Phase IV Study of the Efficacy of Entecavir in Patients With Chronic Hepatitis B Virus Infection and Persistently Normal Alanine Aminotransferase
试验速览
- 阶段
- 4 期
- 入组人数
- 130
- 试验地点
- 4
- 主要终点
- Improvement of liver histology in patients with chronic hepatitis B virus infection and persistently normal ALT receiving entecavir. Please refer to "Description" section for the definiton of improvement of liver histology
研究概览
简要总结
Entecavir (ETV) has shown superior ability to suppress hepatitis B virus (HBV) replication, histology improvement as well as low rate of emergence of resistant mutants. Out of range of clinical recommendations for treatment of chronic hepatitis B (CHB), chronic HBV carriers with persistently normal ALT and viral load more than 10^5 copies/mL have progression of liver disease during long-term follow-up. In addition, certain proportions of these patients do have significant inflammation and fibrosis in liver histology. This study will be able to identify who are at risk of liver disease progression and evaluate efficacy of ETV regarding improvement of liver histology during short-term (1-year) and long-term ETV treatment (3-year).
详细描述
TITLE : A Randomized, Double-blind, Placebo-control Study Evaluating the Efficacy of Entecavir in Patients with Chronic Hepatitis B Virus Infection and Persistently Normal Alanine Aminotransferase INDICATION : Chronic hepatitis B virus infection with persistently normal ALT
OBJECTIVES :
Primary objective To evaluate the efficacy of entecavir (ETV) in improving liver histology in patients with chronic hepatitis B virus infection and persistently normal ALT.
The primary endpoint is to compare the proportion of subjects in each treatment group who achieve the histologic Endpoint, defined as improvement in the necroinflammatory score (≥ 2 point decrease in Knodell HAI score) and no worsening of fibrosis (≥ 1 point increase in the Knodell fibrosis score), at the Week 52 compared to baseline.
Secondary objectives
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
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Male and female subjects aged between 18 and 65 year-old with history of chronic hepatitis B virus infection;
- •Detectable HBsAg at screening and for at least 24 weeks prior to screening or detectable HBsAg for < 24 week and negative for IgM core antibody and confirmation of chronic hepatitis on liver biopsy;
- •ALT should be within normal range in recent one year and at least twice, which are at least 3 month apart;
- •Normal ALT at screening;
- •Screening HBV DNA of more than 10^5 copies/mL by Roche AmplicorTM PCR assay performed by the central laboratory;
- •Evidence of chronic hepatitis on liver biopsy (Knodell HAI Score >= 4) performed ≤ 52 weeks prior to randomization;
- •All women of childbearing potential must have a negative serum or urine pregnancy test.
排除标准
- •Coinfection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV);
- •Other forms of liver disease e.g., alcoholic, autoimmune, biliary disease;
- •Patients with evidence of decompensation of liver disease;
- •Therapy with interferon, thymosin alpha or antiviral agents with activity against hepatitis B (e.g., adefovir, famciclovir, lamivudine, and telbivudine) within 24 weeks of randomization into this study;
- •More than 12 weeks of prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B (e.g., adefovir, famciclovir lamivudine, and telbivudine);
- •Prior therapy with entecavir;
- •Known history of allergy to nucleoside analogues;
- •Hemoglobin < 10.0 g/dL;
- •Platelet count < 75,000/mm3;
- •Absolute neutrophil count< 1500 cells/mm3;
- •Creatinine > 1.5mg/dL (133 μmol/L);
- •Anti-nuclear antibody (ANA) titer > l :160 unless attributable to non-hepatic disease.
研究组 & 干预措施
ETV group
Entecavir 0.5mg at first year; then open with entecavir 0.5mg qd for 2nd, 3rd year
干预措施: Entecavir (Drug)
Placebo group
Placebo at first year, then opne with entecavir 0.5mg qd for 2nd, 3rd year
干预措施: placebo (Drug)
结局指标
主要结局
Improvement of liver histology in patients with chronic hepatitis B virus infection and persistently normal ALT receiving entecavir. Please refer to "Description" section for the definiton of improvement of liver histology
时间窗: 1 year
1. The ratio of liver histology improvement in two groups. 2. Definition of improving liver histology is improvement in the necroinflammatory score (≥ 2 point decrease in Knodell necroinflammation score) and no worsening of fibrosis (≥ 1 point increase in the Knodell fibrosis score) at the week 52 liver biopsy compared to baseline.
次要结局
- Undetectable HBV DNA(1 year and 3 year)
- the reduction of HBV DNA from baseline(1 year and 3 year)
研究者
Ting-Tsung Chang
Clinical Professor
National Cheng-Kung University Hospital