Chronic Hepatitis BPhase 3NCT00605384
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
A Phase 3 study testing Entecavir + Tenofovir and Adefovir + continuing Lamivudine in people with Chronic Hepatitis B, run by Bristol-Myers Squibb at 29 sites in 6 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Entecavir + Tenofovir and Adefovir + continuing Lamivudine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 4 participants
- Where
- 29 sitesin 6 countries
- Study dates
- Aug 2008to Feb 2009
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
29 sites in 6 countries.
29 sites in 6 countries
Turkey (Türkiye)11 sites
Local Institution
Ankara, 06010
Local Institution
Ankara, 06620
Local Institution
Istanbul, 34093
Local Institution
Istanbul, 34098
Local Institution
Istanbul, 34360
Local Institution
Istanbul, 34460
Local Institution
Istanbul, 34722
Local Institution
Izmir, 35100
Local Institution
Kocaeli, 41380
Local Institution
Sihhiye Ankara, 06100
Local Institution
Trabzon, 61080
Italy5 sites
Local Institution
Messina, 98124
Local Institution
Modena, 41100
Local Institution
Naples, 80135
Local Institution
Padova, 35128
Local Institution
San Giovanni Rotondo, 71013
United States4 sites
Rush University Medical Center
Chicago, Illinois, 60612
Cedars Sinai Medical Center
Los Angeles, California, 90048
Local Institution
New York, New York, 10025
Kaiser Permanente Medical Center
San Francisco, California, 94118
Germany4 sites
Local Institution
Berlin, 13353
Local Institution
Bonn, 53105
Local Institution
Düsseldorf, 40237
Local Institution
Mainz, 55131
Poland3 sites
Local Institution
Chorzów, 41-500
Local Institution
Krakow, 31-531
Local Institution
Lublin, 20-089
About this study
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
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
- Being tested
- Entecavir + Tenofovir, Adefovir + continuing Lamivudine
- Medical subject headings
- Hepatitis B, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Entecavir + TenofovirDrug
Also called Baraclude
Tablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks
Adefovir + continuing LamivudineDrug
Tablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks
| Study group | Role | What they receive |
|---|---|---|
| 1 | Experimental | Not described Receives: Drug: Entecavir + Tenofovir |
| 2 | Experimental | Not described Receives: Drug: Adefovir + continuing Lamivudine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Week 48
Secondary outcomes (11)
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.
Measured: Week 96
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.
Measured: 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
by PCR, using the Roche for the Roche COBAS® TaqMan - HPS assay. LLD = 4.8 IU/mL (approximately 28 copies/mL)
Measured: Week 48, Week 96
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
Measured: Weeks 48, Week 96
Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96
by PCR, using the Roche COBAS®TaqMan - HPS assay
Measured: 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
Measured: 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
HBeAg is a hepatitis B viral protein. It is an indicator of active viral replication.
Measured: Baseline, Week 48, Week 96
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)
Measured: Baseline, Week 48, Week 96
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
Measured: Week 48, Week 96
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
Measured: 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
HBV DNA ≥ 50 IU/mL = approximately 300 copies/mL
Measured: Week 48, Week 96
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 Jan 2008 (estimated)
- Study startAug 2008
- Primary completionFeb 2009
- Study completionFeb 2009
Why it stopped: Business Objectives Have Changed
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Chronic Hepatitis BStudies of the same condition, open and under way.
- More trials run by Bristol-Myers SquibbThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bristol-Myers Squibb
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Bristol-Myers Squibb, Study director, Bristol-Myers Squibb
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00605384
- Sponsor's protocol ID
- AI463-137
- Status last verified
- Nov 2010
- First submitted
- 18 Jan 2008
- Last updated
- 23 Nov 2010
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 23 Nov 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00605384
- Acronym / sponsor ID
- AI463-137
- Conditions
- Chronic Hepatitis B
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Business Objectives Have Changed
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Aug 2008
- Primary completion
- Feb 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 31 Jan 2008 (estimated)
- Results
- Posted 10 Aug 2010
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 | Experimental | Drug: Entecavir + Tenofovir |
| 2 | Experimental | Drug: Adefovir + continuing Lamivudine |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Entecavir + TenofovirAlso: BaracludeTablets, Oral Entecavir 1 mg + Tenofovir 300 mg, once daily, 100 weeks | Drug | 1 |
| Adefovir + continuing LamivudineTablets, Oral, Adefovir 10 mg + Lamivudine, 100 mg, once daily, 100 weeks | Drug | 2 |
Primary outcome
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
11 secondary outcomes
Number of Participants Who Achieved an HBV DNA Level <50 IU/mL at Week 96
Time frame: Week 96
Number of Participants With Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs or Laboratory Abnormalities
Time frame: 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
Time frame: Week 48, Week 96
HBV DNA Values at Weeks 48 and 96
Time frame: Weeks 48, Week 96
Mean log10 Reduction From Baseline in HBV DNA at Weeks 48 and 96
Time frame: 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
Time frame: 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
Time frame: Baseline, Week 48, Week 96
Number of Participants Who Were HBeAg-positive at Baseline With HBe Seroconversion at Weeks 48 and 96
Time frame: Baseline, Week 48, Week 96
Number of Participants With Hepatitis-B-Virus Surface Antigen of the (HBsAg) Loss at Weeks 48 and 96
Time frame: Week 48, Week 96
Number of Participants With HBs Seroconversion (HBsAg Loss and Presence of HBsAb) at Weeks 48 and 96
Time frame: 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
Time frame: Week 48, Week 96
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Nov 2010.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Related trials for Chronic Hepatitis B
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A Study of HT-101 and HT-102 in Chronic Hepatitis B (CHB)
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A Phase I Clinical Trial of CPU-YL01 Injection in Patients With Chronic Hepatitis B.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Bristol-Myers Squibb study director
Bristol-Myers Squibb
29 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Entecavir + Tenofovir and Adefovir + continuing Lamivudine in people with Chronic Hepatitis B, run by Bristol-Myers Squibb at 29 sites in 6 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 23 Nov 2010. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 29 sites in Turkey (Türkiye), Italy, United States, Germany, Poland and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Aug 2010). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Participants Who Achieved an Hepatitis B Virus DNA (HBV DNA) Level < 50 IU/mL at Week 48 (time frame: Week 48). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Nov 2010.