A Phase IIIb Study to Compare Entecavir Plus Tenofovir vs. Adefovir Added to Continuing Lamivudine Therapy in Adult Patients With Lamivudine-Resistant Hepatitis B Infection

Phase 3

Terminated

• Conditions: Chronic Hepatitis B
• Interventions: Drug: Entecavir + Tenofovir; Drug: Adefovir + continuing Lamivudine

• Registration Number: NCT00605384
• Lead Sponsor: Bristol-Myers Squibb

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.

Detailed Description

Not available

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study First Submitted: 2008-01-18
• Study First Submitted QC: 2008-01-30
• Study First Posted: 2008-01-31
• Study Start: 2008-08
• Primary Completion: 2009-02
• Study Completion: 2009-02
• Results First Submitted: 2010-07-13
• Results First Submitted QC: 2010-07-13
• Results First Posted: 2010-08-10
• Status Verified: 2010-11
• Last Update Submitted: 2010-11-15
• Last Update Posted: 2010-11-23

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 4

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1	Entecavir + Tenofovir	-
2	Adefovir + continuing Lamivudine	-

Primary Outcome Measures

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

Name	Time	Method
Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96	Week 96	by PCR, using the Roche COBAS®TaqMan - HPS assay; HBV DNA \< 50 IU/mL = approximately 300 copies/mL.
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)	AE=any new untoward medical occurrence or worsening of a pre-existing medical condition which does not necessarily have a causal relationship with this treatment. Related AE=relationship of certain, probable, possible, or missing. SAE=any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or causes prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, and/or is an important medical event.
Number of Participants Who Achieved HBV DNA < the Lower Limit of Detection (LLD) at Weeks 48 and 96	Week 48, Week 96	by PCR, using the Roche for the Roche COBAS® TaqMan - HPS assay. LLD = 4.8 IU/mL (approximately 28 copies/mL)
HBV DNA Values at Weeks 48 and 96	Weeks 48, Week 96	Number of Participants with HBV DNA \<LLD (4.8); LLD to \<50; 50 to \<172; 172 to \<1,720; 1,720 to \<17,200; and ≥17,200 IU/mL (\<LLD (28); 28 to \<300; 300 to \<1,000; 1,000 to \<10,000; 10,000 to \<100,000; and ≥100,000 copies/mL by PCR, using the Roche COBAS®TaqMan - HPS assay
Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96	Week 48, Week 96	by PCR, using the Roche COBAS®TaqMan - HPS assay
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	HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication.
Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96	Baseline, Week 48, Week 96	HBe seroconversion = HBeAg loss and presence of hepatitis B e-antibody (HBeAb)
Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96	Week 48, Week 96	Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection
Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96	Week 48, Week 96	Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection. HBsAb = HBsAg antibodies. HBs Seroconversion = HBsAg loss and presence of HBseAb
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	HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL

Trial Locations

Locations (4)

Cedars Sinai Medical Center; 🇺🇸 Los Angeles, California, United States

Kaiser Permanente Medical Center; 🇺🇸 San Francisco, California, United States

Rush University Medical Center; 🇺🇸 Chicago, Illinois, United States

Local Institution; 🇹🇷 Trabzon, Turkey