Chronic Hepatitis B
Conditions
Keywords
Chronic Hepatitis B, Liver fibrosis, Liver cirrhosis, Tenofovir alafenamide
Brief summary
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.
Interventions
DRUGTenofovir alafenamide
Subjects will be treated for 96 weeks with TAF \[Vemlidy® 25mg QD\] monotherapy
Sponsors
Beijing Ditan Hospital
ShuGuang Hospital
Tianjin Third Central Hospital
Huashan Hospital
The Sixth Peoples Hospital of Zhengzhou
Tianjin Second People's Hospital
Ruijin Hospital
Shanghai East Hospital
Jidong Jia
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Subjects will be treated for 96 weeks with TAF \[Vemlidy® 25mg QD\] monotherapy
Eligibility
Sex/Gender
ALL
Age
18 Years to 69 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of patients with fibrosis regression | Week 96 | Fibrosis stage decrease at least 1 point by Ishak score or Predominantly Regressive by Beijing classification |
| HBV DNA undetectable rate | Week 96 | Serum HBV DNA \<20 IU/mL |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| ALT normalization rate | Week 48 and Week 96 | Proportion of patients with ALT \<= 1.0xULN |
| HBeAg and HBsAg loss and seroconversion rate | Week 48 and Week 96 | Proportions of patients with HBsAg loss and seroconversion to anti-HBs, and proportions of patients with HBeAg loss and seroconversion to anti-HBe. |
| Percentage of liver stiffness decrease >= 30% | Week 48 and Week 96 | Proportion of patients with liver stiffness decrease \>= 30% from baseline to week 48 and 96 |
| Changes of bone mineral density | Week 48 and Week 96 | Percentage changes in spine BMD and hip BMD from baseline to week 48 and 96 |
| Incidence of liver-related endpoint events | Week 96 | liver-related endpoint events: decompensation, HCC, liver transplantation, liver-related death |
| Changes in renal function | Week 48 and Week 96 | Changes of eGFR (estimated Glomerular Filtration rate) from baseline to week 48 and 96 |
| HBV DNA undetectable rate | Week 24, Week 48 and Week 72 | HBV DNA undetectable rate at week 24, 48, and 72 |
Countries
China
Outcome results
None listed