Alternative C activation is involved in the pathogenesis of ANCA-associated 
vasculitis. However, glucocorticoids used as treatment contribute to the 
morbidity and mortality of vasculitis. We determined whether avacopan (CCX168), 
an orally administered, selective C5a receptor inhibitor, could replace oral 
glucocorticoids without compromising efficacy. In this randomized, 
placebo-controlled trial, adults with newly diagnosed or relapsing vasculitis 
received placebo plus prednisone starting at 60 mg daily (control group), 
avacopan (30 mg, twice daily) plus reduced-dose prednisone (20 mg daily), or 
avacopan (30 mg, twice daily) without prednisone. All patients received 
cyclophosphamide or rituximab. The primary efficacy measure was the proportion 
of patients achieving a ≥50% reduction in Birmingham Vasculitis Activity Score 
by week 12 and no worsening in any body system. We enrolled 67 patients, 23 in 
the control and 22 in each of the avacopan groups. Clinical response at week 12 
was achieved in 14 of 20 (70.0%) control patients, 19 of 22 (86.4%) patients in 
the avacopan plus reduced-dose prednisone group (difference from control 16.4%; 
two-sided 90% confidence limit, -4.3% to 37.1%; P=0.002 for noninferiority), and 
17 of 21 (81.0%) patients in the avacopan without prednisone group (difference 
from control 11.0%; two-sided 90% confidence limit, -11.0% to 32.9%; P=0.01 for 
noninferiority). Adverse events occurred in 21 of 23 (91%) control patients, 19 
of 22 (86%) patients in the avacopan plus reduced-dose prednisone group, and 21 
of 22 (96%) patients in the avacopan without prednisone group. In conclusion, 
C5a receptor inhibition with avacopan was effective in replacing high-dose 
glucocorticoids in treating vasculitis.