Tenofovir Alafenamide Versus Entecavir for the Treatment of Chronic Hepatitis B

Study Overview
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Brief Summary
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To compare the efficacy and renal safety of tenofovir alafenamide (TAF) versus entecavir (ETV) in the chronic hepatitis B patients.

Detailed Description
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With high antiviral potency and low drug resistance rate, both ETV and tenofovir disoproxil fumarate (TDF) have been recommended as the first-line antiviral therapy for chronic hepatitis B (CHB). However, risk of renal dysfunction remains an issue in TDF long-term therapy. Tenofovir alafenamide (TAF) is a novel prodrug of tenofovir and is formulated to deliver the active metabolite to target cells more efficiently than TDF at lower doses, thereby reducing systemic exposure to tenofovir. Importantly, TAF had improved renal safety as compared to TDF. TAF has been approved for treating CHB since 2017; however, it is still unknown whether the efficacy and renal safety of TAF is compatible to those of ETV. The investigators aim to conduct an open label, randomized controlled trial comparing TAF with ETV for assessing their efficacy and renal safety in CHB patients. The eligible CHB patients are randomly assigned (1:1) to receive TAF or ETV. After allocation to TAF group or ETV group, study subjects will receive therapy for 3 years (144 weeks).

Official Title
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Tenofovir Alafenamide Versus Entecavir for the Treatment of Chronic Hepatitis B: An Open Label, Randomized Controlled Trial

Conditions
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Hepatitis B, Viral Hepatitis

Intervention / Treatment
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* Drug: Tenofovir alafenamide
* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients more than 20 years old Chronic hepatitis B patients Patients who were indicated for hepatitis B virus antiviral therapy Exclusion Criteria: Decompensated liver disease (Child-Pugh B &C) End stage renal disease (eGRF < 15 ml/min/1.73m2) Prior use of nucleot(s)ide analogues for chronic hepatitis B Prior use of interferon for chronic hepatitis B within six months Known history of human immunodeficiency virus or hepatitis C virus co-infection Concurrent other uncontrolled malignancy Women in pregnancy or lactation Cannot conform to the study protocol of this study

Ages Eligible for Study
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Minimum Age: 20 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 eligible chronic hepatitis B patients are randomly assigned (1:1) to receive once-daily oral doses of tenofovir alafenamide 25 mg or entecavir 0.5mg.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Tenofovir alafenamide group<br>Study subjects will receive tenofovir alafenamide 25 mg/tab once daily for 3 years (144 weeks). | Drug: Tenofovir alafenamide<br>* Tenofovir alafenamide 25mg/tab once daily<br>* Other names: Vemlidy;|
| Active Comparator: Entecavir group<br>Study subjects will receive entecavir 0.5 mg/tab once daily for 3 years (144 weeks). | Drug: Entecavir<br>* Entecavir 0.5mg/tab once daily<br>* Other names: Baraclude;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBV viral suppression | proportion of patients with hepatitis B virus(HBV) -DNA suppression | After 48-week therapy of Tenofovir alafenamide or entecavir | 
| Renal safety: Change of estimated glomerular filtration rate | Change of estimated glomerular filtration rate | After 48-week therapy of Tenofovir alafenamide or entecavir | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Normalization alanine aminotransferase (ALT) | proportion of patients with ALT normalization | After 48-week therapy of Tenofovir alafenamide or entecavir | 
| HBsAg loss | proportion of patients with HBsAg loss | After 48-week therapy of Tenofovir alafenamide or entecavir | 
| HBeAg loss | proportion of patients with HBeAg loss | After 48-week therapy of Tenofovir alafenamide or entecavir | 
| Bone mineral density | change of bone mineral density | After 48-week therapy of Tenofovir alafenamide or entecavir | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hepatitis B, Viral Hepatitis, Tenofovir alafenamide, Entecavir