Phase III Randomized, Double-Blind, Placebo-Controlled Trial of Secukinumab and Glucocorticoid Taper in Giant Cell Arteritis Patients

The primary objective of this study is to demonstrate that the **efficacy** of secukinumab 300 mg administered subcutaneously in combination with a 26-week glucocorticoid (GC) taper regimen is superior to placebo in combination with a 52-week GC taper regimen in participants with giant cell arteritis (GCA), based on sustained remission at Week 52. This is clinically relevant as achieving sustained remission in GCA can significantly reduce the risk of disease-related complications and improve patient outcomes.

Secondary objectives include:

• To demonstrate that the efficacy of secukinumab 300 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, based on cumulative GC dose through Week 52.
• To demonstrate that the efficacy of secukinumab 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, based on sustained remission at Week 52.
• To demonstrate that the efficacy of secukinumab 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, based on cumulative GC dose through Week 52.
• To demonstrate that the effect on participant's quality of life (QoL) of secukinumab 300 mg or 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, based on change of Short Form Health Survey 36 (SF-36) score [Physical Component Summary (PCS)] at Week 52.
• To demonstrate that the effect of secukinumab 300 mg or 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, based on Glucocorticoid Toxicity Index (GTI) at Week 52.
• To demonstrate that the effect on participant's QoL of secukinumab 300 mg or 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, based on change in Functional Assessment of Chronic Illness Therapy Fatigue Scale (FACIT-Fatigue) score at Week 52.
• To evaluate the safety and tolerability of secukinumab.
• To demonstrate that the efficacy of secukinumab 300 mg or 150 mg s.c. in combination with a 26-week GC taper regimen is superior to placebo in combination with a 52-week GC taper regimen, based on time to first use of Escape Treatment or Rescue Treatment due to GCA through Week 52.

The clinical trial involves a total of **163 participants** diagnosed with **Giant cell arteritis (GCA)**. The study population includes both male and female subjects, all of whom are at least 50 years of age. Participants were selected based on their ability to understand and communicate with the investigator, as well as their compliance with study requirements. The trial includes individuals with either new-onset or relapsing GCA, with active disease confirmed by specific clinical criteria and diagnostic imaging. Participants are required to have a current GCA episode that is treatable with a prednisone regimen, in accordance with international guidelines. The study does not specify particular lifestyle considerations such as diet or physical activity. The trial population includes a vulnerable group, as defined by the study's criteria.

The clinical trial is designed as a **randomized**, parallel-group, double-blind, placebo-controlled, multicenter Phase III study. The primary objective is to evaluate the efficacy and safety of **secukinumab** 300 mg and 150 mg administered subcutaneously, in combination with a glucocorticoid taper regimen, compared to placebo in patients with **giant cell arteritis** (GCA). The trial aims to demonstrate the superiority of secukinumab in achieving sustained remission at Week 52. The study is expected to run from September 2021 to July 2027, with participant involvement lasting up to 52 weeks.

Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to confirm eligibility based on specific criteria, including age, diagnosis of GCA, and current disease activity. Following randomization, participants will receive either secukinumab or placebo, alongside a glucocorticoid taper regimen. Study visits will occur at regular intervals to monitor efficacy and safety, including assessments of sustained remission, time to clinical failure, and changes in health-related quality of life measures. The end-of-study visit will conclude the participant's involvement, with a final evaluation of treatment outcomes and any adverse events.

Participants may be withdrawn from the study early if they experience significant adverse events, fail to comply with study procedures, or if the investigator deems it medically necessary. The trial will adhere to rigorous ethical standards, ensuring informed consent is obtained from all participants prior to enrollment. The study will utilize secukinumab and prednisone, with secukinumab administered subcutaneously and prednisone orally, following a specific dosing regimen. The trial's design and procedures are structured to provide robust data on the treatment's efficacy and safety in managing GCA.

The clinical trial involves the administration of **PREDNISONE**, a corticosteroid, as part of the treatment regimen. **PREDNISONE** is provided in tablet form and is administered orally. The maximum daily dose is 60 mg, with a total maximum dose of 3325 mg over a treatment period of up to 52 weeks. The tablets are over-encapsulated and specifically packaged and labeled for the study. Participant compliance with the dosing schedule is monitored throughout the trial.

Another experimental medication used in the trial is **SECUKINUMAB**, a protein-based therapeutic agent. It is administered as a solution for injection, available in a pre-filled syringe. The route of administration is subcutaneous, with a maximum daily dose of 300 mg and a total maximum dose of 14000 mg over a treatment period of up to 276 weeks. The secondary packaging site for **SECUKINUMAB** differs from the authorized product, ensuring study-specific packaging and labeling. Compliance with the administration schedule is closely monitored.

The trial also includes the use of placebos to maintain the double-blind nature of the study. A placebo corresponding to **AIN457** (300 mg/2 mL solution for injection in a pre-filled syringe) and another placebo for **PREDNISONE** (1 mg, 2.5 mg, 5 mg, 20 mg hard gelatin capsule with tablet content) are utilized. These placebos are designed to match the appearance and administration route of the active treatments, ensuring blinding is maintained throughout the study.

The efficacy of the clinical trial will be assessed through a series of predefined endpoints. The primary endpoint is the achievement of **sustained remission** at Week 52, as defined in the trial protocol. Secondary endpoints include the time to clinical failure, measured in days through Week 52, and the cumulative glucocorticoid (GC) dose through the same period. Additional secondary endpoints involve changes in the SF-36 score (Physical Component Summary) and the Glucocorticoid Toxicity Index (GTI) as measured by the Aggregate Improvement Score (AIS) at Week 52. The FACIT-Fatigue score will also be evaluated at this timepoint.

Data collection will occur at various intervals throughout the trial, with a focus on Week 52 for primary and secondary endpoints. The trial will utilize validated scales and patient-reported outcomes to measure changes in health status and quality of life. Safety and tolerability will be monitored by assessing adverse events (AEs) and serious adverse events (SAEs), including their incidence, severity, and relationship to the study drug. Changes in laboratory measures and vital signs will also be tracked to ensure comprehensive safety monitoring.