A Phase III Randomized, Open-Label Active Comparator-Controlled Multicenter Study to Evaluate Efficacy and Safety of Obinutuzumab in Patients With Primary Membranous Nephropathy
试验速览
- 阶段
- 3 期
- 状态
- 进行中（未招募）
- 入组人数
- 142
- 试验地点
- 98
- 主要终点
- Percentage of Participants who Achieve a Complete Remission (CR) at Week 104
研究概览
简要总结
This study will evaluate the efficacy, safety, pharmacodynamics, and pharmacokinetics (PK) of obinutuzumab compared with tacrolimus in participants with primary membranous nephropathy (pMN).
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
- •Diagnosis of primary membranous nephropathy (pMN) according to renal biopsy prior to or during screening
- •Screening urinary protein-to-creatinine ratio (UPCR) >= 5 g/g from 24-hour urine collection after best supportive care for >= 3 months prior to screening or screening UPCR >= 4 g/g after best supportive care for >= 6 months prior to screening
- •eGFR >= 40 mL/min/1.73m^2 or qualified endogenous creatinine clearance >= 40 mL/min/1.73m^2 based on 24-hour urine collection during screening
- •Other inclusion criteria may apply
排除标准
- •Participants with a secondary cause of MN
- •Pregnancy or breastfeeding
- •Evidence of >= 50% reduction in proteinuria during the previous 6 months prior to randomization
- •Severe renal impairment, including the need for dialysis or renal replacement therapy
- •Type 1 or 2 diabetes mellitus
- •Receipt of an excluded therapy, including any anti-CD20 therapy less than 9 months prior to or during screening; or cyclophosphamide, tacrolimus, or cyclosporin less than 6 months prior to or during screening
- •Significant or uncontrolled medical disease which, in the investigator's opinion, would preclude participant participation
- •Known active infection of any kind or recent major episode of infection
- •Major surgery requiring hospitalization within the 4 weeks prior to screening
- •Current active alcohol or drug abuse or history of alcohol or drug abuse within 12 months prior to screening
- •Intolerance or contraindication to study therapies
- •Other exclusion criteria may apply
研究组 & 干预措施
Open Label Treatment: Obinutuzumab
Participants will be randomized at a 1:1 ratio to receive open-label treatment with obinutuzumab according to region and anti-phospholipase A2 receptor (PLA2R) autoantibody titer (using Euroimmun ELISA).
干预措施: Obinutuzumab (Drug)
Open Label Treatment: Obinutuzumab
Participants will be randomized at a 1:1 ratio to receive open-label treatment with obinutuzumab according to region and anti-phospholipase A2 receptor (PLA2R) autoantibody titer (using Euroimmun ELISA).
干预措施: Methylprednisolone (Drug)
Open Label Treatment: Obinutuzumab
Participants will be randomized at a 1:1 ratio to receive open-label treatment with obinutuzumab according to region and anti-phospholipase A2 receptor (PLA2R) autoantibody titer (using Euroimmun ELISA).
干预措施: Acetaminophen (Drug)
Open Label Treatment: Obinutuzumab
Participants will be randomized at a 1:1 ratio to receive open-label treatment with obinutuzumab according to region and anti-phospholipase A2 receptor (PLA2R) autoantibody titer (using Euroimmun ELISA).
干预措施: Diphenhydramine (Drug)
Open Label Treatment: Tacrolimus
Participants will be randomized at a 1:1 ratio to receive open-label treatment with tacrolimus according to region and anti-PLA2R autoantibody titer (using Euroimmun ELISA).
干预措施: Tacrolimus (Drug)
结局指标
主要结局
Percentage of Participants who Achieve a Complete Remission (CR) at Week 104
时间窗: Week 104
次要结局
- Percentage of Participants who Achieve an Overall Remission at Week 104(Week 104)
- Mean Change in T-score from Baseline in the Patient-Reported Outcomes Measurement Information System (PROMIS) Fatigue Scale at Week 104(Baseline to Week 104)
- Duration of CR(Up to 8 years)
- Mean Change from Baseline in the PROMIS Global Assessment of Physical Health Scale at Week 104(Baseline to Week 104)
- Change in anti-PLA2R Autoantibody Titer(Baseline to Week 52)
- Percentage of Participants with AEs of Special Interest (AESIs)(Up to 8 years)
- Peripheral B-cell Counts at Specified Timepoints(Weeks 0 (baseline), 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 117, 130, 156, 182, 208 and every 26 weeks thereafter)
- Percentage of Participants with Adverse Events (AEs)(Up to 8 years)
- Serum Concentrations of Obinutuzumab at Specified Timepoints(Weeks 0 (baseline), 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 117, 130, 143, 156, 169, 182, 195, 208, every 26 weeks thereafter)
- Time to a Sustained Reduction of Estimated Glomerular Filtration Rate (eGFR) >= 30% from Baseline(Up to 8 years)
- Prevalence of Anti-drug Antibodies (ADAs) to Obinutuzumab at Baseline(Open Label: Baseline; Escape Treatment: Week 0)
- Incidence of ADAs during the study(Weeks 2, 4, 12, 24, 26, 36, 52, 64, 76, 88, 104, 130, 156, 182, 208 and every 26 weeks thereafter)
- Percentage of Participants who Achieve CR at Week 76(Week 76)
- Time to Treatment Failure, Meeting Escape Criteria, or Relapse after Complete or Partial Remission(Up to 8 years)