The purpose of this study is to demonstrate the efficacy and safety of subcutaneously (s.c.) administered secukinumab 300 mg in combination with glucocorticoid taper regimen compared to placebo in combination with glucocorticoid taper regimen, in adult patients with new onset of giant cell arteritis (GCA) who are in clinical remission and who are eligible for treatment with glucocorticoid-monotherapy as per current clinical practice and treatment guidelines for the targeted participant population, thereby supporting health technology assessments (HTAs) of secukinumab in Germany.
Recent scientific evidence identified an association between polymorphisms within the IL-17A locus and GCA, supporting a role for IL-17A in vasculitis pathophysiology. Analysis of the inflammatory processes in the aortic wall has indicated that inflammatory cytokines, such as IL-6 and IL-17A are involved in GCA pathogenesis. Elevated IL-17A mRNA levels are correlated with IL-6 and IL-23p19 mRNA levels indicating the involvement of the IL-23/Th17 axis in GCA. With its pleiotropic activity on many different cell types, IL-17A may actively contribute to the inflammatory processes in GCA. In addition, animal studies also support a role of IL-17A as a driver of vasculitis, since mice deficient in IRF-4 binding protein, which have increased IL-21 and IL-17A expression, spontaneously develop arthritis-like joint disease and large vessel vasculitis (LVV). As secukinumab has already demonstrated a positive benefit/risk profile in the treatment of multiple chronic inflammatory diseases, including PsO, PsA and axSpA, and based on the scientific rationale for targeting the IL-17 pathway in GCA as well as on the basis of the currently ongoing Phase 2 Proof-of-Concept trial the which evaluates the efficacy, safety and tolerability of 300 mg secukinumab compared to placebo, in combination with a 26-week prednisolone taper regimen in adult subjects with GCA (EudraCT number: 2018-002610-12) (Venhoff, et al., 2021), inhibition of IL-17A by secukinumab has a potential therapeutic benefit for GCA patients. The purpose of this study is to demonstrate the efficacy and safety of subcutaneously (s.c.) administered secukinumab 300 mg in combination with glucocorticoid taper regimen compared to placebo in combination with glucocorticoid taper regimen, in adult patients with new onset of giant cell arteritis (GCA) who are in clinical remission and who are eligible for treatment with glucocorticoid-monotherapy as per current clinical practice and treatment guidelines for the targeted participant population, thereby supporting health technology assessments (HTAs) of secukinumab in Germany.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
151
Secukinumab will be administered at a dose of 300 mg as s.c. injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter.
Placebo will be administered as s.c. injection at Baseline, Week 1,2,3,4 and then every 4 weeks thereafter.
Novartis Investigative Site
Freiburg im Breisgau, Baden-Wurttemberg, Germany
Novartis Investigative Site
Würzburg, Bavaria, Germany
Novartis Investigative Site
Göttingen, Lower Saxony, Germany
Novartis Investigative Site
Düsseldorf, North Rhine-Westphalia, Germany
Novartis Investigative Site
Dresden, Saxony, Germany
Novartis Investigative Site
Jena, Thuringia, Germany
Novartis Investigative Site
Bad Abbach, Germany
Novartis Investigative Site
Bad Nauheim, Germany
Novartis Investigative Site
Berlin, Germany
Novartis Investigative Site
Berlin, Germany
...and 15 more locations
Time from baseline to first Giant cell arteritis (GCA) clinical relapse
To demonstrate the superiority of secukinumab 300 mg s.c. compared to placebo (both arms in combination with a prednisolone or equivalent taper regimen as per treatment guideline) in delaying the time to first GCA clinical relapse from baseline in participants with new onset of GCA who are in clinical remission and eligible for treatment with glucocorticoid-monotherapy. GCA clinical relapse is defined as both: 1. The recurrence of signs or symptoms attributable to active GCA after clinical remission, which are considered clinically significant by the investigator AND 2. The requirement of a change in the treatment prompted by the recurrence of signs and symptoms i. an increase in prednisolone or equivalent dose AND/OR ii. the addition of a rescue treatment. Definition of clinical remission: absence of signs and symptoms attributable to active GCA as determined by the investigator.
Time frame: Time from baseline to first GCA clinical relapse, assessed at least up to Week 24
Proportion of participants in sustained clinical remission at Week 52
To demonstrate the superiority of secukinumab 300 mg s.c. compared to placebo, measured by the proportion of participants in sustained clinical remission at Week 52. Definition of sustained clinical remission: absence of signs and symptoms attributable to active GCA between BSL until Week 52.
Time frame: Baseline until Week 52
Changes from Baseline to Week 52 in disease activity and quality of life for the PGA score (VAS)
To assess the effect of secukinumab compared to placebo measured by disease activity and quality of life measures at Week 52 for patient global assessment (PGA) of disease activity using a visual analogue scale (VAS)
Time frame: Baseline to Week 52
Changes from Baseline to Week 52 in disease activity and quality of life for the SF-36 (PCS and MCS) score
To assess the effect of secukinumab compared to placebo measured by disease activity and quality of life measures at Week 52 for Short form 36 (SF-36 PCS and MCS)
Time frame: Baseline to Week 52
Changes from Baseline to Week 52 in disease activity and quality of life for Patient assessment of pain (NRS)
To assess the effect of secukinumab compared to placebo measured by disease activity and quality of life measures at Week 52 for patient assessment of pain using a numeric rating scale (NRS)
Time frame: Baseline to Week 52
Time from Baseline to reach prednisolone or equivalent dose below ≤7.5 mg/day
Time to reach prednisolone or equivalent dose below Cushing threshold of ≤7.5 mg/day
Time frame: Baseline to Week 52
Proportion of participants on prednisolone or equivalent dose below Cushing threshold of ≤7.5 mg/day
Proportion of participants on prednisolone or equivalent dose below Cushing threshold of ≤7.5 mg/day
Time frame: Bseline to Week 52
Cumulative prednisolone or equivalent dose
Cumulative prednisolone or equivalent dose through Week 52
Time frame: Baseline through Week 52
Number of participants with Adverse Events
Safety and tolerability assessments over time: incidence and severity of AEs and SAEs; routine safety laboratory parameters To evaluate safety and tolerability of secukinumab 300 mg s.c. in participants with new-onset of GCA who are eligible for treatment with glucocorticoid-monotherapy
Time frame: Baseline up to 52 weeks
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