随机 I 期临床试验——一刀切？
Randomized Phase I Trials - One Size Fits All?
机构信息
Department of Biostatistics and Bioinformatics, Duke University, Durham, NC.
Institute of Health System Science, Feinstein Institutes for Medical Research, Northwell Health, NY.
出版信息
NEJM Evid. 2023 Dec;2(12):EVIDe2300282. doi: 10.1056/EVIDe2300282. Epub 2023 Nov 28.
In this issue of , Gaudet et al. present the safety profile and pharmacodynamics of ARO-APOC3, a small interfering RNA therapeutic that inhibits apolipoprotein C-III (APOC3) mRNA expression in a phase I trial. Assignment to treatment was based on fasting levels of triglycerides. The trial included two double-blinded cohorts with 52 randomly assigned healthy participants and 40 patients with hypertriglyceridemia assigned to escalating doses of ARO-APOC3 at 10, 25, 50, or 100 mg or placebo in a single- and/or repeat-dose (days 1 and 29) regimen. An open-label cohort of patients with chylomicronemia was treated with ARO-APOC3 at 50 mg.
本期《新英格兰医学杂志》刊登了 Gaudet 等人的研究报告，介绍了靶向载脂蛋白 C-III（APOC3）的小干扰 RNA 药物 ARO-APOC3 的安全性特征和药效学。该药物可抑制 APOC3mRNA 的表达，Ⅰ期临床试验采用了基于空腹甘油三酯水平的分组方法。试验共纳入了两个双盲队列，分别有 52 名健康志愿者和 40 名高甘油三酯血症患者入组，按照 10、25、50 或 100mg 递增剂量或安慰剂（单次和/或重复剂量，第 1 天和第 29 天）方案，接受 ARO-APOC3 治疗。另有一个开放标签队列纳入了伴有乳糜微粒血症的患者，给予 50mg 的 ARO-APOC3 治疗。
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