Li Xiaojiao, Xu Jia, Sun Jixuan, Liu Jingrui, Wu Min, Zhang Hong, Zhu Xiaoxue, Li Cuiyun, Zhang Yingjun, Zhu Jing, Chen Yujie, Luo Lin, He Qingwei, Zhuang Yulei, Chen Yunfu, Niu Junqi, Ding Yanhua
Phase I Clinical Trial Center, the First Hospital of Jilin University, Jilin, China.
Sunshine Lake Pharma Co. Ltd., Dongguan, China.
Liver Int. 2025 Jan;45(1):e16213. doi: 10.1111/liv.16213.
Freethiadine is a novel hepatitis B virus capsid assembly modulator. Herein, we report the safety, tolerability, pharmacokinetics and 28-day antiviral activities of freethiadine.
The study consisted of two parts. Part 1 involved a single-ascending-dose, a multiple-ascending-dose and a food effect study. Part 2 was a double-blind, double-dummy, randomised, entecavir-controlled, multi-dose escalation study in chronic hepatitis B (CHB) patients.
A total of 88 healthy subjects and 40 patients with CHB were enrolled in this study. Freethiadine was well tolerated by both healthy subjects and patients. Among freethiadine-treated patients with CHB, the most common drug-related adverse event was alanine aminotransferase elevation (28.1%) (mostly grade 1 or 2). Both HEC160208 and its active metabolite, HEC142106, were rapidly absorbed and eliminated in plasma. Food intake did not significantly influence the exposure of either analyte. Following 28 days of treatment, the mean maximum HBV DNA declines from baseline were -2.76, -3.47, -3.56, -2.89 and -2.55 log IU/mL for the 100 mg BID, 200 mg QD, 200 mg BID and 300 mg QD of freethiadine or entecavir control cohorts, respectively; simultaneously, the mean maximum pregenomic RNA (pgRNA) declines from baseline were -1.69, -2.26, -2.07, -1.47 and -0.06 log copies/mL, respectively.
Freethiadine has an acceptable safety profile and favourable antiviral activity in patients with CHB. These results support further investigations of freethiadine for the treatment of chronic HBV infection.
www.
gov identifier NCT05391360; www.chinadrugtrials.org.cn identifier CTR20212114.
氟硫二氮是一种新型的乙型肝炎病毒衣壳组装调节剂。在此，我们报告氟硫二氮的安全性、耐受性、药代动力学及28天的抗病毒活性。
本研究包括两部分。第1部分涉及单剂量递增、多剂量递增及食物影响研究。第2部分是一项针对慢性乙型肝炎（CHB）患者的双盲、双模拟、随机、恩替卡韦对照、多剂量递增研究。
本研究共纳入88名健康受试者和40名CHB患者。健康受试者和患者对氟硫二氮均耐受性良好。在接受氟硫二氮治疗的CHB患者中，最常见的药物相关不良事件是丙氨酸氨基转移酶升高（28.1%）（大多为1级或2级）。HEC160208及其活性代谢产物HEC142106在血浆中均迅速吸收和消除。食物摄入对两种分析物的暴露均无显著影响。治疗28天后，氟硫二氮100 mg每日两次、200 mg每日一次、200 mg每日两次和300 mg每日一次组或恩替卡韦对照组的HBV DNA平均最大下降值分别从基线下降-2.76、-3.47、-3.56、-2.89和-2.55 log IU/mL；同时，前基因组RNA（pgRNA）平均最大下降值分别从基线下降-1.69、-2.26、-2.07、-1.47和-0.06 log拷贝/mL。
氟硫二氮在CHB患者中具有可接受的安全性和良好的抗病毒活性。这些结果支持进一步研究氟硫二氮用于治疗慢性HBV感染。
www.
gov标识符NCT05391360；www.chinadrugtrials.org.cn标识符CTR20212114。
