NCT00114361

Brief Summary

The purpose of this study is to investigate whether in patients with chronic HBeAg-negative hepatitis B, PEG-IFN-ribavirin combination therapy for 1 year leads to enhanced response (HBV DNA \<10E4 copies/ml and normal ALT 24 weeks after treatment discontinuation) in comparison with pegylated interferon (PEG-IFN) monotherapy.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
138

participants targeted

Target at P25-P50 for phase_3

Timeline
Completed

Started Mar 2005

Longer than P75 for phase_3

Geographic Reach
1 country

1 active site

Status
completed

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

March 1, 2005

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

June 14, 2005

Completed
1 day until next milestone

First Posted

Study publicly available on registry

June 15, 2005

Completed
2.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 1, 2008

Completed
1.9 years until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2010

Completed
Last Updated

June 22, 2010

Status Verified

June 1, 2010

Enrollment Period

3.2 years

First QC Date

June 14, 2005

Last Update Submit

June 18, 2010

Conditions

Keywords

HBeAg-negativechronichepatitis Bviral

Outcome Measures

Primary Outcomes (1)

  • The combined presence of HBV DNA level < 10E4 copies/ml and ALT normalization at the end of follow-up

    may 2008

Secondary Outcomes (5)

  • ALT normalization

    May 2008

  • HBV DNA negativity(undetectable by Taqman PCR)

    May 2008

  • HBsAg loss from serum

    May 2008

  • Improvement liver histology

    May 2008

  • Combined virological, biochemical and histological response

    May 2008

Study Arms (2)

1

ACTIVE COMPARATOR

Ribavirin + Peg IFN

Drug: Ribavirin

2

ACTIVE COMPARATOR

Peg IFN + Placebo

Drug: Peginterferon alpha 2a

Interventions

1200 mg a day, 48 weeks

1

180 µg per week, 48 weeks

2

Eligibility Criteria

Age18 Years - 70 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Chronic hepatitis B
  • Biopsy performed within one year prior to screening or during screening
  • ALT \> 1.5 x ULN
  • HBeAg negative, anti-HBeAg positive
  • HBV DNA \> 10E5 copies/ml
  • Age 18-70 years
  • Written informed consent
  • Hepatic imaging without evidence of HCC
  • All fertile males and females must be using two forms of effective contraception

You may not qualify if:

  • Antiviral therapy against HBV within the previous 6 months; treatment with any investigational drug within 30 days of entry to this protocol
  • Severe hepatitis activity as documented by ALT \> 10 x ULN
  • Advanced liver disease
  • Pre-existent leucopenia or thrombopenia
  • Co-infection with HCV,HDV or HIV
  • Other acquired or inherited causes of liver disease
  • Alpha fetoprotein \> 50 ng/ml.
  • Evidence of severe renal disease
  • Hyper- or hypothyroidism
  • Significant cardiovascular or pulmonary dysfunction, malignancy,immunodeficiency syndromes
  • Immune suppressive treatment within the previous 6 months
  • Contra-indications for alpha-interferon therapy
  • Pregnancy, breast-feeding
  • Any medical condition requiring chronic systemic administration of steroids
  • Substance alcohol or drug abuse
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Erasmus MC department hepatology

Rotterdam, 3000CA, Netherlands

Location

Related Publications (4)

  • Brakenhoff SM, de Knegt RJ, van Campenhout MJH, van der Eijk AA, Brouwer WP, van Bommel F, Boonstra A, Hansen BE, Berg T, Janssen HLA, de Man RA, Sonneveld MJ. End-of-treatment HBsAg, HBcrAg and HBV RNA predict the risk of off-treatment ALT flares in chronic hepatitis B patients. J Microbiol Immunol Infect. 2023 Feb;56(1):31-39. doi: 10.1016/j.jmii.2022.06.002. Epub 2022 Jul 2.

  • Brakenhoff SM, de Knegt RJ, Oliveira J, van der Eijk AA, van Vuuren AJ, Hansen BE, Janssen HLA, de Man RA, Boonstra A, Sonneveld MJ. Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B. J Infect Dis. 2022 Dec 28;227(1):113-122. doi: 10.1093/infdis/jiac210.

  • Brakenhoff SM, de Man RA, Boonstra A, van Campenhout MJH, de Knegt RJ, van Bommel F, van der Eijk AA, Berg T, Hansen BE, Janssen HLA, Sonneveld MJ. Hepatitis B virus RNA decline without concomitant viral antigen decrease is associated with a low probability of sustained response and hepatitis B surface antigen loss. Aliment Pharmacol Ther. 2021 Jan;53(2):314-320. doi: 10.1111/apt.16172. Epub 2020 Nov 21.

  • Farag MS, van Campenhout MJH, Pfefferkorn M, Fischer J, Deichsel D, Boonstra A, van Vuuren AJ, Ferenci P, Feld JJ, Berg T, Hansen BE, van Bommel F, Janssen HLA. Hepatitis B Virus RNA as Early Predictor for Response to Pegylated Interferon Alpha in HBeAg-Negative Chronic Hepatitis B. Clin Infect Dis. 2021 Jan 27;72(2):202-211. doi: 10.1093/cid/ciaa013.

MeSH Terms

Conditions

Hepatitis BBronchiolitis Obliterans Syndrome

Interventions

Ribavirin

Condition Hierarchy (Ancestors)

Blood-Borne InfectionsCommunicable DiseasesInfectionsHepadnaviridae InfectionsDNA Virus InfectionsVirus DiseasesHepatitis, Viral, HumanHepatitisLiver DiseasesDigestive System DiseasesOrganizing PneumoniaBronchiolitis ObliteransBronchiolitisBronchitisBronchial DiseasesRespiratory Tract DiseasesLung Diseases, ObstructiveLung DiseasesGraft vs Host DiseaseImmune System Diseases

Intervention Hierarchy (Ancestors)

RibonucleosidesNucleosidesNucleic Acids, Nucleotides, and Nucleosides

Study Officials

  • Harry LA Janssen, MD PhD

    Foundation of Liver Research

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, INVESTIGATOR
Intervention Model
FACTORIAL
Sponsor Type
OTHER

Study Record Dates

First Submitted

June 14, 2005

First Posted

June 15, 2005

Study Start

March 1, 2005

Primary Completion

May 1, 2008

Study Completion

April 1, 2010

Last Updated

June 22, 2010

Record last verified: 2010-06

Locations