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

Phase 4

Brief Summary: 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: 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.

Recruitment & Eligibility

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Arm && Interventions

Group	Intervention	Description
Switching therapy cohort	Vemlidy	single arm, open label Patients will receive Vemlidy (tenofovir alafenamide, TAF) 25mg, daily for 48 weeks

Primary Outcome Measures

Name	Time	Method
Rate of virological remission (HBV DNA <20 IU/mL)	48 weeks	We will calculate the rate of virological remission (HBV DNA \<20 IU/mL) after retreatment

Secondary Outcome Measures

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

Locations (7): Buddhist Tzu Chi General Hospital, Da-Lin Branch
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Chiayi City, Taiwan
E-da hospital
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Kaohsiung, Taiwan
Chia-Yi Christian Hospital
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Chiayi City, Taiwan
National Taiwan University Hospital, Yun-Lin branch
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Douliu, Taiwan
National Taiwan University Hospital
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Taipei, Taiwan
Taipei City Hospital, Renai Branch
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Taipei, Taiwan
Buddhist Tzu-Chi General Hospital Taipei Branch
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Taipei, Taiwan