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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Hepatitis b; Hepatitis B Reactivation
• Intervention / Treatment: Drug: Vemlidy

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.

• Study Type: Interventional
• Enrollment (Anticipated): 260
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Tung-Hung Su, MD, PhD; Phone Number: 886972651694; Email: tunghungsu@gmail.com
• Study Contact Backup: Name: Pei-Ying Yang, MS; Phone Number: 886965277228; Email: pying0208@gmail.com

Study Locations

• Taiwan
  • Chiayi City, Taiwan
    • Recruiting
    • Buddhist Tzu Chi General Hospital, Da-Lin Branch
    • Contact: Kuo-Chih Tseng, MD; Phone Number: 3240 88652648000; Email: tsengkuochih@gmail.com
  • Chiayi City, Taiwan
    • Recruiting
    • Chia-Yi Christian Hospital
    • Contact: Chi-Yi Chen, MD; Phone Number: 5264 88652765041; Email: 5137ccy@gmail.com
  • Douliu, Taiwan
    • Recruiting
    • National Taiwan University Hospital, Yun-Lin Branch
    • Contact: Yu-Jen Fang, MD; Phone Number: 886972655715; Email: toby851072@gmail.com
  • Kaohsiung, Taiwan
    • Recruiting
    • E-Da Hospital
    • Contact: Yao-Chun Hsu, MD, PhD; Phone Number: 886975209520; Email: holdenhsu@gmail.com
  • Taipei, Taiwan, 100
    • Recruiting
    • National Taiwan University Hospital
    • Contact: Tung-Hung Su, MD, PhD; Phone Number: 886972651694; Email: tunghungsu@gmail.com
  • Taipei, Taiwan
    • Not yet recruiting
    • Buddhist Tzu-Chi General Hospital Taipei Branch
    • Contact: Chia-Chi Wang, MD; Phone Number: 2317 886266289779; Email: uld888@yahoo.com.tw
  • Taipei, Taiwan
    • Recruiting
    • Taipei City Hospital, RENAI Branch
    • Contact: Chih-Lin Lin, MD; Phone Number: 886227099558; Email: lcl@tpech.gov.tw

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 99 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Switching therapy cohort; single arm, open label Patients will receive Vemlidy (tenofovir alafenamide, TAF) 25mg, daily for 48 weeks	Drug: Vemlidy; 25mg Tenofovir Alafenamide; Other Names: Tenofovir Alafenamide (TAF)
No Intervention: Historical continuing therapy cohort; 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?

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

Collaborators and Investigators

• Sponsor: National Taiwan University Hospital
• Collaborators: Chiayi Christian Hospital; E-DA Hospital; Taipei City Hospital; Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation; Dalin Tzu Chi General Hospital; National Taiwan University Hospital, Yun-Lin Branch
• Investigators: Principal Investigator: Tung-Hung Su, MD, PhD, National Taiwan University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2020
• Primary Completion (Anticipated): December 31, 2022
• Study Completion (Anticipated): December 31, 2023

Study Registration Dates

• First Submitted: July 26, 2020
• First Submitted That Met QC Criteria: July 30, 2020
• First Posted (Actual): August 3, 2020

Study Record Updates

• Last Update Posted (Actual): August 5, 2021
• Last Update Submitted That Met QC Criteria: August 4, 2021
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: HBV,clinical relapse,Vemlidy (TAF)
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Tenofovir
• Other Study ID Numbers: 201911095MIPD

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes