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)
试验速览
- 阶段
- 3 期
- 状态
- 招募中
- 入组人数
- 144
- 试验地点
- 1
- 主要终点
- The proportion of patients who achieve overall remission (OR) (Complete remission [CR] or artial remission[PR]) assessed by 24-hour urinary protein to creatinine ratio at Month 24
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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 m
- •Ability to comply with the study protocol, in the investigator's judgment
排除标准
- •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
研究组 & 干预措施
Obinutuzumab
Intravenous infusion of 1,000 mg obinutuzumab at weeks 0, 2, 24 and 26.
干预措施: Cyclophosphamide (CTX) (Drug)
Premedications
The following premedication will be administered prior to all obinutuzumab infusions in all study periods. The administration of all premedication must be completed between 30 and 60 minutes prior to the obinutuzumab infusion:
- Methylprednisolone 80 mg IV infusion and
- Acetaminophen PO (650-1000 mg, or equivalent dose of a similar agent) and
- Ebastine PO (10 mg, or equivalent dose of a similar agent).
干预措施: Glucocorticoids (Drug)
结局指标
主要结局
The proportion of patients who achieve overall remission (OR) (Complete remission [CR] or artial remission[PR]) assessed by 24-hour urinary protein to creatinine ratio at Month 24
时间窗: 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 \[PR\]). 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.
次要结局
- The proportion of patients who achieve overall remission (OR) (Complete remission [CR] or artial remission[PR]) assessed by 24-hour urinary protein to creatinine ratio at Month 6(Month 6)
- The proportion of patients who achieve overall remission (OR) (Complete remission [CR] or artial remission[PR]) assessed by 24-hour urinary protein to creatinine ratio at Month 12(Month 12)
- The proportion of patients who achieve CR assessed by 24-hour urinary protein to creatinine ratio at Month 12(Month 12)
- The proportion of patients who achieve PR assessed by 24-hour urinary protein to creatinine ratio at Month 12(Month 12)
- The proportion of patients who achieve overall remission (OR) (Complete remission [CR] or artial remission[PR]) assessed by 24-hour urinary protein to creatinine ratio at Month 18(Month 18)
- The proportion of patients who achieve CR assessed by 24-hour urinary protein to creatinine ratio at Month 18(Month 18)
- The proportion of patients who achieve PR assessed by 24-hour urinary protein to creatinine ratio at Month 18(Month 18)
- The proportion of patients who achieve CR assessed by 24-hour urinary protein to creatinine ratio at Month 24(Month 24)
- The proportion of patients who achieve PR assessed by 24-hour urinary protein to creatinine ratio at Month 24(Month 24)
- The proportion of patients who achieve immunological remission (serum anti-PLA2R antibody < 2 RU/ml) assessed by anti-PLA2R at Month 3(Month 3)
- The proportion of patients who achieve immunological remission (serum anti-PLA2R antibody < 2 RU/ml) assessed by anti-PLA2R at Month 6(Month 6)
- The proportion of patients who achieve immunological remission (serum anti-PLA2R antibody < 2 RU/ml) assessed by anti-PLA2R at Month 12(Month 12)
- The proportion of patients who achieve immunological remission (serum anti-PLA2R antibody < 2 RU/ml) assessed by anti-PLA2R at Month 18(Month 18)
- The proportion of patients who achieve immunological remission (serum anti-PLA2R antibody < 2 RU/ml) assessed by anti-PLA2R at Month 24(Month 24)
- Time from baseline to CR(ASAP)
- Time from baseline to PR(ASAP)
- Time from baseline to immunological remission(ASAP)
- The proportion of patients who relapse by Month 12(Month 12)
- The proportion of patients who relapse by Month 18(Month 18)
- The proportion of patients who relapse by Month 24(Month 24)
- The proportion of patients who meet the criteria for rescue therapy by Month 24(Month 24)
- The proportion of patients with a ≥50%, 40%, 30% decrease in eGFR(CKD-EPI) from baseline at Month 12(Month 12)
- The proportion of patients with a ≥50%, 40%, 30% decrease in eGFR(CKD-EPI) from baseline at Month 24(Month 24)
- Effect of treatment on renal function, as assessed by the slope of eGFR (CKD-EPI) from baseline to Month 12(Month 12)
- Effect of treatment on renal function, as assessed by the slope of eGFR (CKD-EPI) from baseline to Month 24(Month 24)
- eGFR(CKD-EPI) at Month 12(Month 12)
- eGFR(CKD-EPI) at Month 24(Month 24)
- Time to relapse after CR or PR by month 24(Month 24)
- Scores based on EQ-5D-5L questionnaire indicators at baseline and months 6, 12, 18 and 24(Baseline and months 6, 12, 18 and 24)