A randomized, double-blind, phase 3, non-inferiority trial of pradefovir mesylate versus tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B

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.

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Publication Details

Journal
Hepatology
Published
2026-04-06
DOI
https://doi.org/10.1097/hep.0000000000001754
Primary Topic
Hepatitis B Virus Studies
Type
article
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article

A randomized, double-blind, phase 3, non-inferiority trial of pradefovir mesylate versus tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B

Zhongqiang Gao, Shuang Lü, Lvfeng Yao, Shuilin Sun et al.
Hepatology
Hepatitis B Virus Studies
article

A randomized, double-blind, phase 3, non-inferiority trial of pradefovir mesylate versus tenofovir disoproxil fumarate in Chinese patients with chronic hepatitis B

Zhongqiang Gao, Shuang Lü, Lvfeng Yao, Shuilin Sun, Xiangping Xie, Huizhen HZ. Fan, Qu Hongguang, Zhiyong Jiao, Chenxin Meng, fengjun Liu, Xuebing Yan, J Liu, Leiyan Lv, Xihua Fu, Zhong Bei, Qinming Hu, Dengke Zhang, Hesong Cui, Yuan Shufen, Zhijun Su, X L Wang, Suling Chen, Gao Yanhang, Guoqiang Zhang, Wang Zhongfeng, Xinwen Song, Xue-Bing Chen, Youwen Tan, Zong Zhang, Zhihong Liu, Lei Yu, Fangqi Ge, Hainv Gao, Zhenguo Liu, Qianguo Mao, Guangxia Chen, Guangming Li, Yongfang Jiang, Q. Mao, Guicheng Wu, Wang Xinrui, Kong Fei, Hou Jinlin, Chi Zhang, Dong Xiaoping, Daidi Wang, Shang Jia, Tao Han, Kangxin Yu, Liu Weidong, Yichun Bai, Yuanyuan Xu, Shihong Wu, Guofeng Ding, Weili Jin, Junqi Niu, Wenting Zeng, Wenyan He, Yu Yunsong, Xiuhong Wen, Hu Guoxin, Wenhai Zhao, Yuan Wang, Zhao Weifeng, Xiangjun Li, Xiaobo Lu, Mingque Xiang, Chen Hui, Dang Shuangsuo
article en

Abstract

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.

Hepatology
Yuncheng University (CN), Jiangsu University (CN), Binzhou Medical University (CN), Central South University (CN), Nanchang University (CN), Guiyang Medical University (CN), Shandong University of Aeronautics (CN), Army Medical University (CN), Xinjiang Medical University (CN), Harbin Medical University (CN), Petro-Canada (CA), Xuzhou Medical College (CN), Jilin University (CN), Anhui Medical University (CN), Changzhi Medical College (CN), Yichun University (CN), Wenzhou Medical University (CN), Sir Run Run Shaw Hospital (CN), First Affiliated Hospital of Xinjiang Medical University (CN), Shantou University (CN), Quzhou City People's Hospital (CN), Xian Central Hospital (CN), Tianjin Third Central Hospital (CN), Liuzhou General Hospital (CN), People 's Hospital of Jilin Province (CN), Institute of Marine Biotechnology (DE), First Affiliated Hospital of Guangzhou Medical University (CN), Ruian People's Hospital (CN), Central People's Hospital of Zhanjiang (CN), First People's Hospital of Foshan (CN), Qingzhou City People's Hospital (CN), Second Affiliated Hospital of Nanchang University (CN), Affiliated Hospital of North Sichuan Medical College (CN), Affiliated Hospital of Guizhou Medical University (CN), Yue Bei People's Hospital (CN), The First Hospital of Changsha (CN), Deyang Stomatological Hospital (CN), First Affiliated Hospital of Xinxiang Medical University (CN), Mengchao Hepatobiliary Hospital (CN), Guangzhou First People's Hospital (CN), The 180th Hospital of PLA (CN), Second Affiliated Hospital of Shantou University Medical College (CN), People's Hospital of Xinjiang Uygur Autonomous Region (CN), Fourth Affiliated Hospital of Harbin Medical University (CN), Panyu District Central Hospital (CN), First Hospital of Jilin University (CN), Luoyang Central Hospital Affiliated to Zhengzhou University (CN), First Affiliated Hospital of GuangXi Medical University (CN), Buchang Pharma (China) (CN), Chongqing Three Gorges Central Hospital (CN), Zhejiang Shuren University (CN), Peking University Shenzhen Hospital (CN), The First People’s Hospital of Lianyungang (CN), Anhui Provincial Hospital (CN), The Affiliated Yongchuan Hospital of Chongqing Medical University (CN), Xinjiang Uygur Autonomous Region Uygur Medicine Hospital (CN), Yanbian University Hospital (CN), Southwest Hospital (CN), Second Affiliated Hospital of Xi'an Jiaotong University (CN), Henan Provincial People's Hospital (CN), First Affiliated Hospital of Anhui Medical University (CN), Heze Municipal Hospital (CN), The Central Hospital of Shaoyang (CN), China XD Group (China) (CN), Xuzhou No.1 People's Hospital (CN), Zhenjiang City Fourth People's Hospital (CN), Guang’anmen Hospital (CN), Jingzhou Central Hospital (CN), The Sixth People's Hospital of Zhengzhou (CN), Xiamen Chang Gung Hospital (CN), Qujiang People's Hospital (CN), Second Xiangya Hospital of Central South University (CN), Jinan Infectious Disease Hospital (CN), Anhui Xinhua University (CN), Third Xiangya Hospital (CN), The Sixth People's Hospital of Shenyang (CN), First People's Hospital of Chongqing (CN), Changchun University (CN), Chongqing Three Gorges University (CN), Tianjin Medical University (CN), Southern Medical University (CN), Henan Medical University (CN), Chongqing Medical University (CN), Guangzhou Medical University (CN)
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Hepatitis B Virus Studies
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