Addition of PegIFN Alfa-2a to CHB Patients Treated With Nucleot(s)Ides

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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A Randomized, Controlled, Open-label, Multicenter Clinical Trial to Evaluate the Addition of PegIFN Alfa-2a to CHB Patients Treated With Nucleot(s)Ides

Conditions
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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: 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. Exclusion Criteria: 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 -

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: nucleot(s)ides treated<br>patients who treated with nucleot(s)ides (including lamivudine, adefovir, entecavir, tenofovir) are still using the original treatment for 72 weeks | |
| Active Comparator: PegIFN alfa-2a + nucleot(s)ides treated<br>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 | Drug: PegIFN alfa-2a<br>* chronic hepatitis B patients who treated with nucleot(s)ides (including lamivudine, adefovir, entecavir, tenofovir) arrived HBV DNA <1000copies/ml, and HBsAg<3000IU/ml, then change the treatment to original nucleot(s)ides add on PegIFN alfa-2a, the combined treatment is for 48 weeks, and follow up for 24 weeks<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 achieve HBsAg clearance | 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). | treat for 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants who achieve HBsAg seroconversion | To investigate whether Peg-IFN alfa-2a add on treatment can improve the HBsAg seroconversion in CHB patients at the end of the treatment (48 week). | 48 weeks | 
| Number of participants who achieve HBeAg clearance and seroconversion | To investigate whether Peg-IFN alfa-2a add on treatment can improve HBeAg clearance and seroconversion at the end of the treatment (48 week). | 48 weeks | 
| 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 | 
| Number of participants who achieve HBV DNA<1000 copies/ml | To investigate whether Peg-IFN alfa-2a add on treatment can improve HBV DNA<1000 copies/ml | 12,24 and 48 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBsAg clearance