Overview

The purpose of this study is to determine the 72-hour pharmacokinetics of emulsified avacopan at a dose of 30 mg twice daily given to up to 6 patients with active severe GPA or MPA with diffuse alveolar hemorrhage (DAH) requiring mechanical ventilation for respiratory support.

Eligibility

Inclusion Criteria

• Fulfillment of the definitions of the Second Chapel Hill Consensus Conference for ANCA-associated vasculitis (either granulomatosis with polyangiitis (GPA) or microscopic polyangiitis MPA).
• Positivity for ANCA, directed against PR3 or MPO.
• Diffuse alveolar hemorrhage.
• Respiratory failure requiring mechanical ventilation.
• Severe newly diagnosed disease or severe relapsing disease. Severe new or relapsing disease is defined as at least one major BVAS/WG item or a score ≥ 3 and the investigator deems standard treatment for severe disease is necessary.
• Minimum BVAS-WG of 3.
• Requirement of standard-of-care remission induction therapy for active severe ANCA-associated vasculitis (GPA or MPA).

Exclusion Criteria

• Diagnosis with eosinophilic granulomatosis with polyangiitis (EGPA, formally Churg-Strauss syndrome) as defined by the Chapel Hill consensus conference.
• Allergies: History of severe allergic reaction to avacopan
• History of documented anti-glomerular basement membrane disease (anti-GBM disease)
• Previous administration of avacopan within the last 5 days.
• Concomitant use of a strong CYP3A4 inhibitor.
• Aspartate aminotransferase \[AST\], alanine amino transferase \[ALT\], alkaline phosphatase, or total bilirubin elevation \>2.5 times the upper limit of normal (unless attributed to vasculitis) on routine liver function testing obtained within 3 days prior to anticipated treatment with avacopan.
• Evidence of prior active or current Hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency (HIV) infection.
• Active serious infection, including localized infection.
• Pregnancy and breastfeeding