A Multi-center, Randomized, Active Controlled, Double-blind, Parallel Group Comparison Study and Subsequent Open-label Study of GSK548470 in Patients With Compensated Chronic Hepatitis B Untreated With Nucleic Acid Analogue
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 166
- 试验地点
- 1
- 主要终点
- Mean Change From Baseline in Serum HBV DNA Level at Week 24
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 16 Years 至 69 Years（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
GSK548470 300 mg
GSK548470 300 mg tablet and ETV placebo capsule are administered once daily
干预措施: GSK548470 300 mg tablet (Drug)
ETV 0.5 mg
ETV 0.5 mg capsule and GSK548470 placebo tablet are administered once daily
干预措施: ETV 0.5 mg capsule (Drug)
结局指标
主要结局
Mean Change From Baseline in Serum HBV DNA Level at Week 24
时间窗: Baseline and Week 24
The mean change from Baseline in the hepatitis B virus deoxyribonucleic acid (HBV DNA) level at Week 24 was assessed (lower limit of quantitation : 2.1 log 10 copies/mL). The mean values were adjusted by Baseline HBV DNA levels. Change from Baseline was calculated as the post-Baseline value minus the Baseline value.
次要结局
- Number of Participants Achieving Each Indicated HBsAg Category at Baseline, Week 24, Week 48 and Week 96(Baseline, Week 24, Week 48 and Week 96)
- Number of Participants With Virological Breakthrough Through End of the Study(From Baseline to throughout study)
- Number of Participants With Alanine Aminotransferase (ALT) Normalization at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Mean Change From Baseline in Serum HBV DNA Level at Week 48 and Week 96(Baseline, Week 48 and Week 96)
- Number of Participants With Serum HBV DNA < 2.1 log10 Copies/mL at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants With HBeAg/HBeAb Seroconversion at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants Achieving HBsAg Loss at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants Achieving HBsAg/HBsAb Seroconversion at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants Achieving Each Indicated HBcrAg Category at Baseline, Week 24, Week 48 and Week 96(Baseline, Week 24, Week 48 and Week 96)
- Number of Participants With HBeAg Loss at Week 24, Week 48 and Week 96(Week 24, Week 48 and Week 96)
- Number of Participants With Resistance Related Mutations at Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to Throughout the Study)(Screening, Week 24, Week 48, Week 96 and Virological Breakthrough (Baseline to throughout the study))