A Study of Switch From Nucleotide to Peginterferon Alfa-2a in CHB Patients Achieving HBeAg Loss and HBV DNA <200IU/ml

A Randomized, Multicenter Study Evaluating HBsAg Clearance in CHB Patients Achieving HBeAg Loss and HBV DNA <200copies/ml on Treatment With Nucleotide Analogues and Switched to Peginterferon Alfa-2a

A Randomized, open-label, multicenter study.

The patients after 1-3 years NAs treatment and having achieved HBeAg loss and HBV DNA <200IU/ml will be switched to Pegasys for 48 or 96 weeks (with a 12 weeks period of overlap with the NA for safety reasons). The subjects will be randomized into 2 groups:

Group 1 : 48-week standard treatment by Peginterferon alfa 2a 180µg/week Group 2 : 96-week prolonged treatment by Peginterferon alfa 2a 180µg/week.

All the patients will be followed up for 48 weeks after discontinuation of the study medication.

Note: NAs will be stratified LAM, ETV and ADV, with the ratio 1:1:1.

eligibility criteria: Men and women old of 18 to 65 years with chronic hepatitis B HBeAg positive treated with nucleoside and/or nucleotide analogues for 1-2 years and with partial response (HBeAg loss and HBV DNA <1000copies/ml).

Inclusion Criteria:

• Patients on-treatment with NAs (ADV, ETV or LAM) for 1-3 years, having achieved HBeAg loss at screening, and HBV DNA <200IU/ml for at least 48 weeks
• Male and female patients ≥ 18 to 65 years of age
• Chronic hepatitis B (positive HBsAg for at least 6 months prior to NA therapy start)
• Compensated liver disease (Child-Pugh <6)
• Absence of hepatocellular carcinoma on liver imaging and/or alfa fetoprotein < 50 ng/ml
• Negative urine or blood pregnancy test for women of childbearing potential within 24 hours of first PEG IFN study medication administration
• Able and willing to provide informed consent and abide by the requirements of the study

Exclusion Criteria:

• Neutrophil count <1.5 x 109cells/L or platelet count <90 x 109cells/L
• Co-infections with HIV, HAV, HCV, HDV or HEV
• Women with ongoing pregnancy or breast feeding, or wishing to become pregnant during the study period
• Prolonged and excessive alcohol intake (> 40g/day for men and > 30g/day for women)
• Active intravenous drug abuse
• History or current treatment with telbivudine
• Treatment with immunomodulators (e.g. Interferon) for less than one year before study enrollment
• Treatment with immunosuppressors (including systemic corticosteroids) or anti-neoplastic treatment (including radiation therapy) <=6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
• Serum concentrations of ceruloplasmin or alfa-antitrypsin consistent with an increased risk of metabolic disease
• History or other evidence of chronic pulmonary disease associated with functional limitation
• History of severe cardiac disease
• History of the severe seizure disorder or current anticonvulsivant use
• History of thyroid disease poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
• History or other evidence of severe retinopathy
• History of autoimmune disease or presence of a significant level of auto-antibodies
• Renal insufficiency (creatinine clearance of < 50 ml/min according to the Cockroft and Gault equation), kidney transplant, hemodialysis
• History of depression or uncontrolled psychiatric disorders
• Subjects protected by law or not in a position to give consent
• Patients with reproductive potential not willing to use an effective method of contraception.
• Evidence of an active or suspected cancer or a history of malignancy (other than basocellular carcinoma or in-situ cervical carcinoma)