A randomized open-label prospective trial for comparing combination therapy Peg-Interferon alfa-2a (PEGASYS®) and Adefovir dipivoxil (Hepsera®) and combination therapy Peg-Interferon alfa-2a (PEGASYS®) and Tenofovir disoproxil fumarate (Viread®) versus no treatment in HBeAg negative chronic hepatitis B patients with low viral load*
- Conditions
- chronic hepatitis Bviral hepatitis1001965410047438
- Registration Number
- NL-OMON32978
- Lead Sponsor
- Academisch Medisch Centrum
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Completed
- Sex
- Not specified
- Target Recruitment
- 150
1.Male and female patients > 18 and <= 70 years of age
2.Positive HBsAg for more than 6 months.
3.Negative for HBeAg for more than 6 months.
4.Patients with chronic hepatitis B who are either naive to antiviral treatment, or have received either interferon (IFN) or nucleoside/nucleotide analogues in the past but are still positive for HBsAg.
5.Serum ALT< 5 * ULN as determined by two values taken >14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained during the screening period.
6.Negative urine or serum pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of test drug
1.Patients co-infected with HCV, HIV or who have decompensated liver disease, hepato-cellular carcinoma, significant cardiac disease, significant renal disease, seizure disorders or severe retinopathy.
2.Patients who have received nucleos(t)ide analogues for their chronic hepatitis B within 6 weeks before enrollment or Peg-IFN within 3 months before enrollment.
3.Patients must not have received any other systemic anti-viral, anti-neoplastic or immuno-modulatory treatment (including supraphysiologic doses of steroids or radiation) <3 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study.
4.Positive test at screening for anti-HAV IgM, anti-HIV, HCV RNA. (Patients that have cleared the hepatitis C virus can be included in the study)
5.Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded. Exception: patients who have had a limited (<7 day) course of acyclovir for herpetic lesions more than 1 month prior to the first administration of test drug are not excluded.
6.Evidence of decompensated liver disease (Child Pugh B-C)
7.Serum total bilirubin > twice the upper limit of normal at screening
8.History or other evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease.
9.History or other evidence of a medical condition associated with chronic liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver diseases including Wilson*s disease and alfa1-antitrypsin deficiency, alcoholic liver disease, toxin exposures, thalassemia).
10.Women with ongoing pregnancy or who are breast feeding.
11.Neutrophil count <1500 cells/mm3 or platelet count <80,000 cells/mm3 at screening.
12.Hemoglobin < 7.1 mmol/L (< 11.5 g/dL) for females and < 7.8 mmol/L (< 12.5 g/dL) for men at screening.
13.Serum creatinine level >1.5 times the upper limit of normal at screening.
14.Unstabel ongoing severe psychiatric disease, especially depression. 15.History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, severe psoriasis, rheumatoid arthritis).
16.History or other evidence of chronic pulmonary and cardiac disease associated with functional limitation. Severe cardiac disease (e.g., NYHA Functional Class III or IV, myocardial infarction within 6 months, ventricular tachyarrhythmias requiring ongoing treatment, unstable angina or other significant cardiovascular diseases).
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary objective is to demonstrate the efficacy of combination therapy<br /><br>(Peg-IFN and adefovir or Peg-IFN and tenofovir) for inducing loss of HBsAg<br /><br>compared to no-treatment in HBeAg negative chronic hepatitis B patients with<br /><br>low viral load. </p><br>
- Secondary Outcome Measures
Name Time Method <p>The secondary objectives are to evaluate:<br /><br>a. the rate of HBsAg loss and anti-HBs serconversion,<br /><br>b. To establish predictive markers at baseline and during the first 12 weeks of<br /><br>treatment for response of primary and secundary endpoints.</p><br>