A Study of Pegasys (Peginterferon Alfa-2a) Versus Untreated Control in Children With HBeAg Positive Chronic Hepatitis B

• HBsAg seroconversion (loss of HBsAg and presence of anti-HBs) [ Time Frame: up to 8 years ] [ Designated as safety issue: No ]
• Loss of HBeAg/HBsAg [ Time Frame: up to 8 years ] [ Designated as safety issue: No ]
• Serum alanine aminotransferase (ALT) levels [ Time Frame: up to 8 years ] [ Designated as safety issue: No ]
• Proportion of normal ALT [ Time Frame: up to 8 years ] [ Designated as safety issue: No ]
• HBV DNA levels [ Time Frame: up to 8 years ] [ Designated as safety issue: No ]
• Change in liver elasticity (elastography) [ Time Frame: from baseline to Week 72 ] [ Designated as safety issue: No ]
• Group C: Change in histological findings (liver biopsy) [ Time Frame: from baseline to Week 72 ] [ Designated as safety issue: No ]
• Pharmacokinetics: Area under the concentration-time curve (AUC) [ Time Frame: Weeks 1 and 24, pre-dose and 24-48, 72-96 and 168 hours post-dose ] [ Designated as safety issue: No ]
• Safety: Incidence of adverse events [ Time Frame: up to 8 years ] [ Designated as safety issue: No ]
• Safety: Growth [ Time Frame: up to 8 years ] [ Designated as safety issue: No ]

This parallel group, open label study will evaluate the safety and efficacy of Pegasys (peginterferon alfa-2a) versus untreated control in children (age 3 years to <18 years at baseline) with HBeAg positive chronic hepatitis B. Children without advanced fibrosis and without cirrhosis will be randomized 2:1 to treatment Group A, receiving Pegasys 45-180 mcg subcutaneously weekly for 48 weeks, or to the untreated control Group B. Children with advanced fibrosis will be assigned to treatment group C and receive 48 weeks of treatment with Pegasys. Children in the untreated control Group B who have not experienced seroconversion 48 weeks after randomization may enter the Switch Arm to receive 48 weeks of Pegasys treatment. This offer will be available for 1 year following 48 weeks from randomization. Anticipated time on study treatment is 48 weeks. All subjects will be followed up for 5 years after the end of treatment (A,C,Switch)/principal observation (B) period.

• Drug: peginterferon alfa-2a [Pegasys]
  Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, Weeks 1- 48
• Drug: peginterferon alfa-2a [Pegasys]
  Body surface area adapted doses of 45-180 mcg subcutaneously weekly for 48 weeks, after Week 48 for Group B patients who have not experienced HBeAg seroconversion

• Experimental: A Pegasys
  Intervention: Drug: peginterferon alfa-2a [Pegasys]
• No Intervention: B Untreated Control
• Experimental: C Fibrosis non-randomized
  Intervention: Drug: peginterferon alfa-2a [Pegasys]
• Experimental: Switch
  Intervention: Drug: peginterferon alfa-2a [Pegasys]

Inclusion Criteria:

• Male or female patients, 3 years to <18 years of age at baseline
• Positive HBsAg for more than 6 months
• Positive HBeAg and detectable HBV DNA at screening
• Negative anti-HBs and anti-HBe at screening
• A liver biopsy obtained within the past 2 years prior to baseline (and more than 6 months after the end of previous therapy for hepatitis B) to confirm the presence of advanced fibrosis or exclude cirrhosis
• Compensated liver disease (Child-Pugh Class A)
• Elevated serum alanine transferase (ALT)
• Normal thyroid gland function at screening

Exclusion Criteria:

• Subjects with cirrhosis
• Subjects must not have received investigational drugs or licensed treatments with anti-HBV activity within 6 months of baseline. Subjects 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
• Known hypersensitivity to peginterferon
• Positive test results at screening for hepatitis A, hepatitis C, hepatitis D or HIV infection
• History or evidence of medical condition associated with chronic liver disease other than chronic hepatitis B
• History or evidence of bleeding from esophageal varices
• Decompensated liver disease (e.g. ascites, Child-Pugh Class B or C)
• History of immunologically mediated disease
• Pregnant or lactating females