The Efficacy and Safety of Treatment with Telitacicept in Antineutrophil Cytoplasmic Antibody-associated Nephritis (AAGN)

Inclusion criteria

• Age ≥ 18 years and ≤ 75 years, both male and female are included.
• Clinically diagnosed as granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) according to the definition of the 2012 Chapel Hill Consensus Conference (CHCC).
• Positive serological detection of autoantibodies, defined as follows: positive anti-proteinase 3 (PR3-ANCA) or anti-myeloperoxidase (MPO-ANCA) (previous or screening test results).
• Renal involvement at screening, defined as at least one of the following: (1) At least one renal item in the Birmingham Vasculitis Activity Score (BVAS) version 3.0; (2) According to the pathological classification criteria formulated by the European Vasculitis Society (EUVAS) in 2003, there is active, biopsy-confirmed ANCA-associated nephritis (biopsy must be performed within 1 year before the screening visit or during the screening period); (3) Microscopic examination of urine shows red blood cell casts.
• Voluntarily participate in this clinical trial and sign the informed consent form.

Exclusion criteria

• Life-threatening severe vasculitis (including diffuse alveolar hemorrhage, respiratory failure, intestinal perforation or massive bleeding, cerebral vasculitis, cardiac vasculitis, etc.).
• Secondary vasculitis (such as systemic lupus erythematosus, Henoch-Schönlein purpura, drugs, tumors, infections, primary immunodeficiency, etc.).
• Patients with primary kidney diseases (such as IgA nephropathy, membranous nephropathy and anti-glomerular basement membrane nephritis, etc.).
• Major or uncontrolled diseases unrelated to AAV.
• Rapidly progressive glomerulonephritis with rapid decline in renal function: estimated glomerular filtration rate (eGFR) ≤ 30 ml/min/1.73m² before the first administration, or already receiving continuous dialysis treatment.
• Patients with central nervous system diseases (including epilepsy, psychosis, organic brain syndrome, cerebrovascular accident, encephalitis, central nervous system vasculitis).
• Other multisystem autoimmune diseases including systemic lupus erythematosus, IgA, rheumatoid vasculitis, anti-glomerular basement membrane disease, cryoglobulinemic vasculitis, etc.
• Active hepatitis or a history of severe liver disease or liver lesions (HBsAg positive, or HBcAb positive and HBV-DNA positive), active pulmonary tuberculosis.
• Immunodeficiency, uncontrolled severe infection.
• Abnormal laboratory indicators that need to exclude subjects include but are not limited to the following indicators: total bilirubin ≥ 3 times the upper limit of normal, alanine aminotransferase (ALT) ≥ 3 times the upper limit of normal, aspartate aminotransferase (AST) ≥ 3 times the upper limit of normal, white blood cell (WBC) < 2.5×109/L, hemoglobin (Hb) < 85 g/L, platelet count (PLT) < 50×109/L.
• Received any of the following treatments within 364 days before day 0: a) B-cell targeted therapy (e.g., rituximab, other anti-CD20 drugs, anti-CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS receptor fusion protein [BR3], TACI-Fc); b) abatacept; c) experimental biological products.
• Patients who have undergone kidney transplantation or other organ transplantation.
• Received intravenous immunoglobulin or plasma exchange within 4 weeks before the first administration.
• Pregnant women, lactating women and men or women with plans for childbearing during the trial.
• Participated in other new drug clinical trials within 3 months before the first administration.
• Psychiatric patients with depression or suicidal thoughts.
• Have a history of major organ (such as heart, lung, kidney, liver) transplantation or hematopoietic stem cell/bone marrow transplantation or plan to receive transplantation.
• Those with positive test results within 4 weeks before screening suggesting COVID-19 infection, or those with a severe history of COVID-19 requiring hospitalization within 12 months before screening.
• Those allergic to Telitacicept.
• Other diseases or conditions that the investigator deems inappropriate for participation in this trial.