Telbivudine Versus Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B (TERESA)
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.
Chronic Viral Hepatitis B Without Delta-agent
|Study Design:||Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Randomized, Open-label, Active-control, Single-center Clinical Trial Comparing Switch to Telbivudine Versus Continuation of 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|
- HBsAg titer at 48 weeks [ Time Frame: at 48 weeks ] [ Designated as safety issue: No ]
- Proportion of patients with serum HBsAg decline of ≥0.5 log10 IU/mL and <1.0 log10 IU/mL [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
- Proportion of patients with serum HBsAg decline greater than 1.0 log10 IU/mL [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
- Proportion of patients with serum HBsAg loss [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
- Proportion of patients with serum HBeAg loss or HBeAg seroconversion [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
- Proportion of patients with virologic rebound or genotypic resistance [ Time Frame: up to 48 weeks of treatment ] [ Designated as safety issue: Yes ]
- Proportion of patients with normal ALT [ Time Frame: at 48 weeks of treatment ] [ Designated as safety issue: No ]
- Adverse events: Creatine kinase level, GFR, Muscle events, Other AEs [ Time Frame: up to 48 weeks of treatment ] [ Designated as safety issue: Yes ]
|Study Start Date:||May 2012|
|Estimated Study Completion Date:||December 2014|
|Estimated Primary Completion Date:||December 2014 (Final data collection date for primary outcome measure)|
Telbivudine 600 mg Daily Oral
Other Name: Sebivo
|Active Comparator: Entecavir||
Entecavir 0.5 mg Daily Oral
Other Name: Baraclude
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.
|Contact: Young-Suk Lim, M.D., Ph.D.||+email@example.com|
|Korea, Republic of|
|Asan Medical Center||Recruiting|
|Seoul, Korea, Republic of, 138-736|
|Principal Investigator: Young-Suk Lim, M.D., Ph.D.|
|Principal Investigator:||Young-Suk Lim, M.D., Ph.D.||Asan Medical Center|