Pegylated Interferon(Peg-IFN) in Reducing Relapse Rate in Patients After Discontinuation of NUC Therapy
- Conditions
- Chronic Hepatitis B
- Interventions
- Drug: PegIFN alfa-2a
- Registration Number
- NCT02594293
- Lead Sponsor
- Huashan Hospital
- Brief Summary
This study evaluates whether Peg-IFN alfa-2a can reduce the recurrence rate of hepatitis B in 96 weeks after nucleoside analogue (NUC) withdrawal.
The HBV HBeAg-Negative patients who received NUC anti-virus treatment for 2.5 years and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010) were randomly assigned into three groups: One group discontinue the NUC treatment and follow up for 96 weeks,One discontinue the NUC treatment ,receive Peg-IFN alfa-2a 180 μg by week for 24 weeks and follow up for 72 weeks,The other discontinue the NUC treatment ,receive Peg-IFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks.
- Detailed Description
NUC is a potent inhibitor of hepatitis B viral(HBV) replication, but long-term therapy may be required. Therefore, NUC resistance is an important clinical risk resulting from long-term therapy in chronic hepatitis B (CHB) management. Discontinuation of NUC is a feasible strategy to reduce resistance. However, the high rate of relapse after cessation of NUC treatment in CHB patients remains a big problem. NUC treatment of how to safely stop drug needs to be solved.
Peg-IFN 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. Response to PEG-IFN is frequently sustained after a finite treatment course due to its immune modulating capacity.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 180
- HBeAg-Negative Chronic Hepatitis B Patients：HBsAg-Positive,HBsAb-Negative,HBeAg-Negative,HBeAb-Positive during screening period and before NA treatment
- NUC monotherapy (including adefovir and entecavir) for more than 2.5 years,and reached stopping rule in 《Chinese chronic hepatitis B prevention and treatment guidelines》(2010):the patients who achieved undetectable HBV DNA (<300 copies/mL) with normal alanine aminotransferase (ALT) and the consolidation therapy reached 1.5 years ,total course of the treatment reached 2.5 years can stop NUC therapy
- Willing to stop the drug, and signed a written informed consent
- HBsAb positive in screening period
- Compensated or Decompensated liver cirrhosis:with history of cirrhosis before NUC treatment or Child-Pugh score ≥ 5 or Complications of liver cirrhosis such as ascites, hepatic encephalopathy, esophageal gastric varices bleeding
- Hypersensitivity to interferon(IFN) or its active substance, and ineligible to IFN
- A history of immunoregulation drug therapy within one year before entry including IFN and so on.
- Coinfection with HAV、HCV、HDV、HEV 、HIV or with Other chronic liver diseases such as Alcoholic Liver Disease,Inherited Metabolic Liver Disease,Drug induced Liver Disease and nonalcoholic fatty liver
- Autoimmune disease including Autoimmune hepatitis and Psoriasis and so on.
- 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
- A neutrophil count of less than 1500 per cubic millimeter or a platelet count of less than 90,000 per cubic millimeter
- A serum creatinine level that was more than 1.5 times the upper limit of the normal range
- With other malignant tumors(exclude the cured ones)
- Severe organ dysfunction
- With severe psychiatric condition or nervous disease such as epilepsy, depression, mania, epilepsy, schizophrenia and so on
- Uncontrolled diabetes, hypertension or thyroid disease
- Pregnant women and lactating women or patients with pregnancy plans and not willing to use contraception during the study period
- Participate in other clinical studies at the same time
- Patients unsuitable for the research
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Pegasys 48 weeks PegIFN alfa-2a Discontinue the NA treatment ,PegIFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks
- Primary Outcome Measures
Name Time Method Number of participants who relapse 96 weeks The total number of relapse (HBV DNA\>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.
- Secondary Outcome Measures
Name Time Method HBsAg changes from Baseline 12,24 and 48 weeks Pegasys 24 weeks Group:12,24 weeks and Pegasys 48 weeks Group:12,24,48 weeks
Number of participants who achieve HBsAg seroconversion 24,48,72 weeks post-discontinuation of PegIFN therapy To investigate whether Peg-IFN alfa-2a can improve the HBsAg seroconversion in CHB patients at 24,48 or 72 weeks post-discontinuation of PegIFN therapy compared to the control group ,which will be measured by the number of participants who achieve HBsAg seroconversion. Pegasys 24 weeks Group:48,72,96 weeks and Pegasys 48 weeks Group:72,96 weeks
Number of participants who relapse 48 weeks The total number of relapse (HBV DNA\>2000 IU/ml on 2 separate occasions 1 months apart) during the research period.
Predictive value of other markers for recurrence after NUC withdrawal 48 weeks and 96 weeks To investigate whether the other markers including HBcAb quantification and so on can predict the recurrence of hepatitis B.
Trial Locations
- Locations (19)
Wuhan Seventh People's Hospital
🇨🇳Wuhan, Hubei, China
Changzhou Third People's Hospital
🇨🇳Changzhou, Jiangsu, China
First Affiliated Hospital of Zhejiang University
🇨🇳Hangzhou, Jiangsu, China
Nantong Third People's Hospital
🇨🇳Nantong, Jiangsu, China
Suzhou Fifth People's Hospital
🇨🇳Suzhou, Jiangsu, China
The First Affiliated Hospital of Soochow University
🇨🇳Suzhou, Jiangsu, China
Wuxi Infectious Disease Hospital
🇨🇳Wuxi, Jiangsu, China
Affiliated Hospital of Xuzhou Medical College
🇨🇳Xuzhou, Jiangsu, China
Taicang People's Hospital
🇨🇳Taicang, Jiangsu, China
Shandong Provincial Hospital
🇨🇳Jinan, Shandong, China
Changhai Hospital Affiliated to Second Military Medical University
🇨🇳Shanghai, China
Ruijin Hospital Affiliate to Shanghai Jiao Tong University School of Medicine
🇨🇳Shanghai, China
Shanghai Public Health Clinical Center
🇨🇳Shanghai, China
Shuguang Hospital Affiliate to Shanghai University of Traditional Chinese Medicine
🇨🇳Shanghai, China
The Infectious Disease Hospital of Shanghai Huangpu Distric
🇨🇳Shanghai, China
People's Hospital of Jiangsu Province
🇨🇳Nanjing, Jiangsu, China
The First Affiliated Hospital of Wenzhou Medical University
🇨🇳Wenzhou, Zhejiang, China
Huashan Hospital Affiliated to Fudan University
🇨🇳Shanghai, China
Shanghai Third People's Hospital
🇨🇳Shanghai, China