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

Sponsor

National Taiwan University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT04496882

Collaborator

National Taiwan University Hospital, Yun-Lin Branch (Other), Taipei City Hospital (Other), Chiayi Christian Hospital (Other), Dalin Tzu Chi General Hospital (Other), E-DA Hospital (Other), Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation (Other)

260

Enrollment

Locations

Arms

39.7

Anticipated Duration (Months)

37.1

Patients Per Site

0.9

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis b Hepatitis B Reactivation	Drug: Vemlidy	Phase 4

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 Design

Study Type:

Interventional

Anticipated Enrollment :

260 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Sep 9, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2023

Arms and Interventions

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)

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)

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 99 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria A. Switching therapy cohort

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)
After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN)
The retreatment regimen switches to TAF (within 3 months of clinical relapse)

Historical continuing therapy cohort

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)
After NUC discontinuation, patients had a clinical relapse (HBV DNA > 2000 IU/mL, and ALT > 2x ULN)
The patients continued the original regimen (ETV, TDF) for retreatment (within 3 months of clinical relapse)

Exclusion Criteria

Patients who do not fulfill the discontinuation criteria
Patients who have HCV, HDV or HIV co-infection
Patients who discontinue lamivudine, adefovir, or telbivudine therapy
Patients with liver cirrhosis by ultrasonography and clinical diagnosis

Contacts and Locations

Locations

	Site	City	Country	Postal Code
1	Buddhist Tzu Chi General Hospital, Da-Lin Branch	Chiayi City	Taiwan
2	Chia-Yi Christian Hospital	Chiayi City	Taiwan
3	National Taiwan University Hospital, Yun-Lin branch	Douliu	Taiwan
4	E-da hospital	Kaohsiung	Taiwan
5	National Taiwan University Hospital	Taipei	Taiwan	100
6	Buddhist Tzu-Chi General Hospital Taipei Branch	Taipei	Taiwan
7	Taipei City Hospital, Renai Branch	Taipei	Taiwan