Entecavir/Pegylated Interferon in Immune Tolerant Children With Chronic Hepatitis B Virus (HBV) Infection
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis
Intervention: Entecavir and peginterferon
Intervention description: Entecavir 0.015 mg/kg/day (up to 0.5 mg maximum daily dose) once daily for 48 weeks and Peginterferon alfa-2a 180 µg/1.73m2 subcutaneously once weekly for 40 weeks beginning 8 weeks after entecavir monotherapy).
Intervention MeSH terms: Peginterferon alfa-2a; Entecavir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 3 Years
Maximum age: 18 Years
Healthy volunteers: No
Keywords: Hepatitis B; HBV

Summary:

      The purpose of this study is to determine the safety and efficacy of treatment using a
      combination of drugs (entecavir and pegylated interferon) in children ages 3-<18 years old
      with immunotolerant chronic hepatitis B.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Enrolled in & completed the baseline evaluation in NCT01263600 OR completed necessary
             components of NCT01263600 baseline evaluation by the end of the baseline visit.

          -  3 to <18 years at time of randomization (day 0).

          -  Documented chronic Hepatitis B virus (HBV) infection as evidenced by detection of
             hepatitis B surface antigen (HBsAg) in serum for ≥ 24 weeks prior to baseline OR
             positive HBsAg and negative anti-Hepatitis B core (HBc) immunoglobulin (IgM) within 24
             weeks of baseline visit.

          -  Presence of hepatitis B e-antigen (HBeAg) in serum at the last screening visit within
             6 weeks of baseline visit.

          -  Serum HBV DNA level >10^7 IU/mL on at least 2 occasions at least 12 weeks apart during
             the 52 weeks before baseline visit. The HBV DNA levels must be within 6 weeks of
             baseline visit.

          -  ALT ≤60 U/l in males or ≤40 U/l in females, measured on at least 2 occasions, at
             screening (within 6 weeks prior to baseline visit) & at least 12 weeks prior to the
             screening visit & within the 52 weeks prior to baseline visit.

          -  Compensated liver disease, with normal total bilirubin (except if Gilbert's syndrome),
             direct bilirubin ≤0.5 mg/dL, International Normalized Ratio (INR) ≤1.5, and serum
             albumin ≥3.5 g/dL.

          -  Creatinine clearance 90 ml/min.

          -  Absence of hepatocellular carcinoma on liver ultrasound in the past 48 weeks.

        Exclusion criteria:

          -  Presence of infection with Hepatitis C virus (HCV)-RNA or anti-HCV, anti-Hepatitis D
             virus (HDV), or HIV at screening.

          -  Presence of another cause of liver disease or hepatocellular cancer (HCC) (serum
             alpha-fetoprotein >50ng /ml).

          -  Evidence of decompensated liver disease (Childs B-C).

          -  History or other evidence of a medical condition associated with chronic liver disease
             (e.g., hemochromatosis, autoimmune hepatitis, alcoholic liver disease, toxin
             exposures).

          -  Females who are pregnant or breastfeeding.

          -  Adolescent females unwilling or unable to use an acceptable method of contraception if
             sexually active during the treatment period.

          -  Children currently breastfeeding while their mother is taking lamivudine, or those who
             were exposed to lamivudine for ≥24 weeks via maternal lamivudine treatment during
             pregnancy and/or while breastfeeding.

          -  Previous liver or other organ transplantation including engrafted bone marrow
             transplant.

          -  Hematological abnormalities during the screening period that contraindicate full
             dosing with study drugs, e.g absolute neutrophil count < 1.5 x 10^9 cells/L or
             platelet count < 120 x 10^9 cells/L.

          -  Known allergy to study drugs; peginterferon alfa-2a or entecavir.

          -  Treatment with systemic acyclovir or famciclovir within the previous 6 months.

          -  Need for ongoing use of any antivirals with activity against HBV during the course of
             the study or history of receiving treatment for HBV.

          -  Any use of illegal drugs OR use of alcoholic beverages which in the opinion of a study
             physician is sufficient to prevent adequate compliance with study procedures or
             increase the risk of pancreatitis or hepatotoxicity.

          -  History of immunologically mediated disease (e.g. inflammatory bowel disease,
             idiopathic thrombocytopenic purpura, lupus erythematosus, autoimmune haemolytic
             anemia, scleroderma, severe psoriasis, rheumatoid arthritis).

          -  History or other evidence of bleeding from esophageal varices or consistent with
             decompensated liver disease.

          -  History or other evidence of chronic pulmonary disease associated with functional
             limitation.

          -  History of significant cardiovascular diseases.

          -  History of a severe seizure disorder or current anticonvulsant use.

          -  History or other evidence of severe retinopathy.

          -  History of thyroid disease poorly controlled on prescribed medications. Participants
             with elevated thyroid stimulating hormone concentrations with elevation of antibodies
             to thyroid peroxidase and any clinical manifestations of thyroid disease are excluded.

          -  Concomitant use or use during ≤ 6 months prior to the first dose of study drug of
             anti-neoplastic, immunosuppressive, nephrotoxic or hepatotoxic medication, methadone,
             theophylline or medications that may affect renal excretion or hepatic metabolism are
             not permitted.

          -  Concomitant use of complementary or alternative medications purported to have
             antiviral activity.

          -  A participant may not be co-enrolled in another clinical trial where an
             investigational drug is administered.

          -  Any other condition or situation that in the opinion of a study physician would make
             the participant unsuitable for enrollment or could interfere with the participant
             participating in and completing the study.