Hepatitis B, Chronic
Conditions
Keywords
Hepatitis B, Chronic；HBV infection
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.
Interventions
Once-daily oral dose of 25 mg TMF were maintained in all participants
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
| 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 | — |
| 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. |
Countries
China
Outcome results
None listed