Chronic Hepatitis b, Hepatitis B Reactivation
Conditions
Keywords
HBV,clinical relapse,Vemlidy (TAF)
Brief summary
We will conduct a phase 4, multicenter, open-label trial at 8 academic centers in Taiwan. Chronic hepatitis B patients receiving oral antiviral therapy (entecavir \[ETV\], tenofovir disoproxil fumarate \[TDF\]) for at least 1 year, 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.
Interventions
DRUGVemlidy
25mg Tenofovir Alafenamide
Sponsors
National Taiwan University Hospital
National Taiwan University Hospital, Yun-Lin Branch
Taipei City Hospital
Chiayi Christian Hospital
Dalin Tzu Chi General Hospital
E-DA Hospital
Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
National Taiwan University Hospital Hsin-Chu Branch
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
20 Years to 99 Years
Healthy volunteers
No
Inclusion criteria
A. Switching therapy cohort 1. Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 1 years, and fulfil the following NUCs discontinuation criteria (1)HBeAg-positive patients achieved HBeAg loss, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieved virological remission (HBV DNA \<20 IU/mL) for more than 1 year 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 3.3 months of clinical relapse) B. Historical continuing therapy cohort 1. Chronic hepatitis B patients receiving oral antiviral therapy (ETV, TDF) for at least 1 years, and fulfil the following NUCs discontinuation criteria (1) HBeAg-positive patients achieved HBeAg loss, and received at least 1-year consolidation therapy (2) HBeAg-negative patients achieved virological remission (HBV DNA \<20 IU/mL) for more than 1 year 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 3.3 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 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 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 |
Countries
Taiwan
Contacts
PRINCIPAL_INVESTIGATORTung-Hung Su, MD, PhD
National Taiwan University Hospital
Outcome results
None listed