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

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)

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis B
• Intervention / Treatment: Drug: AAAA; Drug: AAPA; Drug: PAAA

• Study Type: Interventional
• Enrollment (Actual): 480
• Phase: Phase 3

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100044
    • GSK Investigational Site
  • Beijing, China, 100011
    • GSK Investigational Site
  • Chongqing, China, 400038
    • GSK Investigational Site
  • Chongquin, China, 400038
    • GSK Investigational Site
  • Shanghai, China, 200040
    • GSK Investigational Site
  • Guangdong
    • Guangzhou, Guangdong, China, 510515
      • GSK Investigational Site
    • Guangzhou, Guangdong, China, 510630
      • GSK Investigational Site
  • Jilin
    • Changchun, Jilin, China, 130021
      • GSK Investigational Site
  • Shandong
    • Jinan, Shandong, China
      • GSK Investigational Site
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310003
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start: December 1, 2002
• Primary Completion (Actual): March 1, 2008
• Study Completion (Actual): March 1, 2008

Study Registration Dates

• First Submitted: March 5, 2009
• First Submitted That Met QC Criteria: March 5, 2009
• First Posted (Estimate): March 9, 2009

Study Record Updates

• Last Update Posted (Estimate): April 3, 2009
• Last Update Submitted That Met QC Criteria: April 2, 2009
• Last Verified: April 1, 2009

More Information

Terms related to this study

• Keywords: HBV DNA suppression; HBeAg seroconversion; Viral resistance; ALT normalisation
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic
• Other Study ID Numbers: ADF30001