Combination Entecavir and Peginterferon Therapy in HBeAg-Positive Immune-Tolerant Adults With Chronic Hepatitis B
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Intervention: Entecavir and peginterferon
Intervention description: Entecavir 0.5 mg daily orally for 48 weeks plus peginterferon 180 µg sq weekly during weeks 9-48 of treatment.
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: 28.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Hepatitis B; Immune-tolerant hepatitis B; HBV

Summary:

      The investigators evaluated the safety and efficacy of a short lead-in course (8 weeks) of
      entecavir followed by combination of entecavir plus peginterferon alfa-2a for 40 weeks.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Enrolled in & completed the baseline evaluation for NCT01263587 or completed the
             necessary components of NCT01263587 by the end of baseline visit.

          -  >18 years of age at the baseline visit (day 0). Patients >50 years of age at baseline
             will need to have a liver biopsy as standard of care with hepatic activity index (HAI)
             ≤3 & Ishak fibrosis score ≤1 within 96 weeks prior to baseline visit.

          -  Documented chronic HBV infection as evidenced by detection of HBsAg in serum for ≥24
             weeks prior to baseline visit OR at least one positive HBsAg & negative anti-hepatitis
             B core (HBc) immunoglobulin (IgM) within 24 weeks prior to baseline visit OR at least
             one positive HBsAg & two positive HBV DNA over a period of ≥24 weeks prior to baseline
             visit.

          -  Presence of HBeAg in serum at last screening visit within 6 weeks of baseline visit.

          -  Serum HBV DNA level >10˄7 IU/mL on at least two occasions at least 12 weeks apart
             during the 52 weeks before baseline visit. One of the two HBV DNA levels must be
             within 6 weeks of baseline visit.

          -  ALT levels persistently ≤45 U/L in males, ≤30 U/L in females (approx. 1.5 times the
             upper limit of normal (ULN) range) as documented by at least three values: one taken
             28-52 weeks before baseline visit, one taken 6 to 24 weeks before the baseline visit,
             & the final value within 6 weeks prior to baseline visit.

          -  No evidence of hepatocellular carcinoma (HCC) based upon alpha-fetoprotein (AFP) ≤20
             ng/mL at screening visit (up to 6 weeks prior to baseline visit). a. Participants who
             meet American Association for the Study of Liver Diseases (AASLD) criteria for HCC
             surveillance must have negative liver imaging as shown by ultrasound, computerized
             tomography (CT) or magnetic resonance imaging (MRI) within 28 weeks prior to baseline
             visit. b. Participants with AFP >20 ng/mL must be evaluated clinically with additional
             imaging & shown not to have HCC on CT or MRI before they can be enrolled.

        Exclusion Criteria:

          -  History of hepatic decompensation

          -  Evidence of decompensated liver disease prior to or during screening, including direct
             bilirubin >0.5 mg/dL, international normalization ratio (INR) >1.5, or serum albumin
             <3.5 g/dL.

          -  Platelet count <120,000/mm3, hemoglobin <13 g/dL (males) or <12 g/dL (females),
             absolute neutrophil count < 1500 /mm3 (<1000/mm3 for African-Americans) at last
             screening visit.

          -  Previous treatment with medications that have established activity against HBV
             including interferon & nucleos(t)ide analogs ≥24 weeks. Patients with <24 weeks of
             prior HBV treatment & a wash-out period >24 weeks are not excluded.

          -  Known allergy or intolerance to study medications.

          -  Females who are pregnant or breastfeeding. Females of childbearing potential unable or
             unwilling to use a reliable method of contraception during the treatment period.

          -  Renal insufficiency with calculated creatinine clearance <50 mL/min at screening.

          -  History of alcohol or drug abuse within 48 weeks of baseline visit.

          -  Previous liver or other organ transplantation (including engrafted bone marrow).

          -  Any other concomitant liver disease, including hepatitis C or D. Non-alcoholic fatty
             liver disease (NAFLD) with steatosis &/or mild to moderate steatohepatitis is
             acceptable but NAFLD with severe steatohepatitis is exclusionary.

          -  Presence of anti-hepatitis D virus (HDV) or anti-hepatitis C virus (HCV) (unless HCV
             RNA negative) in serum on any occasion in the 144 weeks prior to baseline visit.
             Presence of anti-HIV (test completed within 6 weeks prior to baseline visit).

          -  Pre-existing psychiatric condition(s), including, but not limited to: current moderate
             or severe depression, history of depression requiring hospitalization within the past
             10 years, history of suicidal or homicidal attempt within the past 10 years, history
             of severe psychiatric disorders as determined by a study physician.

          -  History of immune-mediated or cerebrovascular disease, chronic pulmonary or cardiac
             disease associated with functional limitation, retinopathy, uncontrolled thyroid
             disease, poorly controlled diabetes or uncontrolled seizure disorder, as determined by
             a study physician.

          -  Any medical condition that would, in the opinion of a study physician, be predicted to
             be exacerbated by therapy or that would limit study participation.

          -  Any medical condition requiring, or likely to require, chronic systemic administration
             of corticosteroids or other immunosuppressive medications during the course of this
             study.

          -  Evidence of active or suspected malignancy, or a history of malignancy within the 144
             weeks prior to baseline visit (except adequately treated carcinoma in situ or basal
             cell carcinoma of the skin).

          -  Expected need for ongoing use of any antivirals with activity against HBV during the
             course of the study.

          -  Concomitant use of complementary or alternative medications purported to have
             antiviral activity.

          -  Participation in any other clinical trial involving investigational drugs within 30
             days of the baseline visit or intention to participate in another clinical trial
             involving investigational drugs during participation in this study.