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

National Taiwan University Hospital260 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

Eligibility

Sex: ALLMin age: 20 YearsMax age: 99 Years

Medical Language ↔ Plain English

Inclusion Criteria A. Switching therapy cohort 1. 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) 2. After NUC discontinuation, patients had a clinical relapse (HBV DNA \> 2000 IU/mL, and ALT \> 2x ULN) 3. The retreatment regimen switches to TAF (within 3 months of clinical relapse) B. Historical continuing therapy cohort 1. 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) 2. After NUC discontinuation, patients had a clinical relapse (HBV DNA \> 2000 IU/mL, and ALT \> 2x ULN) 3. The patients continued the original regimen (ETV, TDF) for retreatment (within 3 months of clinical relapse) Exclusion Criteria 1. Patients who do not fulfill the discontinuation criteria 2. Patients who have HCV, HDV or HIV co-infection 3. Patients who discontinue lamivudine, adefovir, or telbivudine therapy 4. Patients with liver cirrhosis by ultrasonography and clinical diagnosis

Locations (7)

Buddhist Tzu Chi General Hospital, Da-Lin Branch

Chiayi City, Taiwan

RECRUITING

Chia-Yi Christian Hospital

Chiayi City, Taiwan

RECRUITING

National Taiwan University Hospital, Yun-Lin branch

Douliu, Taiwan

RECRUITING

E-da hospital

Kaohsiung City, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

Buddhist Tzu-Chi General Hospital Taipei Branch

Taipei, Taiwan

NOT_YET_RECRUITING

Taipei City Hospital, Renai Branch

Taipei, Taiwan

RECRUITING

Outcomes

Primary Outcomes

Rate of virological remission (HBV DNA <20 IU/mL)

We will calculate the rate of virological remission (HBV DNA \<20 IU/mL) after retreatment

Time frame: 48 weeks

Secondary Outcomes

Rate of ALT normalization (ALT < 40 U/L) after retreatment

We will calculate the rate of ALT normalization (ALT \< 40 U/L) after retreatment

Time frame: 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

Time frame: 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

Time frame: 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

Time frame: 48 weeks

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

Overview

Conditions

Interventions

Eligibility

Locations (7)

Outcomes

Primary Outcomes

Secondary Outcomes

Central Contacts