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

GlaxoSmithKline (GSK)

Status and phase

Completed

Phase 3

Conditions

Hepatitis B, Chronic

Treatments

Drug: GSK548470 300 mg tablet

Drug: ETV 0.5 mg capsule

Study type

Interventional

Funder types

Industry

Identifiers

NCT01480284

115409

Details and patient eligibility

About

The purpose of this study is to evaluate the efficacy and safety of GSK548470 administered once daily at a dose level of 300 mg to Japanese patients with compensated chronic hepatitis B untreated with any nucleic acid analogue. In efficacy, the non-inferiority of GSK548470 to ETV will be verified using the antiviral effect as the index.

Full description

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.

Enrollment

166 patients

Sex

All

Ages

16 to 69 years old

Volunteers

No Healthy Volunteers

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