Long-term Safety and Efficacy of Tenofovir Amibufenamide in Patients With CHB

Long-term Safety and Efficacy of Tenofovir Amibufenamide in Patients With HBeAg-positive or HBeAg-negative Chronic Hepatitis B - a Multicenter, Open-label Follow-up Study

Tenofovir amibufenamide (TMF) is a novel prodrug of tenofovir that has been widely used in mainland China for the treatment of chronic hepatitis B (CHB). The previous registrational study (NCT03903796) has established the non-inferior virologic efficacy of TMF to tenofovir disoproxil fumarate (TDF), while demonstrating higher rates of alanine aminotransferase (ALT) normalization and improved bone and renal safety profiles. This study presented the long-term efficacy and safety of TMF in a phase IV study.

Study Overview

• Status: Active, not recruiting
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: Tenofovir Amibufenamide（TMF）

Detailed Description

Participants from the Phase III registrational trial of TMF were enrolled and followed for another seven years, starting at week 144 in the Phase III study as the baseline. Once-daily oral dose of 25 mg TMF were maintained in all participants. Clinical assessments were conducted every 24 weeks. The primary efficacy endpoint was the percentage of patients with serum HBV DNA levels below the quantification limit at week (144+) 96.

• Study Type: Interventional
• Enrollment (Actual): 640
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Guangzhou, Guangdong, China, 510060
      • Nanfang Hospital, Southern Medical University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients with HBeAg-positive or HBeAg-negative chronic hepatitis B who completed a pivotal Phase III clinical study of HS-10234-301

Exclusion Criteria:

• 1) Completion of HS-10234-301 pivotal Phase III clinical study Interruption of TMF treatment for more than 24 weeks or continuous use of alternative, commercially available hepatitis B antivirals for more than 24 weeks (Participants who have discontinued TMF for more than 24 weeks can only be enrolled in this study after investigator evaluation and confirmation) 2）Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging). 3)significant bone disease (e.g. osteomalacia, chronic osteomyelitis, osteogenesis imperfecta, osteochrondroses), or multiple bone fractures.

  4）Currently receiving therapy with immunomodulators (e.g. corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion.

  5）Known hypersensitivity to study drugs, metabolites, or formulation excipients.

  6) In the investigator's judgment, current alcohol or substance abuse may interfere with the subject's compliance with the study requirements 7）Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TMF treatment group	Drug: Tenofovir Amibufenamide（TMF）; Once-daily oral dose of 25 mg TMF were maintained in all participants; Other Names: HS-10234

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA lower than in the central laboratory	The primary efficacy endpoint was the proportion of patients with HBV DNA lower than in the central laboratory at week (144+)96.	week (144+)96

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
The proportion of subjects with HBV DNA with lower than in the central laboratory	The proportion of patients with HBV DNA lower than in the central laboratory at week(144+)240、week(144+)336	week(144+)240、week(144+)336
Proportion of subjects with ALT normalization rate	The proportion of patients with normal ALT	week (144+)96、week (144+)240、week (144+)336
Proportion of Patients Achieving HBsAg loss，HBsAg conversion	The denominator of HBsAg loss was the number of HBsAg- positive patients at 144 weeks. The denominator of HBsAg seroconversion was the number of HBsAg positive and anti-HBs negative persons at 144 weeks.	week (144+)96、week (144+)240、week (144+)336
Incidence of resistance mutation	Resistance detection when a virological breakthrough occurs	week (144+)96、week (144+)240、week (144+)336
Progression of liver disease associated with HBV infection	The proportion of patients with new HCC, Decompensated liver cirrhosis, death related to Hepatitis B	week (144+)96、week (144+)240、week (144+)336
Proportion of Patients Achieving HBeAg loss，HBeAg conversion ratio	The denominator of HBeAg loss was the number of HBeAg- positive patients at 144 weeks. The proportion of HBeAg seroconversion was the number of HBeAg positive and anti-HBs negative persons at 144 weeks.	week (144+)96、week (144+)240、week (144+)336
Percent Change from Baseline in Hip and spine Bone Mineral Density (BMD)	measured by dual energy x-ray absorptiometry(DXA)	week (144+)96、week (144+)240、week (144+)336
Change from Baseline in Serum Creatinine		week (144+)96、week (144+)240、week (144+)336
Change in HBV DNA from baseline		week (144+)96、week (144+)240、week (144+)336

Collaborators and Investigators

• Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Junqi Niu, MD, The First Hospital of Jilin University; Principal Investigator: Qing Xie, MD, Ruijin Hospital; Principal Investigator: Xuebing Yan, MD, The Affiliated Hospital of Xuzhou Medical University; Principal Investigator: Wenhong Zhang, MD, Huashan Hospital; Principal Investigator: Jinlin Hou, M.M, Nanfang Hospital, Southern Medical University; Principal Investigator: Guicheng Wu, MD, Chongqing University Affiliated Three Gorges Hospital; Principal Investigator: Peng Hu, MD, The second affiliated hospital of chongqiong medical university; Principal Investigator: Lvfeng Yao, Mengchao Hepatopiliary Hospital of Fujian Medical University; Principal Investigator: Minghua Su, MM, First Affiliated Hospital of Guangxi Medical University; Principal Investigator: Xiaoqing Fu, MM, Hangzhou Xixi Hospital; Principal Investigator: Caiyan Zhao, MD, Third hospital of Hebei Medical University; Principal Investigator: Jia Shang, Henan Provincial People's Hospital; Principal Investigator: Xiaorong Mao, MD, LanZhou University; Principal Investigator: Shufang Yuan, MD, Liuzhou people's Hospital; Principal Investigator: Jie Li, MD, The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School; Principal Investigator: Qin Zhang, MD, Tongren Hospital,Shanghai Jiao Tong University School of Medicine; Principal Investigator: Desheng Xie, MM, Shanghai Fifth People's Hospital; Principal Investigator: Liang Chen, MM, Shanghai Public Health Clinical Center; Principal Investigator: Yao Xie, MD, Beijing Ditan Hospital; Principal Investigator: Jidong Jia, MD, Beijing Friendship Hospital; Principal Investigator: Enqiang Chen, MD, West China Hospital; Principal Investigator: Xingxiang Yang, MM, Sichuan Academy of Medical Sciences; Principal Investigator: Fengmei Wang, MD, Tianjin Third Central Hospital; Principal Investigator: MingQin Lu, MM, The first hospital of Wenzhou Medical University; Principal Investigator: Lihua Sun, MD, First Affiliated Hospital of Xinjiang Medical University; Principal Investigator: Daokun Yang, MM, First Affiliated Hospital of Xinjiang Medical University; Principal Investigator: Huazhong Chen, MM, Taizhou Hospital of Zhejiang Province affiliated to Wenzhou Medical University; Principal Investigator: Min Zhang, MD, Central South University; Principal Investigator: Yan Huang, MD, Xiangya Hospital of Central South University; Principal Investigator: Yawen Luo, MM, Zunyi Medical College; Principal Investigator: Lihua Zhong, MM, The Fourth Affiliated Hospital of Harbin Medical University; Principal Investigator: Min Xie, Guangzhou Eighth People's Hospital; Principal Investigator: Jun Li, MD, Jiangsu Provincial People's Hospital (The First Affiliated Hospital of Nanjing Medical University)

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Actual): June 30, 2024
• Study Completion (Estimated): September 30, 2029

Study Registration Dates

• First Submitted: December 13, 2024
• First Submitted That Met QC Criteria: December 16, 2024
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: December 16, 2024
• Last Verified: December 1, 2024

More Information

Terms related to this study

• Keywords: Hepatitis B, Chronic；HBV infection
• Additional Relevant MeSH Terms: Blood-Borne Infections; Pathologic Processes; Chronic Disease; Disease Attributes; Infections; RNA Virus Infections; Virus Diseases; Digestive System Diseases; Liver Diseases; Hepatitis, Viral, Human; Enterovirus Infections; Picornaviridae Infections; Communicable Diseases; DNA Virus Infections; Hepadnaviridae Infections; Hepatitis, Chronic; Hepatitis A; Hepatitis; Hepatitis B; Hepatitis B, Chronic; Anti-Infective Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Antiviral Agents; Reverse Transcriptase Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: HS-10234-401

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No