慢性乙型肝炎患者的普瑞福韦治疗：多中心、双盲、随机、

StephenW

慢性乙型肝炎患者的普瑞福韦治疗：多中心、双盲、随机、非劣效性 2 期试验的第 24 周结果
高彦航，孔飞，宋新文，贾尚，姚吕峰，夏金宇，彭延中，刘卫东，龚焕宇，毛木，崔和松，韩涛，陈文，吴小璐，杨永峰，闫学兵，金振静, 王鹏, 朱清静, 陈亮, 赵彩艳, 张登科, 金伟丽, 王戴迪, 文秀红, 刘春梅, 贾继东, 毛青, 丁艳华, 金学元, 张宗, 毛千国, 李光明, 俊奇牛
作者备注
临床传染病，第 74 卷，第 11 期，2022 年 6 月 1 日，第 1925-1932 页，https://doi.org/10.1093/cid/ciab763
发表：
2021 年 9 月 6 日
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抽象的
背景

普瑞福韦是阿德福韦的肝脏靶向前药，阿德福韦是一种核苷/核苷酸类似物，具有抗乙型肝炎病毒 (HBV) DNA 聚合酶的抗病毒活性。这项 2 期研究比较了口服 pradefovir（30、45、60 或 75 mg）与富马酸替诺福韦地索普西（TDF；300 mg）的疗效和安全性，旨在为即将进行的 3 期研究确定最合适的 pradefovir 剂量。
方法

初治和有经验（未接受治疗>6 个月）的慢性乙型肝炎患者符合条件。
结果

共有 240 名参与者在研究中被随机分配并接受治疗（每组 48 名）。约 80% 为乙型肝炎 e 抗原 (HBeAg) 阳性，10% 为肝硬化。在第 24 周达到的 HBV DNA 水平从基线降低分别为 5.40、5.34、5.33 和 5.40 log10 IU/mL，普瑞福韦剂量分别为 30-、45-、60- 和 75-mg，而 5.12 log10含 TDF 的 IU/mL。然而，接受 45-、60- 或 75-mg pradefovir 的参与者比接受 TDF 的参与者更多（12%、6% 和 9% 对 3%）。与普瑞福韦 30 和 45 毫克组相比，TDF 组的血清肌酐升高更为显着，并且所有组的血清磷酸盐水平相当。大多数不良事件 (AE) 是轻微的（1 级）。没有报告与治疗相关的严重不良事件。总体而言，AE 和实验室异常与 TDF 组相当。
结论

Pradefovir 和 TDF 在 HBV DNA 水平上表现出相当的降低。所有治疗均安全且耐受性良好。
临床试验注册

NCT00230503和中国药物试验CTR2018042
普瑞福韦、富马酸替诺福韦酯、乙型肝炎、疗效、安全性
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StephenW

Pradefovir Treatment in Patients With Chronic Hepatitis B: Week 24 Results From a Multicenter, Double-Blind, Randomized, Noninferiority, Phase 2 Trial
Yanhang Gao, Fei Kong, Xinwen Song, Jia Shang, Lvfeng Yao, Jinyu Xia, Yanzhong Peng, Weidong Liu, Huanyu Gong, Mao Mu, Hesong Cui, Tao Han, Wen Chen, Xiaolu Wu, Yongfeng Yang, Xuebing Yan, Zhenjing Jin, Peng Wang, Qingjing Zhu, Liang Chen, Caiyan Zhao, Dengke Zhang, Weili Jin, Daidi Wang, Xiuhong Wen, Chunmei Liu, Jidong Jia, Qing Mao, Yanhua Ding, Xueyuan Jin, Zong Zhang, Qianguo Mao, Guangming Li, Junqi Niu
Author Notes
Clinical Infectious Diseases, Volume 74, Issue 11, 1 June 2022, Pages 1925–1932, https://doi.org/10.1093/cid/ciab763
Published:
06 September 2021
Article history

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Abstract
Background

Pradefovir is a liver-targeted prodrug of adefovir, a nucleoside/nucleotide analogue with antiviral activity against hepatitis B virus (HBV) DNA polymerase. This phase 2 study compared the efficacy and safety of oral pradefovir (30, 45, 60, or 75 mg) versus tenofovir disoproxil fumarate (TDF; 300 mg) and aimed to identify the most appropriate dose of pradefovir for the forthcoming phase 3 study.
Methods

Treatment-naive and experienced (not on treatment >6 months) patients with chronic hepatitis B were eligible.
Results

A total of 240 participants were randomized and treated in the study (48 per group). Approximately 80% were hepatitis B e antigen (HBeAg) positive, and 10% had liver cirrhosis. The reductions from baseline in HBV DNA levels achieved at week 24 were 5.40, 5.34, 5.33, and 5.40 log10 IU/mL, with pradefovir doses of 30-, 45-, 60-, and 75-mg, respectively, compared with 5.12 log10 IU/mL with TDF. However, HBeAg loss was attained by more participants who received 45-, 60-, or 75-mg pradefovir than by those receiving TDF (12%, 6%, and 9% vs 3%). The TDF group exhibited a more significant increase in serum creatinine than the pradefovir 30- and 45-mg groups, and serum phosphate levels were comparable among all groups. Most adverse events (AEs) were mild (grade 1). No treatment-related severe AEs were reported. Overall, AEs and laboratory abnormalities were comparable to those in the TDF group.
Conclusions

Pradefovir and TDF exhibited comparable reductions in HBV DNA levels. All treatments were safe and well tolerated.
Clinical Trials registration

NCT00230503 and China Drug Trials CTR2018042
pradefovir, tenofovir disoproxil fumarate, hepatitis B, efficacy, safety
Issue Section:
MAJOR ARTICLES AND COMMENTARIES

StephenW

https://academic.oup.com/cid/adv ... 1162823/ciab763.pdf