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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

Primary Purpose

Chronic Hepatitis B

Status
Terminated
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Entecavir + Tenofovir
Adefovir + continuing Lamivudine
Sponsored by
Bristol-Myers Squibb
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Chronic Hepatitis B

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Cedars Sinai Medical Center
  • Kaiser Permanente Medical Center
  • Rush University Medical Center
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution
  • Local Institution

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Experimental

Arm Label

1

2

Arm Description

Outcomes

Primary Outcome Measures

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

Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at 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
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
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
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
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
Number of Participants Who Were Hepatitis B E-antigen (HBeAg)-Positive at Baseline With Loss of HBeAg at Weeks 48 and 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
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
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
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
HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL

Full Information

First Posted
January 18, 2008
Last Updated
November 15, 2010
Sponsor
Bristol-Myers Squibb
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1. Study Identification

Unique Protocol Identification Number
NCT00605384
Brief Title
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
Official Title
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2010
Overall Recruitment Status
Terminated
Why Stopped
Business Objectives Have Changed
Study Start Date
August 2008 (undefined)
Primary Completion Date
February 2009 (Actual)
Study Completion Date
February 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Bristol-Myers Squibb

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Hepatitis B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
4 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Title
2
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Entecavir + Tenofovir
Other Intervention Name(s)
Baraclude
Intervention Description
Tablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Intervention Type
Drug
Intervention Name(s)
Adefovir + continuing Lamivudine
Intervention Description
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
Primary Outcome Measure Information:
Title
Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48
Description
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
Time Frame
Week 48
Secondary Outcome Measure Information:
Title
Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96
Description
by PCR, using the Roche COBAS®TaqMan - HPS assay; HBV DNA < 50 IU/mL = approximately 300 copies/mL.
Time Frame
Week 96
Title
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities
Description
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.
Time Frame
Day 1 through end of treatment (Week 100 +/- 5 days)
Title
Number of Participants Who Achieved HBV DNA < the Lower Limit of Detection (LLD) at Weeks 48 and 96
Description
by PCR, using the Roche for the Roche COBAS® TaqMan - HPS assay. LLD = 4.8 IU/mL (approximately 28 copies/mL)
Time Frame
Week 48, Week 96
Title
HBV DNA Values at Weeks 48 and 96
Description
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
Time Frame
Weeks 48, Week 96
Title
Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96
Description
by PCR, using the Roche COBAS®TaqMan - HPS assay
Time Frame
Week 48, Week 96
Title
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
Time Frame
Week 48, Week 96
Title
Number of Participants Who Were Hepatitis B E-antigen (HBeAg)-Positive at Baseline With Loss of HBeAg at Weeks 48 and 96
Description
HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication.
Time Frame
Baseline, Week 48, Week 96
Title
Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96
Description
HBe seroconversion = HBeAg loss and presence of hepatitis B e-antibody (HBeAb)
Time Frame
Baseline, Week 48, Week 96
Title
Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96
Description
Hepatitis B surface antigen (HBsAg) = a part of the hepatitis B virus that, when in the blood, is an early marker of infection
Time Frame
Week 48, Week 96
Title
Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96
Description
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
Time Frame
Week 48, Week 96
Title
Number of Participants With Genotypic Resistance Based on Analysis of Samples From Participants With HBV DNA ≥ 50 IU/mL at Weeks 48 and 96
Description
HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL
Time Frame
Week 48, Week 96

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Bristol-Myers Squibb
Organizational Affiliation
Bristol-Myers Squibb
Official's Role
Study Director
Facility Information:
Facility Name
Cedars Sinai Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90048
Country
United States
Facility Name
Kaiser Permanente Medical Center
City
San Francisco
State/Province
California
ZIP/Postal Code
94118
Country
United States
Facility Name
Rush University Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Local Institution
City
New York
State/Province
New York
ZIP/Postal Code
10025
Country
United States
Facility Name
Local Institution
City
Bruxelles
ZIP/Postal Code
1200
Country
Belgium
Facility Name
Local Institution
City
Leuven
ZIP/Postal Code
3000
Country
Belgium
Facility Name
Local Institution
City
Berlin
ZIP/Postal Code
13353
Country
Germany
Facility Name
Local Institution
City
Bonn
ZIP/Postal Code
53105
Country
Germany
Facility Name
Local Institution
City
Duesseldorf
ZIP/Postal Code
40237
Country
Germany
Facility Name
Local Institution
City
Mainz
ZIP/Postal Code
55131
Country
Germany
Facility Name
Local Institution
City
Messina
ZIP/Postal Code
98124
Country
Italy
Facility Name
Local Institution
City
Modena
ZIP/Postal Code
41100
Country
Italy
Facility Name
Local Institution
City
Naples
ZIP/Postal Code
80135
Country
Italy
Facility Name
Local Institution
City
Padova
ZIP/Postal Code
35128
Country
Italy
Facility Name
Local Institution
City
San Giovanni Rotondo
ZIP/Postal Code
71013
Country
Italy
Facility Name
Local Institution
City
Chorzow
ZIP/Postal Code
41-500
Country
Poland
Facility Name
Local Institution
City
Krakow
ZIP/Postal Code
31-531
Country
Poland
Facility Name
Local Institution
City
Lublin
ZIP/Postal Code
20-089
Country
Poland
Facility Name
Local Institution
City
Ankara
ZIP/Postal Code
06010
Country
Turkey
Facility Name
Local Institution
City
Ankara
ZIP/Postal Code
06620
Country
Turkey
Facility Name
Local Institution
City
Istanbul
ZIP/Postal Code
34093
Country
Turkey
Facility Name
Local Institution
City
Istanbul
ZIP/Postal Code
34098
Country
Turkey
Facility Name
Local Institution
City
Istanbul
ZIP/Postal Code
34360
Country
Turkey
Facility Name
Local Institution
City
Istanbul
ZIP/Postal Code
34460
Country
Turkey
Facility Name
Local Institution
City
Istanbul
ZIP/Postal Code
34722
Country
Turkey
Facility Name
Local Institution
City
Izmir
ZIP/Postal Code
35100
Country
Turkey
Facility Name
Local Institution
City
Kocaeli
ZIP/Postal Code
41380
Country
Turkey
Facility Name
Local Institution
City
Sihhiye Ankara
ZIP/Postal Code
06100
Country
Turkey
Facility Name
Local Institution
City
Trabzon
ZIP/Postal Code
61080
Country
Turkey

12. IPD Sharing Statement

Learn more about this trial

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

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