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

Primary Purpose

Hepatitis B, Chronic

Status
Unknown status
Phase
Phase 4
Locations
Taiwan
Study Type
Interventional
Intervention
Entecavir and peginterferon alfa-2a
Placebo and peginterferon
Sponsored by
National Taiwan University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic focused on measuring Hepatitis B, chronic, Peginterferon alfa-2a, Entecavir

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Chronic hepatitis B (presence of HBsAg > 6 months) with HBeAg persistence for more than 3 months
  • Age older than 18 years
  • HBV DNA > 20,000 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

Sites / Locations

  • National Taiwan University Hosptial, Yun-Lin BranchRecruiting
  • Taichung Veterans General HospitalRecruiting
  • National Taiwan University HospitalRecruiting
  • Buddhist Tzu Chi General HospitalRecruiting
  • Far Eastern Memorial HospitalRecruiting
  • Ren-Ai Branch, Taipei Municipal HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Entecavir and peginterferon

Placebo and peginterferon

Arm Description

Entecavir 0.5 mg/day at week 1-4, followed by peginterferon alfa-2a 180 ug/week at week 5-52

Placebo 0.5 mg/day at week 1-4, followed by peginterferon alfa-2a 180 ug/week at week 5-52

Outcomes

Primary Outcome Measures

HBeAg seroconversion rate 6 months after the cessation of therapy

Secondary Outcome Measures

Full Information

First Posted
June 15, 2009
Last Updated
December 19, 2012
Sponsor
National Taiwan University Hospital
Collaborators
National Science Council, Taiwan
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1. Study Identification

Unique Protocol Identification Number
NCT00921180
Brief Title
Entecavir and Pegasys Sequential Therapy Versus Pegasys for HBeAg Positive Chronic Hepatitis B
Official Title
Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Positive Chronic Hepatitis B
Study Type
Interventional

2. Study Status

Record Verification Date
December 2012
Overall Recruitment Status
Unknown status
Study Start Date
February 2007 (undefined)
Primary Completion Date
December 2013 (Anticipated)
Study Completion Date
December 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
National Taiwan University Hospital
Collaborators
National Science Council, Taiwan

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg positive CHB, with the overall HBeAg seroconversion 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. 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 HBeAg seroconversion. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate of adding entecavir early in the course of therapy can improve the treatment response.
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 positive CHB, with the overall HBeAg seroconversion 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. 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 HBeAg seroconversion. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate of adding entecavir early in the course of therapy can improve the treatment response.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic
Keywords
Hepatitis B, chronic, Peginterferon alfa-2a, Entecavir

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
148 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Entecavir and peginterferon
Arm Type
Experimental
Arm Description
Entecavir 0.5 mg/day at week 1-4, followed by peginterferon alfa-2a 180 ug/week at week 5-52
Arm Title
Placebo and peginterferon
Arm Type
Active Comparator
Arm Description
Placebo 0.5 mg/day at week 1-4, followed by peginterferon alfa-2a 180 ug/week at week 5-52
Intervention Type
Drug
Intervention Name(s)
Entecavir and peginterferon alfa-2a
Other Intervention Name(s)
Entecavir (Baraclude) 0.5 mg/day po at week 1-4, Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 5-52
Intervention Description
Entecavir (Baraclude) 0.5 mg/day po at week 1-4 Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 5-52
Intervention Type
Drug
Intervention Name(s)
Placebo and peginterferon
Other Intervention Name(s)
Placebo 0.5 mg/day po at week 1-4, Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 5-52
Intervention Description
Placebo 0.5 mg/day po at week 1-4 Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 5-52
Primary Outcome Measure Information:
Title
HBeAg seroconversion rate 6 months after the cessation of therapy
Time Frame
76 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Chronic hepatitis B (presence of HBsAg > 6 months) with HBeAg persistence for more than 3 months Age older than 18 years HBV DNA > 20,000 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Chen-Hua Liu, MD
Phone
886-2-23123456
Ext
63572
Email
jacque_liu@mail2000.com.tw
First Name & Middle Initial & Last Name or Official Title & Degree
Jia-Horng Kao, MD, PhD
Phone
886-2-23123456
Ext
67307
Email
kaojh@ntu.edu.tw
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Chen-Hua Liu, MD
Organizational Affiliation
National Taiwan University Hospital
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
Jia-Horng Kao, MD, PhD
Organizational Affiliation
National Taiwan University Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Shih-Jer Hsu, MD
Organizational Affiliation
National Taiwan University Hosptial, Yun-Lin Branch
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Chih-Lin Lin, MD
Organizational Affiliation
Ren-Ai Branch, Taipei City Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Cheng-Chao Liang, MD
Organizational Affiliation
Far Eastern Memorial Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Ching-Sheng Hsu, MD
Organizational Affiliation
Buddhist Tzu Chi General Hospital
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Sheng-Shun Yang, MD, PhD
Organizational Affiliation
Taichung Veterans General Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
National Taiwan University Hosptial, Yun-Lin Branch
City
Douliou
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Shih-Jer Hsu, MD
First Name & Middle Initial & Last Name & Degree
Shih-Jer Hsu, MD
First Name & Middle Initial & Last Name & Degree
Ping-Huei Tseng, MD
First Name & Middle Initial & Last Name & Degree
Chieh-Chang Chen, MD
First Name & Middle Initial & Last Name & Degree
Ming-Lun Han, MD
First Name & Middle Initial & Last Name & Degree
Jou-Wei Lin, MD, PhD
First Name & Middle Initial & Last Name & Degree
Jun-Herng Chen, MD
Facility Name
Taichung Veterans General Hospital
City
Taichung
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Sheng-Shun Yang, MD, PhD
First Name & Middle Initial & Last Name & Degree
Sheng-Shun Yang, MD, PhD
Facility Name
National Taiwan University Hospital
City
Taipei
ZIP/Postal Code
10002
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chen-Hua Liu, MD
Phone
+886-2-23123456
Ext
63572
Email
jacque_liu@mail2000.com.tw
First Name & Middle Initial & Last Name & Degree
Chen-Hua Liu, MD
First Name & Middle Initial & Last Name & Degree
Jia-Horng Kao, MD, PhD
First Name & Middle Initial & Last Name & Degree
Chun-Jen Liu, MD, PhD
First Name & Middle Initial & Last Name & Degree
Ming-Yang Lai, MD, PhD
First Name & Middle Initial & Last Name & Degree
Pei-Jer Chen, MD, PhD
First Name & Middle Initial & Last Name & Degree
Ding-Shinn Chen, MD
Facility Name
Buddhist Tzu Chi General Hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ching-Sheng Hsu, MD
First Name & Middle Initial & Last Name & Degree
Ching-Sheng Hsu, MD
First Name & Middle Initial & Last Name & Degree
Chia-Chi Wang, MD
First Name & Middle Initial & Last Name & Degree
Tai-Chung Tseng, MD
Facility Name
Far Eastern Memorial Hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Cheng-Chao Liang, MD
First Name & Middle Initial & Last Name & Degree
Cheng-Chao Liang, MD
Facility Name
Ren-Ai Branch, Taipei Municipal Hospital
City
Taipei
Country
Taiwan
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Chih-Lin Lin, MD
First Name & Middle Initial & Last Name & Degree
Chih-Lin Lin, MD
First Name & Middle Initial & Last Name & Degree
Ping-Yeh Wu, MD

12. IPD Sharing Statement

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

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