The Evaluation of efficacy and safety of Tenofovir in combination with peginterferon alpha-2a subcutaneous for 48 weeks in patients with chronic hepatitis B viral infections (HBV)

This is a randomized, openlabel, national, multicenter, three arm, pilot, investigator initiated study evaluating the efficacy and safety of Tenofovir 300 mg PO in combination with peginterferon alpha2a sc 180 µg in patients with HBeAg positive CHB. The patients will be randomized into three treatment arms at a ratio of 1:1:1 Arm 1: Full course combination therapy: 48 weeks of both peginterferon alpha2a plus Tenofovir disoproxil fumarate Arm 2: Peginterferon alpha2a lead-in therapy: 24 weeks of a ‘lead in’ course of peginterferon monotherapy, followed by 24 weeks of combination peginterferon Arm 3: Peginterferon alpha2a 180mcg weekly for 48 weeks The study consists of four periods: Screening (= 8 weeks prior to Baseline visit), Baseline Visit (Day 1), Treatment Phase (48 weeks) Posttreatment Followup (24 weeks) Study purpose: The primary purpose of this study is to evaluate whether the combination of Peginterferon and Tenofovir therapy may lead to improved antiviral outcomes compared to that typically seen with Peginterferon monotherapy. Objectives: The primary objective of this study is to demonstrate the efficacy of the combination of peginterferon alpha-2a with Tenofovir in achieving sustained HBV suppression as measured by HBsAg loss in adult patients with HBeAg positive CHB Secondary objectives include 1. Evaluating the effect of on HBsAg clearance rates by a lead in phase of Peginterferon monotherapy for 24 weeks prior to combination therapy 2. Evaluating the effect of peginterferon and Tenofovir combination therapy on other parameters of viral suppression including 3. HBV DNA non-detectability, reduction from baseline, and sustained reduction in HBV DNA over the course of the study. 4. HBeAg loss, Anti-HBe seroconversion and reduction in HBeAg titres from baseline 5. HBsAg loss, HBsAb seroconversion and reduction in HBsAg titres from baseline 6. ALT normalization 7. To determine which baseline and ‘on therapy’ markers may be used to predict clinical and virological outcomes including quantitative HBeAg and HBsAg titres, HBV viral load, ALT and HBV genotype In addition a sub Immunological Study will be conducted at 2 of the study sites (Monash Medical Centre and St Vincent’s Hospital Melbourne). Patients recruited at both sites will be invited to participate in smaller subcohort study evaluating innate immune during the treatment and follow up periods to determine whether innate immune function can be used as a predictive marker of treatment induced HBsAg and HBeAg seroconversion.