Efficacy and Safety of Secukinumab in Delaying Relapse in New-Onset Giant Cell Arteritis Patients in Clinical Remission

The primary objective of this study is to demonstrate the **superiority** of secukinumab 300 mg subcutaneously compared to placebo in delaying the time to first clinical relapse of **giant cell arteritis** (GCA) in patients with new-onset GCA who are in clinical remission and eligible for treatment with glucocorticoid monotherapy. This is clinically relevant as it aims to provide an alternative treatment strategy that could potentially reduce the reliance on glucocorticoids, which are associated with significant side effects when used long-term.

Secondary objectives include:

• Demonstrating the superiority of secukinumab 300 mg subcutaneously compared to placebo, measured by the proportion of participants in sustained clinical remission at Week 52.
• Assessing the effect of secukinumab 300 mg subcutaneously compared to placebo on disease activity and quality of life measures at Week 52, including patient global assessment of disease activity, patient assessment of pain, and Short Form 36 (SF-36) scores.
• Evaluating the time to reach a prednisolone or equivalent dose below the Cushing threshold of ≤7.5 mg/day, the proportion of participants on such a dose at Week 52, and the cumulative prednisolone or equivalent dose through Week 52.
• Evaluating the safety and tolerability of secukinumab 300 mg subcutaneously in participants with GCA who are eligible for treatment with glucocorticoid monotherapy.

The clinical trial focuses on patients diagnosed with **Giant Cell Arteritis** (GCA), specifically targeting individuals with new-onset GCA who are in clinical remission and eligible for treatment with glucocorticoid-monotherapy. The study population includes both male and female participants, all of whom are at least 50 years of age. Participants must have been diagnosed with GCA within six weeks of the baseline visit, with specific clinical criteria such as elevated Erythrocyte Sedimentation Rate (ESR) or C-reactive protein (CRP) levels, and symptoms like new-onset localized headache or jaw pain. The trial includes individuals who are in clinical remission at baseline and have not experienced a GCA relapse at that time. Participants are required to be on a prednisolone or equivalent glucocorticoid regimen ranging from 20-60 mg/day at baseline. The sponsor has not provided information regarding the total number of participants in the trial.

The clinical trial is designed as a **randomized**, parallel-group, **double-blind**, placebo-controlled, multicenter study to evaluate the efficacy and safety of subcutaneously administered **secukinumab** in patients with new-onset **giant cell arteritis** (GCA) who are in clinical remission and eligible for treatment with glucocorticoid monotherapy. The primary objective is to demonstrate the superiority of secukinumab 300 mg compared to placebo in delaying the time to first GCA clinical relapse. The trial is expected to last until July 2026, with participant recruitment having commenced in September 2022.

Participants will be involved in the study for a maximum treatment period of 164 weeks. The study includes several key visits: an initial screening visit to confirm eligibility, baseline visit to establish clinical remission, and subsequent follow-up visits to monitor disease activity and treatment response. The end-of-study visit will assess the primary and secondary endpoints, including the time to first GCA clinical relapse and the proportion of participants in sustained clinical remission at Week 52. Participants will also be evaluated for changes in disease activity and quality of life, as well as safety and tolerability assessments over time.

Inclusion criteria require participants to be at least 50 years of age, with a diagnosis of new-onset GCA within six weeks of the baseline visit. Participants must be in clinical remission at baseline and on a prednisolone or equivalent dose of 20-60 mg/day. Conditions for early termination from the study include non-compliance with study requirements or the occurrence of adverse events that compromise participant safety. The trial's design ensures rigorous assessment of the investigational product's efficacy and safety, adhering to high standards of clinical research methodology.

The clinical trial involves the administration of **secukinumab**, marketed under the name Cosentyx, which is a 300 mg solution for injection in a pre-filled syringe. Secukinumab is a recombinant human monoclonal antibody targeting human interleukin (IL)-17A of the IgG1/k class. The pharmaceutical form is a solution for injection, and it is administered via **subcutaneous use**. The dosing regimen involves a maximum daily dose of 300 mg, with a total maximum dose of 13,500 mg over a treatment period of 164 days. The product is manufactured by Novartis Europharm Limited and is specifically packaged and labeled for the study. Participant compliance with the dosing schedule is monitored throughout the trial.

The trial also includes a **placebo** comparator, which is a solution for injection in a pre-filled syringe, designed to match the appearance and administration route of the secukinumab product. The placebo is administered subcutaneously, following the same dosing schedule as the active treatment. This 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 allocation. Both the active treatment and placebo are administered in conjunction with a prednisolone or equivalent taper regimen, as per the treatment guidelines for patients with new-onset giant cell arteritis (GCA) who are in clinical remission and eligible for glucocorticoid monotherapy.

Efficacy in this clinical trial will be assessed using both primary and secondary endpoints. The primary endpoint is the time from baseline to the first clinical relapse of **giant cell arteritis (GCA)**. Secondary endpoints include the proportion of participants in sustained clinical remission at Week 52, changes from baseline to Week 52 in disease activity and quality of life, as measured by the Patient Global Assessment (PGA) score using a Visual Analog Scale (VAS), the Short Form-36 (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores, and the Patient assessment of pain using a Numerical Rating Scale (NRS). Additionally, the time from baseline to reach a prednisolone or equivalent dose below 7.5 mg/day, the proportion of participants on a prednisolone or equivalent dose below the Cushing threshold of 7.5 mg/day at Week 52, and the cumulative prednisolone or equivalent dose through Week 52 will be evaluated.

These efficacy parameters will be measured and collected at specified timepoints, including baseline and Week 52, using validated scales and patient-reported outcomes. The analysis will focus on comparing the efficacy of secukinumab 300 mg subcutaneously administered, in combination with a prednisolone taper regimen, against a placebo in delaying the time to first GCA clinical relapse in patients who are in clinical remission and eligible for glucocorticoid monotherapy. The trial is designed as a randomized, parallel-group, double-blind, placebo-controlled, multicenter study.