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

Foundation for Liver Research

Status and phase: Completed; Phase 3

Conditions: Hepatitis B

Treatments: Drug: Peginterferon alpha 2a; Drug: Ribavirin

Study type: Interventional

Funder types: Other

Identifiers

NCT00114361

HBV05-01

EudraCT: 2004-004736-30

Details and patient eligibility

About

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.

Full 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.

Enrollment: 138 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

Trial design

138 participants in 2 patient groups

1

Active Comparator group

Description:

Ribavirin + Peg IFN

Treatment:

Drug: Ribavirin

2

Active Comparator group

Description:

Peg IFN + Placebo

Treatment:

Drug: Peginterferon alpha 2a