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

June 14, 2005
June 18, 2010
March 2005
May 2008   (final data collection date for primary outcome measure)
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 ]
The combined presence of HBV DNA level < 104 copies/ml and ALT normalization at the end of follow-up
Complete list of historical versions of study NCT00114361 on ClinicalTrials.gov Archive Site
  • 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 ]
  • 1. ALT normalization
  • 2. HBV DNA negativity(undetectable by Taqman PCR)
  • 3. HBsAg loss from serum
  • 4. Improvement liver histology
  • 5. Combined virological, biochemical and histological response
Not Provided
Not Provided
 
48 Weeks Combination Therapy for Patients With HBeAg-negative Chronic Hepatitis B Virus (HBV) Infection
Peginterferon Alfa-2a and Ribavirin Combination Therapy in Patients With HBeAg-negative Chronic HBV Infection (PARC Study)

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Factorial Assignment
Masking: Double Blind (Subject, Investigator)
Hepatitis B
  • Drug: Ribavirin
    1200 mg a day, 48 weeks
  • Drug: Peginterferon alpha 2a
    180 µg per week, 48 weeks
  • Active Comparator: 1
    Ribavirin + Peg IFN
    Intervention: Drug: Ribavirin
  • Active Comparator: 2
    Peg IFN + Placebo
    Intervention: Drug: Peginterferon alpha 2a
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
138
April 2010
May 2008   (final data collection date for primary outcome measure)

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
Both
18 Years to 70 Years
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT00114361
HBV05-01, EudraCT: 2004-004736-30
Yes
Prof. H.L.A. Janssen, Foundation for Liver reseach
Foundation for Liver Research
Not Provided
Principal Investigator: Harry LA Janssen, MD PhD Foundation of Liver Research
Foundation for Liver Research
June 2010

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP