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

December 19, 2012 updated by: National Taiwan University Hospital

Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative Chronic Hepatitis B

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.

Study Overview

Status

Unknown

Conditions

Intervention / Treatment

Detailed Description

Chronic hepatitis B (CHB) is prevalent in the world, with estimated chronic carriers of 350 millions worldwide. 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.

Study Type

Interventional

Enrollment (Anticipated)

300

Phase

  • Phase 4

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

  • Taiwan
      • Douliou, Taiwan
        • Recruiting
        • National Taiwan University Hosptial, Yun-Lin Branch
      • Taichung, Taiwan
        • Recruiting
        • Taichung Veterans General Hospital
      • Taipei, Taiwan, 10002
        • Recruiting
        • National Taiwan University Hospital
        • Contact:
          • Chen-Hua Liu, MD
      • Taipei, Taiwan
        • Recruiting
        • Far Eastern Memorial Hospital
      • Taipei, Taiwan
        • Recruiting
        • Buddhist Tzu Chi General Hospital
      • Taipei, Taiwan
        • Recruiting
        • Ren-Ai Branch, Taipei Municipal Hospital

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 and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Chronic hepatitis B (presence of HBsAg > 6 months) with anti-HBe persistence and abscence of HBeAg for more than 3 months
  • Age older than 18 years
  • HBV DNA > 2,000 IU/mL for more than 2 occasions
  • Serum ALT levels between 2 to 10 folds the upper limit of normal (ULN)
  • A liver biopsy compatible with chronic hepatitis B

Exclusion Criteria:

  • Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for women)
  • Neutropenia (neutrophil count <1,500 per cubic milliliter)
  • Thrombocytopenia (platelet <90,000 per cubic milliliter)
  • Co-infection with hepatitis B virus (HBV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
  • Chronic alcohol abuse (daily consumption > 20 gram per day)
  • Decompensated liver disease (Child-Pugh class B or C)
  • Serum creatinine level more than 1.5 times the upper limit of normal
  • Autoimmune liver disease
  • Neoplastic disease
  • An organ transplant
  • Immunosuppressive therapy
  • Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
  • Evidence of drug abuse
  • Unwilling to have contraception
  • Known allergic reaction to entecavir or peginterferon alfa-2a
  • Unwilling to sign inform consent

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: Entecavir and peginterferon (52 weeks)
Entecavir 0.5 mg/day po at week 1-4 Peginterferon alfa-2a 180 ug/week sc at week 5-52
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
Other Names:
  • Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 5-52
  • Entecavir (Baraclude)0.5 mg/day po at week 1-4
Experimental: Peginterferon (96 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-96
Drug: Peginterferon (Pegasys) (96 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-96
Other Names:
  • Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-96
Active Comparator: Peginterferon (48 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-48
Drug: Peginterferon (Pegasys) (48 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-48
Other Names:
  • Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-48

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment
Time Frame: 2.5 years
2.5 years

Secondary Outcome Measures

Outcome Measure
Time Frame
ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment
Time Frame: 2.5 years
2.5 years

Collaborators and Investigators

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

Sponsor

National Taiwan University Hospital

Collaborators

National Science Council, Taiwan

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

February 1, 2007

Primary Completion (Anticipated)

December 1, 2013

Study Completion (Anticipated)

December 1, 2013

Study Registration Dates

First Submitted

June 8, 2009

First Submitted That Met QC Criteria

June 9, 2009

First Posted (Estimate)

June 10, 2009

Study Record Updates

Last Update Posted (Estimate)

December 20, 2012

Last Update Submitted That Met QC Criteria

December 19, 2012

Last Verified

December 1, 2012

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 950924

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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