Efficacy and Safety of Entecavir With or Without Pegylated Interferon α-2b in Children Aged 3 to 6 Years With Chronic Hepatitis B in the Immune-Clearance Phase (B-Young-Cure-2): A Multicenter, Open-Label, Randomized Controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 60
- 主要终点
- The rate of functional cure
研究概览
简要总结
This study aims to evaluate the efficacy and safety of entecavir monotherapy versus sequential entecavir plus pegylated interferon α-2b in achieving functional cure in immune-active, HBeAg-positive children aged 3-6 years with chronic hepatitis B.
详细描述
This is a multicenter, open-label, randomized controlled, phase 4 trial enrolling 3-6-year-old children with HBeAg-positive CHB in the immune-clearance phase. Participants will be randomly assigned in a 1:1 ratio to two treatment arms, both lasting 96 weeks. The ETV group will receive entecavir (ETV) monotherapy throughout the 96-week treatment course (ETV group). The pegylated interferon (Peg-IFN) group will receive ETV for the first 48 weeks, followed by combination therapy with Peg-IFN α-2b for the remaining 48 weeks (ETV plus IFN combination group). The primary endpoint is the functional cure rate at 24 weeks after treatment discontinuation (week 120). The main secondary endpoints include the rates of undetectable HBV DNA, HBeAg loss, and HBsAg loss at week 24, 48, 72, 96, and 120, and rates of alanine aminotransferase elevation or flares (>5 times of upper limit of normal) and incidence of adverse events at any time during the study. The study will also explore associations between functional cure and baseline or on-treatment parameters. A total of 80 children (40 per group) is required to detect a statistically significant difference between two treatment arms.
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
盲法说明
None (Open Label)
入排标准
- 年龄范围
- 3 Years 至 6 Years（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age between 3 and 6 (more than 3 but less than 7) years;
- •Chronic HBV infection;
- •Positive HBeAg;
- •HBV DNA >1.0×10⁴ IU/mL;
- •Normal upper abdominal ultrasound without cirrhosis or hepatocellular carcinoma;
- •ALT >40 U/L.
排除标准
- •Previous antiviral treatment for chronic HBV infection;
- •Coinfection with hepatitis C, D, E, human immunodeficiency virus (HIV), Epstein-Barr virus, or cytomegalovirus;
- •Previous or current evidence of hepatocellular carcinoma or cirrhosis;
- •Coexistence of any other liver diseases such as autoimmune hepatitis, drug-induced liver injury or Wilson's disease;
- •Coexistence of systemic/other organ disorders (for example with evidence of thyroid disorders);
- •Hemoglobin level <100 g/L;
- •Absolute neutrophil count <1.0×10⁹/L.;
- •Platelet count <125×10⁹/L;
- •Total bilirubin >1 ULN, i.e., 17.1 μmol/L;
- •Albumin level <35 g/L;
- •Concurrent treatment with other drugs, including but not limited to nephrotoxic drugs, immune modulators, cytotoxic drugs, Chinese traditional medicine or supplements, nonsteroidal anti-inflammatory drugs, or steroids.
研究组 & 干预措施
Entecavir plus Peg-IFN α-2b
Receive entecavir for the first 48 weeks, followed by combination therapy with pegylated interferon α-2b for the remaining 48 weeks.
干预措施: Entecavir + Pegylated interferon α-2b (Drug)
Entecavir
Receive entecavir monotherapy throughout the 96-week treatment course.
干预措施: Entecavir (Drug)
结局指标
主要结局
The rate of functional cure
时间窗: At 24 weeks after treatment cessation.
Functional cure is defined as the loss of HBsAg to \<0.05 IU/mL and HBeAg clearance, with or without the presence of hepatitis B surface antibody (HBsAb) and hepatitis B e antibody (HBeAb), and undetectable HBV DNA (\<10 IU/mL) at the end of treatment, sustained through 24 weeks post-treatment.
次要结局
- The rate of HBV DNA undetectable(At week 24, 48, 72, 96, 120 of the study.)
- The rate of HBeAg loss(At week 24, 48, 72, 96, 120 of the study.)
- The rate of HBsAg loss(At week 24, 48, 72, 96, 120 of the study.)
- The rate of alanine aminotransferase elevation or flare(At any time during the study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation.)
- The rate of cytopenia rate(At any time during the study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation.)
- The rate of growth suppression(At week 24, 48, 60, 72, 84, 96, 108, 120 of the study.)
- The rate of thyroid dysfunction(At week 72, 96, and 120 of the study.)
- Any other adverse event(At any time during study, i.e., from the date of patient enrollment through 24 weeks after treatment discontinuation.)
研究者
Qing-Lei Zeng
Professor
The First Affiliated Hospital of Zhengzhou University