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 III

Further Study Details: 

Primary Outcomes: The combined presence of HBV DNA level < 104 copies/ml and ALT normalization at the end of follow-up
Secondary Outcomes: 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
Expected Total Enrollment:  122

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.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

Inclusion Criteria:

• Chronic hepatitis B (HBsAg positive > 6 months)
• Biopsy performed within one year prior to screening or during screening
• ALT > 1.5 x ULN on two occasions within 2 months prior to randomization
• HBeAg negative, anti-HBeAg positive on two occasions within 2 months prior to randomization
• HBV DNA > 10E5 copies/ml
• Age 18-70 years
• Written informed consent
• Hepatic imaging (US, CT or MRI) without evidence of hepatocellular carcinoma within 3 months prior to randomization
• All fertile males and females must preferably be using two forms of effective contraception (combined) during treatment and during the 6 months after treatment end

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 hepatitis C,hepatitis D or human immunodeficiency virus (HIV)
• Other acquired or inherited causes of liver disease
• Alpha fetoprotein > 50 ng/ml.
• Serum creatinine level > 1.5 times ULN at screening or evidence of severe renal disease
• Hyper- or hypothyroidism
• Other significant medical illness that might interfere with this study: significant cardiovascular or pulmonary dysfunction in the previous 6 months, malignancy other than skin basocellular carcinoma in previous 5 years, immunodeficiency syndromes
• Immune suppressive treatment within the previous 6 months
• Contra-indications for alpha-interferon therapy
• Pregnancy, breast-feeding
• Any medical condition requiring, or likely to require, chronic systemic administration of steroids
• Substance alcohol or drug abuse
• Subjects with clinically significant retinal abnormalities
• Subjects with clinically significant hearing abnormalities.
• Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating in and completing the study.
• Hemoglobinopathies
• Subjects with known hypersensitivity to ribavirin or to any component of the tablet.

Please refer to this study by ClinicalTrials.gov identifier  NCT00114361

Elke Verhey      0031.10.4635941    e.verhey@erasmusmc.nl
Wanda Tielemans      0031.10.4635492    w.tielemans@erasmusmc.nl

Netherlands
      Erasmus MC department hepatology, Rotterdam,  3000CA,  Netherlands; Recruiting

Study ID Numbers:  HBV05-01; EudraCT: 2004-004736-30
Record last reviewed:  June 2005
Last Updated:  June 14, 2005
Record first received:  June 14, 2005
ClinicalTrials.gov Identifier:  NCT00114361
Health Authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO); Germany: Federal Institute for Drugs and Medicinal Devices
ClinicalTrials.gov processed this record on 2005-06-21