目的:常染色体隐性遗传性多囊肾病(ARPKD)是一种遗传性疾病,其特征是肾脏大量增大和发育性肝脏缺陷。儿童时期的潜在后果包括需要肾脏替代疗法(KRT)。我们报告了2项正在进行的临床试验(研究204,研究307)的设计,以评估安全性,耐受性,托伐普坦治疗儿童ARPKD的疗效。
方法:两项试验都是跨国的,多中心,开放标签设计。入组时的年龄范围在研究204中为28天至<12周,在研究307中为28天至<18岁。两项研究中的受试者必须具有ARPKD的临床诊断,研究204中的那些人还必须有迹象表明快速进展为KRT的风险,即,全部:肾性肥大症,多发性肾囊肿或肾脏回声增加提示微囊肿,和羊水过少或羊水过少。目标招募是研究204的20名受试者和研究307的≥10名受试者。
结果:研究204的随访时间为24个月(可选的额外治疗长达36个月),研究307的随访时间为18个月。结果包括安全,耐受性,肾功能的变化,以及需要KRT的受试者相对于历史数据的百分比。定期进行安全性评估,以监测治疗对肝功能等参数的可能不利影响,肾功能,流体平衡,电解质水平,和增长轨迹,托伐普坦开始或剂量递增后监测频率增加。
结论:这些试验将提供托伐普坦在没有疾病特异性治疗方案的人群中的安全性和有效性的数据。
背景:研究204:EudraCT2020-005991-36;研究307:EudraCT2020-005992-10。
Autosomal recessive polycystic kidney disease (ARPKD) is a hereditary condition characterized by massive kidney enlargement and developmental liver defects. Potential consequences during childhood include the need for kidney replacement therapy (KRT). We report the design of 2 ongoing clinical trials (Study 204, Study 307) to evaluate safety, tolerability, and efficacy of tolvaptan in children with ARPKD.
Both trials are of multinational, multicenter, open-label design. Age range at enrollment is 28 days to < 12 weeks in Study 204 and 28 days to < 18 years in Study 307. Subjects in both studies must have a clinical diagnosis of ARPKD, and those in Study 204 must additionally have signs indicative of risk of rapid progression to KRT, namely, all of: nephromegaly, multiple kidney cysts or increased kidney echogenicity suggesting microcysts, and oligohydramnios or anhydramnios. Target enrollment is 20 subjects for Study 204 and ≥ 10 subjects for Study 307.
Follow-up is 24 months in Study 204 (with optional additional treatment up to 36 months) and 18 months in Study 307. Outcomes include safety, tolerability, change in kidney function, and percentage of subjects requiring KRT relative to historical data. Regular safety assessments monitor for possible adverse effects of treatment on parameters such as liver function, kidney function, fluid balance, electrolyte levels, and growth trajectory, with increased frequency of monitoring following tolvaptan initiation or dose escalation.
These trials will provide data on tolvaptan safety and efficacy in a population without disease-specific treatment options.
Study 204: EudraCT 2020-005991-36; Study 307: EudraCT 2020-005992-10.