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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01595685
Recruitment Status : Completed
First Posted : May 10, 2012
Last Update Posted : January 26, 2017
Information provided by (Responsible Party):
Young-Suk Lim, Asan Medical Center

Brief Summary:

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

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 98 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Telbivudine
Telbivudine 600 mg Daily Oral
Drug: Telbivudine
Telbivudine 600 mg Daily Oral
Other Name: Sebivo

Active Comparator: Entecavir
Entecavir 0.5 mg Daily Oral
Drug: Entecavir
Entecavir 0.5 mg Daily Oral
Other Name: Baraclude

Primary Outcome Measures :
  1. HBsAg titer at 48 weeks [ Time Frame: at 48 weeks ]

Secondary Outcome Measures :
  1. 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 ]
  2. Proportion of patients with serum HBsAg decline greater than 1.0 log10 IU/mL [ Time Frame: at 48 weeks of treatment ]
  3. Proportion of patients with serum HBsAg loss [ Time Frame: at 48 weeks of treatment ]
  4. Proportion of patients with serum HBeAg loss or HBeAg seroconversion [ Time Frame: at 48 weeks of treatment ]
  5. Proportion of patients with virologic rebound or genotypic resistance [ Time Frame: up to 48 weeks of treatment ]
  6. Proportion of patients with normal ALT [ Time Frame: at 48 weeks of treatment ]
  7. Adverse events: Creatine kinase level, GFR, Muscle events, Other AEs [ Time Frame: up to 48 weeks of treatment ]

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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

Information from the National Library of Medicine

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 identifier (NCT number): NCT01595685

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Korea, Republic of
Asan Medical Center
Seoul, Korea, Republic of, 138-736
Sponsors and Collaborators
Asan Medical Center
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Principal Investigator: Young-Suk Lim, M.D., Ph.D. Asan Medical Center
Publications automatically indexed to this study by Identifier (NCT Number):
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Responsible Party: Young-Suk Lim, Associate Professor, Asan Medical Center Identifier: NCT01595685    
Other Study ID Numbers: AMC2012-0201
First Posted: May 10, 2012    Key Record Dates
Last Update Posted: January 26, 2017
Last Verified: January 2017
Keywords provided by Young-Suk Lim, Asan Medical Center:
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Antiviral Agents
Anti-Infective Agents
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action