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

Phase 4

Active, not recruiting

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: Tenofovir Amibufenamide（TMF）

• Registration Number: NCT06743438
• Lead Sponsor: Jiangsu Hansoh Pharmaceutical Co., Ltd.

Brief Summary

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.

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 Timeline

• Study Start: 2022-03-10
• Primary Completion: 2024-06-30
• Status Verified: 2024-12
• Study First Submitted: 2024-12-13
• Study First Submitted QC: 2024-12-16
• Last Update Submitted: 2024-12-16
• Study First Posted: 2024-12-19
• Last Update Posted: 2024-12-19
• Study Completion: 2029-09-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 640

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
TMF treatment group	Tenofovir Amibufenamide（TMF）	-

Primary Outcome Measures

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

Secondary Outcome Measures

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

Trial Locations

Locations (1)

Nanfang Hospital, Southern Medical University; 🇨🇳 Guangzhou, Guangdong, China