A Multicenter, Open- Label, Randomized, Clinical Trial to Investigate the Efficacy and Safety of OBINOTUZUMAB Versus Cyclophosphamide Combined with Glucocorticoids in Patients with Primary Membranous Nephropathy (Blossom Study)
This is a randomized, parallel group, active-controlled, open-label, Phase III study comparing the efficacy and safety of obinutuzumab versus cyclophosphamide combined with glucocorticoids in patients with primary membranous nephropathy (pMN). Approximately 144 patients with pMN who have been diagnosed by biopsy or serum anti-PLA2R antibody will be enrolled. Compare obinutuzumab against cyclophosphamide combined with glucocorticoids in pMN patients. Based on the hypothesis of non-inferiority in terms of the primary endpoint. Intervention: Intravenous infusion of 1,000 mg obinutuzumab at weeks 0, 2, 24 and 26 Comparator: Cyclical cyclophosphamide and glucocorticoids Methylprednisolone 500 mg iv will be given for 3 consecutive days at the start of month 1,3,5 and followed by prednisone 0.5mg/kg/d (max 40 mg/d) for 27 days. Oral cyclophosphamide will be given for 30 days in month 2, 4, 6.11 / 68 The dosage is adjusted based on the age and renal function (rounded down to the nearest 25 mg, max 100 mg/day, Cyclophosphamide tablets should not be split; if necessary, alternating doses of 50 mg/day and 100 mg/day can be used)： * 2.0 mg/kg/d in patients \< 65 years with eGFR ≥60ml/min * 1.5 mg/kg/d in patients \< 65 years with eGFR\<60ml/min * 1.5 mg/kg/d in patients ≥ 65 years with eGFR ≥60ml/min * 1.0 mg/kg/d in patients ≥ 65 years with eGFR\<60ml/min Randomization: Patients will be stratified based on urine protein (24h UPCR \< 8 g/g or ≥ 8 g/g) and randomized in a 1:1 ratio to receive open-label treatment with either obinutuzumab or cyclophosphamide combined with glucocorticoids.
• Aged 18～75 years (including 18 and 75)old at the time of signing Informed Consent Form
• pMN patients diagnosed according to renal biopsy (original biopsy needs to include light, immunofluorescence, and electron microscopy) within 5 years or serum anti-PLA2R antibody (≥14 RU/ml )
• 24-hour UPCR ≥ 4 g/g and serum albumin (sALB) \< 30 g/L,despite being treated with ACEi and/or ARB for ≥ 6 months prior to screening, or 24-hour UPCR ≥ 5 g/g and sALB \< 30 g/L , despite being treated with ACEi and/or ARB for ≥ 3 months prior to screening; or 24-hour UPCR ≥ 8 g/g and sALB \< 25 g/L, despite being treated with ACEi and/or ARB for ≥ 1 month prior to screening,.
• eGFR ≥40 mL/min/1.73m2 (CKD-EPI), a renal biopsy is required to exclude renal damage due to other co-morbidities if eGFR \<60mL/min/1.73 m2.
• Ability to comply with the study protocol, in the investigator's judgment