A Randomized, Double-blind, Placebo-controlled, Parallel Group, Multicenter, 24-week Study Investigating the Efficacy and Safety of Secukinumab Compared to Placebo in Adult Patients With Moderate to Severe Rotator Cuff Tendinopathy and Failure to Conventional Therapy
Phase: PHASE3
Conditions: Tendinopathy
Sponsor: Novartis Pharmaceuticals

Novartis 
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Clinical Trial Protocol, Amended Version No. 02 
Protocol No. CAIN457FDE05 
Novartis Research and Development 
Clinical Trial Protocol Title: 
A randomized, double-blind, placebo-controlled, parallel 
group, multicenter, 24-week study investigating the 
efficacy and safety of secukinumab compared to placebo in 
adult patients with moderate to severe rotator cuff 
tendinopathy and failure to conventional therapy 
“UnchAIN” 
Clinical Trial Protocol Number: CAIN457FDE05 / NCT05569174
Version Number: 02 (Amended Protocol) 
Compound: AIN457 / Secukinumab 
Brief Title: Study of efficacy and safety of AIN457/secukinumab in patients with 
rotator cuff tendinopathy 
Study Phase: IIIb 
Acronym: UnchAIN 
Sponsor Name: Novartis Pharma GmbH 
Regulatory Agency Identifier Number(s): 2022-001516-26 EudraCT 
Release Date: 10-Jul-2024  
Property of Novartis 
Confidential 
May not be used, divulged, published or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 5.0 14-Jan-2022 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
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 8.6.3 of the Clinical Trial Protocol for SAE criteria and additional 
requirements. Complete SAE report  
• Submit SAE report to Novartis Chief Medical Office and Patient Safety (CMO & 
PS) without undue delay, but under no circumstances later than within 24 hours 
• Notify the Novartis Medical Lead 
 
 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
Table of contents 
Table of contents ................................................................................................................. 3 
List of tables ........................................................................................................................ 7 
List of figures ...................................................................................................................... 7 
Amendment 2 (10-JUL-2024) .................................................................................................... 8 
Amendment 1 (12-JUN-2023) ................................................................................................... 9 
1.1 
Summary ............................................................................................................... 11 
1.2 
Schema .................................................................................................................. 17 
1.3 
Schedule of activities (SoA) .................................................................................. 17 
2 
Introduction ....................................................................................................................... 22 
2.1 
Study rationale ....................................................................................................... 22 
2.2 
Background ........................................................................................................... 22 
 
Epidemiology, clinical features, and socioeconomic impact ................ 22 
2.3 
Benefit/Risk assessment ........................................................................................ 25 
 
Risks of imaging procedures ................................................................ 26 
3 
Objectives, endpoints and estimands ................................................................................ 27 
3.1 
Primary estimands ................................................................................................. 28 
3.2 
Secondary estimands ............................................................................................. 29 
4 
Study design ...................................................................................................................... 29 
4.1 
Overall design ....................................................................................................... 29 
4.2 
Scientific rationale for study design ...................................................................... 30 
4.3 
Justification for dose ............................................................................................. 31 
 
Rationale for choice of background therapy ......................................... 32 
4.4 
Rationale for choice of control drugs (comparator/placebo) ................................ 32 
4.5 
Rationale for public health emergency mitigation procedures .............................. 32 
4.6 
End of study definition .......................................................................................... 32 
5 
Study Population ............................................................................................................... 33 
5.1 
Inclusion criteria .................................................................................................... 34 
5.2 
Exclusion criteria ................................................................................................... 34 
5.3 
Screen failures ....................................................................................................... 37 
 
Replacement policy .............................................................................. 38 
 
Participant numbering ........................................................................... 38 
6 
Study treatment(s) and concomitant therapy..................................................................... 38 
6.1 
Study treatment ..................................................................................................... 38 
 
Additional study treatment and therapies ............................................. 39 
 
Treatment arms/group ........................................................................... 40 
 
Treatment duration ................................................................................ 40 

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6.2 
Preparation, handling, storage, and accountability ............................................... 40 
 
Handling of study treatment ................................................................. 40 
 
Handling of other treatment .................................................................. 41 
 
Instructions for prescribing and taking study treatment ....................... 41 
6.3 
Measures to minimize bias: randomization and blinding ...................................... 42 
 
Treatment assignment, randomization .................................................. 42 
 
Treatment blinding ................................................................................ 42 
 
Emergency breaking of assigned treatment code ................................. 43 
6.4 
Continued access to study treatment after the end of the study ............................ 43 
 
Post-trial access .................................................................................... 43 
6.5 
Reporting of study treatment errors including misuse/abuse ................................ 43 
6.6 
Concomitant therapy ............................................................................................. 44 
 
Concomitant therapy ............................................................................. 44 
 
Prohibited Medication and Procedures ................................................. 44 
 
Rescue medication ................................................................................ 46 
7 
Discontinuation of study treatment and participant discontinuation/withdrawal ............. 47 
7.1 
Discontinuation of study treatment ....................................................................... 47 
7.2 
Participant discontinuation from the study ............................................................ 48 
7.3 
Withdrawal of informed consent and exercise of participants’ data privacy 
rights ...................................................................................................................... 48 
7.4 
Lost to follow-up ................................................................................................... 49 
7.5 
Early study termination by the sponsor ................................................................. 49 
8 
Study Assessments and Procedures .................................................................................. 49 
8.1 
Screening ............................................................................................................... 50 
8.2 
Participant demographics/other Baseline characteristics ...................................... 50 
 
Hepatitis screen, HIV screen ................................................................ 51 
 
X-ray of the shoulder ............................................................................ 51 
 
Ultrasound of the shoulder .................................................................... 51 
8.3 
Efficacy assessments ............................................................................................. 51 
 
The PRO efficacy measures collected for primary, secondary 
 
 objectives: .......................................................................... 51 
 
Appropriateness of efficacy assessments .............................................. 54 
8.4 
Safety assessments ................................................................................................ 54 
 
Physical examinations .......................................................................... 55 
 
Body height and weight ........................................................................ 55 
 
Vital signs ............................................................................................. 55 
 
Clinical safety laboratory tests .............................................................. 55 

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Pregnancy testing .................................................................................. 57 
 
Other safety evaluations ....................................................................... 58 
 
Appropriateness of safety measurements ............................................. 58 
8.5 
Additional assessments ......................................................................................... 59 
 
Clinical Outcome Assessments (COAs) ............................................... 59 
8.6 
Adverse events (AEs), serious adverse events (SAEs), and other safety 
reporting ................................................................................................................ 60 
 
Adverse events ...................................................................................... 61 
 
Serious adverse events .......................................................................... 63 
 
SAE reporting ....................................................................................... 64 
 
Pregnancy ............................................................................................. 65 
 
Surgeries ............................................................................................... 66 
 
Adverse events of special interest ......................................................... 66 
8.7 
Pharmacokinetics .................................................................................................. 66 
8.8 
Biomarkers ............................................................................................................ 66 
8.9 
Immunogenicity assessments ................................................................................ 66 
8.10 
Reporting of study treatment errors, study treatment misuse/abuse and 
overdose ................................................................................................................ 67 
9 
Statistical considerations ................................................................................................... 67 
9.1 
Analysis sets .......................................................................................................... 67 
9.2 
Statistical analyses ........................................... Fehler! Textmarke nicht definiert. 
 
Participant demographics and other Baseline characteristics ............... 67 
 
Treatments ............................................................................................ 68 
9.3 
Primary endpoint(s)/ estimand(s) analysis ............................................................ 68 
 
Definition of primary endpoint(s) ......................................................... 68 
 
Statistical model, hypothesis, and method of analysis ......................... 69 
 
Handling of intercurrent events of primary estimand ........................... 69 
 
Handling of missing values not related to intercurrent event ............... 69 
 
Sensitivity analyses ............................................................................... 69 
 
Supplementary analysis ........................................................................ 69 
9.4 
Secondary endpoint(s)/estimand(s) analysis ......................................................... 69 
 
Efficacy endpoint(s) .............................................................................. 70 
 
Safety endpoints .................................................................................... 70 
 
Patient reported outcomes ..................................................................... 71 
 
 71 
9.6 
Interim analysis ..................................................................................................... 71 
9.7 
Sample size determination .................................................................................... 71 

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10 Supporting documentation and operational considerations .............................................. 72 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations .................. 72 
 
Regulatory and ethical considerations .................................................. 72 
 
Informed consent procedures ................................................................ 73 
 
Data protection ...................................................................................... 74 
 
Committee structure .............................................................................. 74 
 
Data quality assurance .......................................................................... 74 
 
Source documents ................................................................................. 75 
 
Publication policy ................................................................................. 76 
 
Protocol adherence and protocol amendments ..................................... 76 
10.2 
Appendix 2: Abbreviations and definitions .......................................................... 77 
 
List of abbreviations ............................................................................. 77 
 
Glossary of terms .................................................................................. 81 
10.3 
Appendix 3: Clinical laboratory tests .................................................................... 84 
 
Clinically notable laboratory values and vital signs ............................. 84 
10.4 
Appendix 4: Participant Engagement .................................................................... 85 
11 References ......................................................................................................................... 86 

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List of tables 
Table 1-1 
Schedule of Activities ........................................................................... 19 
Table 3-1 
Objectives and related endpoints .......................................................... 27 
Table 6-1 
Investigational and control drug ........................................................... 38 
Table 6-2 
Dose and treatment schedule ................................................................ 41 
Table 6-4 
Prohibited medications ......................................................................... 45 
Table 8-1 
Laboratory tests .................................................................................... 56 
Table 10-1 
Safety Analyses: Expanded Limits and Notable Criteria ..................... 84 
List of figures 
Figure 1-1 
Study design .......................................................................................... 17 
 
 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
Amendment 2 (10-JUL-2024) 
Amendment rationale  
Protocol amendment 2 is implemented as screening for the CAIN457FDE05 study has been 
discontinued on 17-MAY-2024 due to the early termination of Secukinumab Phase 3 trials in 
RCT (Rotator Cuff Tendinopathy). 
The study is currently ongoing and 63 participants have been randomized. Under the previous 
assumptions for the sample size the power will be 24%. Therefore, only a descriptive analysis 
will be performed.   
 
Changes to protocol: 
 
 
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol require IRB/IEC and Health Authority 
approval according to local regulations prior to implementation.  
Section 
Changes made 
Section 5.1 Inclusion criteria 
Clarification that painful arc test needs to be “positive” 
Section 6.1.1 Additional study 
treatment and therapies 
Clarification regarding non-NSAID medication 
Section 7.1 Discontinuation of 
study treatment 
Removal that discontinuation is required in case of 2 missed 
doses 
Section 8.5.1  Clinical Outcome 
Assessments (COAs) 
Clarification that Paper-based PROs can be used as backup 
Section 8.6.1 Adverse Events 
Clarification that adverse events are monitored depending on last 
dose of study treatment  
Section 8.6.3 SAE Reporting 
Inclusion of Hy’s law language 
Section 8.10 Reporting of study 
treatment errors, study 
treatment misuse/abuse and 
overdose 
Section added 
9.2 Statistical analyses 
Updated to reflect that analysis will only be descriptive due to 
early termination of screening. 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
Amendment 1 (12-JUN-2023)  
Amendment rationale  
The main purpose of this protocol amendment is to align with other Secukinumab studies in the 
same indication in order to create comparable study populations and outcomes. This amendment 
contains: 
- 
Update of inclusion criteria describing the severity of the symptoms 
- 
Omission of ECG assessments 
- 
Inclusion of high sensitivity CRP as laboratory parameter in clinical chemistry  
- 
Addition of optional WORC PRO at screening 
- 
Clarification on X-Ray assessment 
- 
Update on study length justification 
- 
Clarification of Run-in phase definition 
 
As of 10-Mar-2023,  9 participants were enrolled. The participants who were already screened 
continue to be enrolled if eligible. The changes and clarifications proposed by this amendment 
are not expected to influence the study population. Impact on study results is not expected. 
 
Changes to protocol and rationale: 
Below is a delineation of the key changes to the protocol. This protocol amendment also 
includes minor changes not noted below but are seen in the track changes version of the 
protocol. In the track changes version, strike through red font is used for deletions and red font 
with underlining is used for insertions.  
 
Section 
Changes made 
Section 1 Protocol summary 
Updated  
Section 1.3. SoA 
ECG omitted from SoA in consistency with Secukinumab 
protocols in this indication.  
Shoulder X-Ray is no longer a study required assessment. It is 
still mentioned as a recommended diagnostic assessment to 
follow the current local guideline (Liem, et.al., 2017). 
An additional assessment of WORC can now be optionally 
performed at Screening to support the severity assessment of the 
disease. Further assessments of WORC remain unchanged. 
 
Section 4.3 Justification for 
dose 
Clarifications as requested by the local EC 
Section 5 Study Population 
Adjustment of inclusion criteria to match study population with 
intended population of patients with moderate to severe RCT 
Section 5.2 Exclusion criteria 
Clarification of wording 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
 
Changes to the protocol 
IRBs/IECs 
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities. 
The changes described in this amended protocol require IRB/IEC and Health Authority 
approval according to local regulations prior to implementation.  
The changes herein affect the Informed Consent. A revised Informed Consent that considers 
the changes described in this protocol amendment has to be submitted for approval.  
 
Section 6.1 Study treatment 
Changes in the physiotherapy regimen were made in order to 
reflect treatment reality. Continuation of in-person physiotherapy 
is generally allowed if it was prescribed prior to the study. 
Clarification that participants with contraindications for NSAIDs 
can be included. 
Section 8.2.2 X-ray of the 
shoulder 
Update  
Section 8.3.1 The PRO efficacy 
measures collected for primary, 
secondary 
 
objectives: 
Addition, that Pain NRS is collected during Run-in phase as well 
Section 8.4 Safety 
assessments 
Updated in accordance with the current aligned wording 
Section 8.4.3 Vital signs 
Assessment of body temperature is not required. 
Former Section 8.4.4 
Electrocardiograms  
Omitted as it is no longer required 
Section 8.4.4 Clinical safety 
laboratory tests 
High sensitivity CRP is added to laboratory marker to provide an 
additional parameter to exclude systematic inflammatory 
conditions 
Section 8.6.1 Adverse events 
Alignment among study protocols investigating secukinumab 
Section 10.2.1 List of 
abbreviations 
Updated 
Section 10.3.1 Clinically notable 
laboratory values and vital 
signs 
Thresholds and calculation of eGFR added 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
1 
Protocol summary 
1.1 
Summary 
Protocol Title: 
A randomized, double-blind, placebo-controlled, parallel group, multicenter, 24-week study 
investigating the efficacy and safety of secukinumab compared to placebo in adult patients with 
moderate to severe rotator cuff tendinopathy and failure to conventional therapy “UnchAIN” 
Brief Title: 
Study of efficacy and safety and of AIN457/secukinumab in patients with rotator cuff 
tendinopathy 
Purpose 
The purpose of this study is to demonstrate the efficacy and safety of AIN457/secukinumab 
300 mg subcutaneous (s.c.) vs. placebo in improving signs and symptoms in participants with 
rotator cuff tendinopathy. Both study arms will be accompanied by patient individualized 
conventional therapy. The study is tailored to support health technology assessments (HTAs) 
of secukinumab in Germany in this indication. 
The study will enroll adult participants with a diagnosis of moderate to severe rotator cuff 
tendinopathy with no tear or partial tear ,who are experiencing active disease for at least 6 weeks 
and no more than 6 months at Baseline and who have failed to respond to conventional therapy. 
Secukinumab will be administered as 7 injections of 300 mg s.c. or placebo s.c. over a 12-week 
period. Participants in both study arms will receive patient individualized conventional therapy 
consisting of home-based standardized physiotherapy and flexible dosing of Non-Steroidal 
Anti-Inflammatory Drugs (NSAIDs) and/or paracetamol as needed (dose decrease and dose 
increase of NSAIDs/paracetamol relative to the optimized starting dose). 
Study Indication /Medical Condition: 
Moderate to severe rotator cuff tendinopathy. 
Treatment type 
Biologic. 
Study type 
Interventional / Phase IIIb 

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Clinical Trial Protocol, Amended Version No. 02 
 
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Objectives, Endpoints, and Estimands: 
Objectives 
Endpoints 
Primary 
• To demonstrate the superiority of 12 
weeks of treatment with secukinumab 
300 mg s.c. compared to placebo (both 
arms in combination with patient 
individualized conventional therapy), in 
participants with moderate to severe 
rotator cuff tendinopathy, based on 
change in Western Ontario Rotator Cuff 
index (WORC) score from Baseline to 
week 24. 
• Mean change in WORC patient reported 
outcome (PRO) score from Baseline to 
week 24  
Secondary 
• To demonstrate the superiority of 
secukinumab 300 mg s.c. compared to 
placebo (both arms in combination with 
patient individualized conventional 
therapy), in participants with moderate 
to severe rotator cuff tendinopathy on 
signs and symptoms as well as activities 
of daily living and quality of life. 
 
 
 
 
 
 
 
 
• To evaluate the safety and tolerability of 
secukinumab in participants with 
moderate to severe rotator cuff 
tendinopathy. 
• Mean change in WORC score in each 
subdomain from Baseline to week 24  
• Mean change in Patient global 
assessment (PaGA) score using a VAS 
(considering the last 24 hours) from 
Baseline to week 24  
•  Mean change in SF-36 survey 
(including all subscales and component 
summary scores) from Baseline to week 
24  
• QuickDASH score from Baseline to 
week 24  
• Mean change in Pain score using a NRS 
(considering the last 24 hours) from 
Baseline to week 24 
• Mean change in EQ-5D-5L health 
related question (VAS) from Baseline to 
week 24 
• Number and proportion of participants 
with adverse events (AEs), serious 
adverse events (SAEs) (incidence, 
severity, and relationship with study 
drug) as well as description of clinically 
laboratory parameters and vital signs 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
Trial Design: 
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, Phase IIIb, 
24-week study to investigate the superior efficacy of AIN457/secukinumab and safety in 
participants with rotator cuff tendinopathy.  
Secukinumab 300 mg s.c. will be compared to placebo (both arms in combination with patient 
individualized conventional therapy) in relieving clinical symptoms at week 24. Approximately 
430 participants (215 per treatment group) will be included with a diagnosis of moderate to 
severe rotator cuff tendinopathy with no tear or partial tear, who are experiencing active disease 
for at least 6 weeks and no more than 6 months at Baseline and who have failed to respond to 
conventional therapy.  
The study consists of a Screening period up to 6 weeks, a 2-week Run-in period, a 12-week 
Treatment period and a 12-week Follow-up period. Treatment and Follow-up period will be 
blinded. The Screening period will assess eligibility. Participants who meet the eligibility 
criteria at Screening will continue to Run-in period and will be randomized. In the Run-in period 
participants should perform 2 weeks of home-based standardized physiotherapy. The Run-in 
period is defined as 14 days prior to Randomization and is commenced beforehand by a 
telephone visit. The study comprises a total of 13 visits. 
Eligible participants will be randomized 1:1 to either receive secukinumab 300 mg s.c. or 
placebo s.c. at Baseline, week 1, 2, 3, 4, 8 and 12 (7 injections in total) (Figure 1-1). 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
Brief Summary: 
The purpose of this study is to investigate the efficacy and safety of AIN457 (secukinumab s.c.) 
compared to placebo in adult patients with moderate to severe rotator cuff tendinopathy and 
failure to conventional therapy.  
• The study duration will be 24 weeks. 
• The treatment duration will be 12 weeks with 12 weeks follow-up. 
• The visit frequency will be weekly until visit 7 and 4-weekly until end of treatment and 4 
follow-up visits. 
Treatment of interest 
The treatment of interest is randomized (the investigational treatment AIN457/secukinumab or 
the control treatment/placebo) in combination with the allowed concomitant medication (patient 
individualized conventional therapy) for moderate to severe rotator cuff tendinopathy and 
home-based standardized physiotherapy. The dose of the allowed concomitant medication for 
moderate to severe rotator cuff tendinopathy is flexible according to participant´s individual 
need during the trial. 
Number of Participants: 
To demonstrate superiority of secukinumab compared with placebo with a 90% power on a 
two-sided, 5% significance level the study will recruit a total of 430 participants assuming drop-
outs and other protocol deviations. 
Key Inclusion criteria 
Participants eligible for inclusion in this study must fulfill all of the following criteria: 
1. Signed informed consent must be obtained prior to participation in the study. 
2. Males and non-pregnant, non-nursing females between 18 and 65 years of age 
3. Rotator cuff tendinopathy (unilateral)  
4. Symptoms present for at least 6 weeks but not more than 6 months at Baseline 
5. Moderate to severe rotator cuff tendinopathy demonstrated by all of the following criteria: 
a. WORC score ≤ 40 at Baseline 
b. Average weekly NRS pain score of ≥ 5 during the 7 days prior to Baseline 
c. Nocturnal pain in shoulder on at least 3 out of 7 days in the week prior to Baseline or 
positive “Painful Arc Test” on examination 
6. Failure to at least 8 weeks of conventional therapy prior to Baseline: inadequate response to 
NSAIDs and/or paracetamol and physiotherapy; or intolerance to NSAIDs and/or 
paracetamol 
Key Exclusion criteria 
Participants 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 participants. 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
1. Greater than 50% partial thickness tear as established by MRI or ultrasound during 
assessment in Run-in phase 
2. Patients who are expected to require glucocorticoid treatment throughout the trial duration 
at Baseline (e.g., systemic, intramuscular, local injections in shoulder) 
3. Previous surgery, or plans for surgery, during the study period, in the affected shoulder 
4. Rheumatologic and chronic inflammatory diseases, including but not limited to 
inflammatory bowel disease, polymyalgia rheumatica (PMR), PsA, axSpA and rheumatoid 
arthritis (RA), fibromyalgia or severe pain disorder unrelated to the target shoulder 
5. Both Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies 
positive at Screening 
6. Either history of adhesive capsulitis/frozen shoulder, or current calcification in the tendon 
(in affected or contralateral shoulder) confirmed clinically or by medical imaging 
7. Symptomatic osteoarthritis of the shoulder (glenohumeral, acromioclavicular) in affected 
or contralateral shoulder confirmed by medical imaging 
8. Patients with traumatic rupture that would be considered eligible for surgery for repair of 
cuff tear.  
9. Neurological conditions including but not limited to cervical radiculopathy, which in the 
opinion of the investigator may explain the patient’s symptoms 
10. Any intra-articular/subacromial glucocorticoid treatment within 12 weeks prior to Baseline 
or more than 2 intra-articular/subacromial glucocorticoid injections for the treatment of the 
current episode of tendinopathy so far  
11. Any oral, intramuscular or i.v. glucocorticoid treatment 12 weeks prior to Baseline or during 
the current tendinopathy, whichever takes longer 
12. Previous platelet rich plasma (PRP) injections or fluoroquinolone/quinolone antibiotics 
within 12 weeks prior to Baseline or during the current tendinopathy, whichever takes 
longer    
13. Neuromuscular or primary/secondary muscular deficiency which limits the ability to 
perform functional measurement (e.g., shoulder strength test) 
14. Previous hyaluronic injections within 12 weeks prior to Baseline or during the current 
tendinopathy, whichever takes longer 
 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
Treatment Groups: 
a) Investigational and control drugs 
Group 
Investigational/ 
Control Drug 
Pharmaceutical Dosage Form 
and Route of Administration 
Group 1 
Secukinumab 
1 x 2mL 300 mg  
PFS injection s.c. 
Group 2 
Placebo 
1 x 2mL  
PFS injection s.c. 
PFS – Pre-Filled Syringe 
b) Additional study treatments  
Patient individualized conventional therapy will be given alongside the investigational drug and 
placebo. Additional study medication will NOT be provided by the Sponsor and has to be 
managed on site level. The patient individualized conventional therapy consists of:  
2.1 Home-based standardized physiotherapy based on MOON regimen (Kuhn, 2009): 
Participants will be instructed on home-based standardized physiotherapy by qualified 
study site personnel at screening visit. Participants will receive printed instructions to 
perform a standardized physiotherapy independently at home once or twice daily until 
study completion. At each visit site personnel will inquire about status of home-based 
standardized physiotherapy to address any questions or hurdles and review instructions 
with participant as needed and will document the status in electronic Case Report Form 
(eCRF) accordingly. Concomitant in-person physiotherapy is not prohibited. However, 
new-onset of in-person physiotherapy should be avoided after randomization. 
2.2 NSAIDs: Dose should be optimized to the individual participant to achieve the best 
efficacy and simultaneously the best tolerability. Dosing should not exceed the respective 
approved dosing and the maximum tolerable dose (e.g., max. dose of 2400 mg/day 
ibuprofen or max. dose of 4000 mg/day paracetamol or as directed by treating physician). 
Should high NSAID doses not be tolerated or contraindicated, participants may receive 
the maximum tolerated NSAID dose in combination with paracetamol as support if 
necessary. The optimized dose of NSAIDs/paracetamol, starting from Run-in period, 
should remain stable until Baseline. Dose adjustments (dose decrease and dose increase 
of NSAIDs/paracetamol relative to the optimized starting dose), discontinuation of 
NSAIDs/paracetamol and switch of NSAIDs are possible at any time throughout the study 
after Baseline. 
 
 
 
2.3 Glucocorticoids: Glucocorticoids may be given, if required. However, they should be 
avoided if possible. Participants who are expected at Baseline to require glucocorticoid 
treatment throughout the trial duration will not be randomized. In case glucocorticoids 

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Clinical Trial Protocol, Amended Version No. 02 
 
Protocol No. CAIN457FDE05 
 
 
 
will be unexpectedly required during the study period (local injections in the shoulder - 
including intramuscular injection or systemic), treatment with glucocorticoids is allowed 
at any time throughout the study. 
 
Local glucocorticoid injections for current tendinopathy should not 
exceed 2 injections during the course of this study. Participants exceeding 2 injections 
continue the study as outlined in the SoA. 
 
1.2 
Schema 
 
Figure 1-1 
Study design 
 
1.3 
Schedule of activities (SoA) 
The SoA lists all  assessments and when they are performed. All data obtained from these 
assessments must be supported in the participant’s source documentation. The “X” in the table 
denotes the assessments to be recorded in the clinical database or received electronically from 
a vendor. The “S” in the table denotes the assessments that are only in the participant’s source 
documentation and do not need to be recorded in the clinical database. 
Participants should be seen for all visits/assessments as outlined in the SoA or as close to the 
designated day/time as possible. Missed or rescheduled visits should not lead to automatic 
discontinuation. 
Participants who discontinue from study treatment should still attend all visits until EoS as 
indicated in the SoA. 
Participants who discontinue from study should be scheduled for a final evaluation visit if they 
agree, as soon as possible, at which time all of the assessments listed for the EOS will be 
performed. At this final visit, the adverse events and concomitant medications not previously 
reported must be recorded on the Case Report Form (CRF). 

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Protocol No. CAIN457FDE05 
 
 
 
PRO measure(s) must be completed before any clinical assessments are performed at any given 
visit. 
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e., pandemic, epidemic or natural disaster that limits or prevents on-site study visits, alternative 
methods of providing continuing care may be implemented by the Investigator as the situation 
dictates. If allowable by a local health authority, national and local regulations and depending 
on operational capabilities, phone calls, virtual contacts (e.g. tele consultation) or visits by site 
staff/ off-site healthcare professional(s) staff to the participant´s home, can replace certain 
protocol assessments, for the duration of the disruption until it is safe for the participant to visit 
the site again. If the Investigator delegates tasks to an off-site healthcare professional, the 
Investigator must ensure the individual(s) is/are qualified and appropriately trained to perform 
assigned duties. The Investigator must oversee their conduct and remain responsible for the 
evaluation of the data collected. 

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Table 1-1 
Schedule of Activities 
Period 
Screening 
Run-in1 
Treatment 
Follow-Up 
 
Visit Name 
Screening 
Run-in 
BL 
Treatment 
EOT 
Follow-up 
EOS 
Visit Number 
1 
2Tel 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12Tel 
13 
Day 
-56 to -15 
-14 to -1 
1 
8 
15 
22 
29 
57 
85 
99 
127 
155 
169 
Week 
-8 
-2 
BL 
1 
2 
3 
4 
8 
12 
14 
18 
22 
24 
Obtained informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Participant History 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demography 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion / exclusion criteria2 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
Relevant medical history/current medical 
conditions 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Physical Examination 
S 
 
S 
 
 
 
 
 
 
 
 
 
S 
Body Height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Body Weight 
X 
 
X 
 
 
 
 
 
 
 
 
 
X 
Vital Signs (Blood pressure and pulse rate) 
X 
 
X 
 
 
 
X 
X 
X 
X 
X 
 
X 
Hepatitis B, C or HIV serology3 
X 
 
X 
 
 
 
 
 
 
 
 
 
 
TB Test (QuantiFERON TB-Gold test) 
S 
 
 
 
 
 
 
 
 
 
 
 
 
Physiotherapy4 
X 
X 
X§ 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hematology 
X 
 
X 
 
 
 
 
 
 
 
 
 
X 
Clinical Chemistry 
X 
 
X 
 
 
 
 
 
 
 
 
 
X 
Urinalysis 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
Lipid panel and glucose 
 
 
X 
 
 
 
 
 
 
 
 
 
X 
RF/anti-CCP antibodies 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Pregnancy and assessments of fertility5 
X 
 
X 
 
 
 
X 
X 
X 
 
X 
 
X 
Shoulder X-Ray6 
(X) 
 
 
 
 
 
 
 
 
 
 
 
 
Shoulder MRI7 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Shoulder US7 
 
 
X 
 
 
 
 
 
 
 
 
 
 

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Period 
Screening 
Run-in1 
Treatment 
Follow-Up 
 
Visit Name 
Screening 
Run-in 
BL 
Treatment 
EOT 
Follow-up 
EOS 
Visit Number 
1 
2Tel 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12Tel 
13 
Day 
-56 to -15 
-14 to -1 
1 
8 
15 
22 
29 
57 
85 
99 
127 
155 
169 
Week 
-8 
-2 
BL 
1 
2 
3 
4 
8 
12 
14 
18 
22 
24 
WORC (PRO)10 
(X) 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
X 
SF-36 (PRO)10 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Patient Global assessment of disease activity - 
VAS (PaGA) (PRO)10 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
X 
QuickDASH (PRO)10 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Pain NRS (PRO)10 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
X 
EQ-5D-5L health related question (VAS) 
(PRO)10 
 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Shoulder/arm strength 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Range of movement (ROM), active and 
passive, including  
- “Painful Arc Test” 
- Empty/full cup test 
- Apley scratch test 
X 
 
X 
 
X 
 
X 
X 
X 
X 
X 
 
X 
Adverse Events 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Prior/concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization 
 
 
X 
 
 
 
 
 
 
 
 
 
 
Study drug administration 
 
 
X 
X 
X 
X 
X 
X 
X 
 
 
 
 
Study completion information 
 
 
 
 
 
 
 
 
 
 
 
 
X 
 

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For all participants who discontinue from the study, the investigator should ensure that the participant completes an EoT-visit 2 weeks after last study treatment, as well as 
an EoS-visit 12 weeks after last study treatment. Unscheduled visits are possible to ensure participant’s welfare.  
 
1 Run-in period to standardize physiotherapy and stabilize NSAIDs. The Run-in period is commenced beforehand by a visit via telephone call (Tel). An on-site visit can 
take place e.g. if an MRT examination of the participant is performed. 
2 Eligibility assessments are conducted at Screening and Baseline visit but recorded only once in the eCRF 
3 Only in case study site/lab personnel comes in contact with blood, tissue or bodily fluids of participants through contact with injection needle, cut, splash on mucous 
membrane or through skin damage; if HIV test is seropositive, it should be confirmed by Western blot 
4 Participants will be instructed on home-based standardized physiotherapy by qualified study site personnel. Participants will receive printed instructions to perform 
standardized physiotherapy (based on MOON regimen, (Kuhn, 2009)) at home until study completion. Site personnel will inquire about the status of home-based 
standardized physiotherapy (based on MOON regimen, (Kuhn, 2009)) to address any questions or hurdles and review instructions with the participant as needed. 
Status of home-based standardized physiotherapy will be documented by site personnel in eCRF at each visit accordingly. 
5 Non post-menopausal women require serum pregnancy tests at Screening and visit 13/EOS; for remaining visits local urine tests to be done. 
6 Performance of shoulder X-Ray is strongly recommended following current national guidelines but not required. If shoulder X-Ray is performed at the discretion of the 
treating physician or if historic X-Ray obtained during the current episode of tendinopathy is available, imaging data should be assessed. 
7 MRI has to be performed maximum 14 days before Baseline. Ultrasound may be performed in participants unable or unwilling to undergo MRI. Ultrasound is not 
required in participants who underwent MRI. 
 
 
 
 
10 Patient reported outcomes must be done before clinical assessments. WORC assessment can optionally be performed at screening. 
 
Tel: Visit can be performed via telephone call. No on-site visit required. 
S: collected as source data only 
§: Site personnel will document in eCRF at Baseline if 2 weeks home-based standardized physiotherapy were performed as per statement of participant. 

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2 
Introduction 
2.1 
Study rationale 
The purpose of this study is to assess the efficacy and safety of AIN457/secukinumab 300 mg 
s.c. vs. placebo in improving signs and symptoms in participants with rotator cuff tendinopathy. 
Both study arms are accompanied by patient individualized conventional therapy. The study is 
tailored to support HTAs of secukinumab in Germany in this indication. Study will enroll adult 
participants with a diagnosis of moderate to severe rotator cuff tendinopathy with no tear or 
partial tear, who are experiencing active disease for at least 6 weeks and no more than 6 months 
at Baseline and who have failed to respond to conventional therapy. Secukinumab will be 
administered as 7 injections of 300 mg s.c. or placebo s.c. over a 12-week period. Participants 
in both study arms will receive patient individualized conventional therapy consisting of home-
based standardized physiotherapy and flexible dosing of NSAIDs and/or paracetamol as needed 
(dose decrease and dose increase of NSAIDs/paracetamol relative to the optimized starting 
dose). Efficacy of secukinumab will be evaluated at the end of week 24, based on validated 
patient reported outcomes (PROs) including improvement in signs and symptoms, physical 
function and quality of life. ROM will be assessed as well.  
Safety will be assessed up to week 24 and participants will be followed up without drug 
treatment from week 12 to week 24. 
2.2 
Background 
 
Epidemiology, clinical features, and socioeconomic impact 
Rotator cuff tendinopathy is a common condition, with a complex pathogenesis. It is clinically 
diagnosed after gradual onset of activity-related pain, weakness, decreased function and range 
of motion, and sometimes localized swelling of the tendon (Riley, 2005; Riley, 2008). Rotator 
cuff tendinopathy is commonly associated with impaired sleep and difficulties in performing 
basic activities of daily life (Consigliere, et al., 2018). While the exact pathophysiology remains 
uncertain, it appears to develop when the pathological responses associated with tendon overuse 
overwhelm the protective/regenerative changes associated with tendon repair (Challoumas, et 
al., 2019). 
Rotator cuff tendinopathy is highly prevalent. Tendinopathies are the most common reason for 
consultation for a musculoskeletal complaint, (Forde, et al., 2005).  
The socioeconomic impact of rotator cuff tendinopathy beyond medical costs is high because 
the condition is associated with long-term productivity loss, sick leave and loss of employment 
(Chard, et al., 1988; Hopkins, et al., 2016). It has been estimated that the median recovery time 
for shoulder tendinopathy is 10 months (Bonde, et al., 2003).  
Diagnosis and clinical evaluation of patients with Rotator cuff tendinopathy 
The diagnosis of rotator cuff tendinopathy is usually made clinically; ultrasonography and MRI 
can enhance the diagnosis (Kaux, et al., 2011). Clinical assessment and diagnosis of rotator cuff 

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tendinopathy involves taking a thorough patient history and performing tests to isolate the 
structure causing the pain and to measure the impairment (e.g., range of movement, extension, 
strength and pain response, rotation resistance) (Lewis, et al., 2015). Potential differential 
diagnoses could be Os Acromiale, Tendinosis calcarea or of rheumatologic ethology (Liem, et 
al., 2017).  
Treatment of rotator cuff tendinopathy 
The goals of rotator cuff tendinopathy treatment are pain reduction and restoration of function. 
Rotator cuff tendinopathy treatment generally follows a progression from conservative, non-
surgical management, through local corticosteroid injections, to surgical management, if 
indicated (Factor, et al., 2014). Rotator cuff disease can be associated with poor long-term 
outcomes (Millar, et al., 2021; Titan, et al., 2016).  
First-line non-surgical treatment includes the conventional modalities of rest, hot and cold 
packs, and physiotherapy (including therapeutic ultrasound, laser therapy, hyperthermia and 
extracorporeal shockwave therapy). Evidence has shown that exercise therapy, either alone or 
combined with manual therapy (i.e., joint and soft tissue mobilization by a healthcare 
professional), can improve pain and mobility. However, some patients report no significant 
improvement with physiotherapy (Pedowitz, et al., 2011; Pieters, et al., 2020). In addition, most 
patients do not recover rapidly with these interventions.  
NSAIDs are the first-line treatment option for pain relief. Evidence suggests that both oral and 
local NSAIDs are effective in relieving pain associated with tendinopathy in the short term (7 
to 14 days) (Andres, et al., 2008). However, long-term use or overuse of NSAIDs is associated 
with risks that include upper gastrointestinal tract bleeding and cardiovascular events (Wolfe, 
et al., 1999; Food and Drug Administration (FDA), 2015). Moreover, NSAIDs have been shown 
to have a negative effect on tendon healing and, thus, could contribute to long-term tissue 
damage (Jomaa, et al., 2020).  
Local corticosteroid injections can provide short-term pain relief, but there is no evidence of 
benefit beyond 6 months (Andres, et al., 2008; Coombes, et al., 2010; Mohamadi, et al., 2017). 
It has also been shown that repeated corticosteroid injections have the potential to accelerate 
tendon degeneration, increasing the risk of tendon rupture (Lipman, et al., 2018). In the 2020 
American Academy of Orthopaedic Surgeons (AAOS) Evidence-Based Clinical Practice 
Guideline on Management of Rotator Cuff Pathology, it is stated that “… it is the opinion of 
the work group that multiple corticosteroid injections may compromise the integrity of the 
rotator cuff, which may affect attempts at subsequent repair.” (AAOS, 2020). 
Non-surgical treatments for rotator cuff tendinopathy have demonstrated efficacy in 40% to 
80% of patients when treatment is prompt (Beaudreuil, et al., 2010). However, it has been 
shown that patients who present with a longer duration and greater severity of symptoms are 
more likely to have a poor response to both corticosteroid injection and/or oral NSAIDs 
(Andres, et al., 2008). In addition, standard of care (SoC) treatments for rotator cuff 
tendinopathy only address symptom relief and are generally not targeted against specific 
pathways to treat the molecular root cause.  

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The German guideline “rotator cuff” only lists NSAID-treatment, physiotherapy, self-guided 
training following professional instruction and cortisone infiltration as evidence based 
conservative therapies (Liem, et al., 2017). 
Surgical treatment can be an option in selected patients if conservative treatment fails. There is 
in general consensus that surgery is mainly indicated for repair of full thickness rotator cuff 
tears. The recently published AAOS guidelines (AAOS, 2020) provide recommendations for 
the treatment of full thickness rotator cuff tears but do not address partial thickness tears or 
rotator cuff tendonitis/rotator cuff bursitis. According to the German guideline surgical 
treatment follows failure of conservative treatment  
Repair of partial thickness tears might be considered if conservative treatment fails or in 
younger patients with traumatic rupture. While factors like age, occupation, and rehabilitation 
time may influence the decision for surgical treatment, clinical studies showed that the 
percentage thickness torn has a major impact on the clinical outcome, with repair of tears > 
50% thickness leading to better results (Matthewson, et al., 2015).  
While surgery is considered beneficial for patients with substantial partial or full thickness tears, 
there is a lack of valid treatment options for patients with rotator cuff tendinopathy with no or 
less than 50% partial thickness tears who are not responding to conservative treatment, based 
on clinical recommendations, might not be eligible for surgery. Additionally, it has been 
reported that 54% of patients with shoulder pain experience ongoing symptoms after 3 years 
(Lewis, 2009).   
Therefore, there is a high, unmet need to provide rotator cuff tendinopathy patients with a 
targeted treatment option that offers rapid onset and maintenance of pain relief and restoration 
of function, leading to better outcomes and improved quality of life. 
Role of interleukin-17A (IL-17A) in Tendinopathy and rationale of Secukinumab 
(AIN457, Cosentyx®) as treatment 
IL-17A is a central cytokine involved in multiple autoimmune and inflammatory processes 
(McGeachy, et al., 2019). It has been shown that IL-17A mediates tendon inflammation, inhibits 
tendon matrix repair, and induces tenocyte apoptosis (Millar, et al., 2016). IL-17A-expressing 
tendon-resident immune cells are present in human tendinopathy, and IL-17A mRNA (modified 
Ribonucleic Acid) and protein levels are increased in early human tendinopathic tissue samples 
(Millar, et al., 2016). In human tenocytes, IL-17A regulates pro-inflammatory cytokines and 
key apoptotic mediators, inducing apoptosis in vitro. As a consequence of this apoptosis, the 
tendon matrix adopts a mechanical inferior type III collagen phenotype (Millar, et al., 2016). 
Thus, evidence suggests that IL-17A is a key player in the pathogenesis of tendinopathy (Millar, 
et al., 2017).  
Recent attention in musculoskeletal research has been given to the immunobiology of the 
enthesis, the specialized connective tissue matrix joining tendon or ligament to bone. This 
fibrous tendon-to-bone interface is a structurally continuous gradient leading from uncalcified 
tendon to calcified bone, with multiple zones differentiated by resident cell types, vascularity, 
and extracellular matrix protein composition. Pathological processes in this area can be 
considered analogous to tendinopathy, as both the enthesis and tendon are sites of high 

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mechanical stress (Gracey, et al., 2020; Millar, et al., 2017). Enthesitis is often a primary 
pathological process underlying skeletal inflammation in the spectrum of diseases defined as 
spondyloarthropathies (SpA) (Benjamin, et al., 2009; Watad, et al., 2018).  
Secukinumab has been shown to provide early and sustained resolution of enthesitis in patients 
with PsA over 2 years (Coates, et al., 2019), and a rapid onset of action of secukinumab 
treatment has been shown for both synovitis and enthesitis over 12 weeks of treatment in PsA 
in study CAIN457F2354 (clinicaltrials.gov, NCT 02662985). Similarly, secukinumab has 
shown sustained benefits in the resolution of enthesitis in axial spondyloarthritis (axSpA), as 
demonstrated in a pooled analysis of the pivotal secukinumab AS trials MEASURE 1 and 
MEASURE 2, as well as the follow-on Phase 3 studies MEASURE 3 and MEASURE 4 
(Deodhar, et al., 2016; Deodhar, et al., 2020).  
The inflammatory conditions being targeted with anti-IL-17A treatment have significant impact 
on activities of daily living and quality of life. Clinically significant improvements in patient-
reported measures of disease impact have been demonstrated in studies in AS (Deodhar, et al., 
2016), PsA (Coates, et al., 2018), and psoriasis (Thaçi, et al., 2015; Rompoti, et al., 2019). 
Based on this converging evidence, neutralization of IL-17A with secukinumab is expected to 
reduce tendon inflammation and halt tendon matrix degeneration, leading to improvement in 
the signs and symptoms of tendinopathy, quality of life, and activities of daily living. 
Secukinumab was therefore investigated as a disease-modifying therapy for rotator cuff 
tendinopathy in a Phase II / proof-of-concept study (CAIN457X2201). 
 
 
 
 
2.3 
Benefit/Risk assessment 
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 and sleep. Ultimately, this should result in few cases of tendinopathy 
progressing to a tear and therefore lessen the need for surgery.  
The placebo participants 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 participants 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 IB. 
Please refer to the IB for a detailed review of the pre-clinical and clinical information on 
secukinumab and risks identified from the clinical experience: 
a) Infections: Secukinumab has the potential to increase the risk for 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 

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and cutaneous candidiasis are uncommon. Caution should be exercised in patients with 
chronic infections or recurrent infections. 
b) Inflammatory Bowel Disease (IBD): Caution should be exercised in patients with IBD and 
those patients need to be followed up closely for disease exacerbation. 
c) Hypersensitivity reactions: Primarily non-serious, mild to moderate urticaria and rare 
cases of anaphylactic reactions (eczema or dermatitis) have been observed.  
d) Immunizations: Live vaccines should not be given concurrently with secukinumab. 
Studies showed, patients in secukinumab treatment receiving inactivated and non-live 
vaccinations given concurrently were able to mount an adequate immune response. 
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. 
Women of childbearing 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 5.2 (Exclusion Criteria). If there is any question that the participant will not reliably 
comply, they should not be entered or continue in the study. 
 
Risks of imaging procedures 
MRI technique will be used during Run-in period to determine the degree of tendon tear. 
Ultrasound may be performed in participants who are unwilling or unable to undergo 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 participant 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 an MRI image quality.  

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3 
Objectives, endpoints and estimands 
Table 3-1 
Objectives and related endpoints 
Objectives 
Endpoint 
Primary Objective 
• To 
demonstrate 
the 
superiority of efficacy of 
12 weeks of treatment with 
secukinumab 300 mg s.c. 
compared to placebo (both 
arms in combination with 
patient 
individualized 
conventional therapy) in 
participants with moderate 
to 
severe rotator cuff 
tendinopathy, based on 
change from Baseline in 
WORC score at week 24. 
Endpoint for primary objective 
• Mean change in WORC patient reported outcome (PRO) 
score from Baseline to week 24  
Secondary Objectives 
• To 
demonstrate 
the 
efficacy of secukinumab 
300 mg s.c. compared to 
placebo (both arms in 
combination with patient 
individualized 
conventional therapy) in 
participants with moderate 
to 
severe rotator cuff 
tendinopathy on signs and 
symptoms and activities of 
daily living, as well as 
quality of life, based on: 
 
Endpoints for secondary objectives 
• Mean change in WORC score in each subdomain from 
Baseline to week 24  
• Mean change in Patient global assessment (PaGA) 
score using a VAS (considering the last 24 hours) from 
Baseline to week 24  
• Mean change inSF-36 survey (including all subscales 
and component summary scores) from Baseline to 
week 24  
• QuickDASH score from Baseline to week 24  
• Mean change in Pain score using a NRS (considering 
the last 24 hours) from Baseline to week 24 
•  Mean change in EQ-5D-5L health related question 
(VAS) from Baseline to week 24 
 
• To evaluate safety and 
tolerability 
of 
secukinumab 300 mg s.c. 
in 
participants 
with 
moderate to severe rotator 
cuff tendinopathy 
• Number and proportion of participants with adverse 
events (AEs), serious adverse events (SAEs) 
(incidence, severity, and relationship with study drug) 
as well as description of clinically laboratory 
parameters and vital signs 
 
 

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3.1 
Primary estimands 
The estimand is the precise description of the treatment effect and reflects strategies to address 
events occurring during trial conduct which could impact the interpretation of the trial results 
(e.g., premature discontinuation of treatment). 
The primary clinical question of interest is: What is the effect of secukinumab 300 mg s.c. 
compared to placebo (both arms in combination with patient individualized conventional 
therapy) in participants with rotator cuff tendinopathy in change in WORC score from Baseline 
to week 24, regardless of treatment discontinuations. 
 
The analysis of the primary endpoint will be based on the following estimand: 
1. Population: Participants as defined by the inclusion/exclusion criteria to reflect the 
targeted rotator cuff tendinopathy population based on the FAS. 
2. Variable: WORC score from Baseline to week 24 
3. Treatment of interest: the randomized treatment (secukinumab 300 mg s.c. and placebo s.c.), 
both arms in combination with patient individualized conventional therapy 
4. Intercurrent events: 
o Treatment discontinuations due to any reason:  

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Treatment policy strategy: interested in treatment effect regardless of these 
events. 
o Other protocol deviations:  
Treatment policy strategy: interested in treatment effect regardless of these 
events. 
5. Summary measure: Difference in mean change in WORC score from Baseline to week 24 
between treatments. 
3.2 
Secondary estimands 
The secondary estimands relating to continuous endpoints (mean change from baseline to Week 
24 in secukinumab/placebo) are defined analogous to the primary estimand. 
4 
Study design 
4.1 
Overall design 
This is a randomized, double-blind, placebo-controlled, parallel-group, multicenter, Phase IIIb, 
24-week study to investigate the superior efficacy of AIN457/secukinumab and safety in 
participants with rotator cuff tendinopathy. Secukinumab 300 mg s.c. will be compared to 
placebo s.c. (both arms in combination with patient individualized conventional therapy) in 
relieving clinical symptoms at week 24. Approximately 430 participants (215 per treatment 
group) will be included with a diagnosis of moderate to severe rotator cuff tendinopathy with 
no tear or partial tear who are experiencing active disease for at least 6 weeks and no more than 
6 months at Baseline and who have failed to respond to conventional therapy.  
The study consists of a 6-week Screening period, a 2-week Run-in period, a 12-week Treatment 
period and a 12-week Follow-up period. Treatment and Follow-up period will be blinded. The 
Screening period will assess eligibility and start participants on home-based standardized 
physiotherapy. The Run-in period is defined as 14 days prior to Randomization and is 
commenced beforehand by a telephone visit.. In the Run-in period participants should perform 
2 weeks of home-based standardized physiotherapy. Participants who meet the eligibility 
criteria at Screening will continue to Run-in period and Baseline evaluations. The study 
comprises a total of 13 visits. Participants will be randomized 1:1 to either receive secukinumab 
300 mg s.c. or placebo s.c. at Baseline, week 1, 2, 3, 4, 8 and 12 (7 injections in total) (Figure 
1-1). 
The population will consist of male and female participants at least 18 years of age, but less 
than or equal to 65 years of age at the time of randomization, with a diagnosis of moderate to 
severe rotator cuff tendinopathy with no tear or partial tear who are experiencing active disease 
for at least 6 weeks and no more than 6 months at Baseline and who have failed conventional 
therapy.  
Participants must have failed to at least 8 weeks of conventional therapy prior to Baseline 
(inadequate response to NSAIDs and/or paracetamol and physiotherapy; or intolerance to 
NSAIDs and/or paracetamol). Furthermore, participants should have performed at least 2 weeks 

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of home-based standardized physiotherapy (during Run-in study period) prior to Baseline. 
Participants will only be included if there are no foreseeable plans for surgery in the affected 
shoulder during the study period. 
Participants must have a WORC score ≤ 40 (where 100 points is symptom-free and 0 worst 
symptoms) at Baseline in combination with an average weekly pain score on NRS ≥ 5 
(corresponding to moderate to severe pain on a 0-10 point scale where 10 indicates worst pain) 
during the past 7 days prior to the Baseline visits.. Participants must have nocturnal pain in 
shoulder on at least 3 out of 7 nights in the week prior to Baseline OR a positive “painful arc 
test” on examination. 
The screening period will be used to assess eligibility and to start/continue participants on 
physiotherapy. In the Run-in period the participant should have 2 weeks of NSAID/paracetamol 
intake and home-based standardized physiotherapy and undergo shoulder MRI (or ultrasound 
if participants are unable or unwilling to undergo MRI) as shown in Section 1.3 Schedule of 
Activities. Participants who meet the eligibility criteria after the Run-in period will go through 
Baseline evaluations. 
Eligible participants 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. The assessments to address the primary 
endpoint will be performed at week 24. 
Participants will come to the out-patient clinic approximately 1-3 hours prior to dosing for the 
evaluations. Dosing will be on-site. 
Safety assessments will include physical examinations, vital signs, standard clinical laboratory 
evaluations (hematology, blood chemistry, and urinalysis), pregnancy and fertility assessments, 
adverse event and serious adverse event monitoring. 
Remote procedures 
The on-site staff will perform certain procedures remotely using telephone-visits according to 
Section 1.3 Schedule of Activities. 
4.2 
Scientific rationale for study design 
The study is tailored to support HTAs of secukinumab in Germany in this indication. Currently, 
no Health Authority guideline exists for developing drugs for the moderate to severe rotator 
cuff tendinopathy indication. 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).  
The participant population with rotator cuff tendinopathy was chosen, as this is one of the most 
frequent tendinopathies. The most common age for development of tendinopathy is between 18 
and 65 years; more than two-thirds of cases will develop in this age group (Hopkins, et al., 
2016; Riel, et al., 2019). Moreover, the clinical evidence for an IL-17 connection has so far only 

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been shown for rotator cuff tendinopathy and has not been investigated for other tendinopathies 
(Millar, et al., 2017). 
During the 2-week Run-in period participants should take NSAIDs/paracetamol at an 
optimized individual dose to achieve the best efficacy and simultaneously the best tolerability.  
Glucocorticoids may be given, if required. However, they should be avoided if possible.  
The rationale for key design elements in this study include: 
Randomization: This decreases the chance of an imbalance in participant characteristics 
between groups, thereby facilitating a valid basis for the treatment comparison. 
Double-blind: Blinding of participants, investigators and sponsor up to the point of week 24, 
the primary endpoint, allows for an unbiased assessment of subjective readouts such as the 
efficacy parameters measured by PROs and as well for adverse events evaluation. The blinding 
is maintained for participants and investigators until the end of the study to ensure reliable 
efficacy and safety measures. The sponsor will be unblinded after the primary endpoint analysis 
at week 24 after database lock.  
Placebo-controlled: A placebo arm is included in this study because it is not known whether 
secukinumab can improve moderate to severe rotator cuff tendinopathy, and because there is 
no disease modifying therapy available. However, a patient individualized conventional therapy 
will be given alongside the investigational drug and placebo. 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. 
4.3 
Justification for dose 
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 (Millar, et 
al., 2017). 
While secukinumab 150 mg and 300 mg regimens are both more efficacious than placebo, the 
300 mg regimen showed higher efficacy on skin endpoints and physical function as measured 
by Health Assessment Questionnaire Disability Index (HAQ-DI). 
Furthermore, secukinumab 300 mg was more efficacious than 150 mg in achieving clinically 
meaningful improvements in skin disease. There was a clear dose response favoring 
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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. 
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-week treatment duration was chosen as this is considered the 
maximum acceptable duration for resolution or partial resolution in moderate to severe 
tendinopathy of the rotator cuff. According to Phase II data, the onset of a potential effect could 
be expected within two weeks. (Millar, et al., 2021) The 12 weeks follow-up after the EoT is 
included to generate follow-up data for potential relapse and to have treatment safety follow-
up data in this indication. Efficacy assessments will be done at week 24 (EoS) due to 
requirements of HTA process in Germany. Patients requiring any additional therapy as per 
discretion of the investigator should be treated according to [6.6.]. 
 
Rationale for choice of background therapy 
A patient individualized conventional therapy will be given alongside the investigational drug 
and placebo in both treatment groups as recommended by the German guideline and fulfilling 
the German HTA requirements. 
4.4 
Rationale for choice of control drugs (comparator/placebo) 
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 NSAIDs is 
allowed, and unexpectedly required steroid injection(s) are permitted.  
4.5 
Rationale for public health emergency mitigation procedures 
In the event of a public health emergency as declared by local or regional authorities (i.e., 
pandemic, epidemic or natural disaster), mitigation procedures may be required to ensure 
participant safety and trial integrity and are listed in relevant sections of the study protocol. 
Notification of the public health emergency should be discussed with Novartis prior to 
implementation of mitigation procedures and permitted/approved by local or regional health 
authorities (HA) and ethics committees as appropriate. 
4.6 
End of study definition 
Study completion is defined as when the last participant completes the last study visit, and any 
repeat assessments associated with this visit have been documented and followed-up 
appropriately by the Investigator, or in the event of an early study termination decision, the date 
of that decision (e.g. each participant will be required to complete the study in its entirety and 
thereafter no further study treatment will be made available to them in the scope of the trial). 

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All randomized and/or treated participants should have a safety follow-up call conducted 60 
days after the last administration of study treatment; however, the 60 days falls within the study 
12-week follow-up period, where no treatment is given. A safety follow-up call is only 
necessary for all participants who discontinued the trial. The information is kept as a source 
documentation. SAE reporting continues during this time period as described in Section 8.6.3  
5 
Study Population 
Male and female participants at least 18 years of age, but less than or equal to 65 years of age 
at the time of randomization, with a diagnosis of moderate to severe rotator cuff tendinopathy 
with no tear or partial tear who are experiencing active disease for at least 6 weeks and no more 
than 6 months at Baseline and who have failed conventional therapy.  
Participants must have failed to at least 8 weeks of conventional therapy prior to Baseline 
(inadequate response to NSAIDs and/or paracetamol and physiotherapy; or intolerance to 
NSAIDs and/or paracetamol). Furthermore, participants should have performed at least 2 weeks 
of home-based standardized physiotherapy (during Run-in study period) prior to Baseline. 
Participants will only be included if there are no foreseeable plans for surgery in the affected 
shoulder during the study period. 
 Participants must have a WORC score ≤ 40 (where 100 points is symptom-free and 0 worst 
symptoms) at Baseline in combination with an average weekly pain score on NRS ≥ 5 
(corresponding to moderate to severe pain on a 0-10 point scale where 10 indicates worst pain) 
during the 7 days prior to Baseline visits. Participants must have nocturnal pain in shoulder on 
at least 3 out of 7 nights in the week prior to Baseline OR a positive “painful arc test” on 
examination. 
The degree of tendon tear must be assessed during the Run-in period. Ultrasound may be 
performed in participants who are unwilling or unable to undergo MRI. Only participants who 
show no tendon tear or less than 50% partial thickness tear are eligible for the study. If 
participants show greater than 50% partial thickness tear, they are not eligible for this study.  
The investigator must ensure that all participants being considered for the study meet the 
eligibility criteria listed in Section 5.1 und 5.2 No additional criteria should be applied by the 
investigator, in order to ensure that the study population will be representative of all eligible 
participants. 
Unless specified otherwise in the inclusion/exclusion criteria, the participant selection and 
inclusion in the study is to be established by checking through all eligibility criteria at both 
Screening and Baseline, except for assessments that according to Section 1.3 Schedule of 
Activities are performed at only one of these visits. In this case, it is acceptable to include the 
participant 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 participant from 
enrollment into the study. 

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5.1 
Inclusion criteria 
Participants eligible for inclusion in this study must fulfill all of the following criteria: 
1. Signed informed consent must be obtained prior to participation in the study. 
2. Males and non-pregnant, non-nursing females between 18 and 65 years of age 
3. Rotator cuff tendinopathy (unilateral)  
4. Symptoms present for at least 6 weeks but not more than 6 months at Baseline 
5. Moderate to severe rotator cuff tendinopathy demonstrated by all of the following criteria: 
a. WORC score ≤ 40 at Baseline 
b. Average weekly NRS pain score of ≥ 5 during the 7 days prior to Baseline 
c. Nocturnal pain in shoulder on at least 3 out of 7 days in the week prior to Baseline 
or positive “Painful Arc Test” on examination 
6. Failure to at least 8 weeks of conventional therapy prior to Baseline: inadequate response 
to NSAIDs and/or paracetamol and physiotherapy; or intolerance to NSAIDs and/or 
paracetamol   
5.2 
Exclusion criteria 
Participants fulfilling any of the following criteria are not eligible for inclusion in this study. 
No additional exclusion criteria may be applied by the investigator, in order to ensure that the 
study population will be representative of all eligible participants. 
1. Greater than 50% partial thickness tear as established by MRI or ultrasound during 
assessment in Run-in phase 
2. Patients who are expected to require glucocorticoid treatment throughout the trial duration 
at Baseline (e.g., systemic, intramuscular, local injections in shoulder) 
3. Previous surgery, or plans for surgery, during the study period, in the affected shoulder 
4. Rheumatologic and chronic inflammatory diseases, including but not limited to: 
inflammatory bowel disease, polymyalgia rheumatica (PMR), PsA, axSpA and RA, 
fibromyalgia or severe pain disorder unrelated to the target shoulder 
5. Both RF and anti-CCP antibodies positive at Screening 
6. Either history of adhesive capsulitis/frozen shoulder, or current calcification in the tendon 
(in affected or contralateral shoulder) confirmed clinically or by medical imaging 
7. Symptomatic osteoarthritis of the shoulder (gleno-humeral, acromioclavicular) in affected 
or contralateral shoulder confirmed by medical imaging 
8. Patients with traumatic rupture that would be considered eligible for surgery for repair of 
cuff tear. 
9. Neurological conditions including but not limited to cervical radiculopathy which in the 
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10. Any intra-articular/subacromial glucocorticoid treatment within 12 weeks prior to Baseline 
or more than 2 intra-articular/subacromial glucocorticoid injections for the treatment of the 
current episode of tendinopathy .  
11. Any oral, intramuscular or i.v. glucocorticoid treatment 12 weeks prior to Baseline or during 
the current tendinopathy, whatever takes longer 
12. Previous platelet rich plasma (PRP) or hyaluronic injections or fluoroquinolone/quinolone 
antibiotics within 12 weeks prior to Baseline or during the current tendinopathy, whichever 
takes longer 
13. Neuromuscular or primary/secondary muscular deficiency which limits the ability to 
perform functional measurement (e.g., shoulder strength test) 
Prohibited Medications and therapies 
14. Use of prohibited medications and procedures including physical therapies such as 
shockwave therapy and others [as listed in Table 6-3] 
15. Previous exposure to secukinumab or any other biologic drug directly targeting IL-17 or IL-
17 receptor 
16. Use of any investigational drug and/or devices within 4 weeks of randomization, or a period 
of 5 half-lives of the investigational drug, whichever is longer 
17. Patients taking high potency opioid analgesics (e.g., methadone, hydromorphone, 
morphine) 
Lab screening 
18. History or current clinically significant liver disease or liver injury as indicated by abnormal 
liver function tests such as serum glutamic oxaloacetic transaminase (SGOT) (aspartate 
aminotransferase, AST), serum glutamic pyruvic transaminase (SGPT) (alanine 
aminotransferase, ALT), alkaline phosphatase, or serum bilirubin. The Investigator should 
be guided by the following criteria: 
AST/ALT may not exceed 3 x the upper limit of normal (ULN). Total bilirubin 
concentration may not exceed 1.5 x ULN. If the total bilirubin concentration is increased 
above ULN, total bilirubin should be differentiated into the direct and indirect reacting 
bilirubin. Any one of these parameters, if elevated above ULN, should be re-checked once 
more as soon as possible, and in all cases, at least prior to randomization, to rule-out 
laboratory error.) Patients with severely reduced kidney function (estimated glomerular 
filtration rate (eGFR) <29 ml/min/1.73m2), or a serum creatinine level exceeding 1.5 mg/dL 
(132.6 μmol/L). 
19. Total White Blood Cell (WBC) count < 3,000/µL, neutrophils < 1,500/µL, hemoglobin < 
8.5 g/dL (85 g/L) or platelet count < 100,000/µL. 
General Medical history/active medical conditions 

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20. History or current diagnosis of significant ECG abnormalities, including clinically 
significant cardiac arrhythmias, e.g., sustained ventricular tachycardia, and clinically 
significant second or third degree atrioventricular block without a pacemaker 
21. History of lymphoproliferative disease or any known malignancy or history of malignancy 
of any organ system within the past 5 years (except for basal cell carcinoma or actinic 
keratoses that have been treated with no evidence of recurrence in the past 3 months, or 
carcinoma in situ of the cervix or non-invasive malignant colon polyps that have been 
removed). 
22. Active ongoing inflammatory diseases or underlying metabolic, hematologic, renal, hepatic, 
pulmonary, neurologic, endocrine, cardiac, infectious or gastrointestinal conditions, which 
in the opinion of the investigator immuno-comprises the participant and/or places the 
participant at unacceptable risk for participation in an immunomodulatory therapy.  
23. Known infection with HIV, hepatitis B or hepatitis C at screening or randomization 
24. History of hypersensitivity to any of the study treatments or excipients or to drugs of similar 
classes. 
25. Active systemic infections during the last two weeks prior to randomization (exception: 
common cold) 
26. History of ongoing, chronic or recurrent infectious disease or evidence of TB infection as 
defined by a positive QuantiFERON TB-Gold test as indicated in the SoA.  
Patients with a positive test may participate in the study if further work up establishes 
conclusively that the patient has no evidence of active tuberculosis. If presence of latent 
tuberculosis is established, then treatment according to guidelines must have been initiated. 
27. Any surgical, medical, psychiatric or additional physical condition that the Investigator feels 
may potentially jeopardize the patient during participation in this study or could interfere 
with the study objectives, conduct or evaluation. 
Pregnancy language (basic contraception level) 
28. Women who have a positive pregnancy result prior to initiation of study drug or are pregnant 
or lactating. 
29. Women of child-bearing potential, defined as all women physiologically capable of 
becoming pregnant, unless they are using effective methods of contraception during dosing 
of study treatment. Effective contraception methods include: 
a. Total abstinence (when this is in line with the preferred and usual lifestyle of the 
participant. Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-
ovulation methods) and withdrawal are not acceptable methods of contraception 
b. Female sterilization (have had surgical bilateral oophorectomy with or without 
hysterectomy), total hysterectomy or bilateral tubal ligation at least six weeks before 
taking investigational drug. In case of oophorectomy alone, only when the reproductive 
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c. Male sterilization (at least 6 months prior to screening). For female participants on the 
study, the vasectomized male partner should be the sole partner for that participant 
d. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or 
cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository  
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). 
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. 
Women are considered post-menopausal and not of childbearing potential if they have had 
12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age 
appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy 
(with or without hysterectomy), total hysterectomy or tubal ligation at least six weeks ago. 
In the case of oophorectomy alone, only when the reproductive status of the woman has been 
confirmed by follow up hormone level assessment is she considered not of childbearing 
potential. 
Other 
30. Inability or unwillingness to undergo repeated venipuncture (e.g., because of poor 
tolerability or lack of access to veins) 
31. Inability or unwillingness to receive injections with PFS 
32. Donation or loss of 400 mL or more of blood within 8 weeks before dosing 
33. Plans for administration of live vaccines during the study period or 6 weeks prior to 
randomization 
5.3 
Screen failures 
A screen failure occurs when a participant who consents to participate in the clinical study is 
subsequently found to be ineligible and therefore not randomly assigned to study treatment. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements and to respond to queries from regulatory authorities. This minimal 
information includes demography, screen failure details, eligibility criteria, and any serious 
adverse event (SAE). 
Participants who sign an ICF and subsequently found to be ineligible prior to randomization 
will be considered a screen failure. The reason for screen failure should be recorded on the 
appropriate CRF. The demographic information, informed consent, and Inclusion/Exclusion 
pages must also be completed for screen failure participants. No other data will be entered into 
the clinical database for participants who are screen failures, unless the participant experienced 
a serious adverse event during the screening phase (see SAE section for reporting details). If 

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the participant fails to be randomized, the IRT must be notified within 2 days of the screen fail 
that the participant was not randomized. 
Participants who are randomized and fail to start treatment, e.g., participants randomized in 
error, will be considered an early terminator. The reason for early termination should be 
recorded on the appropriate CRF. 
All participants 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. 
 
Replacement policy 
No replacement policy will be applied. 
 
Participant numbering 
Each participant is identified in the study by a Participant Number (Participant No.), that is 
assigned when the participant is enrolled for screening and is retained for the participant 
throughout his/her participation in the trial. A new Participant No. will be assigned at every 
subsequent enrollment if the participant is rescreened. The Participant No. consists of the Site 
Number (Site No.) (as assigned by Novartis to the investigative site) with a sequential 
participant number suffixed to it, so that each participant’s participation is numbered uniquely 
across the entire database. Upon signing the ICF, the participant is assigned to the next 
sequential Participant No. available. 
6 
Study treatment(s) and concomitant therapy 
6.1 
Study treatment 
Details on the requirements for storage and management of study treatment, and instructions to 
be followed for participant numbering, prescribing/dispensing and taking study treatment are 
outlined in the IRT manual. 
Table 6-1 
Investigational and control drug 
Study drug name 
Formulation 
Unit dose 
Packaging 
Provided by 
Secukinumab 300 mg  
 1 x 2 mL PFS  
2 mL (300 mg) Double-blind supply 
Novartis 
Placebo 
 1 x 2 mL PFS 
Double-blind supply 
Novartis 
PFS – Pre-Filled Syringe 
Participants will be given the injections by the site staff on site.  
The PFSs are packed in a double blinded fashion and do not need to be prepared. The study 
treatments will be labeled as follows: 

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• Double-blind secukinumab and placebo pre-filled syringe (PFS) will be labeled AIN457 
300 mg/2 ml/Placebo for dosing up to and including Week 12. 
The investigational treatments are to be stored at 2°C to 8°C 
 
Additional study treatment and therapies 
A patient individualized conventional therapy will be given to all participants alongside the 
investigational drug and placebo. Additional study medication will NOT be provided by the 
Sponsor and has to be managed on site level. The patient individualized conventional therapy 
consists of:  
a. Home-based standardized physiotherapy based on MOON regimen (Kuhn, 2009): 
participants will be instructed on home-based standardized physiotherapy by qualified 
study site personnel at screening visit. Participants will receive printed instructions to 
perform standardized physiotherapy at home until study completion. The performance 
is recommended once or twice daily. At each visit site personnel will inquire about status 
of home-based standardized physiotherapy to address any questions or hurdles and 
review instructions with the participant as needed and will document the status in eCRF 
accordingly. Concomitant in-person physiotherapy is allowed. However, new-onset of 
in-person physiotherapy should be avoided after randomization.  
b. NSAIDs: Dose should be optimized to the individual participant to achieve the best 
efficacy and simultaneously the best tolerability. Dosing should not exceed the 
respective approved dosing and the maximum tolerable dose (e.g., max. dose of 
2400 mg/day ibuprofen or max. dose of 4000 mg/day paracetamol or as directed by 
treating physician). Should high NSAID doses not be tolerated or contraindicated, 
participants may receive the maximum tolerated NSAID dose in combination with 
paracetamol as support if necessary. The optimized dose of NSAIDs/paracetamol, 
starting from Run-in period, should remain stable until Baseline. Dose adjustments 
(dose decrease and dose increase of NSAIDs/paracetamol relative to the optimized 
starting dose), discontinuation of NSAIDs/paracetamol and switch of NSAIDs are 
possible after baseline. Participants should keep their regular schedule of NSAID intake 
24 hours ahead of a visit. 
 
 
 
. 
c. Glucocorticoids may be given, if required. However, they should be avoided if possible. 
Participants who are expected at Baseline to require glucocorticoid treatment 
throughout the trial duration will not be randomized. In case glucocorticoids will be 
unexpectedly required during study period (local injections in the shoulder - including 
intramuscular injection or systemic), treatment with glucocorticoids is allowed at any 
time throughout the study. 
 
 Local glucocorticoid injections for current tendinopathy should not exceed 
2 injections during the course of this study. Participants exceeding 2 injections continue 
the study as outlined in the SoA. 

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Treatment arms/group 
Participants will be assigned at visit 3 (Baseline) to one of the following 2 treatment arms in a 
1:1 ratio, with approximately 215 participants per arm.  
• Group 1: Secukinumab 300 mg s.c. (1 x 300 mg) 
• Group 2: Placebo s.c. (1 injection) 
Treatment is administered at Day 1 (Baseline visit), and Weeks 1, 2, 3, 4, 8 and 12. 
 
Treatment duration 
The planned duration of treatment is 12 weeks. Participants may be discontinued from treatment 
earlier due to unacceptable toxicity, disease progression and/or treatment is discontinued at the 
discretion of the investigator or the participant. For participants who in the opinion of the 
investigator are still deriving clinical benefit from AIN457, every effort will be made to 
continue provision of study treatment. 
6.2 
Preparation, handling, storage, and accountability  
Each study site will be supplied with study treatment in packaging as described under Table 6-1 
Investigational and control drugs section. 
A unique medication number is printed on the study medication label. 
Investigator staff will identify the study medication kits to dispense to the participant by 
contacting the IRT and obtaining the medication number(s). The study medication has a 2-part 
label (base plus tear-off label), immediately before dispensing the medication kit to the 
participant, site personnel will detach the outer part of the label from the packaging and affix it 
to the source document. 
AIN457 will be administered to the participant via the s.c. route of administration. Participants 
will be given the injections by the site staff on site. 
Sponsor qualified medical personnel will be readily available to advise on trial related medical 
questions or problems. 
 
Handling of study treatment 
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only the Investigator and designated 
site personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified in the Investigator's Brochure. 
Clinical supplies are to be dispensed only in accordance with the protocol. Technical complaints 
are to be reported to the respective Novartis Country Organization Quality Assurance. 
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the study treatment but no information about 
the participant except for the medication number. 

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The Investigator or designated site staff (blinded) must maintain an accurate record of the 
shipment and dispensing of study treatment in a drug accountability log. Monitoring of drug 
accountability will be performed by field monitors during site or remote monitoring visits, and 
at the completion of the trial. The Investigator must provide accountability also for locally 
sourced materials used for administration (e.g. i.v. bags). 
The Investigator will return all unused study treatment, packaging, drug labels, and a copy of 
the completed drug accountability log to the Novartis monitor or to the Novartis address 
provided in the Investigator folder at each site. 
 
Handling of other treatment 
The handling of other treatments such as NSAIDs and GC injections is within the responsibility 
of the site. 
 
Instructions for prescribing and taking study treatment 
Study treatment (1 x 300 mg s.c. secukinumab or matching placebo) will be administered with 
PFSs throughout the study.  
S.c. administration with pre-filled syringes 
Secukinumab solution for s.c. injection (300 mg in 2.0 mL active/placebo) will be provided in 
PFSs.  
Study treatment interruption should be avoided with the following exceptions: 
Study treatment interruption is only permitted if, in the opinion of the investigator, a participant 
is deemed to be placed at a significant safety risk unless dosing is temporarily interrupted. 
In such cases study treatment should be interrupted only during the time that this risk is present 
and ongoing. Study treatment can be restarted at the next scheduled visit after resolution of the 
safety risk. 
Any study treatment interruption must be recorded on the corresponding eCRF page. 
Table 6-2 
Dose and treatment schedule 
Investigational/ 
Control Drug 
Dose 
Frequency 
Secukinumab 
300 mg: 1 x 2 mL (300 mg) Week 0, 1, 2, 3, 4, 8 and 12 
(7 doses in total) 
Placebo 
1 x 2 mL 
Week 0, 1, 2, 3, 4, 8 and 12 
(7 doses in total) 
 
All kits of study treatment assigned by the Interactive Response Technology (IRT) will be 
recorded in the IRT system. 

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6.3 
Measures to minimize bias: randomization and blinding  
 
Treatment assignment, randomization 
At Baseline visit, all eligible participants will be randomized via Interactive Response 
Technology (IRT) to one of the treatment arms. The Investigator or his/her delegate will contact 
the IRT after confirming that the participant fulfills all the inclusion/exclusion criteria. The IRT 
will assign a randomization number to the participant, which will be used to link the participant 
to a treatment arm and will specify a unique medication number for the first package of study 
treatment to be dispensed to the participant. 
The randomization numbers will be generated using the following procedure to ensure that 
treatment assignment is unbiased and concealed from participants and investigator staff. A 
participant randomization list will be produced by the IRT provider using a validated system 
that automates the random assignment of participant 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 Global Clinical Supply (GCS) using a validated system that automates the random 
assignment of medication numbers to packs containing the study treatment. 
The randomization scheme for participants will be reviewed and approved by a member of the 
Randomization Office. 
Follow the details outlined in the IRT manual regarding the process and timing of treatment 
assignment and randomization of participants. 
 
Treatment blinding 
Participants, investigator staff, persons performing the assessment and the Novartis Clinical 
Trial Team (CTT) will remain blind to the identity of the treatment from the time of 
randomization until database lock. 
The following methods will be used to maintain the blinding: 
(1) Randomization data will be kept strictly confidential until the time of the final database 
lock and will not be accessible by anyone else involved in the study.  
(2) The identity of the treatments will be concealed by the use of study treatment that are 
all identical in packaging, labeling, schedule of administration, appearance, taste, and 
odor. 
Unblinding a single participant at site for safety reasons (necessary for participant management) 
will occur via an emergency system in place at the site. As a result, the participant should be 
discontinued from the study treatment. 
All 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 24. Study monitors will remain blinded throughout the study. 

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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 24.  
 
Emergency breaking of assigned treatment code 
Emergency code breaks must only be undertaken when it is required to in order to treat the 
participant´s safety.  
Most often, discontinuation from study treatment and knowledge of the possible treatment 
assignments are sufficient to treat a study participant who presents with an emergency 
condition. Emergency treatment code breaks are performed using the IRT. When the 
Investigator contacts the system to break a treatment code for a participant, he/she must provide 
the requested participant identifying information and confirm the necessity to break the 
treatment code for the participant. The Investigator will then receive details of the 
investigational drug treatment for the specified participant and a fax or email confirming this 
information. The system will automatically inform the Novartis monitor for the site and the 
study team that the code has been broken. 
It is the Investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT/code break cards at any time in case of emergency. The Investigator 
will need to provide: 
• Protocol number 
• Participant number.  
In addition, oral and written information to the participant must be provided on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable to ensure that unblinding 
can be performed at any time. 
6.4 
Continued access to study treatment after the end of the study 
After study participation, the participant will continue to be treated at the Investigator’s 
discretion according to local practice. Continuing medical care must be provided by the 
investigator and/or referring physician based on participant availability for follow-up or must 
refer them for appropriate ongoing care. 
 
Post-trial access 
A Post Trial Access program is not planned. 
6.5 
Reporting of study treatment errors including misuse/abuse   
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant or 
consumer (EMA definition). 
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol. 

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Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate CRF irrespective of whether or not associated with an AE/SAE. Study treatment 
errors and uses outside of what is foreseen in the protocol, misuse or abuse will be collected 
and reported in the safety database irrespective of it being associated with an AE/SAE within 
24 hours of Investigator’s awareness. For more information on AE and SAE definition and 
reporting, please see the respective sections. 
6.6 
Concomitant therapy 
 
Concomitant therapy 
The investigator must instruct the participant to notify the study site about any new medications 
he/she takes after the participant has been enrolled into the study.  
All medications, procedures, and significant non-drug therapies (including physical therapy and 
blood transfusions) administered after the participant was enrolled into the study must be 
recorded on the appropriate CRFs. 
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 and 
prohibited medication.  
For physiotherapy, please refer to Section 6.1.1 Additional study treatment and details provided 
in the separate Exercise Manual for participants.  
 
Prohibited Medication and Procedures 
Use of the treatments displayed in Table 6-3 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. If 
live vaccination is necessary at week 24, it should be done after assessments at week 24 when 
study is completed. 
Glucocorticoids should be avoided. Participants who are expected to require glucocorticoid 
treatment throughout the trial duration (e.g., systemic, intramuscular, local injections in 
shoulder) will not be enrolled. In case glucocorticoids will be unexpectedly required during 
study period (local injections in the shoulder - including intramuscular injection or systemic), 
the study medication will be nevertheless continued. Reasons for glucocorticoid use, dose and 
duration must be documented. Local glucocorticoid injections for current tendinopathy should 
not exceed 2 injections during the course of this study. Participants exceeding 2 injections 
continue the study as outlined in the SoA. 

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Other physical treatment modalities such as shockwave therapy, therapeutic ultrasound, laser 
therapy, iontophoresis, transcutaneous electrical nerve stimulation, therapeutic x-ray radiation, 
hyperbaric oxygen therapy, magnetic field therapy, hyperthermia are prohibited 12 weeks prior 
to Baseline and during the course of the study. 
Surgery in the affected shoulder leads to the discontinuation of study medication. 
Table 6-3 
Prohibited medications 
Medication 
Prohibited period 
(prior to Baseline) 
Action taken 
Any immunomodulating biologic 
drugs, including but not limited to TNF 
or other biologic drugs targeting IL-17 
or IL-17 receptor2 
Never1 
Discontinue study medication 
Any cell-depleting therapies including 
but not limited to anti-CD20 or 
investigational agents2 
Never 
Discontinue study medication 
DMARDs (e.g., MTX and tofacitinib) 
and apremilast2 
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 
Analgesics other than 
NSAIDs/paracetamol and low strength 
opioids PRN 
2 weeks3 
Discontinue the prohibited medication. 
All medications including dose and 
duration must be recorded and reasons 
for use of other analgesics documented 
High potency opioids 
12 weeks 
Discontinue study medication 
Systemic glucocorticoids 
12 weeks or during the 
current tendinopathy, 
whichever takes longer   
Glucocorticoids should be avoided. 
Participants who are expected to require 
glucocorticoid treatment throughout the 
trial duration will not be recruited. In 
case glucocorticoid use will be 
unexpectedly required during study 
period, the study medication will be 
nevertheless continued. Reasons for 
glucocorticoid use, dose and duration 
must be documented 
Local glucocorticoid injections in the 
shoulder (including intramuscular 
injection) 
12 weeks  
Participants who are expected at Baseline 
to require glucocorticoid treatment 
throughout the trial duration will not be 
recruited. In case glucocorticoid use will 
be unexpectedly required during study 
period, the study medication will be 
nevertheless continued. Reasons for 

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Medication 
Prohibited period 
(prior to Baseline) 
Action taken 
glucocorticoid use, dose and duration 
must be documented. 
Participants should not receive more than 
2 injections during the course of the 
study. Participants exceeding 2 injections 
continue the study as outlined in the SoA 
Fluoroquinolone 
12 weeks or during the 
current tendinopathy, 
whichever takes longer 
Discontinue study medication 
Live vaccinations4 
6 weeks 
Discontinue study medication 
Platelet rich plasma injections in the 
affected shoulder or any other joint 
tendon 
12 weeks or during the 
current tendinopathy, 
whichever takes longer 
Discontinue study medication 
Hyaluronic acid injections in the 
affected shoulder or any other joint 
tendon 
12 weeks or during the 
current tendinopathy, 
whichever takes longer 
Discontinue study medication 
Oral or topical retinoids 
12 weeks 
Discontinue study medication 
1 Never = no prior exposure is allowed, and medication is prohibited from study start and up to and including follow-up 
visit 
2 These agents fall under the category of biologic immunomodulators and are prohibited medications 
3 Period in weeks refers to washout of prohibited medications during screening counted from randomization visit 
Administration of these agents requires study discontinuation 
4 The effect of secukinumab on live vaccines is unknown; therefore, live vaccines should not be administered during 
participation in the study 
 
Rescue medication 
Rescue medication is defined as any new therapeutic intervention or a significant change to 
ongoing therapy made because a participant is experiencing either no benefit from participation 
in the trial or worsening / exacerbation of their disease. Rescue medication will not be provided 
by the sponsor. 
Glucocorticoids may be used as rescue medication. However, if possible, glucocorticoids 
should be avoided. Rescue medication can be used from Baseline as outlined in Section 4.  
Use of rescue medication must be recorded accordingly on the corresponding eCRF.  
Efficacy and safety will be assessed in detail at every study visit (except for visits at week 1 and 
week 3, where efficacy is not assessed). Participants 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.  
Reasons for discontinuation must be recorded accordingly on the corresponding eCRF. 

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7 
Discontinuation of study treatment and participant 
discontinuation/withdrawal 
7.1 
Discontinuation of study treatment 
Discontinuation of study treatment (excluding additional study treatment) for a participant 
occurs when study treatment is permanently stopped for any reason (prior to the planned 
completion of study treatment administration, if any) other than withdrawal of informed consent 
should not be considered as discontinued from the study. Where possible, the participants 
should return for the study visits indicated in the Assessment Schedule during treatment. 
The Investigator must discontinue study treatment for a given participant if, he/she believes that 
continuation would negatively impact the participant's well-being. 
Discontinuation from study treatment is required under the following circumstances: 
• Participant/guardian decision - participant may choose to discontinue study treatment for 
any reason at any time.  
• Pregnancy (see Section 8.4.5 (Safety) and Section 8.6.4 (Pregnancy reporting))  
• The Investigator believes that continuation would negatively impact the safety of the 
participant or the risk/benefit ratio of trial participation.  
• Use of prohibited treatment as per recommendations in the prohibited treatment section 
(6.6.2) including surgeries of the affected shoulder 
• Any situation in which continued study participation might result in a safety risk to the 
participant 
• Following emergency unblinding 
• Emergence of the following adverse events: 
- Any severe or serious adverse event that is not compatible with administration of study 
medication, including adverse events that require treatment with an unacceptable co-
medication 
- Life-threatening infection 
• Any protocol deviation that results in a significant risk to the participant’s safety. 
• Adverse events, abnormal laboratory values or abnormal test results that indicate a safety 
risk to the participant. 
• Any laboratory abnormalities that in the judgment of the Investigator, taking into 
consideration the participant’s overall status, prevents the participant from continuing 
participation in the study. 
The appropriate personnel from the site and Novartis will assess whether investigational drug 
treatment should be discontinued for any participant whose treatment code has been broken 
inadvertently for any reason. 
If discontinuation from study treatment occurs, the Investigator should make a reasonable effort 
to understand the primary reason for the participant’s discontinuation from study treatment and 
record this information.  

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If the participant cannot or is unwilling to attend any visit(s), the site staff should maintain 
regular telephone contact with the participant, or with a person pre-designated by the 
participant. This telephone contact should preferably be done according to the study visit 
schedule. 
After discontinuation from study treatment the participant remains in the study and continues 
the visits as outlined in the SoA. 
The Investigator must also contact the IRT to register the participant’s discontinuation from 
study treatment. 
7.2 
Participant discontinuation from the study 
Participants 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. This final visit should include all EOS assessments.  
At this final visit, the AE and concomitant medications should be recorded in the eCRF: 
For all premature discontinuations, if the patient fails to return for these assessments for 
unknown reasons, every effort (e.g., telephone, e-mail, letter) should be made to contact the 
participant/pre-designated contact as specified in the lost to follow up section. This contact 
should preferably be done according to the study visit schedule. 
If the patient cannot or is unwilling to attend any visit(s), the site staff should maintain regular 
telephone contact with the patient, or with a person pre-designated by the patient. This telephone 
contact should preferably be done according to the study visit schedule. 
Discontinuation from study is when the participant permanently stops receiving the study 
treatment, AND further protocol-required assessments or follow-up, for any reason. 
If the participant agrees, a final evaluation (EoS) at the time of the participant’s study 
discontinuation should be made as detailed in Section 1.3 Schedule of Activities. 
7.3 
Withdrawal of informed consent and exercise of participants’ 
data privacy rights 
Participants may voluntarily withdraw consent to participate in the study for any reason at any 
time. Withdrawal of consent occurs only when a participant:  
• Does not want to participate in the study anymore, and  
• Does not want any further visits or assessments, and  
• Does not want any further study related contacts  
In this situation, the investigator should make a reasonable effort (e.g., telephone, e-mail, letter) 
to understand the primary reason for the participant’s decision to withdraw his/her consent and 
record this information.  
Where consent to the use of personal and coded data is not required, the participant therefore 
cannot withdraw consent. They still retain the right to object to the further use of personal data.  

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Study treatment must be discontinued, and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing.  
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up.  
All efforts should be made to complete the assessments prior to study withdrawal. A final 
evaluation at the time of the participant’s study withdrawal should be made as detailed in the 
assessment table.  
Novartis will continue to retain and use all research results (data) that have already been 
collected for the study evaluation.  
All biological samples not yet analyzed at the time of withdrawal will no longer be used, unless 
permitted by applicable law. They will be stored according to applicable legal requirements. 
7.4 
Lost to follow-up 
For participants whose status is unclear because they fail to appear for study visits or fail to 
respond to any site attempts to contact them without stating an intention to discontinue from 
study treatment or discontinue from study or withdraw consent the Investigator should show 
"due diligence" by documenting in the source documents steps taken to contact the participant, 
e.g., dates of telephone calls, registered letters, etc. A participant should not be considered lost 
to follow-up until due diligence has been completed or until the EoS. 
7.5 
Early study termination by the sponsor 
The study can be terminated by Novartis at any time.  
Reasons for early termination (but not limited to) 
• Unexpected, significant, or unacceptable safety risk to participants enrolled in the study 
• Decision based on recommendations from applicable board(s) after review of safety and 
efficacy data 
• Discontinuation of study treatment development in this indication 
In taking the decision to terminate, Novartis will always consider participant welfare and safety. 
Should early termination be necessary, participants must be seen as soon as possible and treated 
as a participant who discontinued from study treatment: If applicable, an EoT visit and the safety 
follow-up period must be completed. The Investigator may be informed of additional 
procedures to be followed in order to ensure that adequate consideration is given to the 
protection of the participant’s interests. Novartis will be responsible for informing Institutional 
Review Boards (IRBs)/Independent Ethics Committees (IECs) of the early termination of the 
trial. 
8 
Study Assessments and Procedures 
Study procedures and their timing are summarized in Section 1.3 Schedule of Activities. 
Protocol waivers or exemptions are not allowed. Immediate safety concerns should be discussed 

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with Novartis upon occurrence or awareness to determine if the participant should continue or 
discontinue study treatment. 
Adherence to the study design requirements, including those specified in Section 1.3 Schedule 
of Activities, is essential and required for study conduct. Safety/laboratory/analyte results that 
could unblind the study will not be reported to investigative sites or other blinded personnel 
until the study has been unblinded. 
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with 
the samples. 
8.1 
Screening 
Patient’s eligibility for the study will be assessed during the Screening period (Day -42 to -1) 
and at the Baseline Visit. It is permissible to re-screen a participant once if she/he fails the initial 
screening; however, each case must be discussed and agreed with the Sponsor on a case-by-
case basis.  
Patients who fail Screening for any reason may be re-screened once. Patients who are re-
screened must sign a new ICF and be issued a new Patient No. before any study-related 
assessment is performed or any data for the Screening Period are collected for the patient under 
the new Patient No. 
The Investigator or qualified site staff will record the re-screening on the Re-screening eCRF 
page and the applicable Screening number the patient was issued prior to the current Screening 
number. The date of the new informed consent signature must be entered on the Informed 
Consent eCRF page to correspond with the new Screening Patient No. 
The Withdrawal of Consent eCRF page must be completed if consent was withdrawn during 
the Screening Period before the patient was randomized. 
8.2 
Participant demographics/other Baseline characteristics 
Participant demographic and Baseline characteristic data to be collected on all participants and 
recorded in the eCRF include:  
• Year of birth, age, sex, race 
• Source of participant referral (if applicable) 
• Relevant medical history and current medical conditions, not including tendinopathy of 
rotator cuff 
• Relevant tendinopathy of rotator cuff and general medical history/current medical 
condition data (until date of signature of informed consent), such as date of diagnosis of 
tendinopathy, previous tendinopathy therapies, especially pain medication and 
physiotherapy  
• Potential glucocorticoid treatment and information on potential tear on MRI or ultrasound 
will be recorded to assess participants for eligibility  
Whenever possible, diagnoses and not symptoms will be recorded. For screening failures record 
of demographic information, IC/EC and informed consent is sufficient. 

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All prescription medications, over-the-counter drugs and significant non-drug therapies 6 
months prior to the start of the study must be documented. See the protocol Section 6.6.1 
Concomitant Therapy for further details on what information must be recorded on the 
appropriate page of the eCRF. 
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. 
 
Hepatitis screen, HIV screen 
Hepatitis B and/or hepatitis C and/or HIV serology testing are to be performed during screening 
period, only in case study site/lab personnel comes in contact with blood, tissue or bodily fluids 
of participants through contact with injection needle, cut, splash on mucous membrane or 
through skin damage. If HIV test is seropositive, it should be confirmed by 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. 
Results for Hepatitis and HIV tests will be available as source data at the study site and will not 
be recorded within the CRF. 
 
X-ray of the shoulder 
An X-ray of the shoulder is not required but strongly recommended as per national guidelines.  
 
Ultrasound of the shoulder 
Ultrasound may be performed if participants are unable or unwilling to undergo MRI. The 
assessment is to be performed maximum 14 days before Baseline as indicated in Section 1.3 
Schedule of Activities. This must be collected as source data and documented in the eCRF 
accordingly. 
B-mode Ultrasound is utilized to rule out major structural damage to the tendon (i.e., more than 
50% tear) or other shoulder pathologies. 
8.3 
Efficacy assessments 
Planned time points for all efficacy assessments are provided in Section 1.3 Schedule of 
Activities. 
 
The PRO efficacy measures collected for primary, secondary 
 
objectives: 
The impact of tendinopathy on various aspects of participant’s health-related quality of life 
(QoL) will be assessed by the following instruments: 
• The WORC index score (WORC score and WORC score in each subdomain) 
• The QuickDASH score  
• The EQ-5D-5L score 
• SF-36 

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• Assessment of pain (NRS) 
• Patient global assessment score (PaGA VAS) 
 
 
All questionnaires will be available in the local language. The participants will be asked to fill 
in these PROs at the clinic at the visits specified in Section 1.3 Schedule of Activities. 
Study participants 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 participant to complete any missing responses. If participants 
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 participants, including participants who prematurely discontinue prior to the 
study evaluation completion visit. However, if participants refuse to complete PROs, this should 
be documented in study source records. Participants´ refusal to complete study PROs are not 
protocol deviations.  
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 participant. If AEs or SAEs 
are confirmed, then the physician must record the events as per instructions given in Section 8.6 
of the protocol. Investigators should not encourage the participants to change the responses 
reported in the completed questionnaires. 
8.3.1.1 
The Western Ontario Rotator Cuff (WORC) index 
The WORC index 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. The best possible result is 0 (asymptomatic patient) 
and the worst possible result is 2100 (highly symptomatic). The WORC Index has a recall 
period of 1 week and is filled in by the participant at the clinic at visits specified in Section 1.3 
Schedule of Activities. 
8.3.1.2 
The Quick Disability of the Arm, Shoulder and Hand (DASH) 
questionnaire  
The QuickDASH is an abbreviated form of the DASH. It is a patient reported outcome tool, 
which has been developed by the AAOS along with the Institute for Work & Health (Toronto, 
Ontario, Canada) (Institute for Work & Health, 2020). The QuickDASH Index is self-
administered and uses 11 items to measure physical function and symptoms in participants 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 

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most disability. It has a recall period of 1 week. The tool is filled in by the participant at visits 
specified in Section 1.3 Schedule of Activities. 
8.3.1.3 
EuroQol 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 participants. 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). Participants 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 participant of particular health states and the generation of participant 
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 EQ-5D-5L is filled in by the participant at visits specified in Section 1.3 
Schedule of Activities. 
8.3.1.4 
Patient’s assessment of Pain (Pain NRS) 
The score for pain will be assessed by using an 11-point NRS ranging from 0 “no pain at all” 
to 10 “worst possible pain”, after the question “On a numeric scale of 0-10 where would you 
rate your pain at this time”. The Pain NRS is filled in by the participant at visits specified in 
Section 1.3 Schedule of Activities and daily in the participants diary during Run-in phase. 
8.3.1.5 
Participant’s global assessment of disease activity (PaGA VAS) 
The participant’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 PaGA VAS is filled in by the participant at visits specified in Section 1.3 Schedule of 
Activities. 
8.3.1.6 
Short Form Health Survey (SF-36) 
The SF-36 is a widely used and extensively studied instrument to measure health-related 
quality of life among healthy subjects and participants with acute and chronic conditions. 
It consists of eight subscales that can be scored individually: Physical Functioning, Role-
Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role-Emotional, and 

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Mental Health (Ware, et al., 1993). Two overall summary scores, the Physical Component 
Summary (PCS) and the Mental Component Summary (MCS) also can be computed (Ware, 
et al., 1994). The SF-36 has proven useful in monitoring general and specific populations, 
comparing the relative burden of different diseases, differentiating the health benefits 
produced by different treatments, and in screening individual participants. The purpose of the 
SF-36 in this study is to assess the health-related quality of life of participants.  
The standard version with a 4-week recall period is filled in by the participant at visits specified 
in Section 1.3 Schedule of Activities. 
 
 
 
 
  
 
Appropriateness of efficacy assessments 
The efficacy assessments selected are appropriate for this indication/participant population and 
in accordance with German HTA methodology. 
8.4 
Safety assessments 
Safety assessments are specified below with Section 1.3 Schedule of Activities detailing when 
each assessment is to be performed. 
For details on AE collection and reporting, refer to Section 8.6. 
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 
• Height and Weight 
• Vital signs 
• TB screening: QuantiFERON TB-Gold test 
• Laboratory evaluations (Hematology, Clinical Chemistry, Lipid Panel, Glucose, 
Urinalysis) 
• Pregnancy and assessment of fertility 
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e. pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, regular 
phone or virtual calls can occur (according to visit schedule or more frequently if needed) for 
safety monitoring and discussion of the participant´s health status until it is safe for the 
participant to visit the site again. 

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Physical examinations 
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. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
 
Body 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. 
 
Vital signs 
This will include blood pressure and pulse rate measurements after 5 minutes rest in sitting 
position. 
Clinically notable vital signs are defined in Appendix 3: Clinical laboratory tests. 
 
Clinical safety laboratory tests 
Clinically relevant deviations of laboratory test results occurring during or at completion of the 
study must be recorded, as either medical history/current medical conditions or adverse events 
as appropriate 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. 
As per Section 4.5, changes in safety assessments can be added as one of the risk mitigation 
procedures during public health emergency declared by local or regional authorities.  
If participants cannot visit the site for safety lab assessments conducted through central labs, 
local lab collection may be used during a Public Health emergency as declared by Local or 
Regional authorities i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site 
study visits. 
If participants cannot visit the site for protocol specified safety lab assessments, an alternative 
lab (local) collection site may be used. 
A central laboratory will be used for analysis of all safety specimens collected. Details on the 
collection, shipment of samples and reporting of results by the central laboratory are provided 
to investigators in the central laboratory manual. 

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Clinically notable laboratory findings are defined in Appendix 3: Clinical laboratory tests. 
Table 8-1 
Laboratory tests 
Test Category 
Test Name 
Hematology 
Hematocrit, Hemoglobin, Platelet count, Red 
blood cell (RBC) count, and White blood cell 
count (WBC) with differentials (Basophils, 
Eosinophils, 
Lymphocytes, 
Monocytes, 
Neutrophils) (absolute value and %). 
Chemistry 
Albumin, Alkaline phosphatase, ALT 
(SGPT), AST (SGOT), Bicarbonate, 
Blood Urea Nitrogen (BUN)/Urea, 
Calcium, Creatine kinase (CK), 
Creatinine, Gamma-glutamyl-
transferase (GGT),  
high sensitivity CRP, Phosphate, Potassium, 
Sodium, Total Bilirubin, Total Protein, and 
Uric Acid at all timepoints specified in 
Section 1.3 Schedule of Activities. 
If the Total Bilirubin concentration is 
increased above 1.5 times the ULN, Direct 
and Indirect reacting Bilirubin should be 
differentiated. 
Triiodothyronine (T3), Thyroxine (T4), 
Thyroid-stimulating Hormone (TSH), RF, 
anti-CCP Antibodies. Follicle Stimulating 
Hormone (FSH) is only done at screening and 
only in participants who are reported post-
menopausal at screening. 
Urinalysis 
Macroscopic Panel for Blood, Protein, and 
WBC/Leukocytes will be performed at site 
and documented as source data. 
If dipstick measurement results are positive 
(abnormal), results will be captured in the 
CRF. Microscopic Panel must be assessed 
following an abnormal dipstick test with 
results captured in the CRF. 
Hepatitis markers/ HIV serology testing 
HBV Antibody, HCV Antibody, HIV 1/2 
p24 Immunoassay; confirmatory tests by 
Western Blot for HIV, HBV and HCV to be 
measured only in case study site/lab 

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personnel comes in contact with blood, 
tissue or bodily fluids of participants 
through contact with injection needle, cut, 
splash on mucous membrane or through skin 
damage.  
Lipid panel and glucose 
A lipid profile including Cholesterol, 
Glucose, High Density Lipoprotein (HDL), 
Low 
Density 
Lipoprotein 
(LDL) 
and 
Triglycerides will be measured from a fasting 
blood sample. 
Pregnancy Test and Assessment of Fertility 
Serum pregnancy test 
Urine pregnancy test 
Confirmatory serum pregnancy required in 
case of positive urine pregnancy test (see 
Section 8.4.5) 
 
Pregnancy testing 
All pre-menopausal women who are not surgically sterile will have pregnancy testing. 
Additional pregnancy testing might be performed if requested by local requirements. 
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 5.2). 
A serum β-hCG (human Chorionic Gonadotropin) test will be performed in all women at Visit 
1 (screening). All pre-menopausal women who are not surgically sterile at screening will have 
local urine pregnancy tests as indicated in Section 1.3 Schedule of Activities. 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 participant must be discontinued from the 
trial. Pregnancy testing results are kept in the source data documentation. 
As per Section 4.5, changes in safety assessments can be added as one of the risk mitigation 
procedures during public health emergency declared by local or regional authorities.  
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, if 
participants cannot visit the site to have serum pregnancy tests, urine pregnancy test kits may 
be used. Relevant participants can perform the urine pregnancy test at home and report the 
result to the site immediately. 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 
participant must be discontinued from the trial. It is important that participants are instructed to 
perform the urine pregnancy test first and only if the test result is negative proceed with the 
administration of the study treatment. A communication process should be established with the 
participant so that the site is informed and can verify the pregnancy test results.  

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Assessments of Fertility 
Refer to Section 5.2 point 29 for criteria to determine women that are not of child bearing 
potential. 
A woman is considered of childbearing potential from menarche and until becoming post 
menopausal unless permanently sterile. Permanent sterilization methods include hysterectomy, 
bilateral salpingectomy and bilateral oophorectomy. Medical documentation of oophorectomy, 
hysterectomy, or tubal ligation must be retained as source documents. 
A postmenopausal state is defined as no menses for 12 months without an alternative medical 
cause and an appropriate clinical profile. 
In absence of the medical documentation confirming permanent sterilization, or if the post-
menopausal status is not clear, the investigator should use his medical judgment to appropriately 
evaluate the fertility state of the woman and document it in the source document. 
 
Other safety evaluations 
 
8.4.6.1 
Tuberculosis screening 
A central laboratory immunological test (QuantiFERON TB-Gold) must be performed at the 
screening visit to screen the participant population for latent TB infection. The results must be 
known prior to Baseline to determine the participant’s eligibility for the study.  
Participants with a positive test may participate in the study if further work up (according to 
local practice/guidelines) establishes conclusively that  
• the participant has no evidence of active TB 
• if presence of latent TB is established then treatment according to local country guidelines 
must have been initiated. 
Central laboratory test for Tuberculosis screening 
The 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. 
8.4.6.2 
Assessment of anti-CCP antibodies and the rheumatoid factor  
Blood (20 mL) will be obtained at the Screening Visit (Visit 1) for anti-CCP antibodies and RF 
assessment. 
 
Appropriateness of safety measurements 
The safety measures used in this study are standard measures for assessing the safety of a 
biological drug in participants with Rotator Cuff Tendinopathy.  

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8.5 
Additional assessments 
 
Clinical Outcome Assessments (COAs) 
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, COA 
data may be collected remotely (e.g., web portal, telephone interviews) depending on local 
regulations, technical capabilities, and following any applicable training in the required process. 
Clinician reported outcomes (ClinRO) 
The impact of secukinumab 300 mg s.c. on improving signs and symptoms in participants with 
rotator cuff tendinopathy will be assessed by the following ClinRO measures: 
• Range of Movement (ROM) 
Passive and active ROM of the shoulders will be assessed by the investigator at timepoints 
defined in Section 1.3 Schedule of Activities. The ROM assessment will only be done once 
per visit. The results will be recorded in the eCRF. 
The ROM assessment will be done in both arms using a goniometer and includes abduction, 
forward flexion, extension, and internal/external rotation. Additionally, the “Painful Arc 
Test”, the Apley scratch test and the full/empty cup test will be performed: 
- “Painful Arc Test”: The patient expresses pain with movements between 60-120°. Test 
result is given as negative or positive. To be noted both for active and passive ROM. 
- Full/empty cup test: The arm is abducted to 90 degrees, 30 degrees flexion, in the plane 
of the scapula and full internal rotation (empty can) and full external rotation (full can), 
elbow extended. The patient resists downward pressure exerted by the examiner at 
patient´s elbow or wrist. Test result is given as negative or positive. 
- Apley scratch test: With the patient seated, the patient places the hand behind the head 
to touch superior angle of opposite scapula, and the patient places the hand of the 
affected shoulder behind back to touch the inferior angle of opposite scapula. Test result 
is given as negative or positive. The test is done first on the non-affected shoulder, then 
on the affected shoulder. To be done both for active and passive ROM.  
• Shoulder/arm muscle strength 
Shoulder muscle strength will be tested with a handheld dynamometer. For all movements, 
the hand-held device should be applied in a direction perpendicular to the force being 
generated. Each test will be done once per assessment and last for 5s. The results will be 
recorded in the eCRF (in Newtons). The strength tests of the shoulder include adduction, 
abduction in the scapular plane, and internal/external rotation. 
The rotator cuff functional index will be calculated by Novartis using the muscle strength 
measurements as described by (Osbahr, et al., 2006). 
Detailed instructions to assess ClinRO are outlined in the ClinRO manual. 

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Patient reported outcomes (PRO) 
The participant must be given the PRO measure(s) to be completed at the scheduled visit before 
any clinical assessments are conducted. Participant’s refusal to complete all or any part of a 
PRO measure should be documented in the study data capture system and should not be 
captured as a protocol deviation. Handling of protocol deviations can be modified if needed per 
study protocol. 
Participant questionnaires are completed in German language.  
The participant should be given sufficient space and time to complete the self-administered 
PRO measure(s). Trained study-site personnel has to be available for assistance.  
The site personnel should check PRO measure(s) for completeness and ask the participant to 
complete any missing responses. The responses stored electronically in the database will be 
considered the source file. Paper-based PROs can be used as backup if electronic data capture 
is temporarily not available. 
Completed measure(s) must be reviewed and assessed by the Investigator for responses which 
may indicate potential AEs or SAEs before any clinical study examinations. This assessment 
should be documented in study source records. If AEs or SAEs are confirmed, Investigators 
should not encourage the participant to change responses reported in the completed 
questionnaires. Investigators must follow reporting instructions outlined in Section 8.6 of the 
study protocol. 
The impact of secukinumab 300 mg s.c. on improving signs and symptoms in participants with 
rotator cuff tendinopathy will be assessed by PRO measures listed in Section 8.3.1 and 
additionally: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
8.6 
Adverse events (AEs), serious adverse events (SAEs), and other 
safety reporting 
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative). 

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The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up all AEs, considered related to the study treatment or study procedures, or that caused the 
participant to discontinue the study treatment (see Section 7). 
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 8.6.3. 
 
Adverse events 
An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical 
investigation participant after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product. 
The Investigator has the responsibility for managing the safety of individual participant and 
identifying adverse events. 
Novartis qualified medical personnel will be readily available to advise on trial-related medical 
questions or problems. 
The occurrence of adverse events must be sought by non-directive questioning of the participant 
at each visit during the study. Adverse events also may be detected when they are volunteered 
by the participant during or between visits or through physical examination finding, laboratory 
test finding, or other assessments (e.g., patient reported outcomes as described in Section 8.5.1). 
Adverse events must be recorded under the signs, symptoms or diagnosis associated with them, 
and accompanied by the following information (as far as possible) (if the event is serious refer 
to Section 8.6.2): 
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. If the event is due to lack of efficacy or progression 
of underlying illness (i.e., progression of the study indication) the assessment of causality 
will usually be ‘Not suspected.’ The rationale for this guidance is that the symptoms of a 
lack of efficacy or progression of underlying illness are not caused by the trial drug, they 
happen in spite of its administration and/or both lack of efficacy and progression of 
underlying disease can only be evaluated meaningfully by an analysis of cohorts, not on a 
single participant. 
3. Its duration (start and end dates or ongoing) and the outcome must be reported. 
4. Whether it constitutes a SAE (see Section 8.6.2 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:  
• Dose not changed 
• Dose reduced/increased 
• Drug interrupted/permanently discontinued 
6. Its outcome (not recovered/not resolved; recovered/resolved; recovering/resolving, 
recovered/resolved with sequelae; fatal; or unknown). 
Conditions that were already present at the time of informed consent should be recorded in the 
medical history of the participant. 
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms. 
Adverse event monitoring should be continued for at least 84 days after the participant has taken 
the last dose of study treatment. 
Once an adverse event is detected, it must be followed until its resolution or until it is judged to 
be not recovered/not resolved (e.g. continuing at the end of the study), and assessment must be 
made at each visit (or more frequently, if necessary) of any changes in severity, the suspected 
relationship to the interventions required to treat it, and the outcome. 
Information about common side effects already known about the investigational drug can be 
found in the IB. Any new information regarding the safety profile of the medicinal product that 
is identified between IB updates will be communicated as appropriate, for example, via an 
investigator notification (IN) or an aggregate safety finding. New information might require an 
update to the informed consent and has then to be discussed with the participant.  
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 participants with underlying 
disease. Investigators have the responsibility for managing the safety of individual participant 
and identifying adverse events. Clinically notable laboratory values and vital signs are defined 
in Appendix 3: Clinical laboratory tests. 
The Investigator must also instruct each participant to report any new adverse event (beyond 
the protocol observation period) that the participant, or the participant’s personal physician, 
believes might reasonably be related to study treatment. This information must be recorded in 
the eCRF; however, if the AE meets the criteria of an SAE, it must be reported to Novartis. 

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Serious adverse events 
An SAE is defined as any adverse event (appearance of (or worsening of any pre-existing) 
undesirable sign(s), symptom(s) or medical conditions(s)) which meets any one of the following 
criteria: 
• fatal 
• life-threatening 
Life-threatening in the context of a SAE refers to a reaction in which the participant was at risk 
of death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to ICH-E2D Guideline 2004 (EMA, 2004)). 
• results in persistent or significant disability/incapacity 
• constitutes a congenital anomaly/birth defect, fetal death or a congenital abnormality or 
birth defect 
• requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for: 
- routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition  
- elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent 
- social reasons and respite care in the absence of any deterioration in the participant’s 
general condition 
- 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  
• is medically significant, e.g., defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above 
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life-threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant.” Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do 
not result in hospitalization or development of dependency or abuse (please refer to ICH-E2D 
Guideline 2004 (EMA, 2004)). 
All new malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met and the malignant neoplasm is not a disease progression of the 
study indication. 
Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
All reports of intentional misuse and abuse of the product are also considered serious adverse 
events irrespective if a clinical event has occurred. 

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Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction. 
 
SAE reporting 
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
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 safety immediately, without 
undue delay, but under no circumstances later than within 24 hours of obtaining knowledge of 
the events (Note: If more stringent, local regulations regarding reporting timelines prevail). 
Detailed instructions regarding the submission process and requirements are to be found in the 
Investigator folder provided to each site. Information about all SAEs is collected and recorded 
on the Serious Adverse Event Report Form in English; all applicable sections of the form must 
be completed in order to provide a clinically thorough report.  
Screen failures & Run-in failures 
SAEs occurring after the participant has provided informed consent until the time the participant 
is deemed a Screen Failure must be reported to Novartis.  
For participants considered Run-in Failures, SAEs occurring after the participant has provided 
informed consent until the time the participant is deemed a Run-in Failure must be reported to 
Novartis. 
Randomized participants 
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
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 safety immediately, without 
undue delay, under no circumstances later than 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 
participant 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 CMO & PS Department 

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associate may urgently require further information from the investigator for health authority 
reporting. Novartis may need to issue an Investigator Notification (IN) to inform all 
investigators involved in any study with the same study treatment that this SAE has been 
reported.  
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with European (EU 
Guidance 2011/C 172/01 or as per national regulatory requirements in participating countries. 
Any SAEs experienced after the last day of study (which is 12 weeks after last administration 
of study treatment) should only be reported to Novartis Safety if the Investigator suspects a 
causal relationship to study treatment, unless otherwise specified by local law/regulations. 
Reporting of Suspected Hy’s Law cases 
Treatment-emergent elevations in AST or ALT (>3x ULN) in combination with total 
bilirubin >2x ULN or jaundice in the absence of cholestasis (defined as ALP < 2 ULN) or other 
causes of hyperbilirubinemia can be an indicator of severe drug induced liver injury (Hy’s Law). 
For this reason, a potential Hy’s Law case requires expedited reporting, and will be handled as 
a serious adverse event (assessing it as medically significant in the absence of any other 
seriousness criteria). It must be reported as an SAE to the sponsor promptly (i.e., even before 
all other possible causes of liver injury have been excluded). Reporting should include all 
available information, especially that needed for evaluating the diagnosis, severity and 
likelihood that the study treatment caused the reaction. For patient monitoring and to better 
understand potential etiologies, the investigator must initiate a close follow-up until complete 
resolution of the problem and completion of all attempts to obtain supplementary data. The 
Hy’s Law criteria may be changed to increases of 2-fold above baseline values for subjects with 
elevated values before drug exposure. 
 
 
Pregnancy 
For all pre-menopausal women who are not surgically sterile: 
• A serum β-hCG test will be performed in all women at Visit 1 (screening). All pre-
menopausal women who are not surgically sterile at screening will have local urine 
pregnancy tests as indicated in Section 1.3 Schedule of Activities. 
• 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 participant must be 
discontinued from the trial. While pregnancy itself is not considered to be an AE or SAE, 
any pregnancy complication or elective termination of a pregnancy for medical reasons 
will be reported as an AE or SAE. 
• Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs and will be reported as 
such. 
• Any post study pregnancy-related SAE considered reasonably related to the study 
treatment by the Investigator will be reported to Novartis as described in Section 8.6.3. 

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While the Investigator is not obligated to actively seek this information in former study 
participants, he or she may learn of an SAE through spontaneous reporting. 
If a female trial participant becomes pregnant, the study treatment should be stopped, and the 
pregnancy consent form should be presented to the trial participant. The participant must be 
given adequate time to read, review and sign the pregnancy consent form. This consent form is 
necessary to allow the Investigator to collect and report information regarding the pregnancy. 
To ensure participant safety, each pregnancy occurring after signing the informed consent must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should 
be followed up to determine outcome, including spontaneous or voluntary termination, details 
of the birth, and the presence or absence of any birth defects, congenital abnormalities, or 
maternal and/or newborn complications. 
Pregnancy should be recorded and reported by the Investigator to the Novartis CMO&PS. 
Pregnancy follow-up should be recorded on the same form and should include an assessment 
of the possible relationship to the study treatment. Any SAE experienced during pregnancy 
must be reported. 
If a female partner of a male trial participant who took study treatment in this study becomes 
pregnant, pregnancy outcomes should be collected. Consent to report information regarding 
these pregnancy outcomes should be obtained from the mother. 
After consent is provided, the pregnancy reporting will occur up to one year after the estimated 
date of delivery. 
 
Surgeries 
Participants with rotator cuff tendinopathy could require surgery due to symptom worsening or 
progressions of tears. Unblinding should precede surgery. It is recommended to follow the 
DGRh guidance and schedule a surgery 4 weeks after the last secukinumab application. 
Emergency surgeries can take place at any time (Albrecht, et al., 2021).  
 
Adverse events of special interest  
There are no adverse events of special interest. 
8.7 
Pharmacokinetics  
PK parameters are not evaluated in this study. 
8.8 
Biomarkers  
Biomarkers are not evaluated in this study. 
8.9 
Immunogenicity assessments 
Immunogenicity is not evaluated in this study. 

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8.10 
Reporting of study treatment errors, study treatment 
misuse/abuse and overdose 
 
Study treatment errors are unintentional errors in the prescribing, dispensing, and administration 
of study treatment. 
Study treatment misuse refers to situations where the study treatment is intentionally and 
inappropriately used not in accordance with the protocol. 
Study treatment abuse corresponds to the persistent or sporadic, intentional excessive use of 
study treatment, which is accompanied by harmful physical or psychological effects. 
Study treatment errors and uses outside of what is foreseen in the protocol, including misuse or 
abuse, must be reported on the AE (or SAE, if the event meets the definition of an SAE) CRF. 
 
 
9 
Statistical considerations 
The analysis will be conducted on all participant data after database lock for the study. The data 
will be analyzed by Novartis and/or by the designated Contract Research Organization (CRO). 
Any data analysis carried out independently by the investigator should be submitted to Novartis 
before publication or presentation. 
9.1 
Analysis sets 
The Full Analysis Set (FAS) comprises all participants to whom study treatment has been 
assigned by randomization. According to the intent to treat principle, participants will be 
analyzed according to the treatment they have been assigned to during the randomization 
procedure. 
The Safety Set includes all participants who received at least one dose of study/reference 
treatment. Participants will be analyzed according to the study treatment received, where 
treatment received is defined as the randomized/assigned treatment if the participant took at 
least one dose of that treatment or the first treatment received if the randomized/assigned 
treatment was never received. 
9.2 
Statistical analysis 
 
Due to early termination of Secukinumab Phase 3 trials in RCT (Rotator Cuff Tendinopathy) 
screening has been discontinued on 17-MAY-2024. Patients that have been screened until 17-
MAY-2024 can be randomized and all randomized patients can complete the study. A number 
of 63 patients have been randomized, which would lead to 31/32 patients per arm. The resulting 
power under previous assumptions will be ca. 24%. Therefore only a descriptive analysis will 
be performed for all endpoints. 

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Participant demographics and other Baseline characteristics 
Demographic and other Baseline data including disease characteristics will be listed and 
summarized descriptively by treatment group and in total for the FAS and Safety set. 
Categorical data will be presented as frequencies and percentages. For continuous data, mean, 
SD, median, minimum, and maximum will be presented.  
Relevant medical history and current medical conditions at Baseline will be summarized by 
system organ class (SOC), preferred term (PT) and treatment group. 
 
Treatments 
The Safety set will be used for the analyses below. Categorical data will be summarized as 
frequencies and percentages. For continuous data, mean, SD, median, minimum, and maximum 
will be presented. 
The duration of exposure in weeks to secukinumab 300 mg s.c. vs. placebo will be summarized 
by means of descriptive statistics using the safety set. 
Concomitant medications and significant non-drug therapies prior to and after the start of the 
study treatment will be summarized according to the Anatomical Therapeutic Chemical (ATC) 
classification system, by treatment group. 
9.3 
Primary endpoint(s)/ estimand(s) analysis 
The primary objective of this trial is to demonstrate that the efficacy of 12 weeks of treatment 
with secukinumab 300 mg s.c. is superior to placebo (both arms in combination with patient 
individualized conventional therapy), in participants with moderate to severe rotator cuff 
tendinopathy, based on change from Baseline in WORC score at week 24. 
 
Definition of primary endpoint(s) 
WORC (Wessel, et al., 2011) 
The Western Ontario Rotator Cuff Index is a self - reported shoulder- specific QoL measure. 
The WORC Index consists of 21 items grouped in five domains: Physical symptoms (items 1-
6), sports/recreation (items 7-10), work (items 11-14), lifestyle (items 15-18), emotions (items 
19-21). 
The impact of each item is rated on a visual analogue scale (0-100 mm). A score of 0 points 
indicates no impact on QoL, while a score of 100 points indicates the worst-case scenario. Thus, 
it is possible to score from 0 to 2100 points. To present the score in a more clinically meaningful 
format, the score is reported as a percentage of normal by subtracting the total score from 2100, 
dividing by 2100, and multiplying by 100. Total final WORC scores can, therefore, vary from 
0%, the lowest functional status level, to 100%, the highest functional status level. 
Please refer to Section 3.1.  

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Statistical model, hypothesis, and method of analysis 
The alternative hypothesis is that the effect of secukinumab 300 mg s.c. is superior to placebo, 
in patients with moderate to severe rotator cuff tendinopathy, based on change from Baseline 
in WORC score at week 24. The complementary null hypothesis states that there is no difference 
between secukinumab 300 mg s.c. and placebo.  
The primary endpoint (change from Baseline in WORC score at Week 24) will be analyzed by 
a mixed model for repeated measures (MMRM) including all WORC scores available. 
Between-treatment differences in the change from Baseline in WORC score will be evaluated 
using MMRM with treatment group and analysis visits (up to week 24) as factors, and Baseline 
WORC score as continuous covariate. Treatment group by analysis visit will be included in the 
model. An unstructured covariance matrix will be assumed. Least-square mean differences with 
corresponding confidence intervals and p-values will be calculated for each visit time point as 
estimates for the treatment effect. 
 
Handling of intercurrent events of primary estimand 
For the analysis of the primary endpoint, all patients of the FAS will be included. A patient with 
missing assessment will be analyzed by means of a mixed-effect model for repeated measures 
(MMRM), which is valid under the missing at random (MAR) assumption.  
 
Handling of missing values not related to intercurrent event 
The primary endpoint will be analyzed by means of a mixed-effect model for repeated measures 
(MMRM), which is valid under the missing at random (MAR) assumption. Missing data for 
continuous efficacy endpoints due to missed or skipped visits will therefore not be applicable 
to multiple imputation. 
 
Sensitivity analyses 
In case of a substantial amount of missing data, alternative analyses not relying on the MAR 
assumption (e.g. Retrieved Drop-Out, Jump to Reference, Copy Reference) may be considered. 
 
Supplementary analysis 
Supportive analyses to be conducted are primarily related to investigating possible subgroup-
by treatment interaction effects for the following subgroups: 
• Age (≤50 vs. >50) 
• Gender (male vs. female) 
• Concomitant medication (GC infiltration vs. no GC infiltration required) 
9.4 
Secondary endpoint(s)/estimand(s) analysis 
Please refer to Section 3.1.  

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Efficacy endpoint(s) 
Secondary outcomes will be analyzed analogously to the primary endpoint where appropriate, 
e.g. continuous endpoint variables will be evaluated like the primary endpoint using a MMRM, 
with treatment group and analysis visits as factors and each respective baseline score value of 
the endpoint variable as a covariate. Treatment group by analysis visit will be included as 
interaction term in the model. An unstructured covariance matrix will be assumed.  Additionally, 
means standard deviations, median, minimum and maximum values for continuous variables 
will be presented for each visit, as will be the change from baseline. These descriptive statistics 
will also be presented for the primary endpoint. 
 
Safety endpoints 
For all safety analyses, the safety set will be used. All listings and tables will be presented by 
treatment group. 
Safety summaries (tables, figures) include only data from the on-treatment period with the 
exception of Baseline data which will also be summarized where appropriate (e.g., change from 
Baseline summaries). In addition, a separate summary for death including on treatment and post 
treatment deaths will be provided. In particular, summary tables for adverse events (AEs) will 
summarize only on-treatment events, with a start date during the on-treatment period 
(treatment-emergent AEs). 
Adverse events 
All information obtained on adverse events will be displayed by treatment group and 
participant. 
The number (and percentage) of participants with treatment emergent adverse events (events 
that started after the first dose of study medication or events present prior to start of double-
blind treatment but increased in severity based on preferred term) will be summarized in the 
following way: 
• by treatment, primary system organ class and preferred term. 
Separate summaries will be provided for study medication related adverse events, death, serious 
adverse events, other significant adverse events leading to discontinuation, and adverse events 
leading to dose adjustment. 
A participant with multiple adverse events within a primary system organ class is only counted 
once towards the total of the primary system organ class. 
Vital signs 
All vital signs data will be listed by treatment group, patient, and visit/time, and if ranges are 
available, abnormalities will be flagged. Analysis of the vital sign measurements using 
summary statistics for the change from Baseline for each post-Baseline visit will be performed. 
These descriptive summaries will be presented by vital sign and treatment group. Change from 
Baseline will only be summarized for patients with both, Baseline and post-Baseline values.  

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Clinical laboratory evaluations 
All laboratory data will be listed by treatment group, patient, and visit/time, and if ranges are 
available, abnormalities will be flagged. Summary statistics will be provided by treatment and 
visit/time. 
 
Patient reported outcomes 
See Section 9.3 for PRO related to primary objective and Section 9.4 for PROs related to 
secondary objectives. 
 
 
 
  
 
 
9.6 
Interim analysis 
Not applicable. 
9.7 
Sample size determination 
Although the primary endpoint is designed for simple superiority trial, there is a need to make 
stronger assumptions for sample size due to AMNOG requirements. 
Considering the regulatory assumptions of AMNOG (IQWiG: Institut für Qualität und 
Wirtschaftlichkeit im Gesundheitswesen, 2022), the measure of effect size is defined by 
Hedges´ g with the given formula:  
𝐻𝑒𝑑𝑔𝑒𝑠´𝑔= 𝜇1 −𝜇2
𝜎
, 
with 𝜇1 denoting the mean of the secukinumab arm, 𝜇2 denoting the mean of the placebo arm 
and 𝜎 denoting the pooled standard deviation.  
For AMNOG assumption Hedges´g should be significant for a small effect (i. e. >0.2), which 
corresponds to a shifted null hypothesis: 
𝐻0: 𝜇1 −𝜇2 ≤0.2 ∙𝜎 and  
𝐻1: 𝜇1 −𝜇2 > 0.2 ∙𝜎. 
To demonstrate superiority of secukinumab compared with placebo with a 90% power on a 
two-sided, 5% significance level with a shifted null hypothesis, the following assumptions were 
applied: The expected mean in WORC score in the secukinumab arm is 53.3, the observed mean 
in the placebo arm observed in phase II study CAIN457X2201) was 35.9. Due to concomitant 
therapy, we expect the effect in WORC score in the placebo arm to be 40. Assuming the 
common standard deviation 𝜎= 25 as observed in phase II study and using the superiority test 
we obtain a shifted null hypothesis: 
𝐻0: 𝜇1 −𝜇2 ≤5 
and  
𝐻1: 𝜇1 −𝜇2 > 5. 

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Under these assumptions, we obtain a difference in means of 8.3 after considering the shifted 
null hypothesis. This would give us a sample size of 192 participants in each group. To 
compensate for some expected drop-outs and other protocol deviations, a total of 430 patients 
should be recruited into this trial. 
10 
Supporting documentation and operational considerations 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
 
Regulatory and ethical considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
international ethical guidelines 
• Applicable ICH Good Clinical Practice (GCP) guidelines 
• Applicable laws and regulations 
The protocol, protocol amendments, ICF, IB and other relevant documents (e.g. advertisements) 
must be submitted to an IRB/IEC/HA and reviewed and approved by the IRB/IEC/HA before 
the study is initiated. 
Any amendments to the protocol will require IRB/IEC/HA approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.  
Protocols and any substantial amendments/modifications to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an immediate 
hazard to study participants. 
The Investigator will be responsible for the following: 
Signing 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 
Providing oversight of the conduct of the study at the site and adherence to requirements of 21 
CFR, ICH guidelines, the IRB/IEC, EU regulation 536/2014 for clinical studies (if applicable), 
EU Medical Device Regulation 2017/745 for clinical device research (if applicable), and all 
other applicable local regulations. 
Inform Novartis immediately if an inspection of the clinical site is requested by a regulatory 
authority 

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This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for GCP, with applicable local regulations 
(including EU Directive 2001/20/EC or EU Clinical Trial Regulation 536/2014, US CFR 21), 
and with the ethical principles laid down in the Declaration of Helsinki. 
 
Informed consent procedures 
The Investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the participant and answer all questions regarding the study. 
Participants must be informed that their participation is voluntary. Participants will be required 
to sign a statement of informed consent that meets the requirements of 21 CFR 50, local 
regulations, ICH guidelines, privacy and data protection requirements, where applicable, and 
the IRB/IEC or study center. 
Informed consent must be obtained before conducting any study-specific procedures (e.g., all 
of the procedures described in the protocol). The process of obtaining informed consent must 
be documented in the participant source documents.  
The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF. 
A copy of the ICF(s) must be provided to the participant. 
Eligible participants may only be included in the study after providing written (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent.  
Information about common side effects already known about the investigational treatment can 
be found in the IB. This information will be included in the participant informed consent and 
should be discussed with the participant upon obtaining consent and also 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 participant. 
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e. pandemic, epidemic or natural disaster, that may challenge the ability to obtain a standard 
written informed consent due to limits that prevent an on-site visit, Investigator may conduct 
the informed consent discussion remotely (e.g. telephone, videoconference) if allowable by a 
local health authority. 
Guidance issued by local regulatory bodies on this aspect prevails and must be implemented 
and appropriately documented (e.g. the presence of an impartial witness, sign/dating separate 
ICFs by trial participant and person obtaining informed consent, etc.). 

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Data protection 
Participants will be assigned a unique identifier by Novartis. Any participant records or datasets 
that are transferred to Novartis will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred. 
The participant must be informed that his/her personal study-related data will be used 
by Novartis in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent  
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by Novartis, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities. 
Novartis has appropriate processes and policies in place to handle personal data breaches 
according to applicable privacy laws. 
 
Committee structure 
10.1.4.1 Steering committee 
The Steering Committee (SC) will be established comprising investigators in the trial and 
Novartis/Sponsor representatives from the Clinical Trial Team. The SC will ensure transparent 
management of the study according to the protocol through recommending and approving 
modifications as circumstances require. The SC will review protocol amendments as 
appropriate. Together with the clinical trial team, the SC will also develop recommendations 
for publications of study results including authorship rules. The details of the role of the steering 
committee will be defined in the steering committee charter. 
 
Data quality assurance 
Monitoring details describing strategy, including definition of study critical data items and 
processes (e.g. risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan. 
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 25 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of Novartis. No records may be transferred to 
another location or party without written notification to Novartis. 
Data collection 
Designated Investigator staff will enter the data required by the protocol into the eCRF. The 
eCRFs have been built using fully validated secure web-enabled software that conforms to 21 
CFR Part 11 requirements, Investigator site staff will not be given access to the Electronic Data 

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Capture (EDC) system until they have been trained. Automatic validation programs check for 
data discrepancies in the eCRFs, allow modification and/or verification of the entered data by 
the Investigator staff before transfer of the data to the CRO working on behalf of Novartis. 
After database lock, the Investigator will receive copies of the participant data for archiving at 
the investigational site. 
The Investigator/designee is responsible for assuring that the data (entered into eCRF) is 
complete, accurate, and that entry and updates are performed in a timely manner. The 
Investigator must certify that the data entered are complete and accurate. 
After final database lock, the Investigator will receive copies of the participant data for 
archiving at the investigational site. 
All data should be recorded, handled and stored in a way that allows its accurate reporting, 
interpretation and verification. 
Database management and quality control 
Novartis personnel (or designated CRO) will review the data entered by investigational staff 
for completeness and accuracy. Electronic data queries stating the nature of the problem and 
requesting clarification will be created for discrepancies and missing values and sent to the 
investigational site via the EDC system. Designated Investigator site staff are required to 
respond promptly to queries and to make any necessary changes to the data. 
Concomitant treatments and prior medications entered into the database will be coded using the 
World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions and 
adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology. 
Dates of screenings, randomizations, screen failures and study completion, as well as 
randomization codes and data about all study treatment(s) dispensed to the participant and all 
dosage changes will be tracked using an Interactive Response Technology (IRT). The system 
will be supplied by a vendor, who will also manage the database. The data will be sent 
electronically to Novartis (or a designated CRO) at specific timelines. 
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. The 
code break functionality will remain available until study shut down or upon request of 
Novartis. 
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked, and the treatment codes will be unblinded and made 
available for data analysis/moved to restricted area to be accessed by independent programmer 
and statistician. Any changes to the database after that time can only be made after written 
agreement by Novartis development management. 
 
Source documents 
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site. 

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Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available. 
The Investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. The Investigator must also keep the original 
ICF signed by the participant (a signed copy is given to the participant). Definition of what 
constitutes source data and its origin can be found in the source data agreement form.  
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. Study monitors will perform ongoing source data verification 
to confirm that data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently approved 
protocol and any other study agreements, ICH GCP, and all applicable regulatory requirements. 
Key study personnel must be available to assist the field monitor during these visits. Continuous 
remote monitoring of each site’s data may be performed by Novartis or a CRO/ working on 
behalf of Novartis. Additionally, a central analytics organization may analyze data & identify 
risks & trends for site operational parameters and provide reports to Novartis clinical teams to 
assist with trial oversight. 
 
Publication policy 
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required in EudraCT or CTIS public website. In addition, after study completion (defined as 
last participant last visit) and finalization of the study report the results of this trial will be 
submitted for publication and posted in a publicly accessible database of clinical trial results, 
such as the Novartis clinical trial results website and all required health authority websites (e.g., 
clinicaltrials.gov, EudraCT or CTIS public website, etc.). 
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the trial Investigator 
meetings. 
Any data analysis carried out independently by the Investigator should be submitted to Novartis 
before publication or presentation. 
 
Protocol adherence and protocol amendments 
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of participants should be 
administered as deemed necessary on a case-by-case basis. Under no circumstances including 
incidental collection is an Investigator allowed to collect additional data or conduct any 
additional procedures for any purpose including any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the Investigator shall immediately disclose it to 

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Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants. 
Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
Investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and HA, where required, it cannot be implemented.  
Protocol amendments 
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, HA where required, and the IRB/IEC prior to implementation.  
Only amendments that are required for participant safety may be implemented immediately 
provided the HA are subsequently notified by protocol amendment and the reviewing IRB/IEC 
is notified.  
Notwithstanding the need for approval of formal protocol amendments, the Investigator is 
expected to take any immediate action required for the safety of any participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations. 
10.2 
Appendix 2: Abbreviations and definitions 
 
List of abbreviations 
AAOS 
American Academy of Orthopaedical Surgeons 
AE 
Adverse Event 
AESI 
Adverse Events of Special Interest 
ALT 
Alanine Aminotransferase 
anti-CCP 
Anti-Cyclic Citrullinated Peptide  
AP 
Anterior-Posterior 
AS 
Ankylosing Spondylitis 
AST 
Aspartate Aminotransferase 
axSpA 
Axial Spondyloarthritis 
BSA 
Body Surface Area 
BUN 
Blood Urea Nitrogen 
CK 
Creatine Kinase 
CMO & PS 
Chief Medical Office & Patient Safety 
CRP 
C-reactive protein 

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COA 
Clinical Outcome Assessments 
CRF 
Case Report/Record Form (paper or electronic) 
CRO 
Contract Research Organization 
CSR 
Clinical Study Report 
CT 
Computer Tomography 
CTT 
Clinical Trial Team 
ECG 
Electrocardiogram 
eCRF 
electronic Case Report Form 
EDC 
Electronic Data Capture 
EoS 
End of Study 
EoT 
End of Treatment 
eSource 
electronic Source 
EQ-5D-5L 
EuroQol-5D 
EU 
European Union 
FDA 
Food and Drug Administration 
FSH 
Follicle Stimulating Hormone 
g 
Gramm 
GCP 
Good Clinical Practice 
GCS 
Global Clinical Supply 
GGT 
Gamma-Glutamyl Transferase 
h 
Hour 
HA 
Health Authorities 
HAQ-DI 
Health Assessment Questionnaire Disability Index 
hCG 
human Chorionic Gonadotropin 
HDL 
High Density Lipoprotein 
HIV 
Human Immunodeficiency Virus 
HTA 
Health Technology Assessment 
i.v. 
Intravenous 
IB 
Investigator’s Brochure 
ICF 
Informed Consent Form 

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ICH 
International Council for Harmonization of Technical Requirements for 
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 
L 
Liter 
LDL 
Low Density Lipoprotein 
LLN 
Lower Limit of Normal 
MedDRA 
Medical Dictionary for Regulatory Activities 
µL 
micro Liter 
µSv 
micro Sievert 
MID 
Minimal Important Difference 
mL 
milli Liter 
mSv 
milli Sievert 
MMRM 
Mixed Model for Repeated Measures 
MRI 
Magnetic Resonance Imaging 
NRS 
Numeric Rating Scale 
NSAIDs 
Non-Steroidal Anti-Inflammatory Drugs 
PASI 
Psoriasis Area and Severity Index 
PFS 
Pre-Filled Syringe 
PaGA 
Patient Global Assessment 
PK 
Pharmacokinetic(s) 
PMR 
Polymyalgia Rheumatica 
PRO 
Patient Reported Outcome 
PRP 
Platelet Rich Plasma 
PsA 
Psoriatic Arthritis 
PT  
Preferred Term 

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QoL 
Quality of Life 
QuickDASH 
Change in Disability of Arm, Shoulder and Hand Questionnaire 
RA 
Rheumatoid Arthritis 
RBC 
Red Blood Cell 
RDO 
Retrieved drop out 
RF 
Rheumatoid Factor  
RNA 
Ribonucleic Acid 
ROM 
Range-Of-Movement 
s.c. 
Subcutaneous 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Steering Committee 
SF-36 
Short Form 36 
SGOT 
Serum Glutamic Oxaloacetic Transaminase 
SGPT 
Serum Glutamic Pyruvic Transaminase 
SD 
Standard Deviation 
SoA 
Schedule of Activities 
SoC 
Standard of Care 
SpA 
Spondyloarthropathies 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TB 
Tuberculosis 
Tmax 
Time to maximum concentration 
TNF 
Tumor Necrosis Factor-α inhibitor 
TNF-IR 
Tumor Necrosis Factor-α inhibitor Incomplete Responders 
TSH 
Thyroid-Stimulating Hormone 
ULN 
Upper Limit of Normal 
VAS 
Visual Analog Scale 
WBC 
White Blood Cell 
WHO 
World Health Organization 
WORC 
Western Ontario Rotator Cuff (score) 

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Glossary of terms 
Assessment 
A procedure used to generate data required by the study. 
Clinical Outcome 
Assessment (COA) 
A measure that describes or reflects how a participant feels, 
functions, or survives. 
Clinical Trial Team 
A group of people responsible for the planning, execution and 
reporting of all clinical trial activities. Examples of team 
members include the Study Lead, Medical Monitor, Trial 
Statistician, etc. 
Coded Data 
Personal Data, which has been de-identified by the investigative 
center team by replacing personal identifiers with a code. 
Cohort 
A group of individuals who share a common exposure, 
experience or characteristic, or a group of individuals followed-
up or traced over time. 
Control drug 
A study intervention (active or placebo) used as a comparator to 
reduce assessment bias, preserve blinding of investigational drug, 
assess internal study validity, and/or evaluate comparative effects 
of the investigational drug 
Discontinuation from 
study 
Point/time when the participant permanently stops receiving the 
study treatment and further protocol required assessment or 
follow-up, for any reason. No specific request is made to stop the 
use of their samples or data. 
Discontinuation from 
study treatment 
Point/time when the participant permanently stops receiving the 
study treatment for any reason (prior to the planned completion 
of study intervention administration, if any). Participant agrees to 
the other protocol required assessments including follow-up. No 
specific request is made to stop the use of their samples or data. 
Dosage 
Dose of the study treatment given to the participant 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 source 
data/documents used at the point of care. 
End of the clinical trial 
The end of the clinical trial is defined as the last visit of the last 
participant as defined in the protocol. 

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Enrollment 
Point/time of participant entry into the study at which informed 
consent must be obtained. The action of enrolling one or more 
participants. 
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 Novartis and other oversight authorities, as 
appropriate. 
Estimand 
As defined in the ICH E9(R1) addendum, estimand is a precise 
description of the treatment effect reflecting the clinical question 
posed by the trial objective. It summarizes at a population-level 
what the outcomes would be in the same participants under 
different treatment conditions being compared. Attributes of an 
estimand include the population, variable (or endpoint) and 
treatment of interest, as well as the specification of how the 
remaining intercurrent events are addressed and population-level 
summary for the variable. 
Intercurrent events 
Events occurring after treatment initiation that affect either the 
interpretation or the existence of the measurements associated 
with the clinical question of interest. 
Investigational drug/ 
treatment 
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” 
Investigational Medical 
Device 
Medical Device being assessed for safety or performance in a 
clinical investigation. This includes devices already on the 
market and being evaluated for new intended uses, new 
populations, new materials, or design changes. 
Medication number 
A unique identifier on the label of medication kits 
Other treatment 
Treatment that may be needed/allowed during the conduct of the 
study (i.e., concomitant or rescue therapy). 
Participant 
A trial participant (can be a healthy volunteer or a patient). 
"Participant" terminology is used in the protocol whereas term 
"Subject" is used in data collection 

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Participant number 
A unique number assigned to each participant upon signing the 
informed consent. This number is the definitive, unique 
identifier for the participant and should be used to identify the 
participant throughout the study for all data collected, sample 
labels, etc. 
Patient-Reported Outcome 
(PRO) 
A measurement based on a report that comes directly from the 
participant about the status of a participant's health condition 
without amendment or interpretation of the participant's report 
by a clinician or anyone else. 
Personal data 
Participant information collected by the Investigator that is 
coded and transferred to Novartis for the purpose of the clinical 
trial. This data includes participant identifier information, study 
information and biological samples. 
Randomization 
The process of assigning trial participants to investigational 
drug or control/comparator drug using an element of chance to 
determine the assignments in order to reduce bias. 
Randomization number 
A unique identifier assigned to each randomized participant, 
corresponding to a specific treatment arm assignment 
Rescreening 
If a participant fails the initial screening and is considered as a 
Screen Failure, he/she can be invited once for a new Screening 
visit after medical judgment and as specified by the protocol. 
Run-in failure 
A participant who is screened but not randomized/treated after 
the Run-in period (where Run-in period requires adjustment to 
participant’s medications or other intervention). 
Screen failure 
A participant who did not meet one or more criteria that were 
required for participation in the study. 
Source Data/Document 
Source data refers to the initial record, document, or primary 
location from where data comes. The data source can be a 
database, a dataset, a spreadsheet or even hard-coded data, such 
as paper or eSource. 
Start of the clinical trial 
The start of the clinical trial is defined as the signature of the 
informed consent by the first participant 
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  
Treatment arm/group 
A treatment arm/group defines the dose and regimen or the 
combination and may consist of 1 or more cohorts. 
Treatment of interest 
The treatment of interest and, as appropriate, the alternative 
treatment to which comparison will be made. These might be 

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individual 
interventions, 
combinations 
of 
interventions 
administered concurrently, e.g., as add-on to SoC, or might 
consist of an overall regimen involving a complex sequence of 
interventions. This is the treatment of interest used in describing 
the related clinical question of interest, which might or might not 
be the same as the study treatment. 
Variable (or endpoint) 
The variable (or endpoint) to be obtained for each participant that 
is required to address the clinical question. The specification of 
the variable might include whether the participant experiences an 
intercurrent event. 
Withdrawal of consent 
Withdrawal of consent from the study occurs when the participant 
explicitly requests to stop use of their data and/or biological 
samples AND no longer wishes to receive study treatment, AND 
does not agree to further protocol required assessments. This 
request should be in writing (depending on local regulations) and 
recorded in the source documentation. 
This request should be distinguished from a request to 
discontinue the study. Other study participant's privacy rights are 
described in the corresponding ICF. 
10.3 
Appendix 3: Clinical laboratory tests 
 
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 10-1 
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 

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eGFR 
> 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 
 
eGFR is calculated using the following formula: 
eGFRcr = 141 x min(Scr/κ, 1)α x max(Scr/κ, 1)(-1.209) x 0.993Age x 1.018 [if female] x 1.159 [if 
race is black] 
where: 
Scr = standardized serum creatinine in mg/dL 
κ = 0.7 (females) or 0.9 (males) 
α = -0.329 (female) or -0.411 (male) 
min(Scr/κ, 1) is the minimum of Scr/κ or 1.0 
max(Scr/κ, 1) is the maximum of Scr/κ or 1.0 
Age (years) 
in accordance with Levey, A., S., et al. 2009. A New Equation to Estimate Glomerular Filtration 
Rate. Ann Intern Med. 2009, Vol. 150, 9, pp. 604-612. doi: 10.7326/0003-4819-150-9-
200905050-00006 
 
10.4 
Appendix 4: Participant Engagement 
Not applicable. 

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11 
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