A Phase 3 Randomized, Double‑Blind, Placebo‑Controlled Study of Secukinumab 300 mg Subcutaneous in Adults with Moderate to Severe 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 evidence for a more effective treatment option for patients suffering from significant shoulder pain and dysfunction due to RCT, potentially improving their quality of life and functional capacity.

Secondary objectives include:

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

The clinical trial involves a total of **153 participants** diagnosed with **moderate to severe rotator cuff tendinopathy**. The study population includes both male and female subjects, with an age range that corresponds to category code 3, typically representing adults. Participants were selected based on specific criteria, including the presence of unilateral rotator cuff tendinopathy with symptoms persisting for 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 must be refractory to standard care, including NSAIDs and physiotherapy. The trial population includes individuals with tendinopathy confirmed by MRI, without tears or with partial tears not exceeding 50% tendon thickness. Both genders are represented, and the study includes a vulnerable population. Lifestyle considerations such as maintaining a stable NSAID dosage and physiotherapy regimen are required throughout the trial duration.

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 an estimated end date of January 28, 2025. Participants will be involved in the study for the entire duration unless early termination criteria are met, such as adverse events or withdrawal of consent.

The sequence of study visits includes an initial **screening** visit to determine eligibility based on criteria such as symptom duration, pain assessment, and MRI findings. Participants must have unilateral rotator cuff tendinopathy with symptoms persisting for 6 weeks to 6 months, nocturnal shoulder pain, and a specific score on the Western Ontario Rotator Cuff Index (WORC). Following the screening, eligible participants will be randomized to receive either secukinumab or placebo. Subsequent visits will occur at regular intervals, including Day 1, Weeks 4, 16, and 24, to monitor efficacy and safety outcomes. The primary endpoint is the change from baseline in the WORC Physical Symptom Domain score at Week 16. Secondary endpoints include improvements in WORC scores and patient-reported outcomes, as well as safety assessments through adverse events and laboratory parameters.

The end-of-study visit will occur at Week 24, where final assessments will be conducted. Participants are expected to adhere to a stable regimen of NSAIDs and physiotherapy throughout the study. Conditions for early termination include significant adverse events, non-compliance with study procedures, or the development of exclusionary medical conditions. The trial aims to provide robust data on the efficacy of secukinumab in improving physical shoulder symptoms in this patient population.

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 treatment period for Secukinumab is 12 weeks, with a total maximum dose of 2100 mg. The administration of Secukinumab is facilitated by a pre-filled syringe device, which does not have a CE mark. 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 a similar manner to maintain the double-blind nature of the study.

Auxiliary treatments include **anti-inflammatory and antirheumatic products, non-steroids**, which are administered orally. The maximum daily dose for these products is 3200 mg, with a total maximum dose of 896 g over a treatment period of 40 days. Another auxiliary treatment involves **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 days. Additionally, **opioids** are used as auxiliary treatment, administered orally with a maximum daily dose of 400 mg and a total maximum dose of 67.2 g over 24 days.

Participant compliance with the dosing schedule is monitored throughout the trial to ensure adherence to the treatment protocol. The study is designed to assess the safety and efficacy of Secukinumab compared to placebo in adult patients with active rotator cuff tendinopathy.

Efficacy in this clinical trial will be assessed by evaluating the improvement in physical shoulder symptoms in adult patients with active rotator cuff tendinopathy. The primary endpoint 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 WORC PSD at Week 16, the proportion of participants receiving **secukinumab** compared to placebo who achieve an increase of 50 points in 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 involve the proportion of participants achieving an improvement of at least 40 points from Baseline in 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. Safety and tolerability will be assessed by monitoring adverse events (AEs) and serious adverse events (SAEs), including their incidence, severity, and relationship with the study drug. The incidence of 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 also be evaluated. The trial is designed as a randomized, parallel-group, double-blind, placebo-controlled, multicenter Phase 3 study, with an estimated end date of January 28, 2025.