Chronic Hepatitis b, HBV Infection
Conditions
Keywords
Normal Alanine Aminotransferase, Treatment, Effectiveness, Safety
Brief summary
This is a multicenter, randomized, open, blank controlled trial ，in order to evaluate the effectiveness and safety of Amibufenamide（TMF） in the treatment of chronic hepatitis B virus infection patients with normal ALT .
Detailed description
Although the indications for antiviral therapy for patients with chronic hepatitis B have been gradually expanded in different guidelines, antiviral treatment efficacy remains unclear among patients with alanine aminotransferase (ALT) \< 1 upper limits of normal (ULN). This study aimed to evaluate the the effectiveness and safety of TMF for these patients. Tenofovir amibufenamide (TMF; codename: HS-10234), another formulation of tenofovir, shared the same ProTide technology as tenofovir alafenamide, which can provide more efficient intracellular delivery than TDF.
Interventions
TMF, 25mg QD, from baseline to 240 weeks
Sponsors
Jiangsu Hansoh Pharmaceutical Co., Ltd.
Ruijin Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
The subjects were randomly divided into two groups. One group received TMF treatment for 48 weeks. Aonther group received no antiviral therapy and served as a blank control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study screening. 2. Male and non-pregnant, non-lactating females, from 18 up to 65 years of age (based on the date of the screening visit). A negative serum pregnancy test at screening is required for female subjects of childbearing potential. 3. Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months). 4. Normal alanine aminotransferase: serum HBV DNA \>20 IU/mL and serum ALT level ≤ULN (40 IU/L) during screening. 5. Treatment-naive subjects will be eligible for enrollment. 6. Must be willing and able to comply with all study requirements.
Exclusion criteria
1. Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study. 2. Males and females of reproductive potential who are unwilling to use an effective, protocol specified method(s) of contraception during the study. 3. Co-infection with HCV virus, HIV, HEV or HDV or combined with autoimmune liver disease, metabolism-related fatty liver disease, drug-induced liver injury; 4. Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging). 5. Any history of, or current evidence of, clinical hepatic decompensation (e.g. ascites encephalopathy or variceal hemorrhage) or liver stiffness over 9kpa measured by TE. 6. Abnormal hematological and biochemical parameters, including: Hemoglobin \< 10 g/dl Absolute neutrophil count \< 0.75 × 10\^9/L Platelets ≤ 50 × 10\^9/L AST \> 10 × ULN Total Bilirubin \> 2.5 × ULN Albumin \< 3.0 g/dL INR \> 1.5 × ULN (unless stable on anticoagulant regimen) eGFR\<50mL/min 7. Received solid organ or bone marrow transplant. 8. Malignancy within the 5 years prior to screening, with the exception of specific cancers that are cured by surgical resection (basal cell skin cancer, etc). 9. Currently receiving therapy with immunomodulators (e.g. corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion. 10. Complicated with uncontrollable cardiovascular and cerebrovascular diseases. 11. Subjects on prohibited concomitant medications. Subjects on prohibited medications, otherwise eligible, will need a wash out period of at least 30 days,Known hypersensitivity to study drugs, metabolites, or formulation excipients. 12. Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance. 13. Any other clinical condition or prior therapy that, in the opinion of the Investigator, would make the subject unsuitable for the study or unable to comply with dosing requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL | Week 48 | The primary efficacy endpoint was the proportion of patients with HBV DNA \< 20 IU/mL at week 48 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Evaluation the proportion of Patients Achieving Hepatitis B Surface Antigen (HBsAg) Loss | Week 48，Week 96，Week 144，Week 240 | Proportion of patients achieving Hepatitis B surface antigen (HBsAg) loss |
| Evaluation the proportion of Patients Achieving HBsAg Seroconversion | Week 48，Week 96, Week 144, Week 240 | Proportion of patients achieving HBsAg seroconversion |
| Evaluation the proportion of Patients Achieving HBeAg Seroconversion | Week 48，Week 96，Week 144, Week 240 | Proportion of patients achieving HBeAg seroconversion |
| Evaluation the proportion of Patients Achieving HBeAg Loss | Week 48，Week 96，Week 144 ，Week 240 | Proportion of patients Achieving HBeAg Loss |
| Evaluation the change from Baseline in HBsAg | Week 48，Week 96，Week 144，Week 240 | Change from baseline in HBsAg |
| Evaluation the percentage of Participants with resistance | Week 48，Week 96，Week 144，Week 240 | Percentage of participants with resistance |
| Evaluation the change from Baseline in HBV DNA | Week 48，Week 96，Week 144，week 240 | Change from baseline in HBV DNA |
| Evaluation the proportion of Patients with get hepatitis acute attack（ALT >5 ULN (40 IU/L)） | Week 48，Week 96，Week 144，Week 240 | Proportion of patients with get hepatitis acute attack（ALT \>5 ULN (40 IU/L)） |
| Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL | Week 96，Week 144，Week 240 | — |
| Evaluation the change from Baseline in Bone biomarker（β-CTX and P1NP） | Week 48，Week 96，Week 144，Week 240 | — |
| Evaluation the change from Baseline in sCR | Week 48，Week 96，Week 144，Week 240 | — |
| AE ,SAE | Week 48，Week 96，Week 144，Week 240 | — |
| The proportion of subjects with liver-related events | Week 48，96，144，192，240 | Liver decompensation, acute-on-chronic liver failure, hepatocellular carcinoma, liver transplantation, all-cause mortality |
| Evaluation the change from Baseline in liver fibrosis | Week 48，Week 96，Week 144，Week 240 | Change from baseline in liver fibrosis |
Countries
China
Outcome results
None listed