Chronic Hepatitis b Patients Switch to tAf After Discontinuation of Nucleoside Analogue

Study Overview
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Brief Summary
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We will conduct a phase 4, multicenter, open-label trial at 7 academic centers in Taiwan. Chronic hepatitis B patients receiving oral antiviral therapy (entecavir [ETV], tenofovir disoproxil fumarate [TDF]) for at least 2 years, and fulfil the following nucleos(t)ide analogs discontinuation criteria. After nucleos(t)ide analogs discontinuation, patients had a clinical relapse and retreatment regimen switches to TAF. The protocol will be approved by Institutional Review Board (IRB) or Research ethic committee (REC) of each site and will be conducted in accordance with the principles of Declaration of Helsinki and the International Conference on Harmonization for Good Clinical Practice. Each patient provides written informed consent before enrollment.

Detailed Description
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Tenofovir alafenamide (TAF) is a new generation of oral antiviral drugs with similar antiviral activities to tenofovir disoproxil fumarate (TDF) and reduces the adverse effects of nephrotoxicity and bone mineral density reduction. This drug has already been reimbursed by National Health Insurance, and can be used for the treatment of patients with chronic hepatitis B. This is a single-arm prospective clinical trial to enroll patients who discontinued entecavir (ETV) and tenofovir disoproxil fumarate (TDF) and experienced a clinical hepatitis flare up. They can be retreated with TAF for 48 weeks without postponing a 3-month observation period for alanine aminotransferase (ALT) level. The virological control, ALT level recovery, and changes in liver fibrosis, hepatitis B surface antigen, hepatitis B core-associated antigen, and renal function will be observed during retreatment. In addition, a group of patients with the same characteristics who received retreatment with entecavir or TDF will be collected as a control group for comparison. We believe this study can help us understand the clinical benefits of switching to TAF for retreatment after hepatitis flare in patients to discontinue oral antiviral agents.

Official Title
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The Clinical Efficacy of Tenofovir Alafenamide-switching Therapy in Patients With Chronic Hepatitis B Experiencing Clinical Flare-up After Discontinuation of Nucleos[t]Ide Analogues Therapy

Conditions
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Chronic Hepatitis b, Hepatitis B Reactivation

Intervention / Treatment
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* Drug: Vemlidy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria A. Switching therapy cohort Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 2 years, and fulfil the following NUCs discontinuation criteria (1)HBeAg-positive patients achieving HBeAg seroclearance, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieving undetectable HBV DNA for more than 1 year (on 3 occasions, 6 months apart) After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN) The retreatment regimen switches to TAF (within 3 months of clinical relapse) B. Historical continuing therapy cohort Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 2 years, and fulfil the following NUCs discontinuation criteria (1) HBeAg-positive patients achieving HBeAg seroclearance, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieving undetectable HBV DNA for more than 1 year(on 3 occasions, 6 months apart) After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN) The patients continued the original regimen (ETV, TDF) for retreatment (within 3 months of clinical relapse) Exclusion Criteria Patients who do not fulfill the discontinuation criteria Patients who have HCV, HDV or HIV co-infection Patients who discontinue lamivudine, adefovir, or telbivudine therapy Patients with liver cirrhosis by ultrasonography and clinical diagnosis

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 99 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: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Switching therapy cohort<br>single arm, open label Patients will receive Vemlidy (tenofovir alafenamide, TAF) 25mg, daily for 48 weeks | Drug: Vemlidy<br>* 25mg Tenofovir Alafenamide<br>* Other names: Tenofovir Alafenamide (TAF);|
| No Intervention: Historical continuing therapy cohort<br>By retrospectively review medical records, The patients continued the original regimen (ETV, TDF) for retreatment (within 3 months of clinical relapse) | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of virological remission (HBV DNA <20 IU/mL) | We will calculate the rate of virological remission (HBV DNA <20 IU/mL) after retreatment | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of ALT normalization (ALT < 40 U/L) after retreatment | We will calculate the rate of ALT normalization (ALT < 40 U/L) after retreatment | 48 weeks | 
| Rate of HBsAg change after retreatment compared with baseline | We will investigate the rate of HBsAg change after retreatment compared with the baseline HBsAg | 48 weeks | 
| Rate of HBcrAg change after retreatment compared with baseline | We will investigate the rate of hepatitis B core-related antigen (HBcrAg) change after retreatment compared with baseline HBcrAg | 48 weeks | 
| Rate of M2BPGi level change after retreatment compared with baseline | We will investigate the rate of Mac-2 binding protein glycosylation isomer (M2BPGi) level change after retreatment compared with baseline M2BPGi level | 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV,clinical relapse,Vemlidy (TAF)