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©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
Tenofovir disoproxil fumarate in Chinese chronic hepatitis B patients: Results of a multicenter, double-blind, double-dummy, clinical trial at 96 weeks
Xiao-Fan Chen, Ya-Nan Fan, Chong-Wen Si, Yan-Yan Yu, Jia Shang, Zu-Jiang Yu, Qing Mao, Qing Xie, Wei Zhao, Jun Li, Zhi-Liang Gao, Shan-Ming Wu, Hong Tang, Jun Cheng, Xin-Yue Chen, Wen-Hong Zhang, Hao Wang, Zhong-Nan Xu, Ling Wang, Jun Dai, Jing-Hang Xu
Xiao-Fan Chen, Ya-Nan Fan, Chong-Wen Si, Yan-Yan Yu, Jing-Hang Xu, Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, Beijing 100034, China
Jia Shang, Department of Infectious Diseases, Henan Provincial People's Hospital, Zhengzhou 450003, Henan Province, China
Zu-Jiang Yu, Department of Infectious Diseases, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Qing Mao, Department of Infectious Diseases, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing 400038, China
Qing Xie, Department of Infectious Diseases, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai 200025, China
Wei Zhao, Department of Infectious Diseases, The Second Affiliated Hospital of Southeast University, Nanjing 210011, Jiangsu Province, China
Jun Li, Department of Infectious Diseases, The First Affiliated Hospital with Nanjing Medical University, Nanjing 210029, Jiangsu Province, China
Zhi-Liang Gao, Department of Infectious Diseases, The Third Affiliated Hospital, Sun Yat-sen University, Guangzhou 510630, Guangdong Province, China
Shan-Ming Wu, Department of Infectious Diseases, Shanghai Public Health Clinical Center, Fudan University, Shanghai 201052, China
Hong Tang, Department of Infectious Diseases, West China Hospital of Sichuan University, Chengdu 610041, Sichuan Province, China
Jun Cheng, Center of Hepatology, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China
Xin-Yue Chen, Department of International Medical, Beijing Youan Hospital, Capital Medical University, Beijing 10069, China
Wen-Hong Zhang, Department of Infectious Diseases, Huashan Hospital, Fudan University, Shanghai 200040, China
Hao Wang, Department of Infectious Diseases, Peking University People's Hospital, Beijing 100044, China
Zhong-Nan Xu, Ling Wang, Jun Dai, Clinical Center, Jiangsu Chia-tai Tianqing Pharmaceutical Co., Ltd, Nanjing 210000, Jiangsu Province, China
Author contributions: Chen XF and Fan YN wrote the article; Yu YY, Xu JH, and Si CW formatted and revised the article; Shang J, Yu ZJ, Mao Q, Xie Q, Zhao W, Li J, Gao ZL, Wu SM, Tang H, Cheng J, Chen XY, Zhang WH, and Wang H provided data from various clinical centers; Xu ZN, Wang L, and Dai J made statistics.
Supported by The 13th Five-year Science and Technology Major Project of China, on the Prevention and Treatment of Major Infectious Diseases, No. 2017ZX10202202.
Institutional review board statement: The study was reviewed and approved by the Ethics Committees of the 14 study sites, including Peking University First Hospital, China, and all procedures performed in this study were in accordance with the ethical standards of the institutional research committee and with the 1964 Helsinki Declaration and its later amendments (approval No. 2013L01048).
Clinical trial registration statement: This study is registered at ClinicalTrials.gov. The registration identification number is NCT02287857.
Informed consent statement: All study participants, or their legal guardian, provided informed written consent prior to study enrollment.
Conflict-of-interest statement: Nothing to declare.
Data sharing statement: Data sets are available from the corresponding author (yyy@bjmu.edu.cn). The presented data are anonymized, and the risk of identification is low. No additional data are available.
CONSORT 2010 statement: The authors have read the CONSORT 2010 statement, and the manuscript was prepared and revised according to the CONSORT 2010 statement.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
http://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Jing-Hang Xu, MD, PhD, Professor, Department of Infectious Diseases, Center for Liver Diseases, Peking University First Hospital, No. 8 Xishiku Street, Xicheng District, Beijing 100034, China. ddcatjh@sina.com
Received: December 17, 2020
Peer-review started: December 17, 2020
First decision: January 7, 2021
Revised: January 24, 2021
Accepted: April 21, 2021
Article in press: April 21, 2021
Published online: June 26, 2021
ARTICLE HIGHLIGHTS
Research background
Tenofovir disoproxil fumarate (TDF) is a prodrug of a nucleotide analogue. As an antiviral drug, TDF has been proposed in the first-line treatment of chronic hepatitis B (CHB). The National Medical Products Administration has approved two brand names of TDF, namely, Qingzhong, which was commercialized by Jiangsu Chia-tai Tianqing Pharmaceutical Co Ltd., and Viread, which was commercialized by GlaxoSmithKline.
Research motivation
The safety and efficacy of Viread have been confirmed in previous trials. However, the cost of long-term treatment with Viread is high. As a generic TDF drug, Qingzhong exhibited comparable efficacy and safety with Viread in the treatment of naive Chinese CHB patients during a 48-wk trial, thus providing a less expensive option for treating CHB. However, the long-run performance of Qingzhong in the treatment of CHB remains unevaluated.
Research objectives
To investigate the efficacy and safety of the two TDF agents in the treatment of Chinese CHB patients.
Research methods
This is a 5-year-long, multicenter, double-blinded, double-dummy, randomized-controlled, non-inferiority phase III trial, in which 330 Chinese CHB patients were finally included. The decrease in plasma level of hepatitis B virus (HBV) DNA was continuously monitored. In addition, viral suppression, alanine aminotransferase (ALT) levels, hepatitis B e antigen (HBeAg) loss rates, and HBeAg seroconversion rates were also determined.
Research results
Among the 330 CHB patients involved in this trial, there were 232 HBeAg(+) CHB participants. For these participants, the decrease in mean HBV DNA level relative to the baseline value was comparable between Groups A and B at the 96th week. In addition, similar percentages of participants in the two groups exhibited undetectable levels of HBV DNA, HBeAg loss, and HBeAg seroconversion at the 96th week. Similar results were observed for the remaining 98 HBeAg(-) CHB participants: Similar degrees of reduction in mean HBV DNA level relative to the baseline and similar percentages of participants who had undetectable levels of HBV DNA were observed between the two groups at the 96th week. Finally, the two groups of participants [participants with both HBeAg(+) and HBeAg(-) CHB] presented with similar rates of ALT normalization and similar incidences of adverse events.
Research conclusions
This 96-wk-long phase III trial demonstrated the effectiveness and safety of utilizing Qingzhong in the treatment of Chinese patients with HBeAg (+) and HBeAg (-) CHB—the TDF drug showed comparable efficacy and safety with Viread. Hence, with its lower cost, Qingzhong may become a better choice for Chinese CHB patients who need long-term treatment with TDF drugs in the future.
Research perspectives
Since this study only elaborated the performance of Qingzhong during a 96-wk period, the longer-term safety and efficacy of the TDF drug remain unsure. Therefore, the longer-term performance of Qingzhong in the treatment of CHB patients warrants further attention.
