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

Chronic Hepatitis b Clinical Trial

— CHANGE  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04496882
• Other study ID #: 201911095MIPD
• Status: Recruiting
• Phase: Phase 4
• Start date: September 9, 2020
• Est. completion date: December 31, 2023

Study information

• Verified date: August 2021
• Source: National Taiwan University Hospital
• Contact: Tung-Hung Su, MD, PhD
• Phone: 886972651694
• Email: tunghungsu[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Recruiting
• Enrollment: 260
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years to 99 Years

Eligibility

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

Related Conditions & MeSH terms

• Chronic Hepatitis b
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B Reactivation
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Vemlidy
25mg Tenofovir Alafenamide

Locations

Country	Name	City	State
Taiwan	Buddhist Tzu Chi General Hospital, Da-Lin Branch	Chiayi City
Taiwan	Chia-Yi Christian Hospital	Chiayi City
Taiwan	National Taiwan University Hospital, Yun-Lin branch	Douliu
Taiwan	E-da hospital	Kaohsiung
Taiwan	Buddhist Tzu-Chi General Hospital Taipei Branch	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Taipei City Hospital, Renai Branch	Taipei

Sponsors (7)

Lead Sponsor	Collaborator
National Taiwan University Hospital	Chiayi Christian Hospital, Dalin Tzu Chi General Hospital, E-DA Hospital, National Taiwan University Hospital, Yun-Lin Branch, Taipei City Hospital, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	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
Secondary	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