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

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00605384
• Other study ID #: AI463-137
• Status: Terminated
• Phase: Phase 3
• First received: January 18, 2008
• Last updated: November 15, 2010
• Start date: August 2008
• Est. completion date: February 2009

Study information

• Verified date: November 2010
• Source: Bristol-Myers Squibb
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 4
• Est. completion date: February 2009
• Est. primary completion date: February 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Entecavir + Tenofovir
Tablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
• Adefovir + continuing Lamivudine
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks

Locations

Country	Name	City	State
Belgium	Local Institution	Bruxelles
Belgium	Local Institution	Leuven
Germany	Local Institution	Berlin
Germany	Local Institution	Bonn
Germany	Local Institution	Duesseldorf
Germany	Local Institution	Mainz
Italy	Local Institution	Messina
Italy	Local Institution	Modena
Italy	Local Institution	Naples
Italy	Local Institution	Padova
Italy	Local Institution	San Giovanni Rotondo
Poland	Local Institution	Chorzow
Poland	Local Institution	Krakow
Poland	Local Institution	Lublin
Turkey	Local Institution	Ankara
Turkey	Local Institution	Ankara
Turkey	Local Institution	Istanbul
Turkey	Local Institution	Istanbul
Turkey	Local Institution	Istanbul
Turkey	Local Institution	Istanbul
Turkey	Local Institution	Istanbul
Turkey	Local Institution	Izmir
Turkey	Local Institution	Kocaeli
Turkey	Local Institution	Sihhiye Ankara
Turkey	Local Institution	Trabzon
United States	Rush University Medical Center	Chicago	Illinois
United States	Cedars Sinai Medical Center	Los Angeles	California
United States	Local Institution	New York	New York
United States	Kaiser Permanente Medical Center	San Francisco	California

Sponsors (1)

Lead Sponsor	Collaborator
Bristol-Myers Squibb

Countries where clinical trial is conducted

United States,  Belgium,  Germany,  Italy,  Poland,  Turkey, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Week 48	No
Secondary	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.	Week 96	No
Secondary	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.	Day 1 through end of treatment (Week 100 +/- 5 days)	Yes
Secondary	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)	Week 48, Week 96	No
Secondary	HBV DNA Values at Weeks 48 and 96	Number of Participants with HBV DNA	Weeks 48, Week 96	No
Secondary	Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96	by PCR, using the Roche COBAS®TaqMan - HPS assay	Week 48, Week 96	No
Secondary	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	No
Secondary	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.	Baseline, Week 48, Week 96	No
Secondary	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)	Baseline, Week 48, Week 96	No
Secondary	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	Week 48, Week 96	No
Secondary	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	Week 48, Week 96	No
Secondary	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	Week 48, Week 96	No

External Links

•   BMS Clinical Trials Disclosure
•   For FDA Safety Alerts and Recalls refer to the following link: http://www.fda.gov/MEDWATCH/safety.htm