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

NCT00605384 | Terminated Phase 3 Results

• 1 other identifier: AI463-137
• Study Type: interventional
• Target: 4
• Locations: 6 countries
• Sites: 29

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.

Conditions

Chronic Hepatitis B

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (11)

• 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

Study Arms (2)

1

EXPERIMENTAL

Drug: Entecavir + Tenofovir

2

EXPERIMENTAL

Drug: Adefovir + continuing Lamivudine

Interventions

Entecavir + Tenofovir DRUG

Tablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks

Also known as: Baraclude

1

Adefovir + continuing Lamivudine DRUG

Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks

2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Bristol-Myers Squibb: lead

Study Sites (29)

Cedars Sinai Medical Center

Los Angeles, California, 90048, United States

Location

Kaiser Permanente Medical Center

San Francisco, California, 94118, United States

Location

Rush University Medical Center

Chicago, Illinois, 60612, United States

Location

Local Institution

New York, New York, 10025, United States

Location

Local Institution

Brussels, 1200, Belgium

Location

Local Institution

Leuven, 3000, Belgium

Location

Local Institution

Berlin, 13353, Germany

Location

Local Institution

Bonn, 53105, Germany

Location

Local Institution

Düsseldorf, 40237, Germany

Location

Local Institution

Mainz, 55131, Germany

Location

Local Institution

Messina, 98124, Italy

Location

Local Institution

Modena, 41100, Italy

Location

Local Institution

Naples, 80135, Italy

Location

Local Institution

Padua, 35128, Italy

Location

Local Institution

San Giovanni Rotondo, 71013, Italy

Location

Local Institution

Chorzów, 41-500, Poland

Location

Local Institution

Krakow, 31-531, Poland

Location

Local Institution

Lublin, 20-089, Poland

Location

Local Institution

Ankara, 06010, Turkey (Türkiye)

Location

Local Institution

Ankara, 06620, Turkey (Türkiye)

Location

Local Institution

Istanbul, 34093, Turkey (Türkiye)

Location

Local Institution

Istanbul, 34098, Turkey (Türkiye)

Location

Local Institution

Istanbul, 34360, Turkey (Türkiye)

Location

Local Institution

Istanbul, 34460, Turkey (Türkiye)

Location

Local Institution

Istanbul, 34722, Turkey (Türkiye)

Location

Local Institution

Izmir, 35100, Turkey (Türkiye)

Location

Local Institution

Kocaeli, 41380, Turkey (Türkiye)

Location

Local Institution

Sihhiye Ankara, 06100, Turkey (Türkiye)

Location

Local Institution

Trabzon, 61080, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Hepatitis B, Chronic

Interventions

entecavir; Tenofovir; adefovir

Condition Hierarchy (Ancestors)

Hepatitis B; Blood-Borne Infections; Communicable Diseases; Infections; Hepadnaviridae Infections; DNA Virus Infections; Virus Diseases; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Organophosphonates; Organophosphorus Compounds; Organic Chemicals; Adenine; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Following review of business priorities, BMS decided to terminate this study at an early stage. This was a strategic decision, not based on clinical or safety concerns. Due to limited data, no conclusions on safety and efficacy can be made.

Results Point of Contact

• Title: BMS Study Director
• Organization: Bristol-Myers Squibb

Clinical.Trials@bms.com

Study Officials

• Bristol-Myers Squibb

  Bristol-Myers Squibb

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: January 18, 2008
• First Posted: January 31, 2008
• Study Start: August 1, 2008
• Primary Completion: February 1, 2009
• Study Completion: February 1, 2009
• Last Updated: November 23, 2010
• Results First Posted: August 10, 2010

Record last verified: 2010-11

Locations

PL (3); BE (2); TU (11); DE (4); US (4); IT (5)