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.
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.
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.
Patients with a secondary cause of MN (e.g. hepatitis B, systemic lupus erythematosus, medications, malignancies)
Type 1 or 2 diabetes mellitus
eGFR <40 mL/min/1.73m2 (CKD-EPI) or dialysis or kidney transplantation
Evidence of 50% reduction in proteinuria or serum anti-PLA2R antibody within 6 months prior to screening
Parallel
Obinutuzumab
DrugDrug: Obinutuzumab Intravenous infusion of 1,000 mg obinutuzumab at weeks 0, 2, 24 and 26.
CTX combined with Glucocorticoids
DrugDrug: 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 40mg/d) for 27 days. Drug: CTX Oral cyclophosphamide will be given for 30 days in month 2, 4, 6.
The proportion of patients who achieve overall remission (OR) (Complete remission [CR] or prtial remission[PR]) assessed by 24-hour urinary protein to creatinine ratio at Month 24
Collect 24-hour urine from patients in the 24th month and measure the 24-hour urinary protein to creatinine ratio (24-hour UPCR) to evaluate the proportion of patients achieving total response (OR) (complete response \[CR\] or partial response \[PR\]).
The proportion of patients who achieve overall remission (OR) (Complete remission [CR] or prtial remission[PR]) assessed by 24-hour urinary protein to creatinine ratio at Month 6
Collect 24-hour urine from patients in the 6th month and measure the 24-hour urinary protein to creatinine ratio (24-hour UPCR) to evaluate the proportion of patients achieving total response (OR) (complete response \[CR\] or partial response \[PR\]). * CR is defined as a urinary protein-to-creatinine ratio (UPCR) ≤0.3 g/g (24-hour urine). * PR is defined as reduction of urinary protein-to-creatinine ratio (UPCR) (24-hour urine) from baseline ≥ 50% ,plus ≤3.5 g/g but \>0.3 g/g.
The proportion of patients who achieve overall remission (OR) (Complete remission [CR] or prtial remission[PR]) assessed by 24-hour urinary protein to creatinine ratio at Month 12
Collect 24-hour urine from patients in the 12th month and perform 24-hour urinary protein to creatinine ratio (24-hour UPCR) testing to evaluate the proportion of patients who achieve OR(Complete remission \[CR\] or prtial remission\[PR\]) . * CR is defined as a urinary protein-to-creatinine ratio (UPCR) ≤0.3 g/g (24-hour urine) * PR is defined as reduction of urinary protein-to-creatinine ratio (UPCR) (24-hour urine) from baseline ≥ 50% ,plus ≤3.5 g/g but \>0.3 g/g
The proportion of patients who achieve CR assessed by 24-hour urinary protein to creatinine ratio at Month 12
Collect 24-hour urine from patients in the 12th month and measure the 24-hour urinary protein to creatinine ratio (24-hour UPCR) to evaluate the proportion of patients achieving CR. · CR is defined as a urinary protein-to-creatinine ratio (UPCR) ≤0.3 g/g (24-hour urine).
The proportion of patients who achieve PR assessed by 24-hour urinary protein to creatinine ratio at Month 12
Collect 24-hour urine from patients in the 12th month and measure the 24-hour urinary protein to creatinine ratio (24-hour UPCR) to evaluate the proportion of patients achieving PR. * PR is defined as reduction of urinary protein-to-creatinine ratio (UPCR) (24-hour urine) from baseline ≥ 50% ,plus ≤3.5 g/g but \>0.3 g/g.
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