Phase 3 Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue

This study is a multicenter, randomized, active comparator-controlled, double-blind, parallel-group comparison study in Japanese patients with compensated chronic hepatitis B untreated with any nucleic acid analogue and its subsequent open-label study. Efficacy and safety will be compared between once-daily dosing of GSK548470 300 mg and once-daily dosing of ETV 0.5 mg, and subsequently the efficacy and safety of GSK548470 administered long term will be investigated. A total of 165 subjects will be assigned to the GSK548470 group or the ETV group at a ratio of 2:1. The subjects will be assigned by stratified randomization in terms of HBe antigen and serum HBV-DNA level. The primary purpose is to verify the non-inferiority of GSK548470 to ETV using as an index the change amount of HBV-DNA level at Week 24 from the baseline level. The secondary purpose is to investigate the efficacy and safety of GSK548470 300 mg administered once daily for a long term.

Inclusion criteria

• The ability to understand and sign a written informed consent form
• 16 to 69 years of age at the time of informed consent
• Females of childbearing potential must have a negative pregnancy test and agree to avoidance of pregnancy
• Subject must show QTc < 450 millisecond (msec) or < 480 msec with Bundle Branch Block
• Chronic HBV infection, defined as positive serum HBsAg for at least 6 month, or negative serum IgM-HBc antibody
• HBeAg positive; HBV-DNA >= 6 log10 copies/mL, HBeAg negative; HBV-DNA >= 5 log10 copies/mL
• Serum ALT >= 31 U/L and <= 10 × ULN
• Creatinine clearance >= 70 mL/min
• Haemoglobin >= 8 g/dL
• WBC >= 1,000 /mm3
• Nucleic acid analogue naïve, i.e., no prior therapy for over 6 months in the past
• No mutation that shows resistance in LAM, ETV and/or TDF at screening

Exclusion criteria

• Decompensated liver disease
• Co-infection with HIV or HCV
• Autoimmune hepatitis rather than chronic hepatitis B
• Subject with serious complication
• Received or have a plan for solid organ or bone marrow transplantation
• Has proximal tubulopathy
• History of hypersensitivity to nucleoside and/or nucleotide analogues
• Evidence of hepatocellular carcinoma by diagnostic imaging at screening and/or serum α-fetoprotein > 50 ng/mL at screening
• History of HCC
• Received any nucleoside, nucleotide, interferon or HB vaccine therapy within 24 weeks prior to initiation
• Received overdose NSAIDs, excluding temporary or topical use, within 7 days prior to initiation
• Received drugs for injection containing glycyrrhizin as the main component within 4 weeks prior to initiation
• Received drugs causing renal impairment, competitors of renal excretion, immunosuppressants, chemotherapeutics and/or corticosteroids within 8 weeks prior to initiation
• Participation in another clinical study within 6 months of study entry or planned participation in another clinical study after entry to this study
• Woman who is pregnant, lactating, possibly pregnant or planning a pregnancy during the study period
• Psychiatry disorder or cognitive disorder that may affect the subject ability to give informed consent or to follow specified study procedures
• History of alcohol or drug abuse
• Any condition or situation that may interfere with the subject's participation in the study