A Study to Evaluate Addition of Peginterferon Alfa-2a to Chronic Hepatitis B (CHB) Patients Treated With NAs

Study Overview
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Brief Summary
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This study evaluates whether addition of Peginterferon alfa-2a to CHB Patients Treated with nucleoside analogues (NAs) can enhance the rate of HBsAg clearance at end of treatment. This study is a Randomized, open-label, multi-center study. The CHB patients with NAs treatment and have achieved HBV DNA <15 IU/ml、HBeAg <100 PEIU/ml、HBsAg positive and HBsAg<1500 IU/ml will be randomized into 2 groups: Group 1 (Combination group): Maintain NAs treatment while add 48-week standard treatment by Peginterferon alfa 2a 180µg/week Group 2 (Mono NA group) : Maintain NAs treatment for 49 weeks. Note: NAs including: LAM, ADV, ETV, or TDF.

Official Title
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A Randomized, Open-label, Multi-center Clinical Trial to Evaluate Addition of Peginterferon Alfa-2a to CHB Patients Treated With NAs and Achieved HBV DNA<15 IU/ml、HBeAg<100 PEIU/ml、HBsAg Positive and HBsAg<1500 IU/ml.

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: Peginterferon alfa-2a


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female patients >18 and ≤65 years of age; Diagnosed chronic hepatitis B (HBsAg(+) for over 6 months before nucleos(t)ide analogues treatment) Patients had achieved HBV DNA<15 IU/ml、HBeAg<100 PEIU/ml、HBsAg positive and HBsAg<1500 IU/ml on treatment of Nucleoside (acid) Analogues (including LAM, ADV, ETV, and TDF ) Exclusion Criteria: Decompensated liver disease: including ascites, hepatic encephalopathy, esophagogastric-varicosis and fissure bleeding and other decompensated complication; Hypersensitive to interferon(IFN) or its active substance, and ineligible to IFN; A history of immunoregulation drug therapy within 1 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 100ng/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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Combination group<br>Maintain NAs treatment while add 48-week standard treatment by Peginterferon alfa 2a 180µg/week | Drug: Peginterferon alfa-2a<br>* 180ug/0.5ml,hypodermic injection once a week<br>* Other names: Pegasys;|
| No Intervention: Mono NA group<br>Maintain NAs mono-therapy oral-daily for 48 weeks. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The rate of HBsAg loss | To determine the response rate will be evaluated by HBsAg loss defined as HBsAg level lower than 0.05 IU/ml after 48 week treatment, compared with control group. | 48 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Decline of HBeAg quantification | Quantitative HBeAg reduction at Weeks 12, 24 and 48 compared with baseline level. Quantitative HBeAg value unit was calculated using 'Paul Ehrlich Institute units per millilitre' (PEIU/ml). | 12 weeks, 24 weeks, 48 weeks of treatment | 
| Decline of HBsAg quantification | Quantitative HBsAg reduction at Weeks 12, 24 and 48 compared with baseline level. Quantitative HBsAg calculated using 'International Units Per Millilitre' (IU/mL). | 12 weeks, 24 weeks, 48 weeks of treatment | 
| The rate of HBeAg loss |  | 48 weeks | 
| The rate of HBeAg seroconversion |  | 48 weeks | 
| The rate of HBsAg seroconversion |  | 48 weeks | 
| Sustained virological response rate | Sustained virological response rate will be presented as rate of HBV DNA <15 IU/ml | 12 weeks, 24 weeks, 48 weeks of treatment |