Efficacy Optimizing Research of Chronic Hepatitis B Patients With Inadequate Response to NUC Therapy

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the efficacy and safety of generic entecavir monotherapy or in combination with adefovir for chronic hepatitis B patients with inadequate response to NUC therapy

Official Title
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A Multi-center, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Generic Entecavir Monotherapy or in Combination With Adefovir for Chronic Hepatitis B Patients With Inadequate Response to NUC Therapy

Conditions
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Hepatitis B

Intervention / Treatment
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* Drug: Entecavir
* Drug: Entecavir, Adefovir
* Drug: Entecavir, Adefovir


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female aged 18-65 years; Capable of understanding and signing the informed consent. Willing to comply with the study requirements; Serum HBsAg positive and ALT<10ULN at study screening; Patients have been treated with one nucleoside/nucleotide analogue for more than 6 months and are still on treatment; Exclusion Criteria: History of viral breakthrough or genotypic resistance on previous therapy; History of decompensated liver function, or current signs/symptoms of decompensation e.g. ascites, variceal bleeding, encephalopathy or spontaneous peritonitis; Patient has a history of hepatocellular carcinoma(HCC) or findings suggestive of possible HCC; Other protocol defined exclusion criteria.

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 |
| --- | --- |
| Active Comparator: A<br>oral entecavir 1mg daily for 104 weeks | Drug: Entecavir<br>* patients will receive oral entecavir 1mg, daily for 104 weeks.<br>|
| Active Comparator: B<br>oral entecavir 1mg daily and adefovir 10mg daily for 104 weeks | Drug: Entecavir, Adefovir<br>* patients in this arm will receive oral entecavir 1mg daily and adefovir 10mg daily for 104 weeks<br>|
| Active Comparator: C<br>oral entecavir 0.5mg daily and adefovir 10mg daily for 104 weeks | Drug: Entecavir, Adefovir<br>* patients in this arm will receive oral entecavir 0.5mg daily and adefovir 10mg daily for 104 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| proportion of subjects with hepatitis B virus (HBV)DNA<300copies/ml at week 104 |  | week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| serum HBV DNA reduction from baseline at week 104 |  | week 104 | 
| The proportion of subjects with ALT normalization at week 104 |  | week104 | 
| The proportion of subjects with HBeAg loss and seroconversion at week 104 |  | week104 | 
| The proportion of subject with HBsAg loss and seroconversion at week 104 |  | week104 | 
| The proportion of subjects with mutations of rtN236T/A181V, rtL180M/rtM204V/rtT184/rtS202 and/or rtM250 at week 104 |  | week104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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chronic hepatitis B, inadequate response, NUC therapy