Tenofovir Versus Tenofovir + Telbivudine for Chronic Hepatitis B
Status:
Unknown status
Trial end date:
2020-07-01
Target enrollment:
Participant gender:
Summary
Chronic Hepatitis B is the most common cause of chronic viral liver disease worldwide
afflicting 350 million persons, leading to significant morbidity and mortality due to liver
disease and HCC in 20-40% of infected persons. With the advent of nucleoside analogues, this
rescued patients with significant risk of disease progression, but in most circumstances,
therapy was needed long term as HBsAg seroclearance was an uncommon occurrence, and stopping
therapy was associated with relapse of disease and hepatitis B flares. The use of pegylated
interferons showed increased HBeAg seroconversion and HBsAg seroclearance rates compared to
nucleoside analogues , however combination nucleos(t)ide analogue therapy has been quite
disappointing. However a recent showed that the combination of telbivudine and tenofovir in a
response guided therapy design, had a remarkable 6% HBsAg seroclearance at week 52 in
patients. Such results require further confirmation. There is currently an unmet need for the
large number of patients on long term nucleoside analogue therapy who have not achieved HBeAg
seroconversion or HBsAg seroclearance. Such patients are seeking alternatives to long term
therapy hence an exploration of other therapeutic strategies is attractive. An additional
benefit of telbivudine has been the surprising improvement in renal function and this study
seeks to examine whether this can improve the renal impairment that may be seen with
tenofovir. Our study proposes to examine if the combination of tenofovir and telbivudine can
improve endpoints. Patients fulfilling inclusion and exclusion criteria will be randomized to
tenofovir or tenofovir and telbivudine (1:1 ratio). The primary endpoint will be a qHBsAg
reduction of >1log at week 96, which may predict future HBsAg seroclearance, which is also a
secondary endpoint. An additional primary endpoint is increase in eGFR in the combination arm
compared to the monotherapy arm. The study aims to enroll 146 patients randomized 1:1 ratio
(73:73) patients. Multivariate analysis will be performed of baseline and on-treatment
factors that predict the primary outcome.
Phase:
Phase 4
Details
Lead Sponsor:
Seng Gee Lim
Collaborators:
National Medical Research Council (NMRC), Singapore Singapore Clinical Research Institute