A Randomized, Controlled, Open-label, Multicenter Clinical Trial to Evaluate the Addition of PegIFN Alfa-2a to CHB Patients Treated With Nucleot(s)Ides
试验速览
- 阶段
- 4 期
- 入组人数
- 196
- 主要终点
- Number of participants who achieve HBsAg clearance
研究概览
简要总结
This study evaluates whether PegIFN alfa-2a add on can improve CHB patients HBsAg clearance at the end of 48 weeks treatment. The CHB patients who received nucleot(s)ides anti-virus treatment and reached HBV DNA<1000 copies/ml and HBsAg<3000 IU/ml, were randomly assigned into two groups: One group continue the nucleot(s)ides treatment for 72 weeks, the other add on PegIFN alfa-2a on the basis of the original treatment for 48 weeks, and follow up for 24 weeks.
详细描述
nucleot(s)ides is a potent inhibitor of hepatitis B viral(HBV) replication, but long-term therapy may be required, and it is difficult for CHB patients to achieve HBsAg clearance by using nucleot(s)ides. Therefore, it is need take long-term therapy if chronic hepatitis B (CHB) choose to use nucleot(s)ides, and in another way, nucleot(s)ides resistance is an important clinical risk. More and more young patients want to stop treating, and discontinuation of nucleot(s)ides is a feasible strategy to reduce resistance. However, it is really easy to relapse if patients did not arrive HBsAg clearance. PegIFN alfa-2a can clear HBV by direct anti-viral and immune regulation mechanisms including enhancing natural killer cell response, increased cluster of differentiation 8(CD8 +) T lymphocytes and other mechanisms to restore and enhance the immune response in patients with CHB; and what's more, patients are safety after discontinuing.
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
- •Male and female subjects,18-65 years
- •positive for hepatitis B surface antigen (HBsAg) and negative for antibodies to HBsAg (anti-HBs antibodies) for at least 6 months before NAs treated
- •nucleot(s)ides monotherapy (including lamivudine, adefovir, entecavir, tenofovir) and achieved HBV DNA<1000 copies/mL with HBsAg <3000 IU/mL, positive or negative for HBeAg, and negative for anti-HBs antibodies
- •Subjects with no contra-indications to Peginterferon alfa therapy as detailed in the label (Hypersensitivity to the active substance, to alpha interferon, or to any of the excipients; Autoimmune hepatitis; Severe hepatic dysfunction or decompensated cirrhosis of the liver; A history of severe pre-existing cardiac disease, including unstable or uncontrolled cardiac disease in the previous six months)
- •Subjects who are not co-infected with Hepatitis A Virus, Hepatitis C Virus or HIV
- •Female subjects not pregnant or breast feeding when Peginterferon alfa treatment commenced, and aware of the requirement to use an effective method of contraception during therapy
- •Written informed consent signed.
排除标准
- •positive for Hepatitis A Virus Ab, HCV-RNA or positive for Hepatitis C Virus Ab, HDV Ab, HEV Ab or positive for HIV Ab in screening period
- •Hepatocellular carcinoma(HCC) or alpha feto protein(AFP) levels more than 100 ng/ml and Hepatic malignant potential of Imaging examination or AFP levels more than 100 ng/ml for 3 months
- •Compensated or Decompensated liver cirrhosis: with history of cirrhosis before nucleot(s)ides treatment or Child-Pugh score ≥ 5 or Complications of liver cirrhosis such as ascites, hepatic encephalopathy, esophageal gastric varices bleeding
- •Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on
- •Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period
- •A history of immunoregulation drug therapy within one year before entry including IFN and so on
- •Have a history of alcohol abuse
- •With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on
- •A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter
- •Severe organ dysfunction
- •With other malignant tumors(exclude the cured ones)
- •Uncontrolled diabetes, hypertension or thyroid disease
- •A serum creatinine level that was more than 1.5 times the upper limit of the normal range
- •Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN
- •Participate in other clinical studies at the same time
- •Patients unsuitable for the research -
研究组 & 干预措施
PegIFN alfa-2a + nucleot(s)ides treated
patients who treated with nucleot(s)ides (including lamivudine, adefovir, entecavir, tenofovir), then will add PegIFN alfa-2a to the original nucleot(s)ides for 48 weeks, then follow up for 24 weeks
干预措施: PegIFN alfa-2a (Drug)
结局指标
主要结局
Number of participants who achieve HBsAg clearance
时间窗: treat for 48 weeks
To investigate whether Peg-IFN alfa-2a add on treatment can improve the HBsAg clearance in CHB patients at the end of the treatment (48 week).
次要结局
- HBsAg changes from Baseline(12,24 and 48 weeks)
- Number of participants who achieve HBV DNA<1000 copies/ml(12,24 and 48 weeks)
- Number of participants who achieve HBsAg seroconversion(48 weeks)
- Number of participants who achieve HBeAg clearance and seroconversion(48 weeks)
研究者
Peng Hu
Director of Department of infection disease
The Second Affiliated Hospital of Chongqing Medical University