A Phase 2, Open-Label Study to Evaluate the Safety and Efficacy of Budoprutug (TNT119) in Subjects With Primary Membranous Nephropathy (PMN)
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 45
- 试验地点
- 56
- 主要终点
- Incidence of Treatment-Emergent Adverse Events (TEAEs)
研究概览
简要总结
To evaluate the safety and tolerability of three dose regimens of budoprutug in subjects with PMN
详细描述
Budoprutug is a humanized, immunoglobulin (Ig) G1 monoclonal antibody that selectively binds to CD19 and is projected to deplete targeted cells through antibody-dependent cellular cytotoxicity (ADCC). This Phase 2, open-label, multicenter study evaluates the safety, pharmacodynamics, and preliminary efficacy of three intravenous dose regimens of budoprutug in adult subjects with primary membranous nephropathy (PMN) who are anti-PLA2R antibody positive and have persistent proteinuria despite optimized RAAS inhibition. Approximately 45 subjects will be enrolled across three sequential dose cohorts, each receiving a single IV dose of budoprutug on Day 1, Day 15, Day 169 and Day 183. Subjects will be followed through Week 48, with extended follow-up for B-cell recovery as needed.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Confirmed diagnosis of PMN with positive anti-PLA2R antibodies
- •CD19+ B cell count ≥40 cells/μL
- •UPCR ≥2.0 g/g
- •eGFR ≥35 mL/min/1.73 m²
- •Stable RAAS inhibitor therapy
- •Blood pressure <150/90 mmHg at baseline
- •Adequate hematologic, hepatic, and renal function
- •Willing to use effective contraception (both sexes)
- •Other inclusion criteria may apply
排除标准
- •Secondary Membranous Nephropathy
- •Rapidly progressive glomerulonephritis or other glomerulopathies
- •Prior B cell-depleting therapy within 24 weeks
- •Recent use of immunosuppressants
- •Active or high-risk infections
- •History of malignancy
- •Pregnancy or breastfeeding
- •Recent major surgery or hospitalization
- •Other exclusion criteria may apply
研究组 & 干预措施
Cohort 1: Dose Level A
干预措施: budoprutug (Drug)
Cohort 2: Dose Level B
干预措施: budoprutug (Drug)
Cohort 3: Dose Level C
干预措施: budoprutug (Drug)
结局指标
主要结局
Incidence of Treatment-Emergent Adverse Events (TEAEs)
时间窗: Up to Week 48
Number of participants experiencing TEAEs, graded per NCI CTCAE v5.0.
次要结局
- Complete Remission Rate(Week 48)
- Change in total B Cell Count(Up to Week 48)
- Change in Anti-PLA2R Antibodies(Up to Week 48)
- Complete or Partial Remission Rate(Week 48)
- Change in Proteinuria(Up to Week 48)
- Change in UACR(Up to Week 48)
- Change in eGFR(Up to Week 48)
- Area Under the Curve (AUC)(Up to Week 48)
- Maximum Observed Plasma Concentration (Cmax)(Up to Week 48)
- Time to Maximum Observed Concentration (Tmax)(Up to Week 48)
- Terminal Half-Life (T1/2)(Up to Week 48)
- Apparent Clearance (CL/F)(Up to Week 48)
- Volume of Distribution (Vd)(Up to Week 48)