the list provided at the 
beginning of this protocol.
The following pharmacokinetic parameter will be determined using the actual recorded 
sampling times with Phoenix WinNonlin (Version 6.4 or higher): Cmin.
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8.9
Other assessments
8.9.3
Immunogenicity 
Blood samples for immunogenicity (anti-AIN457 antibodies) will be taken pre-dose at the 
scheduled time points as indicated in Table 8-1. 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 subject discontinues from the study at any timepoint, 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 
lab to the sites 
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The detailed methods for immunogenicity assessment will be described in the Bioanalytical 
Data Report.
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9
Safety monitoring
9.1
Adverse events
An adverse event (AE) is any untoward medical occurrence (i.e., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a subject 
after providing written informed consent for participation in the study until the end of study 
visit. Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product.
In addition, all reports of intentional misuse and abuse of the study treatment are also 
considered an adverse event irrespective if a clinical event has occurred. See Section 9.5 for 
an overview of the reporting requirements.
The occurrence of adverse events must be sought by non-directive questioning of the subject 
at each visit during the study. Adverse events also may be detected when they are volunteered 
by the subject during or between visits or through physical examination finding, laboratory 
test finding, or other assessments.
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria:

They induce clinical signs or symptoms,

They are considered clinically significant,

They require therapy.
Clinically significant abnormal laboratory values or test results should be identified through a review 
of values outside of normal ranges/clinically notable ranges, significant changes from baseline or the 
previous visit, or values which are considered to be non-typical in patients with underlying disease. 
Investigators have the responsibility for managing the safety of individual subject and 
identifying adverse events. Clinically notable vital signs are defined in Appendix 1.
Adverse events should be recorded on the Adverse Events CRF under the signs, symptoms or 
diagnosis associated with them, and accompanied by the following information:
1. The severity grade:

Mild: Usually transient in nature and generally not interfering with normal activities

Moderate: Sufficiently discomforting to interfere with normal activities

Severe: Prevents normal activities
2. Its relationship to the study treatment

Yes or

No
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 9.2 for definition of SAE) and which
seriousness criteria have been met
5. Action taken regarding investigational treatment.

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All adverse events must be treated appropriately. Treatment may include one or more of 
the following: 

No action taken (e.g. further observation only)

Investigational treatment dosage increased/reduced

Investigational treatment interrupted/withdrawn

Concomitant medication or non-drug therapy given

Hospitalization/prolonged hospitalization (see Section 9.2 for definition of SAE)
6. its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving,
recovered/resolved with sequelae; fatal; or unknown).
Information about common side effects already known about the investigational drug can be 
found in the IB or will be communicated between IB updates in the form of Investigator 
Notifications.  
Once an adverse event is detected, it must be followed until its resolution or until it is judged 
to be permanent, and assessment should be made at each visit (or more frequently, if 
necessary) of any changes in severity, the suspected relationship to the investigational drug, 
the interventions required to treat it, and the outcome.
The investigator must also instruct each subject to report any new adverse event (beyond the 
protocol observation period) that the subject, or the subject’s personal physician, believes 
might reasonably be related to study treatment. This information must be recorded in the 
investigator’s source documents; however, if the AE meets the criteria of an SAE, it must be 
reported to Novartis.
*Refer to the Site Operations Manual for data capture methodology regarding AE collection
for subjects that fail screening.
9.2
Serious adverse event reporting
9.2.1
Definition of SAE
An SAE is defined as any adverse event (appearance of (or worsening of any pre-existing) 
undesirable sign(s), symptom(s) or medical conditions(s)) which meets any one of the 
following criteria:

Is fatal or life-threatening

Results in persistent or significant disability/incapacity

Constitutes a congenital anomaly/birth defect

Requires inpatient hospitalization or prolongation of existing hospitalization, unless
hospitalization is for:

Routine treatment or monitoring of the studied indication, not associated with any
deterioration in condition

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
Elective or pre-planned treatment for a pre-existing condition that is unrelated to the
indication under study and has not worsened since the start of study drug

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 subject’s
general condition

Is medically significant, e.g. defined as an event that jeopardizes the subject or may
require medical or surgical intervention.
All malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.
Life-threatening in the context of a SAE refers to a reaction in which the 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 ICH-E2D Guideline 2004).
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 
subject 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 ICH-E2D Guideline 2004).
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
All AEs (serious and non-serious) are captured on the CRF; SAEs also require individual 
reporting to Novartis Chief Medical Office and Patient Safety (CMO & PS) as per 
Section 9.2.2.
9.2.2
SAE reporting
Information about all SAEs is collected and recorded on the Serious Adverse Event Report 
Form; 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 study treatment, 
complete the SAE Report Form in English, and submit the completed form within 24 hours to
Novartis.
Screen Failures & Run-In Failures
Note the following requirement for Screen Failures: SAEs occurring after the subject has 
provided informed consent until the time the subject is deemed a Screen Failure must be 
reported to Novartis. 
For subjects considered Run-In Failures, SAEs occurring after the subject has provided 
informed consent until the time the subject is deemed a Run-In Failure must be reported to 
Novartis.

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Randomized Subjects
To ensure subject safety, every SAE, regardless of causality, occurring after the subject has 
provided informed consent and until the last day of study (which is 12 weeks after last 
administration of study treatment) must be reported to Novartis within 24 hours of learning of 
its occurrence as described below. 
Any SAEs experienced after this period should only be reported to Novartis if the investigator 
suspects a causal relationship to study treatment. 
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.
Follow- up information provided must describe whether the event has resolved or continues, if 
and how it was treated, whether the blind was broken or not (if applicable) and whether the 
subject continued or withdrew from study participation. 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.
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert 
(new occurrence) and is thought to be related to the study treatment a 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. 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.
Follow the detailed instructions outlined in the Site Operations Manual regarding the 
submission process for reporting SAEs to Novartis.   
Note: SAEs must be reported to Novartis within 24 hours of the investigator learning of its 
occurrence/receiving follow-up information.
9.3
Liver safety monitoring
There has been no safety signal for liver toxicity with secukinumab to date in approximately 
13,000 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.

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9.4
Renal safety monitoring
There has been no safety signal for nephrotoxicity with secukinumab to date in approximately 
13,000 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 subjects with laboratory tests 
containing clinically significant abnormal values (see Appendix 1 for notable laboratory 
values) are to be followed until the values return to normal ranges or until a valid reason, 
other than treatment related AE, is defined. Standard renal function tests (blood urea nitrogen, 
serum creatinine) will be obtained at regular intervals, but special measures for renal safety 
monitoring are not planned.
9.5
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/subject 
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.
All study treatment errors and uses outside of what is foreseen in the protocol will be 
collected in the dose administration record (DAR) CRF. Study treatment errors are only to be 
reported to Chief Medical Office and Patient Safety (CMO & PS) department if the treatment 
error is associated with an SAE. 
All instances of misuse or abuse must be documented in the adverse event (AE) CRF 
irrespective of the misuse/abuse being associated with an AE/SAE. In addition, all instances 
of misuse or abuse must be reported to Novartis Chief Medical Office and Patient Safety 
(CMO & PS). As such, instances of misuse or abuse are also to be reported using the SAE 
form/CRF. Table 9-1 summarizes the reporting requirements.
Table 9-1
Guidance for capturing study treatment errors
Treatment error type
Document in Dose 
Administration 
(DAR) CRF 
Document in AE 
CRF
Complete SAE form/CRF 
Unintentional study 
treatment error
Yes
Only if associated 
with an AE
Only if associated with an 
SAE
Misuse/Abuse
Yes
Yes 
Yes, even if not associated 
with a SAE
For more information on AE and SAE definition and reporting requirements, 
please see Section 9.1 and Section 9.2, respectively.

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9.6
Pregnancy reporting
All pre-menopausal women who are not surgically sterile will have a urine pregnancy test. 
A positive urine pregnancy test requires immediate interruption of study drug until serum 
β-hCG is performed and found to be negative.
To ensure subject 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 must be recorded on the Pharmacovigilance Pregnancy Form and reported by the 
investigator to the local Novartis Chief Medical Office and Patient Safety (CMO & PS) 
Department. Pregnancy follow-up should be recorded on the same form and should include an 
assessment of the possible relationship to the study treatment. 
Any SAE experienced during the pregnancy and unrelated to the pregnancy must be reported 
on a SAE form.
The study drug must be discontinued*, though the subject may stay in the study, if she wishes 
to do so. All assessments that are considered as a risk during pregnancy must not be 
performed. The subject may continue all other protocol assessments. 
Pregnancy outcomes should be collected for the female partners of any males who took study 
treatment in this study. Consent to report information regarding these pregnancy outcomes 
should be obtained from the mother. 
10
Data review and database management
10.1
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 (eCRF) 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 monitor will 
visit the site to check the completeness of subject records, the accuracy of data capture / data 
entry, the adherence to the protocol and to Good Clinical Practice, the progress of enrollment, 
and ensure that study drug is being stored, dispensed, and accounted for according to 
specifications. Key study personnel must be available to assist the monitor during these visits.
Continuous remote monitoring of each site’s data may be performed by Novartis or CRO 
working on behalf of Novartis. Additionally, a central analytics organization may analyze data 
and identify risks & trends for site operational parameters, and provide reports to Novartis 
Clinical Teams to assist with trial oversight.

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The investigator must maintain source documents for each subject in the study, consisting of 
case and visit notes (hospital or clinic medical records) containing demographic and medical 
information, laboratory data, electrocardiograms, and the results of any other tests or 
assessments. All information on CRFs must be traceable to these source documents in the 
subject's file. The investigator must also keep the original informed consent form signed by 
the subject (a signed copy is given to the subject).
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 the recording of data that will be 
used for all primary and safety variables. Additional checks of the consistency of the source 
data with the CRFs are performed according to the study-specific monitoring plan. 
No information in source documents about the identity of the subjects will be disclosed.
10.2
Data collection
Designated investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms using fully validated software that conforms to 21 CFR Part 11 
requirements. Designated investigator site staff will not be given access to the EDC system 
until they have been trained. Automatic validation programs check for data discrepancies and, 
by generating appropriate error messages, allow the data to be confirmed or corrected before 
transfer of the data to the CRO working on behalf of Novartis. The Investigator must certify 
that the data entered into the Electronic Case Report Forms are complete and accurate. 
After database lock, the investigator will receive copies of the subject data for archiving at the 
investigational site.
Data not requiring a separate written record will be defined in the Site Operations Manual and 
Assessment schedule (Section 8.1) and can be recorded directly on the CRFs. All other data 
captured for this study will have an external originating source (either written or electronic) 
with the CRF not being considered as source.
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification.
10.3
Database management and quality control
Novartis staff and CRO working on behalf of Novartis review the data entered into the CRFs 
by investigational staff for completeness and accuracy and instruct the site personnel to make 
any required corrections or additions. Queries are sent to the investigational site using an 
electronic data query. Designated investigator site staff is required to respond to the query and 
confirm or correct the data. If the electronic query system is not used, a paper Data Query 
Form will be faxed to the site. Site personnel will complete and sign the faxed copy and fax it 
back to CRO working on behalf of Novartis who will make the correction to the database. 
The signed copy of the Data Query Form is kept at the investigator site.

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Concomitant medications entered into the database will be coded using the WHO Drug 
Reference List, which employs the Anatomical Therapeutic Chemical classification system. 
Medical history/current medical conditions and adverse events will be coded using the 
Medical dictionary for regulatory activities (MedDRA) terminology.
Laboratory samples will be processed centrally and the results will be sent electronically to 
Novartis (or a designated CRO).
Details regarding patient diary, PRO, and CRO data collection will be provided in SOM.
At the conclusion of the study, the occurrence of any emergency code breaks will be 
determined after return of all code break reports and unused drug supplies to Novartis. 
The occurrence of relevant protocol deviations will be determined. After these actions have 
been completed and the database has been declared to be complete and accurate, it will be 
locked and the treatment codes will be unblinded and made available for data analysis. 
Any changes to the database after that time can only be made after written agreement by 
Novartis management.
10.4
Data Monitoring Committee
Not required.
10.5
Adjudication committee
Not required.
11
Data analysis
The analysis will be conducted on all subject 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.
11.1
Analysis sets
For all analysis sets, subjects will be analyzed according to the study treatment(s) received.
The safety analysis set will include all subjects that received any study drug.
The PK analysis set will include all subjects with at least one available valid (i.e. not flagged 
for exclusion) PK concentration measurement, who received any study drug and with no 
protocol deviations that impact on PK data.
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The PD analysis set will include all subjects with available PD data and no protocol 
deviations with relevant impact on PD data.
11.2
Subject demographics and other baseline characteristics
All data for background and demographic variables will be listed by treatment group and 
subject. Summary statistics will be provided by treatment group.
Relevant medical history, current medical conditions, results of laboratory screens, drug tests 
and any other relevant information will be listed by treatment group and subject.
11.3
Treatments
Data for study drug administration (rescue medication) and concomitant therapies will be 
listed by treatment group and subject.
11.4
Analysis of the primary variable(s)
The primary aim of this study is to assess the efficacy of secukinumab 300 mg s.c. vs. placebo 
in patients with overuse rotator cuff tendinopathy in relieving clinical symptoms at week 14
11.4.1
Primary Variable(s)
The primary variable, the WORC score, will be available at Baseline and weeks 2, 4, 8, 12 
and 14
11.4.2
Statistical model, hypothesis, and method of analysis
The primary end-point (change from baseline in WORC score at Week 14) will be analyzed 
by repeated measures analysis of covariance including all WORC scores available. Change at 
Week 14 will be compared between treatments to address the primary objective. The baseline 
WORC score will be included as a covariate. The stratification factors partial tear/no tear and 
previous steroid injection (yes/no) will be included in the model as fixed effects. A 95% one-
sided (90% two-sided) confidence interval for the treatment effect at Week 14 will be reported. 
Missing variables will be considered missing at random.
Initially, models with an unstructured within-subject covariance and a separate mean for each 
treatment and time point will be fitted. These models may be reduced in number of covariance 
and mean parameters by model comparison using tools such as the BIC criterion for model fit.
11.4.3
Handling of missing values/censoring/discontinuations
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11.4.4
Summary statistics of safety
Vital signs
All vital signs data will be listed by treatment group, subject, and visit/time and if ranges are 
available abnormalities (and relevant orthostatic changes) will be flagged. Summary statistics 
will be provided by treatment and visit/time.
Clinical laboratory evaluations
All laboratory data will be listed by treatment group, subject, and visit/time and if normal 
ranges are available abnormalities will be flagged. Summary statistics will be provided by 
treatment and visit/time.
Adverse events
All information obtained on adverse events will be displayed by treatment group and subject.
The number and percentage of subjects with adverse events will be tabulated by body system 
and preferred term with a breakdown by treatment. A subject with multiple adverse events 
within a body system is only counted once towards the total of this body system.
11.4.5
Sensitivity analyses
Not applicable.
11.5
Analysis of secondary variable(s)
Secondary variables include:

Change from baseline in WORC score at weeks 2, 4, 8, 12, 18 and 24

Disability of Arm, Shoulder and Hand Questionnaire (QuickDASH) score at weeks 2, 4, 8,
12, 14, 18 and 24

American Shoulder and Elbow Surgeons Shoulder Evaluation Form(ASES) score at
weeks 2, 4, 8, 12, 14, 18 and 24

EQ5D score at weeks 2, 4, 8, 12, 14, 18 and 24

Pain score using a VAS scale (considering the last 24 hours) at weeks 2, 4, 8, 12, 14, 18
and 24

Patient global assessment (PGA) score using a VAS scale (considering the last 24 hours),
at weeks 2, 4, 8, 12, 14, 18 and 24

Physician global assessment (PhGA) score using a VAS scale (considering the last
24 hours), at weeks 2, 4, 8, 12, 14, 18 and 24

MRI Sein score at weeks 8, 14 and 24
Secondary variables (except Sein score) will be summarized descriptively and analyses 
similar to the primary analysis will be performed.

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The secondary endpoint (Sein MRI score at week 14) will be analyzed by ordinal categorical 
regression. A model with an additive treatment effect on the cumulative logistic scale will be 
used, and the common treatment effect estimated and reported together with 90% asymptotic 
two-sided confidence intervals. Baseline SEIN score will be included as a covariate and the 
stratification factors, partial tear/no tear and previous steroid injection (yes/no) will be 
included in the model as fixed effects.
11.5.1
Efficacy / Pharmacodynamics
Not Applicable
11.5.2
Safety
Vital signs
All vital signs data will be listed by treatment group, subject, and visit/time and if ranges are 
available abnormalities (and relevant orthostatic changes) will be flagged. Summary statistics 
will be provided by treatment and visit/time.
Clinical laboratory evaluations
All laboratory data will be listed by treatment group, subject, and visit/time and if normal 
ranges are available abnormalities will be flagged. Summary statistics will be provided by 
treatment and visit/time.
Adverse events
All information obtained on adverse events will be displayed by treatment group and subject.
The number and percentage of subjects with adverse events will be tabulated by body system 
and preferred term with a breakdown by treatment. A subject with multiple adverse events 
within a body system is only counted once towards the total of this body system.
11.5.3
Pharmacokinetics
11.5.4
Pharmacokinetic / pharmacodynamic correlation analysis
Not Applicable.
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11.5.5
Other assessments
Immunogenicity
All immunogenicity results will be listed by treatment group, subject and visit/time.
11.6
Analysis of exploratory variables
The statistical analysis for exploratory variables will be described in the RAP.
11.7
Sample size calculation
From (de Witte et al 2012), one can infer an SD of change in the WORC score from baseline 
to 6 weeks of approximately 22 percentage points. By conservatively assuming a linear 
increase in the change score variability, the 14 week SD would by 22 multiplied by the square 
root of 1.53 (14/6); that is, 34 percentage points.
Assuming a clinically meaningful difference of 20 percentage points results in an effect size 
of 20/34=0.59. With this effect size, 40 subjects per group completing week 14 will provide 
power exceeding 80% to detect a significant difference between treatments by one-sided test 
at significance level 0.05.
11.8
Power for analysis of key secondary variables
To address the secondary MRI endpoint (Sein score at Week 14), the sample size of 
40 subjects per group completing Week 14 will also provide approximately 80% power to 
detect an odds ratio at or above 50%, i.e., that the odds of a Sein score improvement is at least 
50% higher in the treated group than in the placebo group, again by one-sided test at nominal 
significance level 0.05. This assumes a proportional cumulative odds model as described in 
(Whitehead 1993).
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11.9
Interim analyses
12
Ethical considerations
12.1
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 Code of Federal 
Regulations Title 21, and Japanese Ministry of Health, Labor, and Welfare), and with the 
ethical principles laid down in the Declaration of Helsinki.
12.2
Responsibilities of the investigator and IRB/IEC
Before initiating a trial, the investigator/institution must obtain approval/favorable opinion 
from the Institutional Review Board/Independent Ethics Committee (IRB/IEC) for the trial 
protocol, written informed consent form, consent form updates, subject recruitment 
procedures (e.g. advertisements) and any other written information to be provided to subjects. 
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.
For multi-center trials, a Coordinating Investigator will be selected by Novartis by the time of 
Last Patient Last Visit to be a reviewer and signatory for the clinical study report. 
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12.3
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.
12.4
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 or overseen by 
Novartis Pharma Auditing and Compliance Quality Assurance (or CRO working on behalf of 
Novartis), 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.
13
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 subjects should be 
administered as deemed necessary on a case by case basis. Under no circumstances is an 
investigator allowed to collect additional data or conduct any additional procedures for any 
research related purpose involving any investigational drugs under the protocol.
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.
13.1
Protocol amendments
Any change 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. 
Amendments that are intended to eliminate an apparent immediate hazard to subjects may be 
implemented immediately, provided the Health Authorities are subsequently notified by 
protocol amendment and the reviewing IRB/IEC is notified. 
Notwithstanding the need for approval of formal protocol amendments, the investigator is 
expected to take any immediate action required for the safety of any subject included in this 
study, even if this action represents a deviation from the protocol. In such cases, the reporting 
requirements identified in Section 9 (Safety Monitoring) must be followed and the Study Lead 
informed.

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References
References are available upon request.
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Bauer S, Wang A, Butler R, et al (2014) Reliability of a 3T MRI protocol for objective 
grading of supraspinatus tendonosis and partial thickness tears. J Orthopaedic Surg Res 9:128.
Chen XM, Cui LG, He P, et al (2013) Shear wave elastographic characterization of normal
and torn achilles tendons: a pilot study. J Ultrasound Med; 32: 449-455.
Coombes BK, Bisset L, Vicenzino B (2010) Efficacy and safety of corticosteroid injections 
and other injections for management of tendinopathy: a systematic review of randomised 
controlled trials. Lancet; 376:1751-67.
de Vos RJ, Weir A, van Schie HT, et al (2010) Platelet-rich plasma injection for chronic 
Achilles tendinopathy: a randomized controlled trial. JAMA; 303:144-9.
de Witte PB, Henseler JF, Nagels J, et al (2012) The Western Ontario rotator cuff index in 
rotator cuff disease patients: a comprehensive reliability and responsiveness validation study. 
Am J Sports Med; 40:1611-9.
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00003439.pdf
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Hodgson RJ, O’Connor PJ, Hensor EMA, et al (2012) Contrast-enhanced MRI of the 
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Radiology; 85:1482-1487. doi:10.1259/bjr/45423226.
Hume PA, Reid D and Edwards T (2006) Epicondylar injury in sport: epidemiology, type, 
mechanisms, assessment, management and prevention. Sports Medicine 36, 151-170.
ICH E2D (2004) Clinical Safety Data Management: Definitions and Standards for expedited 
reporting. (Internet) Available from: 
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00002807.pdf  Accessed on: 02Dec2016.

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Kaux JF, Forthomme B, Goff CL, et al (2011) Current opinions on tendinopathy. J Sports Sci 
Med;10:238-253.
Kirkley A, Alvarez C and Griffin S (2003) The Development and Evaluation of a Disease-
specific Quality-of-Life Questionnaire for Disorders of the Rotator Cuff: The Western Ontario 
Rotator Cuff Index. Clin J Sport Med; 13:84–92.
Krogh TP, Fredberg U, Stengaard-Pedersen K, et al (2013) Treatment of lateral epicondylitis 
with platelet-rich plasma, glucocorticoid, or saline: a randomized, double-blind, placebo-
controlled trial. Am J Sports Med 41:625-35.
Littlewood C, Ashton J, Chance-Larsen K, et al (2013) Exercise for rotator cuff tendinopathy: 
a systematic review. Physiotherapy; 98:101-9.
Maffulli N, Wong J and Almekinders LC (2003) Types and epidemiology of tendinopathy. 
Clinics in Sports Medicine 22, 675-692.
McGonagle D and Benjamin M (2009) Entheses, enthesitis and enthesopathy. Reports on 
rheumatic diseases series 6. 4: 1-6.
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Mohamadi A, Chan JJ, Claessen FM, et al (2017) Corticosteroid Injections Give Small and 
Transient Pain Relief in Rotator Cuff Tendinosis: A Meta-analysis. Clin. Orthop. Relat. 
Res.;475:232-243.
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information (2016).
Richards RR, An K-N, Bigliani LU, et al (1994) A standardized method for the assessment of 
shoulder function. J Shoulder Elbow Surg; 3:347-352.
Riley G (2005) Chronic tendon pathology: molecular basis and therapeutic implications. 
Expert Rev Mol Med;7:1-25.
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4:82-9.
Scott A and Ashe MC (2006) Common tendinopathies in the upper and lower extremities. 
Current Sports Medicine Reports; 5:233-241.
Sein ML, Walton J, Linklater J, et al (2007) Reliability of MRI assessment of supraspinatus 
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Whitehead J (1993), Sample size calculations for ordered categorical data. Statistics in 
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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 15-1
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