Combination Therapy of Pegylated Interferon Alfa-2a and Tenofovir Versus Tenofovir Monotherapy in Chronic Hepatitis B
Condition: Hepatitis B
MeSH terms: Hepatitis A; Hepatitis B; Hepatitis B, Chronic; Hepatitis
Intervention: Tenofovir; Peginterferon-alfa 2a and tenofovir
Intervention description: 300 mg daily for 192 weeks (4 years); A combination of peginterferon-alfa 2a 180 µg weekly plus tenofovir 300 mg daily for 24 weeks and then only tenofovir 300 mg daily for 168 weeks (3.5 years).
Intervention MeSH terms: Tenofovir; Peginterferon alfa-2a
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 201.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This clinical trial compares the efficacy of peginterferon plus tenofovir for 24 weeks
      followed by monotherapy with tenofovir for a further 3.5 years to the efficacy of tenofovir
      alone given for 4 years in patients with chronic hepatitis B. The primary measure of outcome
      will be HBsAg loss in serum at 48 weeks after stopping all antiviral therapy (sustained
      off-treatment response).
    

Eligibility criteria:

        Inclusion criteria:

          -  Participant is enrolled in the HBRN Cohort Study (NCT01263587) or completed the
             necessary components of the cohort baseline evaluation by the end of the baseline
             visit for this study

          -  18 years or older

          -  Chronic hepatitis B infection as evidenced by at least one of the following:

               1. HBsAg positive result within 8 weeks prior to randomization and another time at
                  least 24 weeks prior to randomization with no HBsAg negative result in between.

               2. HBsAg positive within 8 weeks prior to randomization and HBV DNA ≥1000 IU/mL on 2
                  occasions at least 24 weeks apart (can include result from screening visit within
                  8 weeks of randomization)

          -  Hepatitis B e antigen positive or negative

          -  Serum HBV DNA ≥1000 IU/mL on 2 occasions at least 4 weeks apart within the 32 weeks
             prior to randomization (can include result from screening visit within 8 weeks of
             randomization)

          -  At least 2 elevated serum alanine aminotransferase (ALT) levels (> 30 U/L for males,
             >20 U/L for females) 4 weeks apart, and no more than 32 weeks apart, with the second
             being within 8 weeks of randomization

          -  Compensated liver disease

          -  No evidence of hepatocellular carcinoma (HCC)

          -  Liver biopsy done that shows findings consistent with chronic hepatitis B with
             histology activity index (HAI) ≥3 (necroinflammatory component only) or Ishak fibrosis
             score ≥1 or both, as assessed by the local study pathologist on review of a liver
             biopsy done within 144 weeks of randomization

          -  Females of child bearing potential must agree to use an adequate method of
             contraception throughout the study and must have a negative pregnancy test immediately
             prior to the start of treatment

        Exclusion criteria:

          -  Serum ALT ≥450 U/L for males and ≥300 U/L for females

          -  Treatment with interferon or nucleos(t)ide analogues for hepatitis B within 48 weeks
             of randomization

          -  More than 48 weeks of therapy with nucleos(t)ide analogues for hepatitis B at any time
             in the past

          -  History of hepatic decompensation including but not limited to ascites, variceal
             bleeding, or hepatic encephalopathy

          -  Known allergy or intolerance to any of the study medications

          -  Females who are pregnant or breastfeeding

          -  Previous organ transplantation including engrafted bone marrow transplant

          -  Any other concomitant liver disease, including hemochromatosis, hepatitis C or D;
             Participants with severe steatohepatitis will be excluded (participants with
             non-alcoholic fatty liver disease [NAFLD] with steatosis only and/or mild to moderate
             steatohepatitis are acceptable)

          -  Positive anti-HIV

          -  Renal insufficiency with calculated (by Modification of Diet in Renal Disease (MDRD)
             method) creatinine clearance <60 mL/min within 8 weeks prior to randomization

          -  Platelet count <90,000 /mm3, hemoglobin <13 g/dL (males) or <12 g/dL (females),
             absolute neutrophil count <1500 /mm^3 (<1000/mm^3 for African-Americans) within 8
             weeks prior to randomization

          -  History of active alcohol or drug abuse within 48 weeks of screening.

          -  Pre-existing psychiatric condition(s), including but not limited to: Current moderate
             or severe depression as determined by the study physician, history of depression
             requiring hospitalization within past 10 years, history of suicidal or homicidal
             attempt within the past 10 years, or history of severe psychiatric disorders including
             but not limited to schizophrenia, psychosis, bipolar disorder

          -  History of immune-mediated disease, or cerebrovascular, chronic pulmonary or cardiac
             disease associated with functional limitation, retinopathy, uncontrolled thyroid
             disease, poorly controlled diabetes or uncontrolled seizure disorder

          -  Any medical condition that would 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 last
             144 weeks (except adequately treated carcinoma in situ or basal cell carcinoma of the
             skin)

          -  Need for ongoing use of any antivirals with activity against HBV during the course of
             the study

          -  Any other condition that in the opinion of the investigator would make the participant
             unsuitable for enrollment or could interfere with the participant participating in and
             completing the study.

          -  Participation in any other clinical trial involving investigational drugs within 30
             days of randomization or intention to participate in another clinical trial during
             this study.