HBsAg Related Response Guided Therapy

Study Overview
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Brief Summary
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Primary objective: Compare Pegasys RGT overall response rate (i.e., HBeAg seroconversion rate) with Pegasys mono historical response rate at week 72 (48 week treatment with 24 week follow up) Secondary objective : The changes of HBsAg titer The rate of combined HBeAg seroconversion and HBV DNA < 300 copies/mL The rate of serum HBV DNA < 300 copies/mL ⅳ. The rate of ALT normalization The rate of HBsAg loss ⅵ. The rate of serum HBV DNA < 10,000 copies/mL

Detailed Description
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After 12w treatment of Pegasys, depends on results of quantitative HBsAg test, Patients will be allocated to one of three groups. HBsAg >20,000 : study termination Group A :1,500<HBsAg≤ 20,000 Group B : .HBsAg ≤ 1500 At week 48, according to HbeAg seroconversion, patients will be allocated to one of two sub-groups(A-1, A-2, B-1, B-2) Patients are seen for evaluation at treatment weeks 4,8,12,24,36,48. Post-treatment assessments will be performed at 4,12 and 24 week during off-treatment phase for the assessment of the primary and main secondary endpoints of the study.

Official Title
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A Multi Center, Phase IIIb Study to Evaluate the Efficacy of Response Guided Therapy Using Quantitative HBsAg Measurement in Patient With HBeAg Positive Chronic Hepatitis B:

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Peginterferon alfa-2a
* Drug: Entecavir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years Positive HBsAg for more than 6 months, positive HBeAg, detectable HBV DNA(patients must have > 100,000 copies/ml as measured by PCR) and anti-HBs negative Elevated serum ALT > 2ULN but ≤ 10 × ULN as determined by two abnormal values taken ≥ 14 days apart during the six months before the first dose of study drug with at least one of the determinations obtained ≤ 35 days prior to the first dose. Exclusion Criteria: Patients must not have received antiviral therapy for their chronic hepatitis B. Patients who are expected to need systemic antiviral therapy other than that provided by the study at any time during their participation in the study are also excluded. Exception: patients who have had less than 6 months treatment of NA(Nucleos(t)ide analog) and more than 1 year wash-out period for systemic antiviral therapy and negative results in the NA resistance test at baseline are not excluded. Positive test at screening for HAV IgM Ab, HCV-RNA or HCV Ab, HDV Ab or HIV Ab. Diagnosed hepatic cellular carcinoma Any evidence of decompensated liver disease (Childs B-C)

Ages Eligible for Study
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Minimum Age: 18 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: HBsAg quantification>20,000 IU/ml<br>stop peginterferon alfa 2a if patients reach HBsAg quantification>20,000 Iu/ml at 12w | Drug: Peginterferon alfa-2a<br>* Duration and combination<br>* Other names: Pegasys;|
| Sham Comparator: HBsAg<=1500IU/ml<br>extend peginterferon alfa 2a until 48weeks | Drug: Peginterferon alfa-2a<br>* Duration and combination<br>* Other names: Pegasys;|
| Sham Comparator: HBsAg >1500 <=20,000 IU/ML<br>add Entecavir for 12w with peginterferon alfa 2a then, extend peginterferon alfa 2a until 48w | Drug: Peginterferon alfa-2a<br>* Duration and combination<br>* Other names: Pegasys;Drug: Entecavir<br>* combination<br>* Other names: Baraclude Tab;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| HBeAg seroconversion |  | 24 weeks post treatment follow up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The changes of HBsAg titer |  | baseline and 24weeks post treatment follow up | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Peginterferon alfa 2a, Entecavir, Response Guided Therapy, Chronic Hepatitis B