Clinical Trials Logo

Clinical Trial Summary

1. Adefovir add-on therapy is superior to switching to adefovir monotherapy or entecavir 1mg monotherapy for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R)

2. Long-term adefovir add-on therapy was effective for viral suppression. However, the economic burden for such dual antiviral therapy is heavy because of infinite treatment.

3. Tenofovir disoproxil fumarate (TDF) is a potent antiviral agent. TDF demonstrated potent antiviral efficacy in a subset of lamivudine experienced HBeAg-positive patients. TDF is also superior to ADV in HBeAg-negative and HBeAg-positive treatment-naive patients.

4. Theoretically, TDF can replace LAM/ADV when viral suppression has been achieved by LAM/ADV combination treatment in LAM-R CHB patients.


Clinical Trial Description

Hepatitis B virus (HBV) is a partially double-stranded DNA virus. HBV infection can induce a spectrum of disease ranging from asymptomatic infection to severe chronic liver diseases, including cirrhosis and hepatocellular carcinoma (HCC). Chronic HBV infection is also a major cause of HCC in Taiwan. Over 350 millions people worldwide are chronically infected with HBV. Lamivudine was the first marketing and is the first-line oral anti-viral agent for the therapy of chronic hepatitis B. Infinite nucleoside analogue therapy may be needed for long-term viral suppression especially in patients with HBeAg-negative chronic hepatitis B. The initial randomized studies demonstrated the clinical benefit and safety of lamivudine in both hepatitis B e antigen (HBeAg)-positive and -negative chronic hepatitis B patients. But as high as 20% of the cases under 1-year lamivudine treatment developed genotypic resistance, which defined as the presence of YMDD mutation on the HBV polymerase region. Genotypic resistance is almost always associated with virological breakthrough and exacerbation of liver function. Long-term lamivudine therapy was reported increase HBeAg seroconversion and provided clinical improvement in ALT levels. However, in a four-year follow-up study, YMDD-variant HBV was detected in as high as 67% of patients under lamivudine treatment. Several clinical studies have proven that adefovir add-on therapy is superior to switching to adefovir monotherapy or entecavir 1mg monotherapy for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R). Currently, AASLD and EASL guidelines recommend adefovir add-on therapy as a standard treatment for LAM-R CHB patients. Long-term adefovir add-on therapy was effective for viral suppression (8). However, the economic burden for such dual antiviral therapy is heavy because of infinite treatment.

Tenofovir disoproxil fumarate (TDF) is a potent antiviral agent. TDF and ETV are recommended oral first-line therapies for CHB. TDF demonstrated potent antiviral efficacy in a subset of lamivudine experienced HBeAg-positive patients. TDF is also superior to ADV in HBeAg-negative and HBeAg-positive treatment-naive patients. Theoretically, TDF can replace LAM/ADV when viral suppression has been achieved by LAM/ADV combination treatment in LAM-R CHB patients. This clinical trial is a proof of concept study to evaluate the efficacy of switching to TDF monotherapy in such patients. ;


Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


NCT number NCT01491295
Study type Interventional
Source Taipei Veterans General Hospital, Taiwan
Contact Yi-Hsiang Huang, MD, PhD
Phone 886-2-28712121
Email yhhuang@vghtpe.gov.tw
Status Recruiting
Phase Phase 4
Start date September 2012
Completion date December 2019

See also
  Status Clinical Trial Phase
Recruiting NCT04496882 - Chronic Hepatitis b Patients Switch to tAf After Discontinuation of Nucleoside Analogue Phase 4
Completed NCT04083716 - A Study to Assess the Relative Bioavailability and Food Effect of ABI-H2158 in Healthy Adults Phase 1
Not yet recruiting NCT03038802 - A Randomised Controlled Phase 1 Study of Vaccine Therapy for Control or Cure of Chronic Hepatitis B Virus Infection Phase 1/Phase 2
Completed NCT05310487 - Phase 1 Study of 162, a Novel Neutralizing Antibody Targeting Hepatitis B Surface Antigen, in Healthy Adult Subjects Phase 1
Recruiting NCT06070051 - Dose-Escalation Prime/Boost Therapeutic Vaccination Study Of 2 Chimp Adenoviral Vectors in Adults With Chronic HBV On Nucleos(t)Ide Therapy Phase 1
Terminated NCT05001022 - A Study of ALG-020572 Drug to Evaluate Safety, Tolerability, Pharmacokinetics and Pharmacodynamics After Single Doses in Healthy Volunteers and Multiple Doses in CHB Subjects Phase 1
Recruiting NCT04139850 - The Establishment of Korean Hepatitis B Patients Cohort
Recruiting NCT05343481 - Efficacy of VTP-300 in Chronic Hepatitis B Infection Phase 2
Not yet recruiting NCT05490836 - Functional Cure Rate of Peg-IFNα-2b Combined With TAF in HBeAg Negative CHB Patients N/A
Recruiting NCT04543565 - Pradefovir Treatment for the Patients With Chronic Hepatitis B Virus Infections: a Phase3 Study Phase 3
Active, not recruiting NCT02894918 - A Study to Evaluate Addition of Peginterferon Alfa-2a to Chronic Hepatitis B (CHB) Patients Treated With NAs Phase 4
Not yet recruiting NCT02793791 - Prophylactic Treatment of Hepatic Dysplastic Nodules in HBsAg Positive Patients N/A
Recruiting NCT02287857 - Efficacy and Safety of Domestic Tenofovir Tablets in Chinese Patients With Chronic Hepatitis B N/A
Recruiting NCT01965418 - A Clinical Evaluation on Traditional Chinese Medicine Diagnosis and Treatment Program Blocking and Reversing Hepatitis B-related Liver Fibrosis - a Randomized, Controlled, Double-blind, Multi-center Clinical Trial Phase 4
Terminated NCT01872988 - Tenofovir Antiviral Therapy Following Transarterial Chemoembolization for HBV Related Hepatocellular Carcinoma Phase 3
Recruiting NCT01487876 - Efficacy and Safety of Dual-plasmid Hepatitis B Virus DNA Vaccine in Chronic Hepatitis B Patients Phase 2
Completed NCT01531166 - A Cohort Study in Korean Patients With Chronic Hepatitis B (CHB) Receiving Pegylated Interferon N/A
Not yet recruiting NCT01436539 - Study of Effects and Safety Between Adefovir Dipivoxil Plus Polyene Phosphatidylcholine Versus Adefovir Dipivoxil Alone in Chronic Hepatitis B Patients Phase 4
Recruiting NCT01360892 - Prediction of Incidence of Liver Cancer by Use of Real-time Tissue Elastography N/A
Recruiting NCT01360879 - Assessment of Liver FIBROsis by Real-time Tissue ELASTography in Chronic Liver Disease N/A