A randomized, parallel-group, 24 week, double-blind, placebo-controlled, multicenter Phase 3 study to assess the efficacy and safety of secukinumab compared to placebo in adult patients with active rotator cuff tendinopathy

The primary objective of this study is to demonstrate that the efficacy of **secukinumab** 300 mg subcutaneously is superior to placebo in improving physical shoulder symptoms in participants with moderate to severe rotator cuff tendinopathy (RCT) at Week 16. This is clinically relevant as it aims to provide a more effective treatment option for patients suffering from significant shoulder pain and dysfunction due to RCT, potentially improving their quality of life and physical capabilities.

Secondary objectives include: - Demonstrating the superiority of secukinumab over placebo in achieving a clinically meaningful response in improving physical shoulder symptoms at Week 16. - Demonstrating the efficacy of secukinumab in improving symptoms caused by RCT and the associated impact on day-to-day functioning at Week 16. - Demonstrating the efficacy of secukinumab in improving physical function at Week 16. - Evaluating the ability of secukinumab to improve physical symptoms at Week 24. - Evaluating the pharmacokinetics of secukinumab in the population with moderate to severe RCT. - Evaluating the safety, immunogenicity, and tolerability of secukinumab in participants with moderate to severe RCT.

The clinical trial involves a total of **106 participants** diagnosed with **moderate to severe rotator cuff tendinopathy**. The study population includes both male and female subjects, with an age range of 18 to 65 years. Participants were selected based on specific criteria, including unilateral rotator cuff tendinopathy with a symptom duration of 6 weeks to 6 months, nocturnal shoulder pain, and a total WORC percentage score of 40 or less at screening and baseline visits. Additionally, participants must have an average weekly numerical rating scale pain score of 5 or higher and be refractory to standard care, including NSAIDs and physiotherapy. The trial population is required to maintain a stable NSAID and physiotherapy regimen throughout the study. The presence of tendinopathy in the affected shoulder must be confirmed via MRI, with no tear or a partial tear of up to 50% tendon thickness. The study does not exclude vulnerable populations, and lifestyle factors such as diet and physical activity are not specified as part of the selection criteria.

The clinical trial is designed as a **randomized**, parallel-group, double-blind, placebo-controlled, multicenter Phase 3 study. The primary objective is to assess the efficacy and safety of **secukinumab** compared to placebo in adult patients with moderate to severe **rotator cuff tendinopathy**. The trial is expected to last for 24 weeks, with participant involvement beginning from the screening visit and continuing through to the end-of-study visit. The trial will commence with a screening visit to confirm eligibility based on criteria such as symptom duration, pain assessment, and MRI findings. Participants will be randomly assigned to receive either secukinumab or placebo, with secukinumab administered subcutaneously at a dose of 300 mg. The primary endpoint is the change from baseline in the Western Ontario Rotator Cuff Index (WORC) Physical Symptom Domain score at Week 16. Secondary endpoints include various measures of improvement in WORC scores and safety assessments, including adverse events and laboratory parameters.

Study visits are scheduled at baseline, followed by regular follow-up visits at Weeks 4, 16, and 24. These visits are designed to monitor the efficacy and safety of the treatment, with assessments including the collection of secukinumab serum concentrations and evaluation of patient-reported outcomes. The end-of-study visit will occur at Week 24, marking the conclusion of the participant's involvement in the trial. Participants are expected to adhere to a stable regimen of NSAIDs and physiotherapy throughout the study, with any deviation potentially leading to early termination from the trial. Conditions that may lead to early termination include significant adverse events or non-compliance with the study protocol. The trial aims to demonstrate the superiority of secukinumab over placebo in improving physical shoulder symptoms, thereby providing valuable insights into the management of rotator cuff tendinopathy.

The clinical trial involves the administration of **Secukinumab**, a solution for injection in a pre-filled syringe. Secukinumab is administered subcutaneously at a dosage of 300 mg. The maximum daily dose is 300 mg, with a total maximum dose of 2100 mg over a treatment period of 12 weeks. The administration involves the use of a pre-filled syringe, which is not CE marked. The trial aims to demonstrate the efficacy of Secukinumab in improving physical shoulder symptoms in participants with moderate to severe rotator cuff tendinopathy.

In addition to the experimental treatment, a **placebo** is used as a comparator. The placebo is designed to mimic the Secukinumab 150 mg/1 mL solution for injection in a pre-filled syringe. The placebo is administered in the same manner as Secukinumab, subcutaneously, to maintain the double-blind nature of the study.

Auxiliary treatments include **Opioids**, which are administered orally. The maximum daily dose for opioids is 400 mg, with a total maximum dose of 67.2 g over a 24-week period. Another auxiliary treatment is **Other analgesics and antipyretics**, also administered orally, with a maximum daily dose of 3900 mg and a total maximum dose of 655.2 g over 24 weeks. Additionally, **Anti-inflammatory and antirheumatic products, non-steroids** are used, administered orally with a maximum daily dose of 3200 mg and a total maximum dose of 896 g over a 40-week period.

The efficacy of secukinumab in the treatment of active **rotator cuff tendinopathy** will be assessed through a randomized, double-blind, placebo-controlled, multicenter Phase 3 clinical trial. The primary endpoint for evaluating efficacy is the change from baseline in the Western Ontario Rotator Cuff Index (WORC) Physical Symptom Domain (PSD) score at Week 16. Secondary endpoints include the proportion of participants achieving an improvement of at least 40 points from baseline in the WORC PSD at Week 16, the proportion of participants receiving secukinumab compared to placebo who achieve an increase of 50 points in the WORC Total score at Week 16, and the change from baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) - Short Form (SF) Upper Extremity score at Week 16. Additional secondary endpoints include the proportion of participants achieving an improvement of at least 40 points from baseline in the WORC PSD at Week 24, and the change from baseline in WORC PSD at Week 24.

Secukinumab serum concentrations will be measured on Day 1 and at Weeks 4 and 16 to further assess efficacy. The safety and tolerability of secukinumab will also be evaluated by monitoring adverse events (AEs) and serious adverse events (SAEs), including their incidence, severity, and relationship with the study drug. Clinically significant changes in laboratory parameters and vital signs, as well as the incidence of binding and neutralizing anti-drug antibodies (ADAs) at Day 1 and Week 16, will be assessed. The trial is designed to demonstrate that secukinumab 300 mg subcutaneously is superior to placebo in improving physical shoulder symptoms in participants with moderate to severe rotator cuff tendinopathy at Week 16.