Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF)

Study Overview
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Brief Summary
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Tenofovir alafenamide (TAF) is a new prodrug of tenofovir developed to treat patients with chronic hepatitis B virus (HBV) infection. Whereas, the long-term effect of TAF to liver fibrosis is still unknown. Here, we enrolled treatment naive CHB patients with biopsy-proven significant fibrosis (METAVIR fibrosis stage ≥ F2). All enrolled subjects will be treated with TAF monotherapy for 96 weeks. After 96 weeks of therapy, the second liver biopsy will be performed to evaluate the rate of liver fibrosis regression. During this study, all subjects will be assessed for laboratory tests, imaging examination at baseline, first 12-week and every 24-week during follow-up.

Official Title
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Regression of Liver Fibrosis by Tenofovir Alafenamide (TAF) in Treatment-Naive CHB Related Fibrosis/Cirrhosis: a 96w Open-label Multicenter Study

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Tenofovir alafenamide


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18-69 years old (inclusive); BMI (18-30 kg/m2); Chronic hepatitis B virus (HBV) infection, defined as positive serum hepatitis B s-antigen (HBsAg) for more than 6 months; or chronic hepatitis B proven by live biopsy; Not received nucleoside (acid) analogue and/or interferon therapy (treatment-naive); Liver biopsy performed within 6 months before treatment and had readable biopsy slides or agrees to have a biopsy performed prior to baseline; METAVIR fibrosis stage ≥ F2; For patients without cirrhosis (F2/3), HBV DNA levels >2000 IU/mL before treatment; For patients with cirrhosis (F4), HBV DNA >20 IU/mL before treatment; ALT≤10 ULN before treatment; Creatinine clearance ≥ 50 mL/min; Agreement not to undertake other HBV systemic antiviral or interferon (IFN) regimens during participation in this study; Willing and able to provide written informed consent. Exclusion Criteria: Patients with Child-Turcotte-Pugh（CTP）score ≥ 7; Patients with decompensated cirrhosis: including ascites, hepatic encephalopathy, esophageal varices bleeding or other complications of decompensated cirrhosis or liver transplantation; Patients co-infection with hepatitis C virus (HCV), human immunodeficiency virus (HIV), or hepatitis delta virus (HDV), or alcoholic liver diseases, autoimmune liver disease, genetic liver disease, drug-induced liver injury, non-alcoholic fatty liver disease or other chronic liver diseases; Patients with evidence of hepatocellular carcinoma (HCC) by imaging with or without AFP; Patients with other uncured malignant tumors; Patients with organ or bone marrow transplantation; Patients currently receiving therapy with immunomodulators (eg, corticosteroids, etc.), investigational agents, nephrotoxic agents, or agents susceptible of modifying renal excretion; Patients who are allergic to any component of TAF; Patients who recently or newly started bisphosphate (within 1 month); Patients with active alcohol or drug abuse or history of alcohol or drug abuse (hinder compliance with treatment, or participation in the study or interpretation of results considered by the Investigator); Patients with significant renal, cardiovascular, pulmonary, or neurological disease Males and females of reproductive potential who are unwilling to use an effective method of contraception during the study; Pregnant women, women who are breast feeding or who believe they may wish to become pregnant during the course of the study; Not suitable for this study identified by researchers.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 69 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
Intervention Model: Single Group Assignment
Interventional Model Description: Subjects will be treated for 96 weeks with TAF [Vemlidy® 25mg QD] monotherapy
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TAF group<br>TAF [Vemlidy® 25mg QD] monotherapy | Drug: Tenofovir alafenamide<br>* Subjects will be treated for 96 weeks with TAF [Vemlidy® 25mg QD] monotherapy<br>* Other names: Vemlidy®;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with fibrosis regression | Fibrosis stage decrease at least 1 point by Ishak score or Predominantly Regressive by Beijing classification | Week 96 | 
| HBV DNA undetectable rate | Serum HBV DNA <20 IU/mL | Week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of liver stiffness decrease >= 30% | Proportion of patients with liver stiffness decrease >= 30% from baseline to week 48 and 96 | Week 48 and Week 96 | 
| HBV DNA undetectable rate | HBV DNA undetectable rate at week 24, 48, and 72 | Week 24, Week 48 and Week 72 | 
| ALT normalization rate | Proportion of patients with ALT <= 1.0xULN | Week 48 and Week 96 | 
| HBeAg and HBsAg loss and seroconversion rate | Proportions of patients with HBsAg loss and seroconversion to anti-HBs, and proportions of patients with HBeAg loss and seroconversion to anti-HBe. | Week 48 and Week 96 | 
| Changes in renal function | Changes of eGFR (estimated Glomerular Filtration rate) from baseline to week 48 and 96 | Week 48 and Week 96 | 
| Changes of bone mineral density | Percentage changes in spine BMD and hip BMD from baseline to week 48 and 96 | Week 48 and Week 96 | 
| Incidence of liver-related endpoint events | liver-related endpoint events: decompensation, HCC, liver transplantation, liver-related death | Week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver fibrosis, Liver cirrhosis, Tenofovir alafenamide, Chronic Hepatitis B