Efficacy and Safety of Obinutuzumab Beta in Primary IgA Nephropathy With Active Pathological Lesions

Ki vehet részt

• 1. Willing to participate, able to complete treatment, follow-up, and related examinations, and able to provide written informed consent
• 2. Age 18 to 70 years, inclusive; male or female
• 3. Primary IgA nephropathy confirmed by kidney biopsy within 6 months before enrollment, with at least one of the following pathological features: E1: endocapillary hypercellularity; C1 or C2: cellular or fibrocellular crescents (C1: at least 1 glomerulus with crescents and involved glomeruli ≤25%; C2: >25% glomeruli with crescents); Fibrinoid necrosis of capillary loops in at least one glomerulus
• 4. Received stable optimized supportive care for at least 12 weeks before screening, including maximum allowed or maximum tolerated dose of ACEi or ARB. For participants with contraindications or intolerance to ACEi/ARB, the reason must be documented. SGLT2i or MRA may be used according to clinical indications if the dose has been stable for at least 12 weeks before screening. Background therapy should generally remain stable during the study, except for adjustments for safety or clinical needs
• 5. Two 24-hour urinary protein measurements during screening both ≥1.0 g/day, at least 7 days apart, with persistent microscopic hematuria (>3 red blood cells per high-power field)
• 6. Estimated glomerular filtration rate (eGFR) ≥30 mL/min/1.73 m² at screening, calculated using the CKD-EPI formula

Ki nem vehet részt

• 4. Prior kidney transplantation
• 5. Within 12 weeks before screening, received any of the following: Systemic glucocorticoids (prednisone or equivalent, including budesonide enteric-coated capsules) >10 mg/day for >14 consecutive days; Immunosuppressants/modulators (e.g., mycophenolate, cyclosporine, calcineurin inhibitors, cyclophosphamide, azathioprine, leflunomide, hydroxychloroquine); Chinese patent medicines with immunosuppressive effects (e.g., Tripterygium or Qingteng preparations); Or anticipated need for any of the above therapies during the study as assessed by the investigator
• 6. Within 6 months before study treatment, received biologics such as CD20 monoclonal antibodies, CD38 monoclonal antibodies, APRIL monoclonal antibodies (e.g., sibeprenlimab), BAFF/APRIL fusion proteins, cytokine inhibitors, or complement pathway drugs
• 1. Systemic diseases that may cause IgA deposition in the renal mesangium, including but not limited to IgA vasculitis, ankylosing spondylitis, and systemic lupus erythematosus
• 3. Other glomerular diseases (e.g., C3 glomerulopathy, diabetic nephropathy, membranous nephropathy)
• 7. Any cardiovascular or cerebrovascular event within 6 months: myocardial infarction, unstable angina, ventricular arrhythmia, NYHA class III or IV congestive heart failure, stroke, etc
• 8. Active infection or high-risk latent infection
• 10. Malignancy diagnosed within the past 5 years (except cured basal cell carcinoma of the skin or carcinoma in situ of the cervix)
• 12. Known allergy to any component of obinutuzumab beta
• 13. Any condition that, in the investigator's judgment, makes the participant unsuitable for the study
• 2. Kidney biopsy showing any of the following: Tubular atrophy or interstitial fibrosis >50% (Oxford T2); Crescents in >50% of glomeruli, or clinical presentation suggesting rapidly progressive glomerulonephritis (e.g., rapid eGFR decline with massive proteinuria/hematuria); ≥50% globally sclerotic glomeruli; Isolated S1 without podocytopathy features (e.g., podocyte hypertrophy/tip lesion)
• 9. Poorly controlled blood pressure at screening: systolic BP ≥130 mmHg or diastolic BP ≥80 mmHg (excluding hemodynamic fluctuation-induced proteinuria elevation)
• 11. Breastfeeding or pregnant women, or men and women of childbearing potential unwilling to use adequate contraception during the study