Clinical trial NCT04496882: Chronic Hepatitis b Patients Switch to tAf After Discontinuation of Nucleoside Analogue
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
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis b
Hepatitis B Reactivation
Keywords: HBV,clinical relapse,Vemlidy (TAF)
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
Collaborators: name: National Taiwan University Hospital, Yun-Lin Branch
name: Taipei City Hospital
name: Chiayi Christian Hospital
name: Dalin Tzu Chi General Hospital
name: E-DA Hospital
name: Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation
First posted: 2020-08-03
Enrollment: 260
Sex: ALL
Minimum age (years): 20
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Rate of virological remission (HBV DNA <20 IU/mL)
timeFrame: 48 weeks
Secondary outcomes:
measure: Rate of ALT normalization (ALT < 40 U/L) after retreatment
timeFrame: 48 weeks
measure: Rate of HBsAg change after retreatment compared with baseline
timeFrame: 48 weeks
measure: Rate of HBcrAg change after retreatment compared with baseline
timeFrame: 48 weeks
measure: Rate of M2BPGi level change after retreatment compared with baseline
timeFrame: 48 weeks
Other outcomes:
Locations:
city: Chiayi City
country: Taiwan
facility: Buddhist Tzu Chi General Hospital, Da-Lin Branch
city: Chiayi City
country: Taiwan
facility: Chia-Yi Christian Hospital
city: Douliu
country: Taiwan
facility: National Taiwan University Hospital, Yun-Lin branch
city: Kaohsiung
country: Taiwan
facility: E-da hospital
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
city: Taipei
country: Taiwan
facility: Buddhist Tzu-Chi General Hospital Taipei Branch
city: Taipei
country: Taiwan
facility: Taipei City Hospital, Renai Branch
Study officials:
affiliation: National Taiwan University Hospital
name: Tung-Hung Su, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: