A Study of Pegasys (Peginterferon Alfa-2a) Added to Nucleos(t)Ide Analogue Treatment in Patients With HBeAg-Negative Chronic Hepatitis B Genotype D Showing Stable HBV DNA Suppression

• Proportion of patients with HBsAg decrease >/=1 log10 IU/ml from baseline to Week 48 [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• Change in HBsAg levels [ Time Frame: from baseline to Week 96 ] [ Designated as safety issue: No ]
• Proportion of patients with HBsAg </= 0.05 UI/ml at Week 48 [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• Proportion of patients with HBsAg </= 0.05 UI/ml at Week 72 [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• Proportion of patients with HBsAg </= 0.05 UI/ml at Week 96 [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• HBsAg levels according to IL28B genotypes [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• HBsAg levels according to IP-10 serum levels [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: approximately 2.5 years ] [ Designated as safety issue: No ]

This open-label, single-arm, multicenter study will evaluate the efficacy and safety of adding Pegasys (peginterferon alfa-2a) to nucleos(t)ide analogue (NAs) treatment in patients with HBeAg-negative chronic hepatitis B genotype D showing stable HBV DNA suppression. After a 12-week Lead-in period on treatment with NA, patients with a HBsAg decline <0.5 log10 IU/ml will enter the Add-on period to receive Pegasys 180 mcg subcutaneously weekly for 48 weeks in addition to their current NA treatment. Follow-up will be a further 48 weeks, during which the patients will continue their NA treatment.

• Drug: peginterferon alfa-2a [Pegasys]
  180 mcg subcutaneously weekly, 48 weeks
• Drug: nucleos(t)ide analogues
  Adenovir, entecavir, lamivudine or tenofovir

Inclusion Criteria:

• Adult patients, 18 - 65 years of age
• Chronic hepatitis B
• Negative for HBeAg
• On monotherapy with any nucleos(t)ide analogue (NA) but telbivudine at enrolment, and HBV DNA persistently below 20 IU/ml for at least 12 months
• HBsAg >100 IU/ml at the beginning of the Lead-in phase, confirmed before addition of Pegasys
• Showing a steady HBsAg kinetic (HBsAg decrease <0.5 log10 IU/ml from Week -12 to start of the Add-on phase)
• Negative pregnancy test for women of childbearing potential
• Women of childbearing potential and fertile males with female partners of childbearing potential must be using reliable contraception during and for 3 months after the Add-on phase

Exclusion Criteria:

• Coinfection with HAV, HCV, HDV, HIV
• Evidence of decompensated liver disease (Child-Pugh >/=6)
• History or other evidence of a medical condition associated with chronic liver disease (e.g. hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin exposure)
• Known hypersensitivity to peginterferon alfa-2a
• Pregnant of breastfeeding women
• Evidence of alcohol and/or drug abuse
• History of severe psychiatric disease, especially depression
• History of immunologically mediated disease
• History or evidence of bleeding from esophageal varices or other conditions consistent with decompensated liver disease
• History or evidence of severe pulmonary disease associated with functional limitations
• History of severe cardiac disease
• History of severe seizure disorder or current anticonvulsant use
• Evidence of an active or suspected cancer or a history of malignancy (other than basocellular carcinoma or in situ cervical carcinoma) within 5 years prior to study entry
• History of having received any systemic anti-neoplastic (including radiation) or immunomodulatory (including systemic corticosteroids) treatment </= 6 months prior to the first dose or the expectation that such a treatment will be needed at any time during the study
• History or other evidence of severe retinopathy