Pegylated Interferon(Peg-IFN) in Reducing Relapse Rate in Patients After Discontinuation of NUC Therapy

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Prospective, Randomized, Controlled Clinical Trial to Evaluate the Role of Peg-IFN Alfa-2a in Reducing RelapSe Rate in Patients With Hepatitis B e Antigen(HBeAg)-nEgative Chronic Hepatitis B After Discontinuation of NUC Therapy

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: PegIFN alfa-2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Controlled Group<br>Discontinue the NA treatment and follow up for 96 weeks | |
| Experimental: Pegasys 48 weeks<br>Discontinue the NA treatment ,PegIFN alfa-2a 180 μg by week for 48 weeks and follow up for 48 weeks | Drug: PegIFN alfa-2a<br>* 180 μg/ 0.5 ml ,hypodermic injection once a week<br>* Other names: Pegasys;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who relapse | The total number of relapse (HBV DNA>2000 IU/ml on 2 separate occasions 1 months apart) during the research period. | 96 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who relapse | The total number of relapse (HBV DNA>2000 IU/ml on 2 separate occasions 1 months apart) during the research period. | 48 weeks | 
| Number of participants who achieve HBsAg seroconversion | To investigate whether Peg-IFN alfa-2a can improve the HBsAg seroconversion in CHB patients at the point of 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:24 weeks and Pegasys 48 weeks Group:48 weeks | At the point of discontinuation of PegIFN therapy | 
| Number of participants who achieve HBsAg seroconversion | 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 | 24,48,72 weeks post-discontinuation of PegIFN therapy | 
| HBsAg changes from Baseline | Pegasys 24 weeks Group:12,24 weeks and Pegasys 48 weeks Group:12,24,48 weeks | 12,24 and 48 weeks | 
| Predictive value of other markers for recurrence after NUC withdrawal | To investigate whether the other markers including HBcAb quantification and so on can predict the recurrence of hepatitis B. | 48 weeks and 96 weeks |