Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative Chronic Hepatitis B
试验速览
- 阶段
- 4 期
- 入组人数
- 300
- 试验地点
- 6
- 主要终点
- HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment
研究概览
简要总结
Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Therefore, efforts on the various combinations with the currently available drugs are needed to improve the overall response rates. The simultaneous combination therapy with oral nucleoside and peginterferon alfa-2a from large-scaled randomized trials did not show a superior response rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the assumption that early viral suppression by lamivudine can restore the immune function to facilitate the later immunomodulatory response by peginterferon alfa-2a. Furthermore, prior studies using 24 months of standard interferon alfa showed better ALT normalization and HBV suppression rates to 12 months of therapy. With the recent introduction of entecavir, the more potent oral nucleoside with few drug resistance, sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBV viral suppression. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate if adding entecavir early in the course of therapy or extending the treatment duration of peginterferon alfa-2a can improve the treatment response.
详细描述
Chronic hepatitis B (CHB) is prevalent in the world, with estimated chronic carriers of 350 millions worldwide. Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Therefore, efforts on the various combinations with the currently available drugs are needed to improve the overall response rates. The simultaneous combination therapy with oral nucleoside and peginterferon alfa-2a from large-scaled randomized trials did not show a superior response rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the assumption that early viral suppression by lamivudine can restore the immune function to facilitate the later immunomodulatory response by peginterferon alfa-2a. Furthermore, prior studies using 24 months of standard interferon alfa showed better ALT normalization and HBV suppression rates to 12 months of therapy. With the recent introduction of entecavir, the more potent oral nucleoside with few drug resistance, sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBV viral suppression. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate if adding entecavir early in the course of therapy or extending the treatment duration of peginterferon alfa-2a can improve the treatment response.
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
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Chronic hepatitis B (presence of HBsAg > 6 months) with anti-HBe persistence and abscence of HBeAg for more than 3 months
- •Age older than 18 years
- •HBV DNA > 2,000 IU/mL for more than 2 occasions
- •Serum ALT levels between 2 to 10 folds the upper limit of normal (ULN)
- •A liver biopsy compatible with chronic hepatitis B
排除标准
- •Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for women)
- •Neutropenia (neutrophil count <1,500 per cubic milliliter)
- •Thrombocytopenia (platelet <90,000 per cubic milliliter)
- •Co-infection with hepatitis B virus (HBV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
- •Chronic alcohol abuse (daily consumption > 20 gram per day)
- •Decompensated liver disease (Child-Pugh class B or C)
- •Serum creatinine level more than 1.5 times the upper limit of normal
- •Autoimmune liver disease
- •Neoplastic disease
- •An organ transplant
- •Immunosuppressive therapy
- •Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
- •Evidence of drug abuse
- •Unwilling to have contraception
- •Known allergic reaction to entecavir or peginterferon alfa-2a
- •Unwilling to sign inform consent
研究组 & 干预措施
Entecavir and peginterferon (52 weeks)
Entecavir 0.5 mg/day po at week 1-4 Peginterferon alfa-2a 180 ug/week sc at week 5-52
干预措施: Entecavir and peginterferon (Pegasys) (52 weeks) (Drug)
Peginterferon (96 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-96
干预措施: Peginterferon (Pegasys) (96 weeks) (Drug)
Peginterferon (48 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-48
干预措施: Peginterferon (Pegasys) (48 weeks) (Drug)
结局指标
主要结局
HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment
时间窗: 2.5 years
次要结局
- ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment(2.5 years)