A Comparative Study of the Antiviral Efficacy and Safety of Entecavir Plus Tenofovir Versus Adefovir Added to Continuing Lamivudine in Adults With Lamivudine- Resistant Chronic Hepatitis B Virus Infection

Bristol-Myers Squibb4 sites in 2 countries4 target enrollmentAugust 2008

ConditionsChronic Hepatitis B

InterventionsEntecavir + Tenofovir Adefovir + continuing Lamivudine

DrugsEntecavir + Tenofovir Adefovir + continuing Lamivudine

Overview

Phase: Phase 3
Intervention: Entecavir + Tenofovir
Conditions: Chronic Hepatitis B
Sponsor: Bristol-Myers Squibb
Enrollment: 4
Locations: 4
Primary Endpoint: Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48
Status: Terminated
Last Updated: 15 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

Brief Summary

The purpose of this clinical research study is to find out whether a combination of entecavir (ETV) plus tenofovir (TNF) works better against Hepatitis B virus than adefovir (ADV) added to continuing lamivudine (LVD) therapy in patients whose Hepatitis B virus (HBV) is resistant against lamivudine. The safety of this treatment will also be studied.

Registry

clinicaltrials.gov

Start Date

August 2008

End Date

February 2009

Last Updated

15 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Bristol-Myers Squibb

Eligibility Criteria

Inclusion Criteria

•Chronic HBV infection
•History of lamivudine (LVD) treatment, and lamivudine resistance (LVDr), receiving LVD at screening visit
•Compensated liver function
•HBV DNA ≥ 172,000 IU/mL
•Hepatitis B e-antigen (HBeAg)-positive or HBeAg-negative

Exclusion Criteria

•Evidence of decompensated cirrhosis
•Coinfection with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis D virus (HDV)
•Recent history of pancreatitis
•Serum alpha fetoprotein \> 100 ng/mL
•Except lamivudine, any prior therapy with nucleoside or nucleotide analogue antiviral agents with activity against hepatitis B

Arms & Interventions

1

Intervention: Entecavir + Tenofovir

2

Intervention: Adefovir + continuing Lamivudine

Outcomes

Primary Outcomes

Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48

Time Frame: Week 48

using the Roche COBAS® TaqMan HBV Test for use with the High Pure System (HPS) assay, by Polymerase Chain Reaction (PCR); HBV DNA \< 50 IU/mL = approximately 300 copies/mL

Secondary Outcomes

Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96(Week 96)
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities(Day 1 through end of treatment (Week 100 +/- 5 days))
Number of Participants Who Achieved HBV DNA < the Lower Limit of Detection (LLD) at Weeks 48 and 96(Week 48, Week 96)
HBV DNA Values at Weeks 48 and 96(Weeks 48, Week 96)
Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96(Week 48, Week 96)
Number of Participants With Alanine Aminotransferase (ALT) > 1 x Upper Limit of Normal (ULN) at Baseline Who Achieved ALT Normalization (≤ 1 x ULN) at Weeks 48 and 96(Week 48, Week 96)
Number of Participants Who Were Hepatitis B E-antigen (HBeAg)-Positive at Baseline With Loss of HBeAg at Weeks 48 and 96(Baseline, Week 48, Week 96)
Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96(Baseline, Week 48, Week 96)
Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96(Week 48, Week 96)
Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96(Week 48, Week 96)
Number of Participants With Genotypic Resistance Based on Analysis of Samples From Participants With HBV DNA ≥ 50 IU/mL at Weeks 48 and 96(Week 48, Week 96)