The Efficacy and Safety of Tenofovir Amibufenamide to Treat Low-level Viraemia After Entecavir Treatment

Study Overview
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Brief Summary
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The goal of this observational study is to explore the efficacy and safety of Tenofovir Amibufenamide (TMF) in Entecavir (ETV) treated chronic hepatitis B patients with low-level viraemia. The main question it aims to answer is: The efficacy and safety of TMF in chronic hepatitis B patients with low-level viraemia. What is the appropriate treatment for ETV treated chronic hepatitis B patients with low-level viraemia. Participants will choose to maintain their original regimen (ETV) or switch to TMF After being fully informed of the benefits and risks of treatment. Researchers will compare ETV and TMF to see if there is a difference in the efficacy of the two drugs in chronic hepatitis B patients with low-level viraemia.

Official Title
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To Evaluate the Efficacy and Safety of Tenofovir Amibufenamide in Chronic Hepatitis B (CHB) Patients With Low-level Viraemia (LLV) After Entecavir Treatment

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: TMF


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be able to understand and sign a written informed consent, which must be obtained prior to screening. Male and non-pregnant, non-lactating female subjects who have reached the age of 18-65 years (based on the date of signed informed consent). Female subjects of childbearing age with a negative serum pregnancy test. Documented signs of chronic HBV infection (e.g., HBsAg positive for more than 6 months. Subjects treated with ETV over 1 year will be able to be enrolled in the study. Subjects with 20 ≤ HBV-DNA < 2000 IU/mL at screening (including intermittent and continuous low-level viraeima). Must be willing and able to comply with all study requirements. Exclusion Criteria: Female patients who are pregnant or breastfeeding or who plan to become pregnant during the study period. Men and women of childbearing potential who are unwilling to use an effective method of contraception as defined in the protocol during the study period. Co-infection with HAV HCV, HIV, HDV or HEV; or co-infection with autologous liver, metabolism-related fatty liver, or drug-induced liver injury. Diagnosis of hepatocellular carcinoma by imaging (with evidence of hepatocellular carcinoma) Patients who have received a solid organ or bone marrow transplant History of malignancy within 5 years prior to screening, except for specific tumors cured by surgical resection (basal cell dermal skin cancer, etc.); patients evaluated for probable malignancy were ineligible. Currently receiving treatment with immunomodulators (e.g., corticosteroids), investigational drugs, nephrotoxic drugs, or drugs capable of regulating renal excretion. Drugs that modulate renal excretion. Renal, cardiovascular, pulmonary, or neurological disease that is considered severe by the investigator. Severe bone disease (e.g., osteochondrosis, chronic osteomyelitis, osteogenesis imperfecta, chondromalacia) or multiple fractures. Subjects receiving a contraindicated combination drug (subjects receiving a contraindicated drug require a minimum 30-day washout period) and known hypersensitivity reactions to study drugs, metabolites or formulation excipients. Current alcohol or drug abuse that, in the investigator's judgment, may interfere with the subject's compliance with study requirements. Any other clinical condition that, in the opinion of the investigator, would render the subject unsuitable for the study or unable to comply with the dosing requirements medical condition or prior treatment. Prior or existing clinical liver failure (Child-Pugh score ≥ grade B).

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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| ETV group<br>Participants in this group will continue ETV daily until the end of the study. | |
| TMF group<br>Participants in this group will switch to TMF 25 mg, daily until the end of the study. | Drug: TMF<br>* switch ETV to TMF<br>* Other names: Heng Mu;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportions of undetectable HBV DNA in patients treated with ETV and TMF at week 48. | Undetectable HBV DNA is defined as below 20 IU/mL. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportions of undetectable HBV DNA in patients treated with ETV and TMF at week 24. | Undetectable HBV DNA is defined as below 20 IU/mL. | 24 weeks | 
| The proportions of ALT normalization in patients treated with ETV and TMF at week 24 and 48. | There are two criteria for ALT normalization. Criteria1: below 40 U/L. Criteria2: Males: ALT<30U/L, female: ALT<19U/L. | 24 weeks and 48 weeks | 
| Comparing pgRNA levels from baseline at week 24 and 48. |  | 24 weeks and 48 weeks | 
| Comparing HBcrAg levels from baseline at week 24 and 48. |  | 24 weeks and 48 weeks | 
| The proportions of undetectable pgRNA in patients treated with ETV and TMF at week 24 and 48. | Undetectable pgRNA is defined as below 100 pg/mL. | 24 weeks and 48 weeks | 
| The proportions of undetectable HBcrAg in patients treated with ETV and TMF at week 24 and 48. |  | 24 weeks and 48 weeks | 
| Comparing degree of liver fibrosis from baseline at week 24 and 48. | Evaluation of liver fibrosis including Fibroscan, APRI and FIB-4. | 24 weeks and 48 weeks | 
| Comparing the change of creatinine clearance rate from baseline at week 24 and 48. |  | 24 weeks and 48 weeks | 
| The types, incidence and severity of adverse events and serious adverse events during treatment were evaluated in both groups |  | Week 48 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis b, Entecavir, Tenofovir Amibufenamide, Low-level viraemia