Article
Author: Wang, Daidi ; Hong, Liang ; Yu, Kangxin ; Wang, Xiaozhong ; Zhao, Wenhai ; Liu, Fengjun ; Meng, Chenxin ; Chen, Hui ; Gao, Yufeng ; Lu, Shuang ; Zhang, Zong ; Yao, Lvfeng ; Li, GuangMing ; Wang, Xinrui ; Dang, Shuangsuo ; Yan, Xuebing ; Liu, Zhenguo ; Xie, Xiangping ; Jin, Weili ; Chen, Xuebing ; Fu, Xihua ; Song, Xinwen ; Chen, Suling ; Ge, Fangqi ; Liu, Zhihong ; Su, Zhijun ; Yu, Yunsong ; Yu, Lei ; Zhao, Weifeng ; Bai, Yichun ; Zhang, Chi ; Ding, Guofeng ; Xu, Yuanyuan ; Fan, Huizhen ; Gao, Zhongqiang ; Zeng, Wenting ; Sun, Shuilin ; Han, Tao ; Shang, Jia ; Mao, Qianguo ; Wen, Xiuhong ; Wu, Guicheng ; Zhong, Bei ; Qu, Hongguang ; Yuan, Shufen ; Chen, Guangxia ; He, Wenyan ; Hu, Guoxin ; Lv, Leiyan ; Jiang, Yongfang ; Cui, Hesong ; Mao, Qing ; Zhang, Guoqiang ; Li, Xiangjun ; Hu, Qinming ; Jiao, Zhiyong ; Wang, Yuan ; Tan, Youwen ; Wang, Zhongfeng ; Liu, Weidong ; Hou, Jinlin ; Xiang, Mingque ; Wu, Shihong ; Kong, Fei ; Niu, Junqi ; Zhang, Dengke ; Liu, Jinfeng ; Dong, Xiaoping ; Gao, Hainv ; Gao, Yanhang ; Lu, Xiaobo
Background and Aims::Pradefovir mesylate is a novel liver-targeting prodrug of adefovir developed using HepDirect technology. We report that the phase 3 trial is to compare the efficacy and safety of pradefovir versus tenofovir disoproxil fumarate (TDF) in patients with chronic hepatitis B (CHB).
Approach and Results::
This ongoing randomized, double-blind, non-inferiority, phase 3 study was conducted at 58 sites in China. Patients with CHB were randomly assigned (2:1) to receive either 45 mg daily pradefovir or 300 mg daily TDF with a matching placebo. The primary efficacy endpoint was defined as the proportion of patients whose HBV DNA level was <29 IU/mL at week 48. All participants who received at least 1 dose of the study drug were included in efficacy and safety analyses with pre-specified renal and bone endpoints at week 96. A total of 1170 patients were screened during the study, and 908 patients received the study drug. At week 48, viral suppression (HBV DNA <29 IU/mL) rates of pradefovir were non-inferior to TDF in HBeAg-positive [−1.8% (95% CI: −9.7 to 6.1)] and HBeAg-negative [2.6% (95% CI: −5.1 to 10.3)] patients, using a non-inferiority margin of −12%. By week 96, HBeAg-positive patients showed significantly greater HBsAg decline (≥1 log
10
IU/mL) with pradefovir (39.3% vs. 29.9%). Pradefovir demonstrated a more favorable safety profile at week 96, including significantly fewer drug-related adverse events (58.6% vs. 71.9%), improved bone/renal safety, and a lower incidence of elevated creatine phosphokinase–MB.
Conclusions::Pradefovir should be a highly recommended treatment option for adult patients with CHB.