A Randomized, Double-blind, Placebo Controlled Study to Evaluate Efficacy and Safety of Nefecon in Patients With Primary IgA (Immunoglobulin A) Nephropathy at Risk of Progressing to End-stage Renal Disease (NefIgArd)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 365
- 试验地点
- 142
- 主要终点
- Part A: Ratio of Urine Protein to Creatinine Ratio (UPCR) at 9 Months Compared to Baseline
研究概览
简要总结
The overall aim of the study is to evaluate the efficacy, safety, and tolerability of Nefecon 16 mg per day in the treatment of patients with primary IgAN (Immunoglobulin A nephropathy) at risk of progressing to end-stage renal disease (ESRD), despite maximum tolerated treatment with renin-angiotensin system (RAS) blockade using angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II type I receptor blockers (ARBs).
详细描述
This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the efficacy, safety, and tolerability of oral Nefecon compared to matching placebo in patients with primary IgAN on a background of optimized RAS inhibitor therapy. The study will consist of 2 parts, Part A and Part B. Part A will include a 9 month blinded Treatment Period, and a 3-month Follow up Period. Part B of the study will consist of a 12-month observational Follow up Period; no study drug will be administered during Part B. Part A and B will be blinded. Safety will be monitored by an independent Data Safety Monitoring Board.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Female or male patients ≥18 years
- •Biopsy-verified IgA nephropathy
- •Stable dose of RAS inhibitor therapy (ACEIs and/or ARBs) at the maximum allowed dose or Maximum Tolerated Dose (MTD) according to the 2012 KDIGO (Kidney Disease: Improving Global Outcomes) guidelines
- •Urine protein creatinine ratio ≥1 g/24hr
- •eGFR ≥35 mL/min per 1.73 m2 and ≤90 mL/min per 1.73 m2 using the Chronic Kidney Diseae Epidemiology Collaboration (CKD-EPI) formula
- •Willing and able to give informed consent
排除标准
- •Systemic diseases that may cause mesangial IgA deposition.
- •Patients who have undergone a kidney transplant.
- •Patients with acute or chronic infectious disease including hepatitis, tuberculosis, human immunodeficiency virus (HIV), and chronic urinary tract infections.
- •Patients with liver cirrhosis, as assessed by the Investigator.
- •Patients with a diagnosis of type 1 or type 2 diabetes mellitus which is poorly controlled.
- •Patients with history of unstable angina, class III or IV congestive heart failure, and/or clinically significant arrhythmia, as judged by the Investigator;
- •Patients with unacceptable blood pressure control defined as a blood pressure consistently above national guidelines for proteinuric renal disease, as assessed by the Investigator
- •Patients with diagnosed malignancy within the past 5 years.
研究组 & 干预措施
Nefecon
Nefecon 16 mg once daily by mouth for 9 months.
干预措施: Nefecon (Drug)
Placebo oral capsule
Placebo oral capsule once daily by mouth for 9 months.
干预措施: Placebo oral capsule (Drug)
结局指标
主要结局
Part A: Ratio of Urine Protein to Creatinine Ratio (UPCR) at 9 Months Compared to Baseline
时间窗: 9 months
Part A primary endpoint: The ratio of Urine Protein to Creatinine Ratio (UPCR) (based on 24-hour urine collections) at 9 months following the first dose of study drug compared to baseline. Ratio being: UPCR at 9 months in g/gram divided with UPCR at Baseline in g/gram
Part B: Time-weighted Average of Estimated Glomerular Filtration Rate (eGFR)
时间窗: Up to 2 years and 1 month
Part B Primary endpoint: Time-weighted average of estimated glomerular filtration rate (eGFR) recordings observed at each time point over 2 years. The eGFR (CKD-EPI) at 2 years (which must have been repeated to provide a second value obtained within 14 to 35 days) was the geometric mean of the 2 assessments.
次要结局
- Part A: Ratio of Urine Albumin to Creatinine Ratio (UACR) at 9 Months(9 months)
- Part A: Ratio of eGFR at 9 Months(9 months)
- Part A: Ratio of eGFR at 12 Months(12 months)
- Part B: Time to 30% Reduction in eGFR(Over 2 years)
- Part B: Time to Receiving Rescue Medication.(Over 2 years)
- Part B: Ratio of UPCR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months(12, 18 and 24 months)
- Part B: Ratio of UACR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months(12 to 24 months)
- Part B: Ratio of eGFR Compared to Baseline Averaged Over Time Points Between 12 and 24 Months(12 to 24 months)
- Part B: Proportion of Patients Without Microhematuria(12 to 24 months)
- Part B: Short Form 36 (SF-36) Quality of Life Assessment at 9 Months.(9 months)
- Part B: Short Form 36 (SF-36) Quality of Life Assessment at 24 Months.(24 months)