Study of Efficacy and Safety of AIN457/Secukinumab in Patients With Rotator Cuff Tendinopathy

Study Overview
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Brief Summary
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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 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.

Detailed Description
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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 initiated by a telephone visit 14 days prior to Randomization. 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).

Official Title
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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

Conditions
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Tendinopathy

Intervention / Treatment
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* Drug: secukinumab
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed informed consent must be obtained prior to participation in the study. Males and non-pregnant, non-nursing females between 18 and 65 years of age Rotator cuff tendinopathy (unilateral) with positive Painful Arc Test on examination Symptoms present for at least 6 weeks but not more than 6 months at Baseline Moderate to severe rotator cuff tendinopathy demonstrated by all of the following criteria: WORC score ≤ 40 at Baseline NRS pain score ≥ 5 at Baseline and at least 3 days of the past 7 days prior to Baseline Nocturnal pain at least 4 out of past 7 days in the week prior to Baseline 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 Exclusion Criteria: Greater than 50% partial thickness tear as established by MRI or ultrasound during assessment in Run-in phase Patients who are expected to require glucocorticoid treatment throughout the trial duration at Baseline (e.g., systemic, intramuscular, local injections in shoulder) Previous surgery, or plans for surgery, during the study period, in the affected shoulder 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 Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies positive at Screening History of adhesive capsulitis/frozen shoulder or calcification in the tendon (in affected or contralateral shoulder) confirmed clinically or by medical imaging Symptomatic osteoarthritis of the shoulder (glenohumeral, acromioclavicular) in affected or contralateral shoulder confirmed by medical imaging Patients with traumatic rupture that would be considered eligible for surgery for repair of cuff tear. Neurological conditions including but not limited to cervical radiculopathy, which in the opinion of the investigator may explain the patient's symptoms Any intra-articular/subacromial glucocorticoid treatment within 12 weeks prior to Baseline or more than 2 injections for the current tendinopathy. Any oral, intramuscular or i.v. glucocorticoid treatment 12 weeks prior to Baseline or during the current tendinopathy, whichever takes longer Previous platelet rich plasma (PRP) injections or fluoroquinolone/quinolone antibiotics within 12 weeks prior to Baseline or during the current tendinopathy, whichever takes longer Neuromuscular or primary/secondary muscular deficiency which limits the ability to perform functional measurement (e.g., shoulder strength test) Previous hyaluronic injections within 12 weeks prior to Baseline or during the current tendinopathy, whichever takes longer

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: secukinumab<br>AIN457 300 mg subcutaneously (s.c.) for 12 weeks | Drug: secukinumab<br>* AIN457 300 mg subcutaneously for 12 weeks<br>* Other names: AIN457;|
| Placebo Comparator: Placebo<br>Placebo subcutaneously for 12 weeks | Other: Placebo<br>* Placebo to match AIN457 subcutaneously for 12 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score at Week 14 in All Patients | WORC PRO score at week 24. The WORC Index consists of 21 items divided into 5 Domains: Physical Symptoms (6 items), Sport/Recreation (4 items), Work Function (4 items), Lifestyle Function (4 items) and Emotional Function (3 items). The total scores and sub scores used were the percentages of the normal scores with 0 being worst and 100 being best. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The Western Ontario Rotator Cuff (WORC) Patient Reported Outcome (PRO) Score in each subdomain | WORC PRO score at week 24. The WORC Index consists of 21 items divided into 5 Domains: Physical Symptoms (6 items), Sport/Recreation (4 items), Work Function (4 items), Lifestyle Function (4 items) and Emotional Function (3 items). The total scores and sub scores used were the percentages of the normal scores with 0 being worst and 100 being best. | Week 24 | 
| Patient Global Assessment (PaGA) Score | The patient's global assessment of disease activity is performed using a 100 mm Visual Analog Scale (VAS) ranging from no activity to most active in the last 24 hours. The scale range for PGA score is 0-100, 0 being the best possible outcome (no disease activity) and 100 being the worst possible outcome (maximal disease activity). | Week 24 | 
| Disease activity and quality of life for the Short Form 36 (SF-36v2) score | To assess the effect of secukinumab compared to placebo measured by disease activity and quality of life measures at Week 52 for Short form 36v2 Score range is from 0 to 100. Higher scores indicate better health status. | Week 24 | 
| Disability of Arm, Shoulder and Hand Questionnaire Score (QuickDASH) Over Time | Patient Reported Outcome: Disability of Arm, Shoulder and Hand (QuickDASH) This questionnaire asks about symptoms as well participant's ability to do certain activities - ranging from 1 (No difficulty) to 5 (Unable). The scale range for QuickDASH total score is 0-100, 0 being the best possible outcome and 100 being the worst possible outcome | Week 24 | 
| Pain Score Using a Numeric Rating Scale (NRS) | Pain intensity is assessed by a Numeric Rating Scale (NRS) which is measured in a scale of 11 points. The scale range for pain score is 0-10, 0 being the best possible outcome (no pain) and 10 being the worst possible outcome (worst pain). | Week 24 | 
| EQ-5D-5L Index Score | Patient Reported Outcome: Statistical analysis results of EQ-5D-5L Index score, which contains 5 items to assess Health Status (mobility, self-care, usual activity, pain/discomfort, and anxiety/depression). Overall scores range from 0 to 1 with lower scores representing a higher level of dysfunction. | Week 24 | 
| Number of participants with Adverse Events | Safety and tolerability assessments over time: incidence and severity of AEs and SAEs; routine safety laboratory parameters To evaluate safety and tolerability of secukinumab 300 mg s.c. in participants with moderate to severe rotator cuff tendinopathy. | Baseline up to Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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shoulder, rotator cuff, IL-17A-Ab, AIN457X, Impingement syndrome