A Randomized, Multicenter Study Evaluating HBsAg Clearance in CHB Patients Achieving HBeAg Loss and HBV DNA <200copies/ml on Treatment With Nucleotide Analogues and Switched to Peginterferon Alfa-2a
试验速览
- 阶段
- 不适用
- 入组人数
- 300
- 试验地点
- 1
- 主要终点
- determine the response rate (HBsAg clearance at Week 48 and 96)
研究概览
简要总结
A Randomized, open-label, multicenter study.
The patients after 1-3 years NAs treatment and having achieved HBeAg loss and HBV DNA <200IU/ml will be switched to Pegasys for 48 or 96 weeks (with a 12 weeks period of overlap with the NA for safety reasons). The subjects will be randomized into 2 groups:
Group 1 : 48-week standard treatment by Peginterferon alfa 2a 180µg/week Group 2 : 96-week prolonged treatment by Peginterferon alfa 2a 180µg/week.
All the patients will be followed up for 48 weeks after discontinuation of the study medication.
Note: NAs will be stratified LAM, ETV and ADV, with the ratio 1:1:1.
详细描述
eligibility criteria: Men and women old of 18 to 65 years with chronic hepatitis B HBeAg positive treated with nucleoside and/or nucleotide analogues for 1-2 years and with partial response (HBeAg loss and HBV DNA <1000copies/ml).
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 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients on-treatment with NAs (ADV, ETV or LAM) for 1-3 years, having achieved HBeAg loss at screening, and HBV DNA <200IU/ml for at least 48 weeks
- •Male and female patients ≥ 18 to 65 years of age
- •Chronic hepatitis B (positive HBsAg for at least 6 months prior to NA therapy start)
- •Compensated liver disease (Child-Pugh <6)
- •Absence of hepatocellular carcinoma on liver imaging and/or alfa fetoprotein < 50 ng/ml
- •Negative urine or blood pregnancy test for women of childbearing potential within 24 hours of first PEG IFN study medication administration
- •Able and willing to provide informed consent and abide by the requirements of the study
排除标准
- •Neutrophil count <1.5 x 109cells/L or platelet count <90 x 109cells/L
- •Co-infections with HIV, HAV, HCV, HDV or HEV
- •Women with ongoing pregnancy or breast feeding, or wishing to become pregnant during the study period
- •Prolonged and excessive alcohol intake (> 40g/day for men and > 30g/day for women)
- •Active intravenous drug abuse
- •History or current treatment with telbivudine
- •Treatment with immunomodulators (e.g. Interferon) for less than one year before study enrollment
- •Treatment with immunosuppressors (including systemic corticosteroids) or anti-neoplastic treatment (including radiation therapy) <=6 months prior to the first dose of study drug or the expectation that such treatment will be needed at any time during the study
- •Serum concentrations of ceruloplasmin or alfa-antitrypsin consistent with an increased risk of metabolic disease
- •History or other evidence of chronic pulmonary disease associated with functional limitation
- •History of severe cardiac disease
- •History of the severe seizure disorder or current anticonvulsivant use
- •History of thyroid disease poorly controlled on prescribed medications. Patients with elevated thyroid stimulating hormone concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
- •History or other evidence of severe retinopathy
- •History of autoimmune disease or presence of a significant level of auto-antibodies
- •Renal insufficiency (creatinine clearance of < 50 ml/min according to the Cockroft and Gault equation), kidney transplant, hemodialysis
- •History of depression or uncontrolled psychiatric disorders
- •Subjects protected by law or not in a position to give consent
- •Patients with reproductive potential not willing to use an effective method of contraception.
- •Evidence of an active or suspected cancer or a history of malignancy (other than basocellular carcinoma or in-situ cervical carcinoma)
研究组 & 干预措施
48-week standard treatment
48-week standard treatment by Peginterferon alfa 2a 180µg/week
干预措施: Peginterferon alfa 2a (Drug)
96-week prolonged treatment
96-week prolonged treatment by Peginterferon alfa 2a 180µg/week
干预措施: Peginterferon alfa 2a (Drug)
结局指标
主要结局
determine the response rate (HBsAg clearance at Week 48 and 96)
时间窗: 1 year
To determine the response rate (HBsAg clearance at Week 48 and 96) in subjects who are being treated by NAs and achieved a combined response which consists of both HBeAg loss and HBV DNA \<1000 copies/ml
次要结局
- HBsAg/HBeAg/HBV DNA changes/ALT normalization /HBsAg seroconversion at EOT and EOF(1 year)
研究者
Hong Ren
Principal Investigator
The Second Affiliated Hospital of Chongqing Medical University