Telbivudine Versus Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B (TERESA)
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|ClinicalTrials.gov Identifier: NCT01595685|
Recruitment Status : Completed
First Posted : May 10, 2012
Last Update Posted : January 26, 2017
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.
|Condition or disease||Intervention/treatment||Phase|
|Chronic Viral Hepatitis B Without Delta-agent||Drug: Telbivudine Drug: Entecavir||Phase 3|
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.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||98 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|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|
|Study Start Date :||May 2012|
|Actual Primary Completion Date :||December 2014|
|Actual Study Completion Date :||December 2014|
Telbivudine 600 mg Daily Oral
Telbivudine 600 mg Daily Oral
Other Name: Sebivo
Active Comparator: Entecavir
Entecavir 0.5 mg Daily Oral
Entecavir 0.5 mg Daily Oral
Other Name: Baraclude
- HBsAg titer at 48 weeks [ Time Frame: at 48 weeks ]
- 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 ]
- Proportion of patients with serum HBsAg decline greater than 1.0 log10 IU/mL [ Time Frame: at 48 weeks of treatment ]
- Proportion of patients with serum HBsAg loss [ Time Frame: at 48 weeks of treatment ]
- Proportion of patients with serum HBeAg loss or HBeAg seroconversion [ Time Frame: at 48 weeks of treatment ]
- Proportion of patients with virologic rebound or genotypic resistance [ Time Frame: up to 48 weeks of treatment ]
- Proportion of patients with normal ALT [ Time Frame: at 48 weeks of treatment ]
- Adverse events: Creatine kinase level, GFR, Muscle events, Other AEs [ Time Frame: up to 48 weeks of treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01595685
|Korea, Republic of|
|Asan Medical Center|
|Seoul, Korea, Republic of, 138-736|
|Principal Investigator:||Young-Suk Lim, M.D., Ph.D.||Asan Medical Center|