Inclusion Criteria

• Age > 18 years.
• Kidney biopsy showing crescentic IgA nephropathy within 6 months of enrolment.
• Quantified creatinine clearance > 20 ml/min/1.73m2.
• Proteinuria > 750 mg/24h while on maximum tolerated dose of RAS blockade.
• Hematuria defined as > 10 RBC/hpf or hemoglobinuria >1+.
• Patients need to be in adequate supportive care (blood pressure < 125/85mmHg, lifestyle advice, and maximum doses tolerable of RAS blockade) at least 4 weeks prior to enrollment.
• Patients would receive dietary and lifestyle counseling prior enrollment: low protein (0.8-1.0 g/kg/day) diet, low sodium (2 grams/day) intake, indication for smoke cessation, and fish oil supplementation during the 4 weeks run-in period.
• Has signed an informed consent form prior to any study-related procedures.

Exclusion Criteria

• Creatinine clearance < 20 ml/min/1.73 m2.
• Liver function tests > 2x upper limit of normal. (Serious cases of hepatotoxicity have been reported in patients with Avacopan during first approval and ADVOCATE study (29) (30).
• Severe interstitial fibrosis and tubular atrophy (IFTA > 70% on renal biopsy).
• Active cancer or acute non-controlled infection (including HIV, HBV, HCV).
• Women who are pregnant or breastfeeding.
• Immunosuppression treatment: 
  • Rituximab 12 months prior to enrollment;
  • MMF, CYC, or immunomodulatory agents 3 months prior to enrollment;
  • AZA 3 months prior to enrollment;
  • Glucocorticoids 1 month prior to enrollment.
• Secondary IgA nephritis (associated with gastrointestinal diseases, infection, autoimmune, malignancy, respiratory tract, or skin).
• ANCA-associated vasculitis or other vasculitis diagnostic defined by ACR criteria/Chapel Hill Consensus conference.
• Contraindication to use any of the protocol treatments (glucocorticoids, Avacopan).
• Unable to give written consent form.

Note: Other protocol defined Inclusion/Exclusion Criteria may apply.

Eligibility last updated 6/13/2024. Questions regarding updates should be directed to the study team contact.