6/28/23, 12:03 AM ADVOCATE Pathway Feedback Search Clinical Topics Home Studies ADVOCATE ADVOCATE Disease Disease Disease Eosinophilic granulomatosis wit Granulomatosis with polyangiitis Microscop Trial question Is C5a receptor inhibitor avacopan noninferior to oral prednisone for the treatment of patients with ANCA-associated vasculitis? Study design Multi-center Double blinded RCT Population Characteristics of study participants 44.0% female N = 331 56.0% male 331 patients (144 female, 186 male) Inclusion criteria: patients with ANCA-associated vasculitis Key exclusion criteria: pregnant or breast-feeding, alveolar hemorrhage requiring pulmonary ventilation support at screening, any other known multi-system autoimmune disease, dialysis or plasma exchange within 12 weeks prior to screening, history of kidney transplantation, received intravenous corticosteroids > 3,000 mg methylprednisolone equivalent within 4 weeks prior to screening, taking an oral daily dose of a corticosteroid > 10 mg prednisone-equivalent for > 6 weeks continuously prior to screening Interventions https://web.pathway.md/studies/reca5phYFZehi1Yw5 1/2 6/28/23, 12:03 AM ADVOCATE Pathway N=166 avacopan (oral dose of 30 mg BID plus prednisone-matching placebo and cyclophosphamide or rituximab) N=165 prednisone (an oral dose of 60 mg per day on a tapering schedule plus avacopan- matching placebo and cyclophosphamide or rituximab) Primary outcome Remission at week 26 72.3 % 72.3 70.1 54.2 % 36.1 % Difference not exceeding nonferiority margin 18.1 % 0.0 % Avacopan Prednisone Difference not exceeding nonferiority margin in remission at week 26 (72.3% vs. 70.1%; AD 3.4%, 95% CI -6 to 12.8) Secondary outcomes Significant increase in sustained remission at week 52 (65.7% vs. 54.9%; AD 12.5%, 95% CI 2.6 to 22.3) Significant decrease in least-squares mean for Glucocorticoid Toxicity Index Cumulative Worsening Score at week 26 (39.7 vs. 56.6; AD -16.8, 95% CI -25.6 to -8) Significant decrease in least-squares mean for Glucocorticoid Toxicity Index Aggregate Improvement Score at week 26 (11.2 vs. 23.4; AD -12.1, 95% CI -21.1 to -3.2) Safety outcomes No significant differences in any adverse events, serious adverse events, any serious infection. Significant differences in any adverse event possibly related to corticosteroids (66.3% vs. 80.5%), life-threatening adverse event (4.8% vs. 8.5%). Conclusion In patients with ANCA-associated vasculitis, avacopan was noninferior to prednisone with respect to remission at week 26. Reference David R W Jayne, Peter A Merkel, Thomas J Schall et al. Avacopan for the Treatment of ANCA- Associated Vasculitis. N Engl J Med. 2021 Feb 18;384(7):599-609. Open reference URL https://web.pathway.md/studies/reca5phYFZehi1Yw5 2/2