48 Weeks Combination Therapy for Patients With HBeAg-negative Chronic Hepatitis B Virus (HBV) Infection

This study has been completed.
Sponsor:
Information provided by:
Foundation for Liver Research
ClinicalTrials.gov Identifier:
NCT00114361
First received: June 14, 2005
Last updated: June 18, 2010
Last verified: June 2010
  Purpose

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.


Condition Intervention Phase
Hepatitis B
Drug: Ribavirin
Drug: Peginterferon alpha 2a
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Official Title: Peginterferon Alfa-2a and Ribavirin Combination Therapy in Patients With HBeAg-negative Chronic HBV Infection (PARC Study)

Resource links provided by NLM:


Further study details as provided by Foundation for Liver Research:

Primary Outcome Measures:
  • The combined presence of HBV DNA level < 10E4 copies/ml and ALT normalization at the end of follow-up [ Time Frame: may 2008 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ALT normalization [ Time Frame: May 2008 ] [ Designated as safety issue: No ]
  • HBV DNA negativity(undetectable by Taqman PCR) [ Time Frame: May 2008 ] [ Designated as safety issue: No ]
  • HBsAg loss from serum [ Time Frame: May 2008 ] [ Designated as safety issue: No ]
  • Improvement liver histology [ Time Frame: May 2008 ] [ Designated as safety issue: No ]
  • Combined virological, biochemical and histological response [ Time Frame: May 2008 ] [ Designated as safety issue: No ]

Enrollment: 138
Study Start Date: March 2005
Study Completion Date: April 2010
Primary Completion Date: May 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Ribavirin + Peg IFN
Drug: Ribavirin
1200 mg a day, 48 weeks
Active Comparator: 2
Peg IFN + Placebo
Drug: Peginterferon alpha 2a
180 µg per week, 48 weeks

Detailed Description:

Despite the introduction of newer drugs for the treatment of chronic hepatitis B, there is still no optimal treatment. Pegylated interferon alfa has proven sustained efficacy in approximately 30-40% of patients with HBeAg-positive or HBeAg-negative chronic hepatitis B. It is likely that combination therapy of pegylated interferon alfa with ribavirin in chronic hepatitis B is more effective than pegylated interferon alfa monotherapy. In chronic hepatitis C, adding ribavirin to pegylated interferon therapy doubled the sustained response rate (29% vs. 56%) and has become the standard option of treatment.

To investigate the effect of the treatment with pegylated interferon and ribavirin on the amount of inflammation and fibrosis in the liver, a liver biopsy will be performed within one year prior to screening and at the end of follow-up.

When patients with chronic hepatitis B are treated outside any study with pegylated interferon, they visit the outpatient clinic approximately every month for blood samples. So in this study the amount of blood samples taken from every patient is not increased as compared with treatment outside a study.

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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
  • Subjects with clinically significant retinal abnormalities
  • Subjects with clinically significant hearing abnormalities
  • Hemoglobinopathies
  • Subjects with known hypersensitivity to ribavirin
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00114361

Locations
Netherlands
Erasmus MC department hepatology
Rotterdam, Netherlands, 3000CA
Sponsors and Collaborators
Foundation for Liver Research
Investigators
Principal Investigator: Harry LA Janssen, MD PhD Foundation of Liver Research
  More Information

No publications provided

Responsible Party: Prof. H.L.A. Janssen, Foundation for Liver reseach
ClinicalTrials.gov Identifier: NCT00114361     History of Changes
Other Study ID Numbers: HBV05-01, EudraCT: 2004-004736-30
Study First Received: June 14, 2005
Last Updated: June 18, 2010
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
Germany: Federal Institute for Drugs and Medical Devices

Keywords provided by Foundation for Liver Research:
HBeAg-negative
chronic
hepatitis B
viral

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Digestive System Diseases
DNA Virus Infections
Enterovirus Infections
Hepadnaviridae Infections
Hepatitis, Viral, Human
Liver Diseases
Picornaviridae Infections
RNA Virus Infections
Virus Diseases
Interferon-alpha
Peginterferon alfa-2a
Ribavirin
Anti-Infective Agents
Antimetabolites
Antiviral Agents
Immunologic Factors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014