A Prospective, Open-Label, Randomized, Controlled, Multicenter Clinical Study of Pegylated Interferon Alfa-2b in Reducing Relapse Rates After Nucleos(t)ide Analogue Withdrawal in HBeAg-Negative Chronic Hepatitis B Patients with Low-Level HBsAg
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 入组人数
- 360
- 试验地点
- 1
- 主要终点
- Number of participants who relapse
研究概览
简要总结
All enrolled patients must meet the European Guidelines for the Prevention and Treatment of Chronic Hepatitis B (EASL, 2017) recommended discontinuation criteria, that is, HBeAg-negative chronic hepatitis B patients without fibrosis or cirrhosis who have undetectable HBV DNA for more than 3 years after receiving NUC treatment can attempt to discontinue the drug. At the same time, the patient's HBsAg level will not be higher than 1000 IU/mL. The study will set up three groups, group A directly stopped nucleoside analogues, follow-up to 96 weeks; Group B received PegIFNα-2b monotherapy for 48 weeks, group C received PegIFNα-2b combined with NUC treatment for 48 weeks, group B and group C stopped all antiviral drugs after completing 48 weeks of treatment, and then followed up for 96 weeks, a total of 144 weeks of follow-up. This study aims to further optimize the design on the basis of previous clinical studies to observe whether sequential interferon or combined with NUC therapy can reduce the virological relapse rate of HBeAg-negative chronic hepatitis B patients with low HBsAg level after 96 weeks of discontinuation, and to observe the impact on the functional cure rate.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 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
- •Aged between 18 and 65 (inclusive), regardless of gender;
- •Fibroscan ≤ 7.4kpa;
- •HBeAg-negative CHB patients: HBsAg positive, HBeAg negative, HBsAb negative and HBeAb positive before receiving NUC treatment and during screening in this study;
- •HBeAg-negative chronic hepatitis B patients without liver cirrhosis who have been viral-negative for more than 3 years after receiving NUC treatment, and they meet the 2017 EASL guideline discontinuation standard (HBV DNA is lower than the lower limit of detection, that is, <20 IU/ml);
- •HBsAg≤1000 IU/ml;
- •Have the intention to stop taking the drug, and sign a written informed consent.
排除标准
- •HBsAb positive during screening;
- •Patients with hepatitis B cirrhosis in the compensatory and decompensated stage: patients with a clear history of cirrhosis (imaging or histological evidence) or Child-Pugh score ≥5 before NUC treatment, or complications of cirrhosis in the decompensated stage such as ascites, hepatic encephalopathy, esophageal variceal hemorrhage, etc.;
- •Patients who are allergic to alpha interferon and its drug ingredients, and the researchers judge that alpha interferon is not suitable for patients;
- •Received immunomodulators (including interferon, etc.) within 1 year before screening;
- •Combined with HAV, HCV, HDV, HEV, HIV infection, alcoholic liver disease, genetic metabolic liver disease, drug liver disease, non-alcoholic fatty liver disease and other chronic liver diseases;
- •Combined with autoimmune diseases, including autoimmune liver disease, psoriasis, etc.
- •Patients with primary liver cancer or screening with AFP greater than 100 ng/ml and imaging findings indicating the possibility of malignant liver occupation; Or AFP greater than 100 ng/ml for 3 months;
- •Neutrophil count < 1.5 x 109 cells /L or platelet count < 90 x 109 cells /L;
- •Creatinine is 1.5 times higher than the upper limit of normal;
- •Patients with other malignant tumors (excluding cured patients);
- •Patients with serious diseases of heart, lung, kidney, brain, blood and other important organs;
- •Patients with severe neurological and psychiatric disorders (such as epilepsy, depression, mania, seizures, schizophrenia, etc.);
- •Control unstable diabetes, hypertension, thyroid disease, etc.;
- •Pregnant and lactating women or patients who had pregnancy plans during the study period and did not want to use contraception;
- •Participate in other clinical investigators;
- •Patients who were not considered suitable for participation in this study by the investigators.
研究组 & 干预措施
PegIFN alfa-2b 48 weeks
Discontinue the NUC treatment ,PegIFN alfa-2b for 48 weeks and follow up for 96 weeks
干预措施: PegIFN alfa-2b (Drug)
PegIFN alfa-2b and NUC 48 weeks
Discontinue the NUC treatment ,PegIFN alfa-2b and NUC for 48 weeks, then follow up for 96 weeks
干预措施: PegIFN alfa-2b and NUC (Drug)
结局指标
主要结局
Number of participants who relapse
时间窗: 96 weeks after stopping NAs
the cumulative virological relapse rate (HBV DNA\>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.
次要结局
- Number of participants who relapse(72 weeks after stopping all antivirals)
- Number of participants who relapse Clinically(72 weeks and 96 weeks after stopping all antivirals)
- Number of participants who achieve HBsAg clearance and HBsAg seroconversion(96 weeks after stopping all antivirals)
- Number of participants who restart treatment(96 weeks after stopping all antivirals)
研究者
Jiming Zhang
chief physician,professor
Huashan Hospital