Chronic Viral Hepatitis B Without Delta-agent Clinical Trial
Official title:
A Randomized, Open-label Trial Comparing Telbivudine vs, Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B Who Have Achieved Serum HBV DNA Undetectability by Preceding Entecavir Treatment
The goal of chronic hepatitis B (CHB) treatment is complete and permanent eradication of
hepatitis B virus (HBV) from patient's body, which is best represented by serum HBsAg loss
accompanied by undetectable serum HBV DNA level.
While the most recently approved nucleos(t)ide analogues (NA) have marked antiviral potency
and can induce HBV DNA undetectability in the majority of patients through prolonged
treatment, NA need to be given long term, almost indefinitely, in most cases because they
suppress HBV DNA only during therapy. For example, even after HBeAg-loss by a potent NA,
suppression of serum HBV DNA to undetectable level is sustained only in about 23%-37% at 24
weeks off treatment. Thus, continuous therapy with NA until HBsAg clearance remains
necessary in a majority of cases.
The recent availability of commercial quantitative assays of serum hepatitis B surface
antigen (HBsAg) has enabled quantitative HBsAg to be used as a biomarker for prognosis and
treatment response in CHB. It has been suggested that HBsAg decline during lamivudine or
entecavir therapy is slower and less pronounced compared to interferon treatment, despite a
higher effect on HBV DNA suppression. Based on HBsAg kinetics, it has been estimated that
the predicted median time to HBsAg loss in patients treated with lamivudine or entecavir is
more than 30 years. Thus, treatment that can induce rapid decline of HBsAg would have clear
advantage in reducing the treatment duration required to achieve HBsAg-loss.
Interestingly, in a recent preliminary study, 24-weeks of treatment with telbivudine has
induced HBsAg decline as comparable to pegylated interferon treatment. Although there has
been no head-to-head trial comparing NAs in inducing HBsAg decline, previous studies
consistently suggested that the decline of HBsAg is greater during telbivudine treatment
compared with lamivudine or entecavir.
Thus, in this clinical trial, the investigators will investigate whether telbivudine is more
effective in inducing HBsAg decline compared with entecavir in HBeAg-positive CHB patients
who have achieved undetectable serum HBV DNA by preceding entecavir treatment.
A single-center randomized active-controlled open-label superiority trial
- Patients will be randomly assigned 1:1 to receive telbivudine (600 mg/day) or ongoing
entecavir (0.5 mg/day) for 48 weeks.
- Eligible patients will be randomized using blocks of permuted treatment assignments
after stratification by HBsAg level (1,000 IU/mL-5,000 IU/mL and ≥5,000 IU/mL IU/mL)
and by entecavir treatment duration (1 year-2 year, ≥2 year).
- Because over 98% of Korean patients with CHB have HBV genotype C,9 HBV genotype will
not determined or be regarded as a stratification factor.
- There will be no interruption in entecavir therapy before randomization.
- Patients' treatment information will be retrospectively collected during entecavir
treatment phase as well (DNA change, HBeAg status, HBsAg titre, ALT, and treatment
duration. etc)
- Patients will be screened within 4 weeks before randomization to determine study
eligibility.
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01639092 -
Tenofovir vs. Tenofovir Plus Entecavir in Entecavir-Resistant Chronic Hepatitis B
|
Phase 4 | |
| Completed |
NCT01639066 -
Tenofovir Plus Entecavir vs. Tenofovir in Adefovir-Resistant Chronic Hepatitis B
|
Phase 4 |