Telbivudine Versus Entecavir in Reducing Serum HBsAg Levels in Patients With HBeAg-positive Chronic Hepatitis B (TERESA)

January 24, 2017 updated by: Young-Suk Lim, Asan Medical Center

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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

Enrollment (Actual)

98

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria: All of below

  • HBsAg titer > 1,000 IU/mL
  • HBeAg positive at study entry and at the baseline of ETV treatment
  • HBV DNA undetectable (<15 IU/mL) at least 2 occasions of more than 3 months apart
  • Treatment with entecavir (0.5 mg/day) for more than 1 year
  • Patient is ambulatory.
  • Patient is able and willing to give informed consent.

Exclusion Criteria: Any of below

  • Prior exposure to oral nucloes(t)ide analogue other than entecavir
  • Prior any exposure to interferon or pegylated interferon
  • Cirrhosis with Child-Pugh score ≥8
  • Hepatocellular carcinoma Identified or suspected
  • Other malignancy
  • Prior organ transplantation
  • Under immunosuppressive agent
  • Renal insufficiency (serum creatinine > 1.4)
  • Pregnant woman or willing to be pregnant woman or man

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Telbivudine
Telbivudine 600 mg Daily Oral
Drug: Telbivudine
Telbivudine 600 mg Daily Oral
Other Names:
  • Sebivo
Active Comparator: Entecavir
Entecavir 0.5 mg Daily Oral
Drug: Entecavir
Entecavir 0.5 mg Daily Oral
Other Names:
  • Baraclude

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
HBsAg titer at 48 weeks
Time Frame: at 48 weeks
at 48 weeks

Secondary Outcome Measures

Outcome Measure
Time Frame
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
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
at 48 weeks of treatment
Proportion of patients with serum HBsAg loss
Time Frame: at 48 weeks of treatment
at 48 weeks of treatment
Proportion of patients with serum HBeAg loss or HBeAg seroconversion
Time Frame: at 48 weeks of treatment
at 48 weeks of treatment
Proportion of patients with virologic rebound or genotypic resistance
Time Frame: up to 48 weeks of treatment
up to 48 weeks of treatment
Proportion of patients with normal ALT
Time Frame: at 48 weeks of treatment
at 48 weeks of treatment
Adverse events: Creatine kinase level, GFR, Muscle events, Other AEs
Time Frame: up to 48 weeks of treatment
up to 48 weeks of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Asan Medical Center

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

May 1, 2012

Primary Completion (Actual)

December 1, 2014

Study Completion (Actual)

December 1, 2014

Study Registration Dates

First Submitted

May 8, 2012

First Submitted That Met QC Criteria

May 9, 2012

First Posted (Estimate)

May 10, 2012

Study Record Updates

Last Update Posted (Estimate)

January 26, 2017

Last Update Submitted That Met QC Criteria

January 24, 2017

Last Verified

January 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • AMC2012-0201

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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