A randomized, parallel-group, double-blind, placebo-controlled, multicenter Phase III trial to evaluate efficacy and safety of secukinumab administered subcutaneously versus placebo, in combination with a glucocorticoid taper regimen, in patients with polymyalgia rheumatica (PMR)

The primary objective of this study is to demonstrate that the efficacy of **secukinumab** 300 mg administered subcutaneously in combination with a 24-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 24-week GC taper regimen in participants with polymyalgia rheumatica (PMR) who have recently relapsed. This is assessed based on the proportion of participants achieving sustained remission at Week 52. The clinical relevance of this objective lies in potentially providing a more effective treatment option for PMR, a condition characterized by muscle pain and stiffness, which can significantly impact the quality of life.

Secondary objectives include: - Demonstrating the efficacy of secukinumab 150 mg s.c. in combination with a 24-week GC taper regimen compared to placebo, based on sustained remission and complete sustained remission at Week 52. - Evaluating the efficacy of secukinumab 300 mg and 150 mg s.c. in combination with a 24-week GC taper regimen compared to placebo, based on adjusted annual cumulative GC dose and time to first use of escape or rescue treatment. - Assessing the effect on participants' Quality of Life (QoL) of secukinumab 300 mg and 150 mg s.c. in combination with a 24-week GC taper regimen compared to placebo, based on changes from baseline in FACIT-Fatigue and HAQ-DI scores at Week 52. - Demonstrating the safety and tolerability of secukinumab 300 mg s.c./150 mg s.c. in participants with PMR who have recently relapsed. - Assessing the occurrence of GC-related adverse events in participants receiving secukinumab 300 mg s.c./150 mg s.c. versus placebo.

The clinical trial involves a total of **172 participants** diagnosed with **Polymyalgia Rheumatica** (PMR). The study population includes both male and female participants who are at least 50 years of age. Participants were selected based on their recent relapse of PMR and their history of treatment with glucocorticoids. The trial specifically targets individuals who have experienced at least one episode of PMR relapse while attempting to taper prednisone. Participants must have been treated according to local treatment recommendations and be on a stable dose of prednisone at the time of screening. The trial does not specify any particular lifestyle considerations such as diet or physical activity. The study population includes a vulnerable group, as defined by the trial's criteria. The selection process ensures that participants meet the necessary medical and demographic criteria to assess the efficacy of secukinumab in combination with a glucocorticoid taper regimen.

The clinical trial is a **randomized**, parallel-group, **double-blind**, placebo-controlled, multicenter Phase III study designed to evaluate the efficacy and safety of **secukinumab** administered subcutaneously versus placebo, in combination with a glucocorticoid taper regimen, in patients with **polymyalgia rheumatica** (PMR). The primary objective is to demonstrate that the efficacy of secukinumab 300 mg subcutaneously, in combination with a 24-week glucocorticoid taper regimen, is superior to placebo in achieving sustained remission at Week 52. The trial is expected to conclude by February 2026, with recruitment having commenced in May 2023.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on criteria such as age, diagnosis of PMR, and history of glucocorticoid treatment. Following randomization, participants will attend regular follow-up visits to monitor treatment efficacy and safety, with assessments including the proportion of participants achieving sustained remission and changes in fatigue and disability scores. The end-of-study visit will occur at Week 52, marking the completion of the trial for each participant.

The expected duration of participant involvement is approximately 52 weeks. Conditions that may lead to early termination from the study include the occurrence of serious adverse events, non-compliance with the study protocol, or withdrawal of consent. The trial will ensure rigorous monitoring of safety and tolerability, with all adverse events and serious adverse events being documented and assessed for their relationship to the study drug. The study will also evaluate secondary endpoints such as the time to first use of escape or rescue treatment and the adjusted annual cumulative glucocorticoid dose through Week 52.

The clinical trial involves the administration of **Secukinumab**, a protein-based medication, as the experimental treatment. Secukinumab is provided in the form of a solution for injection in a pre-filled syringe. The active substance, secukinumab, is administered subcutaneously at a dosage of 300 mg. The maximum daily dose is 300 mg, with a total maximum dose of 4800 mg over the treatment period. The treatment is scheduled to last for a maximum of 52 weeks. The secondary packaging site for this product differs from the authorized product, which is a notable change in the study.

**Prednisone** is used as a non-experimental treatment in the study. It is a chemical-based medication provided in tablet form. Prednisone is administered orally with a maximum daily dose of 15 mg and a total maximum dose of 1155 mg over a 24-week period. Prednisone is known for its ability to decrease inflammation and suppress immune system activity. The study utilizes a specific packaging for prednisone, which is distinct from the standard packaging.

A **placebo** is also employed in the trial, specifically as a comparator to the secukinumab treatment. The placebo is designed to mimic the 150 mg/1 mL solution for injection in a pre-filled syringe, although it contains no active substance. The placebo is used to maintain the double-blind nature of the study, ensuring that neither the participants nor the investigators are aware of the treatment assignments.

The efficacy of the clinical trial will be assessed by evaluating the proportion of participants achieving **sustained remission** at Week 52. This is the primary endpoint of the study. Secondary endpoints include the proportion of participants achieving complete sustained remission at Week 52, the adjusted annual cumulative glucocorticoid (GC) dose through Week 52 adjusted by the duration of study follow-up, and the time to first use of escape or rescue treatment as measured in days through Week 52. Additionally, changes from baseline in the FACIT-Fatigue score and HAQ-DI score at Week 52 will be measured. Safety and tolerability will also be assessed by monitoring all adverse events (AEs) and serious adverse events (SAEs), as well as clinically significant changes in clinical laboratory measures and vital signs.