NCT00917761

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.

Trial Health

43
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Enrollment
300

participants targeted

Target at P75+ for phase_4

Timeline
Completed

Started Feb 2007

Longer than P75 for phase_4

Geographic Reach
1 country

6 active sites

Status
unknown

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

February 1, 2007

Completed
2.4 years until next milestone

First Submitted

Initial submission to the registry

June 8, 2009

Completed
2 days until next milestone

First Posted

Study publicly available on registry

June 10, 2009

Completed
4.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2013

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

December 1, 2013

Completed
Last Updated

December 20, 2012

Status Verified

December 1, 2012

Enrollment Period

6.8 years

First QC Date

June 8, 2009

Last Update Submit

December 19, 2012

Conditions

Hepatitis B, Chronic

Keywords

Hepatitis B, chronicPeginterferon alfa-2aEntecavir

Outcome Measures

Primary Outcomes (1)

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

    2.5 years

Secondary Outcomes (1)

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

    2.5 years

Study Arms (3)

Entecavir and peginterferon (52 weeks)

EXPERIMENTAL

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)

Peginterferon (96 weeks)

EXPERIMENTAL

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

Drug: Peginterferon (Pegasys) (96 weeks)

Peginterferon (48 weeks)

ACTIVE COMPARATOR

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

Drug: Peginterferon (Pegasys) (48 weeks)

Interventions

Entecavir and peginterferon (Pegasys) (52 weeks)DRUG

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

Also known as: Entecavir (Baraclude)0.5 mg/day po at week 1-4, Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 5-52
Entecavir and peginterferon (52 weeks)
Peginterferon (Pegasys) (96 weeks)DRUG

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

Also known as: Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-96
Peginterferon (96 weeks)
Peginterferon (Pegasys) (48 weeks)DRUG

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

Also known as: Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-48
Peginterferon (48 weeks)

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

National Taiwan University Hosptial, Yun-Lin Branch

Douliu, Taiwan

RECRUITING

Taichung Veterans General Hospital

Taichung, Taiwan

RECRUITING

National Taiwan University Hospital

Taipei, 10002, Taiwan

RECRUITING

Buddhist Tzu Chi General Hospital

Taipei, Taiwan

RECRUITING

Far Eastern Memorial Hospital

Taipei, Taiwan

RECRUITING

Ren-Ai Branch, Taipei Municipal Hospital

Taipei, Taiwan

RECRUITING

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavirpeginterferon alfa-2a

Condition Hierarchy (Ancestors)

Hepatitis BBlood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitis, ChronicHepatitisLiver DiseasesDigestive System DiseasesChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Study Officials

  • Chen-Hua Liu, MD

    National Taiwan University Hospital

    STUDY CHAIR

  • Jia-Horng Kao, MD, PhD

    National Taiwan University Hospital

    PRINCIPAL INVESTIGATOR

  • Shih-Jer Hsu, MD

    National Taiwan University Hosptial, Yun-Lin Branch

    PRINCIPAL INVESTIGATOR

  • Chih-Lin Lin, MD

    Ren-Ai Branch, Taipei City Hospital

    PRINCIPAL INVESTIGATOR

  • Cheng-Chao Liang, MD

    Far Eastern Memorial Hospital

    PRINCIPAL INVESTIGATOR

  • Ching-Sheng Hsu, MD

    Buddhist Tzu Chi General Hospital

    PRINCIPAL INVESTIGATOR

  • Sheng-Shun Yang, MD, PhD

    Taichung Veterans General Hospital

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Chen-Hua Liu, MD

CONTACT

886-2-23123456jacque_liu@mail2000.com.tw

Jia-Horng Kao, MD, PhD

CONTACT

886-2-23123456kaojh@ntu.edu.tw

Study Design

Study Type
interventional
Phase
phase 4
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

June 8, 2009

First Posted

June 10, 2009

Study Start

February 1, 2007

Primary Completion

December 1, 2013

Study Completion

December 1, 2013

Last Updated

December 20, 2012

Record last verified: 2012-12

Locations

TW(6)