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

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.

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.