The Effectiveness and Safety of TMF in the Treatment of Chronic Hepatitis B Patients With Normal ALT.

Study Overview
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Brief Summary
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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 at week 48.

Detailed Description
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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.

Official Title
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A Prospective, Randomized, Blank Control, Multicenter Study to Evaluate the Efficacy and Safety of Alanine Aminotransferase（TMF）in the Treatment of Chronic Hepatitis B Patients With Normal Alanine Aminotransferase.

Conditions
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HBV Infection, Chronic Hepatitis b

Intervention / Treatment
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* Drug: Tenofovir Amibufenamide（TMF）


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must have the ability to understand and sign a written informed consent form, which must be obtained prior to initiation of study screening. 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. Documented evidence of chronic HBV infection (e.g. HBsAg positive for more than 6 months). Normal alanine aminotransferase: serum HBV DNA >20 IU/mL and serum ALT level ≤ULN (40 IU/L) during screening. Treatment-naive subjects will be eligible for enrollment. Must be willing and able to comply with all study requirements. Exclusion Criteria: Pregnant women, women who are breastfeeding or who believe they may wish to become pregnant during the course of the study. Males and females of reproductive potential who are unwilling to use an effective, protocol specified method(s) of contraception during the study. Co-infection with HCV virus, HIV, HEV or HDV or combined with autoimmune liver disease, metabolism-related fatty liver disease, drug-induced liver injury; Evidence of hepatocellular carcinoma (e.g. as evidenced by recent imaging). 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. 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 Received solid organ or bone marrow transplant. 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). Currently receiving therapy with immunomodulators (e.g. corticosteroids), investigational agents, nephrotoxic agents, or agents capable of modifying renal excretion. Complicated with uncontrollable cardiovascular and cerebrovascular diseases. 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. Current alcohol or substance abuse judged by the investigator to potentially interfere with participant compliance. 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TMF treatment group<br>TMF 25mg QD, from baseline to 48 weeks | Drug: Tenofovir Amibufenamide（TMF）<br>* TMF, 25mg QD, from baseline to 48 weeks<br>* Other names: HengMu;|
| No Intervention: Blank control group<br>No antiviral therapy is given. If ALT>2 ULN (40 IU/L) for HBeAg-positive patients or > ULN for HBeAg-negative patients during the study period, blank control group can be switched to TMF treatment once a day, 25mg/ time orally until the end of the study. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation the percentage of Participants with Hepatitis B Virus (HBV) DNA < 20 IU/mL | The primary efficacy endpoint was the proportion of patients with HBV DNA < 20 IU/mL at week 48 | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation the change from Baseline in HBV DNA | Change from baseline in HBV DNA | Week 48 | 
| Evaluation the proportion of Patients Achieving Hepatitis B Surface Antigen (HBsAg) Loss | Proportion of patients achieving Hepatitis B surface antigen (HBsAg) loss | Week 48 | 
| Evaluation the proportion of Patients Achieving HBsAg Seroconversion | Proportion of patients achieving HBsAg seroconversion | Week 48 | 
| Evaluation the proportion of Patients Achieving HBeAg Seroconversion | Proportion of patients achieving HBeAg seroconversion | Week 48 | 
| Evaluation the proportion of Patients Achieving HBeAg Loss | Proportion of patients Achieving HBeAg Loss | Week 48 | 
| Evaluation the change from Baseline in HBsAg | Change from baseline in HBsAg | Week 48 | 
| Evaluation the percentage of Participants with resistance | Percentage of participants with resistance | Week 48 | 
| Evaluation the change from Baseline in liver fibrosis | Change from baseline in liver fibrosis | Week 48 | 
| Evaluation the proportion of Patients with get hepatitis acute attack（ALT >5 ULN (40 IU/L)） | Proportion of patients with get hepatitis acute attack（ALT >5 ULN (40 IU/L)） | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Normal Alanine Aminotransferase, Treatment, Effectiveness, Safety