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

Primary Purpose

Hepatitis B, Chronic

Status

Unknown status

Phase

Phase 4

Locations

Taiwan

Study Type

Interventional

Intervention

Entecavir and peginterferon (Pegasys) (52 weeks)

Peginterferon (Pegasys) (96 weeks)

Peginterferon (Pegasys) (48 weeks)

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 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

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 3

Arm Type

Experimental

Active Comparator

Arm Label

Entecavir and peginterferon (52 weeks)

Peginterferon (96 weeks)

Peginterferon (48 weeks)

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment

Secondary Outcome Measures

ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment

Full Information

NCT ID

NCT00917761

First Posted

June 8, 2009

Last Updated

December 19, 2012

Sponsor

National Taiwan University Hospital

Collaborators

National Science Council, Taiwan

1. Study Identification

Unique Protocol Identification Number

NCT00917761

Brief Title

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

Official Title

Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative 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 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.

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.

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

None (Open Label)

Allocation

Randomized

Enrollment

300 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Entecavir and peginterferon (52 weeks)

Arm Type

Experimental

Arm Description

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

Arm Title

Peginterferon (96 weeks)

Arm Type

Experimental

Arm Description

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

Arm Title

Peginterferon (48 weeks)

Arm Type

Active Comparator

Arm Description

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

Intervention Type

Drug

Intervention Name(s)

Entecavir and peginterferon (Pegasys) (52 weeks)

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

Intervention Type

Drug

Intervention Name(s)

Peginterferon (Pegasys) (96 weeks)

Other Intervention Name(s)

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

Intervention Description

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

Intervention Type

Drug

Intervention Name(s)

Peginterferon (Pegasys) (48 weeks)

Other Intervention Name(s)

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

Intervention Description

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

Primary Outcome Measure Information:

Title

HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment

Time Frame

2.5 years

Secondary Outcome Measure Information:

Title

ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment

Time Frame

2.5 years

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Chen-Hua Liu, MD

Phone

886-2-23123456

Ext

63572

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

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

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

Learn more about this trial

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

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