A Phase 2/3, Multicenter, Randomized, Active-Controlled, Open-label Study to Evaluate the Efficacy and Safety of Zanubrutinib in Patients With Primary Membranous Nephropathy
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 178
- 试验地点
- 95
- 主要终点
- Part 1: Change from Baseline in Urine Protein Creatinine Ratio (UPCR)
研究概览
简要总结
The primary objectives of this study are: In Part 1 to evaluate the efficacy of zanubrutinib as measured by proteinuria reduction, and in Part 2 to evaluate the efficacy of zanubrutinib compared with tacrolimus as measured by complete remission rate, in participants with primary membranous nephropathy (PMN) who are on optimal supportive care.
详细描述
Our company, previously known as BeiGene, is now officially BeOne Medicines. Because some of our older studies were sponsored under the name BeiGene, you may see both names used for this study on this website.
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
- •Biopsy-confirmed PMN within 5 years before the initial screening (ie, the day the informed consent is signed)
- •UPCR (based on 24-hour urine collection) > 3.5 at initial screening and at confirmation assessment
- •Treatment with a maximally tolerated or allowed dose of an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) for ≥ 24 weeks before randomization (12 weeks before initiation of study drug for Part 1) and with adequate blood pressure control (blood pressure < 130/80 mmHg, measured on ≥ 2 occasions [not on the same day] within 4 weeks before the assignment of study treatment)
- •Anti-PLA2R antibody > 50 RU/mL at confirmation assessment (Part 1 only)
排除标准
- •Participants with a secondary cause of membranous nephropathy
- •Type 1 or 2 diabetes mellitus with hemoglobin A1c (HbA1c) ≥ 7% at screening
- •Severe renal disease as determined by rapid decline in eGFR (defined as > 15 mL/min/1.73m^2 within 24 weeks prior to randomization, not otherwise explained)
- •A known history of a primary immunodeficiency or an underlying condition such as human immunodeficiency virus (HIV) infection or splenectomy that predisposes the participant to infections
- •Patients at risk for tuberculosis at screening
- •Known infection with serologic status reflecting active or chronic hepatitis B virus infection, or presence of hepatitis C virus antibody
- •Severe hepatic insufficiency (Child-Pugh C)
- •Clinically significant cardio-cerebrovascular diseases
- •Note: Other protocol defined Inclusion/Exclusion criteria may apply.
研究组 & 干预措施
Part 2: Tacrolimus
Participants will receive tacrolimus capsules twice daily for 64 weeks.
干预措施: Tacrolimus (Drug)
Part 2: Zanubrutinib High Dose
Participants will receive zanubrutinib twice daily.
干预措施: Zanubrutinib (Drug)
Part 1: Zanubrutinib High Dose
Participants will receive zanubrutinib twice daily.
干预措施: Zanubrutinib (Drug)
Part 2: Zanubrutinib Low Dose
Participants will receive zanubrutinib once daily.
干预措施: Zanubrutinib (Drug)
结局指标
主要结局
Part 1: Change from Baseline in Urine Protein Creatinine Ratio (UPCR)
时间窗: Baseline and Week 24
Part 2: Number of Participants Achieving Complete Remission
时间窗: Week 104
Complete remission is defined as: UPCR (based on 24-hour urine collection) ≤ 0.3, AND a stable estimated glomerular filtration rate (eGFR) (remains unchanged or decreases by \< 15% compared with the baseline)
次要结局
- Part 1: Number of participants with Treatment Failure(Week 24)
- Part 1: Number of Participants with Immunological Response(Week 24)
- Part 1: Number of Participants with Complete Remission(Week 24, Week 52, Week 76, and Week 104)
- Part 1: Number of Participants with Overall Remission(Week 24, Week 52, Week 76, and Week 104)
- Part 1: Number of Participants with Relapse(Week 104)
- Part 1: Number Of Participants with Treatment-Emergent Adverse Events (TEAEs)(From the first dose of study drug and up to 30 days after study drug discontinuation; up to approximately 68 weeks)
- Part 2: Number of Participants with Overall Remission(Week 24, Week 52, Week 76, and Week 104)
- Part 2: Number of Participants with Complete Remission(Week 24, Week 52, and Week 76)
- Part 2: Number of participants with Treatment Failure(Week 24, Week 52, Week 76, and Week 104)
- Part 2: Time to First Complete Remission(Up to approximately 104 weeks)
- Part 2: Time to First Overall Remission(Up to approximately 104 weeks)
- Part 2: Number of Participants with Relapse(Week 104)
- Part 2: Time to First Relapse(Up to approximately 104 weeks)
- Part 2: Health Related quality of Life (HRQoL) Using the Kidney Disease and Quality of Life instrument™ - 36 items (KDQoL-36)(Up to approximately 104 weeks)
- Part 2: Health Related quality of Life (HRQoL) Using European Quality of Life 5-Dimensions 5-Levels Health Questionnaire (EQ-5D-5L)(Up to approximately 104 weeks)
- Number of Participants with ≥ 30% Estimated Glomerular Filtration Rate (eGFR) Reduction from Baseline(Baseline, Week 52, and Week 104)
- Part 2: Number of Participants with TEAEs(From the first dose of study drug and up to 30 days after study drug discontinuation; up to approximately 68 weeks)