A Study of Pegylated Interferon Alfa-2A in Combination With Lamivudine or Entecavir Compared With Untreated Control Group in Children With Hepatitis B Envelope Antigen (HBeAg)-Positive Chronic Hepatitis B (CHB) in the Immune-Tolerant Phase
Condition: Pediatric Immuno-Tolerant Chronic Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis; Hepatitis, Chronic
Intervention: Entecavir; Lamivudine; Pegylated Interferon Alfa-2A
Intervention description: Participants will receive entecavir, either as a film-coated tablet or oral solution, once daily at a dose of 0.015 milligrams per kilogram (mg/kg) (maximum daily dose of 0.5 mg).; Participants will receive lamivudine, either as a film-coated tablet or oral solution, once daily at a dose of 3 mg/kg (maximum daily dose of 100 mg).; Participants will receive pegylated interferon-alfa-2A at a body surface area (BSA) based dose of 180 micrograms per 1.73 square meter (mcg/1.73m^2) BSA.
Intervention MeSH terms: Interferons; Interferon-alpha; Lamivudine; Interferon alpha-2; Peginterferon alfa-2a; Entecavir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 62.0
Sex: All
Minimum age: 3 Years
Maximum age: 17 Years
Healthy volunteers: No

Summary:

      This randomized, controlled, parallel group, open-label multicenter study will evaluate the
      efficacy and safety of a combination of pegylated interferon alfa-2A (Pegasys) plus
      lamivudine or entecavir compared with an untreated control group in participants with HBeAg
      positive CHB in the immune tolerant phase. NOTE: STUDY RECRUITMENT HAS BEEN TERMINATED
    

Eligibility criteria:

        Inclusion Criteria:

          -  Positive for HBsAg and HBeAg for more than 6 months prior to baseline

          -  Detectable HBV-DNA (>20,000 IU/mL) as measured by polymerization chain reaction (PCR)
             or hybridization on at least 2 occasions at least one month apart with the latest
             determination obtained less than or equal to (</=) 42 days prior to baseline

          -  Compensated liver disease (Child-Pugh Class A clinical classification)

          -  Either Liver biopsy performed within 2 years prior to baseline showing no or minimal
             fibrosis (Liver Biopsy Scores and stable normal ALT levels (less than or equal to
             upper limit of normal [ULN]) during the 6 months leading up to baseline (including two
             separate occasions at least 1 month apart over the 6 months prior to baseline).
             Screening ALT levels must be normal (</= ULN) OR Stable normal ALT levels (</= ULN),
             during the 1 year leading up to baseline (including three separate occasions at least
             1 month apart over the 1 year prior to baseline) and no signs of hepatocellular
             carcinoma (HCC), advanced fibrosis/cirrhosis, or splenomegaly on liver abdominal
             ultrasound at screening. Screening ALT levels must be normal (</= ULN)

        Exclusion Criteria:

          -  Participants who have received investigational drugs or licensed treatments with anti
             HBV activity (Exception: Participants who have had a limited [</= 7-day] course of
             acyclovir for herpetic lesions more than 1 month before the study baseline visit are
             not excluded)

          -  Participants who have participated in any other clinical trial or who have received
             any investigational drug within 6 months prior to baseline

          -  Known hypersensitivity to interferon (IFN), pegylated interferon-alfa-2a or lamivudine
             or entecavir

          -  Positive test results at screening for hepatitis A virus Immunoglobulin M (IgM)
             antibody (Ab), anti-hepatitis C virus (HCV) Ab, anti- hepatitis D (HDV) Ab or
             anti-human immunodeficiency virus (HIV) Ab

          -  Decompensated liver disease (e.g., Child-Pugh Class B or C clinical classification or
             clinical evidence such as ascites or varices)

          -  Advanced fibrosis or cirrhosis

          -  Suspicion of HCC on liver abdominal ultrasound (all patients to have liver abdominal
             ultrasound within 6 months prior to baseline)

          -  History or other evidence of a medical condition associated with chronic liver disease
             other than CHB including metabolic liver diseases such as hemochromatosis, Wilson's
             disease or alpha-1 anti-trypsin deficiency

          -  Active substance abuse within 6 months prior to screening

          -  Sexually active females of childbearing potential and sexually active males who are
             not willing to utilize reliable contraception during treatment and for 90 days
             following the end of treatment

          -  Females who are pregnant or who are breastfeeding (females of childbearing potential
             who have a positive urine or serum pregnancy test result within 24 hours of baseline
             are excluded)