A Efficacy and Safety Study of Adefovir Dipivoxil to Treat Chinese Patients With HBeAg+ve Chronic Hepatitis B

Study Overview
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Brief Summary
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The purpose of this study is to determine whether Adefovir Dipivoxil is effective and safe in treatment of Chinese Patients with HBeAg positive Chronic Hepatitis B for 5 years.

Official Title
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A Multi-Centre, Double-Blind , Randomized, Placebo-Controlled Phase II/III Study of Adefovir Dipivoxil for the Treatment of Chinese Patients With HBeAg Positive Chronic Hepatitis B Followed by Long-Term (5 Years Total) Adefovir Dipivoxil Treatment. (Report on Year 1 and Year 2 Data)

Conditions
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Chronic Hepatitis B

Intervention / Treatment
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* Drug: AAAA
* Drug: AAPA
* Drug: PAAA


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 18-65 years Presence of HBsAg and HBeAg at the time of screening and for at least 6 months prior to screening. Positive HBV DNA plasma assay with screening value equal or more than 10 (6) copies/mL (Roche COBAS AMPLICORTM HBV MONITOR Test, LLOD less than 300 copies/mL) at the time of screening (within 4 weeks of randomisation). Evidence of elevated serum ALT levels defined as serum ALT level greater than or equal to 2.0 times (inclusive) the upper limit of the normal range (ULN) in the previous 6 months, and serum ALT levels greater than 1.0 times the ULN at the time of screening. Exclusion Criteria: Evidence of hepatocellular carcinoma; Clinical signs of liver decompensation; Serum creatinine more than 1.5 mg/dL; ALT more than 10 x ULN; seropositivity for hepatitis C or D virus or HIV; Lamivudine therapy within 3 months prior to screening; ADV therapy or any other anti-HBV therapy within the previous 6 months; Use of systemic antiviral agents, immunomodulators, immunosuppressive therapy, Chinese Traditional Medicines or agents known to lower ALT levels during the study.

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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Adefovir Dipivoxil<br>ADV 10mg tablets once daily | Drug: AAAA<br>* Adefovir Dipivoxil (12 weeks) + open lable Adefovir Dipivoxil (28 weeks) + Adefovir Dipivoxil (12 weeks) + Open label Adefovir Dipivoxil (52-260weeks)<br>Drug: AAPA<br>* Adefovir Dipivoxil (12 weeks) + Open label Adefovir Dipivoxil (28 weeks) + placebo (12 weeks) + open label-Adefovir Dipivoxil (52-260 weeks)<br>Drug: PAAA<br>* Placebo (12 weeks) + Open label Adefovir Dipivoxil (28 weeks) + Adefovir Dipivoxil (12 weeks) + Open label Adefovir Dipivoxil (52-260 weeks)<br>|
| Placebo Comparator: Adefovir Dipivoxil matched placebo<br>Adefovir Dipivoxil matched placebo one tablet once daily | Drug: AAPA<br>* Adefovir Dipivoxil (12 weeks) + Open label Adefovir Dipivoxil (28 weeks) + placebo (12 weeks) + open label-Adefovir Dipivoxil (52-260 weeks)<br>Drug: PAAA<br>* Placebo (12 weeks) + Open label Adefovir Dipivoxil (28 weeks) + Adefovir Dipivoxil (12 weeks) + Open label Adefovir Dipivoxil (52-260 weeks)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The log10 reduction in HBV DNA from baseline at week 12 between ADV 10mg and matching placebo |  | Week 12 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The proportion of subjects with ALT normalisation |  | Week 52, 104, 156, 208, 260 | 
| log10 reduction in serum HBV DNA |  | Week 52, 104, 156, 208, 260 | 
| The proportion of subjects with HBV DNA 10(5) copies/mL or a 2 log10 reduction from Baseline HBV DNA level |  | Week 52, 104, 156, 208, 260 | 
| The proportion of subjects with HBeAg loss |  | Week 52, 104, 156, 208, 260 | 
| The proportion of subjects with HBeAg seroconversion |  | Week 52, 104, 156, 208, 260 | 
| The proportion of subjects developing N236T and A181V HBV DNA genotypic mutations associated with ADV resistance |  | Week 52, 104, 156, 208, 260 | 
| The proportion of subjects with HBV DNA undetectable (<300 copies/mL) |  | Week 52, 104, 156, 208, 260 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HBV DNA suppression, ALT normalisation, Viral resistance, HBeAg seroconversion