ongitudinal analysis of HBV-specific T cell responses in patients with HBeAg-negative chronic hepatitis B (CHB) treated with pegylated interferon alfa-2a (40 KD) (PEGASYS, Ro 25-8310). Immunology sub-study for a selected subgroup of patients participating in study ML 18253

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: Not specified

Inclusion Criteria

? Male and female patients >18 and <55 years of age ? Chronic hepatitis B: HBsAg-positive for >6 months, anti-HBs negative, HBeAg-negative, anti-HBe positive ? ALT >ULN but <10x ULN and HBV-DNA between 105 and 107 copies/mL or ALT >2.5x ULN but <10x ULN and HBV-DNA >105 copies /mL ? Liver biopsy carried out within the preceding 18 months demonstrating liver disease consistent with chronic hepatitis with Ishak Fibrosis Score >2 ? Patients with a histological diagnosis of cirrhosis (Ishak Fibrosis Score 6) and compensated liver disease (Child A, score 5) can be included. ? Negative urine or blood pregnancy test (for women of childbearing potential) documented within the 24-hour period prior to the first dose of study drug.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

? Interferon-based therapy or any systemic anti-HBV <12 months prior to the first dose of randomized treatment.? Antiviral, anti-neoplastic or immuno-modulatory treatment (including supraphysiologic doses of steroids and radiation) <12 months prior to the first dose of randomized treatment (except for <7 days of acyclovir for herpetic lesions more than 1 month prior to first administration of randomized treatment).Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation are also excluded.? Patients who were non responders (with evidence by ALT >1.5x ULN and HBV DNA >100,000 copies/mL on treatment) to a previous IFN therapy will be excluded.Patients who developed clinical resistance to lamivudine (re-emergence of HBV DNA >100,000 copies/mL after an initial drop at the beginning of therapy) will be excluded.? Compensated liver disease Child A score 6 or decompensated liver disease (Child B or C) or history or other evidence of GI bleeding or endoscopic evidence of GI varices >grade 2.? Positive test at screening for anti-HAV IgM, anti-HIV, anti-HCV, anti-HDV IgG ? History or other evidence of a medical condition associated with chronic liver disease other than HBV (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease including Wilson's disease and alpha1-antitrypsin deficiency, alcoholic liver disease, toxin exposures, thalassemia) ? Women with ongoing pregnancy or breast feeding ? Neutrophil count <1500 cells/mm3 or platelet count <90,000 cells/mm3 at screening ? Hemoglobin <11.5 g/dL for females and <12.5 g/dL for men at screening ? Serum creatinine level >1.5 times the upper limit of normal at screening or evidence of severe renal disease ? History of severe psychiatric disease, especially depression.Severe psychiatric disease is defined as treatment with an antidepressant medication or a major tranquilizer at therapeutic doses for major depression or psychosis, respectively, for at least 3 months at any previous time or any history of the following: a suicidal attempt, hospitalization for psychiatric disease, or a period of disability due to a psychiatric disease.? Evidence of drug abuse or treatment with methadone within one year of study entry ? Patients consuming alcohol in excess of 20g/day for women and 30g/day for men in the 6 months preceding enrollment ? History of a severe seizure disorder or current anticonvulsant use ? History of immunologically mediated disease (e.g., inflammatory bowel disease, idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune hemolytic anemia, scleroderma, psoriasis, rheumatoid arthritis etc.) ? History or other evidence of chronic pulmonary disease associated with functional limitation ? History of 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) ? History of major organ transplantation with an existing functional graft ? History or other evidence of severe illness or any other conditions which would make the patient, in the opinion of the investigator, unsuitable for the study ? Evidence of an active or suspected cancer or a history of malignancy where the risk of recurrence is 20% within 2 years.Patients with a lesion suspicious for hepatic malignancy on a screening imaging study will be excluded.? Patients w

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: This is an exploratory immunological investigation which has the objective to understand the extent and nature of the antigen-specific and non-specific immune defects in patients with HBeAg-negative CHB and their modulation by therapy with PEGASYS during the first 6 months of treatment;Secondary Objective: -;Primary end point(s): This is an exploratory immunological study.

Secondary Outcome Measures