Entecavir and Pegasys Sequential Therapy Versus Pegasys for HBeAg Negative Chronic Hepatitis B

Summary

Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Therefore, efforts on the various combinations with the currently available drugs are needed to improve the overall response rates. The simultaneous combination therapy with oral nucleoside and peginterferon alfa-2a from large-scaled randomized trials did not show a superior response rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the assumption that early viral suppression by lamivudine can restore the immune function to facilitate the later immunomodulatory response by peginterferon alfa-2a. Furthermore, prior studies using 24 months of standard interferon alfa showed better ALT normalization and HBV suppression rates to 12 months of therapy. With the recent introduction of entecavir, the more potent oral nucleoside with few drug resistance, sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBV viral suppression. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate if adding entecavir early in the course of therapy or extending the treatment duration of peginterferon alfa-2a can improve the treatment response.

Conditions

• Hepatitis B, Chronic

Interventions

DRUG

Entecavir and peginterferon (Pegasys) (52 weeks)

Entecavir 0.5 mg/day po at week 1-4 Peginterferon alfa-2a 180 ug/week sc at week 5-52

DRUG

Peginterferon (Pegasys) (96 weeks)

Peginterferon alfa-2a 180 ug/week sc at week 1-96

DRUG

Peginterferon (Pegasys) (48 weeks)

Peginterferon alfa-2a 180 ug/week sc at week 1-48

Sponsors & Collaborators

• National Science and Technology Council, Taiwan

  collaborator OTHER_GOV

• National Taiwan University Hospital

  lead OTHER

Principal Investigators

• Chen-Hua Liu, MD · National Taiwan University Hospital

• Jia-Horng Kao, MD, PhD · National Taiwan University Hospital

• Shih-Jer Hsu, MD · National Taiwan University Hosptial, Yun-Lin Branch

• Chih-Lin Lin, MD · Ren-Ai Branch, Taipei City Hospital

• Cheng-Chao Liang, MD · Far Eastern Memorial Hospital

• Ching-Sheng Hsu, MD · Buddhist Tzu Chi General Hospital

• Sheng-Shun Yang, MD, PhD · Taichung Veterans General Hospital

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

PARALLEL

Eligibility

Min Age

18 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2007-02-28

Primary Completion

2013-12-31

Completion

2013-12-31

Countries

• Taiwan

Study Locations