The objective of this study is to compare the long-term efficacy of treatment with combination therapy with peginterferon plus tenofovir versus tenofovir monotherapy in the treatment of chronic hepatitis B.
This is a randomized (1:1) parallel group design trial comparing (i) Tenofovir DF 300 mg daily for 192 weeks (4 years) and (ii) peginterferon alfa-2a 180 µg weekly for 24 weeks plus Tenofovir DF 300 mg daily for 192 weeks (4 years). Enrolled participants will be stratified by HBeAg status (positive/negative), genotype (A vs. all others) and cirrhosis (present vs. absent). After 192 weeks of treatment, participants meeting criteria for treatment discontinuation will stop treatment and be followed for 48 weeks (total duration of treatment and follow up is 240 weeks). A liver biopsy will be obtained at the end-of-treatment (week 192) to assess improvement in histology. Emtricitabine/tenofovir coformulated as Truvada, approved for treatment of HIV but not for treatment of HBV infection, will be offered to patients with primary nonresponse, partial virological response or confirmed virologic breakthrough.
- Participant is enrolled in the HBRN Cohort Study (NCT01263587) and has completed the baseline evaluation
- 18 years or older
- Chronic hepatitis B infection as evidenced by either of the following:
1. HBsAg positive result at screening (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 plus absence of detectable anti-HBc IgM in serum at screening (within 8 weeks prior to randomization).
- Hepatitis B e antigen positive or negative
- Serum HBV DNA ≥1000 IU/mL on 2 occasions at least 4 weeks, and no more than 24 weeks, apart with the second being within 8 weeks of randomization
- Two elevated serum ALT levels 4 weeks apart, and no more than 24 weeks apart, with the second being within 8 weeks of randomization
- Treatment Naive for the last 48 weeks
- Compensated liver disease
- No evidence of HCC
- Liver biopsy (done as standard of care) that shows findings consistent with chronic hepatitis B with histology activity index (HAI) ≥5 (necroinflammatory component only) or Ishak fibrosis score ≥2 or both, as assessed by the local study pathologist on review of a liver biopsy done within 96 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
- Serum ALT ≥450 IU/L for males and ≥300 IU/L for females
- History of hepatic decompensation including but not limited to ascites, variceal bleeding, or hepatic encephalopathy
- Liver biopsy with ≥3+/4 iron in hepatocytes by Prussian blue stain
- 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 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 MDRD method) creatinine clearance <50 mL/min, at the screening visit
- Platelet count <90,000 /mm3, hemoglobin <13 g/dl (males) or <12 g/dl (females), absolute neutrophil count <1500 /mm3 (<1000/mm3 for African-Americans) during the screening visit
- 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 and 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.W. Ray Kim, M.D.
Last updated: 04/30/2013
NCT ID: NCT01369212