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

NCT01595685 | Completed Phase 3

• 1 other identifier: AMC2012-0201
• Study Type: interventional
• Target: 98
• Locations: 1 country
• Sites: 1

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.

Conditions

Chronic Viral Hepatitis B Without Delta-agent

Keywords

HBeAg-positive

Outcome Measures

Primary Outcomes (1)

• HBsAg titer at 48 weeks

  at 48 weeks

Secondary Outcomes (7)

• Proportion of patients with serum HBsAg decline of ≥0.5 log10 IU/mL and <1.0 log10 IU/mL

  at 48 weeks of treatment

• Proportion of patients with serum HBsAg decline greater than 1.0 log10 IU/mL

  at 48 weeks of treatment

• Proportion of patients with serum HBsAg loss

  at 48 weeks of treatment

• Proportion of patients with serum HBeAg loss or HBeAg seroconversion

  at 48 weeks of treatment

• Proportion of patients with virologic rebound or genotypic resistance

  up to 48 weeks of treatment

Study Arms (2)

Telbivudine

EXPERIMENTAL

Telbivudine 600 mg Daily Oral

Drug: Telbivudine

Entecavir

ACTIVE COMPARATOR

Entecavir 0.5 mg Daily Oral

Drug: Entecavir

Interventions

Telbivudine DRUG

Telbivudine 600 mg Daily Oral

Also known as: Sebivo

Telbivudine

Entecavir DRUG

Entecavir 0.5 mg Daily Oral

Also known as: Baraclude

Entecavir

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Asan Medical Center: lead

Study Sites (1)

Asan Medical Center

Seoul, 138-736, South Korea

Location

Related Publications (1)

• An J, Lim YS, Kim GA, Han SB, Jeong W, Lee D, Shim JH, Lee HC, Lee YS. Telbivudine versus entecavir in patients with undetectable hepatitis B virus DNA: a randomized trial. BMC Gastroenterol. 2017 Jan 19;17(1):15. doi: 10.1186/s12876-017-0572-2.

  PMID: 28103819 DERIVED

MeSH Terms

Interventions

Telbivudine; entecavir

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Young-Suk Lim, M.D., Ph.D.

  Asan Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 8, 2012
• First Posted: May 10, 2012
• Study Start: May 1, 2012
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: January 26, 2017

Record last verified: 2017-01

Locations

KR (1)