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

Hepatitis B Clinical Trial

Official title:

Peginterferon Alfa-2a and Ribavirin Combination Therapy in Patients With HBeAg-negative Chronic HBV Infection (PARC Study)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00114361
• Other study ID #: HBV05-01
• Secondary ID: EudraCT: 2004-00
• Status: Completed
• Phase: Phase 3
• First received: June 14, 2005
• Last updated: June 18, 2010
• Start date: March 2005
• Est. completion date: April 2010

Study information

• Verified date: June 2010
• Source: Foundation for Liver Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 138
• Est. completion date: April 2010
• Est. primary completion date: May 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Investigator)

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B

Intervention

Drug:
• Ribavirin
1200 mg a day, 48 weeks
• Peginterferon alpha 2a
180 µg per week, 48 weeks

Locations

Country	Name	City	State
Netherlands	Erasmus MC department hepatology	Rotterdam

Sponsors (1)

Lead Sponsor	Collaborator
Foundation for Liver Research

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The combined presence of HBV DNA level < 10E4 copies/ml and ALT normalization at the end of follow-up		may 2008	No
Secondary	ALT normalization		May 2008	No
Secondary	HBV DNA negativity(undetectable by Taqman PCR)		May 2008	No
Secondary	HBsAg loss from serum		May 2008	No
Secondary	Improvement liver histology		May 2008	No
Secondary	Combined virological, biochemical and histological response		May 2008	No