Chronic Hepatitis BPhase 2NCT01020565
A Study in Japan of the Safety and Antiviral Activity With Chronic Hepatitis B Infection
A Phase 2 study testing Entecavir in people with Chronic Hepatitis B, run by Bristol-Myers Squibb.
Trial summary
The objectives of this study are to demonstrate that entecavir has antiviral activity with undetectable at Week 48, and to assess the safety and the pharmacokinetic in Japanese patients given entecavir at each dose of 0.1 and 0.5 mg for 52 weeks Read more about this study
- Who is it for?
- Ages 20 to 75 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- Entecavir
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 60 participants
- Where
- No sites listed yet
- Study dates
- Feb 2003to Feb 2005
- Phase
- Phase 2
- Are there results?
- None posted in the registry
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 20 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Documentation of chronic hepatitis B infection by ALL of the following:
- Positive for HBsAg OR, negative for IgM core antibody and confirmation of chronic hepatitis B on liver biopsy
- Positive for HBeAg OR negative for HBeAg
- Documented HBV Viremia on 2 or more occasions and at screening visit: Viremia on sample drawn AND HBV DNA of ≥ 10*5* copies/mL by PCR assay at the screening visit
- ALT in the range of 1.3 to 10 x ULN
Who cannot join
None listed.
About this study
Official title: A Phase II Study in Japan of the Safety and Antiviral Activity of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection
The objectives of this study are to demonstrate that entecavir has antiviral activity with undetectable at Week 48, and to assess the safety and the pharmacokinetic in Japanese patients given entecavir at each dose of 0.1 and 0.5 mg for 52 weeks
- Conditions
- Chronic Hepatitis B
- Being tested
- Entecavir
- 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.
EntecavirDrug
Also called Baraclude, BMS-200475
Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks
| Study group | Role | What they receive |
|---|---|---|
| Entecavir (0.1 mg) | Experimental | Not described Receives: Drug: Entecavir |
| Entecavir (0.5 mg) | Experimental | Not described Receives: Drug: Entecavir |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg
Measured: Week 52 (end of dosing) plus 5 days
Incidence of laboratory abnormalities of entecavir at doses of 0.5 and 1 mg for 52 weeks
Measured: Week 52 (end of dosing) plus 5 days
Proportion of subjects with reduction in HBV DNA by ≥2 log10 or to undetectable level (<400 copies/mL) by PCR assay
Measured: Week 48
Secondary outcomes (15)
Mean change from baseline in log10 HBV DNA measured by PCR assay for each entecavir dose (0.5 and 1 mg) at Week 48
Measured: Baseline, Week 48
Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48
Measured: Week 48
Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48
Measured: Week 48
Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48
Measured: Week 48
Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at Week 48
Measured: Week 48
Proportion of subjects HBeAg-positive at baseline who have Complete Response [undetectable HBV DNA levels by PCR assay, negative for HBeAg and normal serum ALT] at Week 48
Measured: Week 48
Proportion of subjects HBeAg-negative at baseline who have Complete Response [undetectable HBV DNA levels by PCR assay, remain negative for HBeAg and normal serum ALT] at Week 48
Measured: Week 48
Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug
Measured: Week 72
Proportion of subjects w/ histological improvement in liver (improvement in necroinflammatory score (≥2 points decrease, Knodell HAI3 score) & no worsening of fibrosis (≥1 point increase, Knodell fibrosis score) at Wk 48 liver biopsy compared to baseline
Measured: Baseline, Week 48
Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis
Measured: Week 52
Relationship between HBV isolates (genotypes A,B,C, etc.) at baseline and antiviral activity
Measured: Week 48, or at end of dosing (up to Week 52)
Incidence of resistance mutations of HBV isolates in subjects who have a rise in HBV DNA (by ≥1 log above the nadir for that subject) while on study drug.
Measured: Week 48, or at end of dosing (up to Week 52)
Mutation of HBV DNA polymerase at Week 48 from baseline
Measured: Baseline, Week 48
Plasma concentrations of entecavir at selected time points during the treatment period
Measured: pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36
Population pharmacokinetic assessment of entecavir developed from concentration-time data obtained from healthy subjects
Measured: pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2009 (estimated)
- Study startFeb 2003
- Primary completionFeb 2005
- Study completionFeb 2005
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 60 participants (estimated)
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
- NCT01020565
- Sponsor's protocol ID
- AI463-053
- Status last verified
- Jun 2010
- First submitted
- 24 Nov 2009
- Last updated
- 6 Aug 2010
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Kobashi H, Takaguchi K, Ikeda H, Yokosuka O, Moriyama M, Imazeki F, Kage M, Seriu T, Omata M, Sakaguchi K, Shiratori Y. Efficacy and safety of entecavir in nucleoside-naive, chronic hepatitis B patients: phase II clinical study in Japan. J Gastroenterol Hepatol. 2009 Feb;24(2):255-61. doi: 10.1111/j.1440-1746.2008.05593.x.
PubMed 19215336
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2010. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study in Japan of the Safety and Antiviral Activity of Entecavir (BMS-200475) in Adults With Chronic Hepatitis B Infection
- ClinicalTrials.gov ID
- NCT01020565
- Acronym / sponsor ID
- AI463-053
- Conditions
- Chronic Hepatitis B
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 60 participants (estimated)
- Lead sponsor
- Bristol-Myers SquibbIndustry (pharma, biotech, devices)
- Study start
- Feb 2003
- Primary completion
- Feb 2005 (actual)
- Study completion
- Feb 2005 (actual)
- First posted
- 25 Nov 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The objectives of this study are to demonstrate that entecavir has antiviral activity with undetectable at Week 48, and to assess the safety and the pharmacokinetic in Japanese patients given entecavir at each dose of 0.1 and 0.5 mg for 52 weeks
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Entecavir (0.1 mg) | Experimental | Drug: Entecavir |
| Entecavir (0.5 mg) | Experimental | Drug: Entecavir |
Who may qualify
- Ages
- 20 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Documentation of chronic hepatitis B infection by ALL of the following:
- ALT in the range of 1.3 to 10 x ULN
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| EntecavirAlso: Baraclude, BMS-200475Tablet, P.O., 0.1 OR 0.5 mg, once daily, 52 weeks | Drug | Entecavir (0.1 mg), Entecavir (0.5 mg) |
Primary outcome
Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg
Time frame: Week 52 (end of dosing) plus 5 days
Incidence of laboratory abnormalities of entecavir at doses of 0.5 and 1 mg for 52 weeks
Time frame: Week 52 (end of dosing) plus 5 days
Proportion of subjects with reduction in HBV DNA by ≥2 log10 or to undetectable level (<400 copies/mL) by PCR assay
Time frame: Week 48
15 secondary outcomes
Mean change from baseline in log10 HBV DNA measured by PCR assay for each entecavir dose (0.5 and 1 mg) at Week 48
Time frame: Baseline, Week 48
Proportion of subjects who achieve undetectable HBV DNA (<400 copies/mL) by PCR assay at Week 48
Time frame: Week 48
Proportion of subjects HBeAg-positive at baseline who have loss of HBeAg from serum at Week 48
Time frame: Week 48
Proportion of subjects HBeAg-positive at baseline who achieve seroconversion (loss of HBeAg and appearance of HBeAb) at Week 48
Time frame: Week 48
Proportion of subjects with abnormal ALT at baseline who achieve normalization of serum ALT (<1.25 x ULN) at Week 48
Time frame: Week 48
Proportion of subjects HBeAg-positive at baseline who have Complete Response [undetectable HBV DNA levels by PCR assay, negative for HBeAg and normal serum ALT] at Week 48
Time frame: Week 48
Proportion of subjects HBeAg-negative at baseline who have Complete Response [undetectable HBV DNA levels by PCR assay, remain negative for HBeAg and normal serum ALT] at Week 48
Time frame: Week 48
Proportion of subjects who achieve Complete Response, and remain Complete response for 24 weeks after stopping drug
Time frame: Week 72
Proportion of subjects w/ histological improvement in liver (improvement in necroinflammatory score (≥2 points decrease, Knodell HAI3 score) & no worsening of fibrosis (≥1 point increase, Knodell fibrosis score) at Wk 48 liver biopsy compared to baseline
Time frame: Baseline, Week 48
Changes in liver histology as assessed by the New Inuyama Classification for histological assessment of chronic hepatitis
Time frame: Week 52
Relationship between HBV isolates (genotypes A,B,C, etc.) at baseline and antiviral activity
Time frame: Week 48, or at end of dosing (up to Week 52)
Incidence of resistance mutations of HBV isolates in subjects who have a rise in HBV DNA (by ≥1 log above the nadir for that subject) while on study drug.
Time frame: Week 48, or at end of dosing (up to Week 52)
Mutation of HBV DNA polymerase at Week 48 from baseline
Time frame: Baseline, Week 48
Plasma concentrations of entecavir at selected time points during the treatment period
Time frame: pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36
Population pharmacokinetic assessment of entecavir developed from concentration-time data obtained from healthy subjects
Time frame: pre-dosing, Week 2 or 4, Week 12, Week 24 and Week 36
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Aug 2010.
- Background: PubMed 19215336Kobashi H, Takaguchi K, Ikeda H, Yokosuka O, Moriyama M, Imazeki F, Kage M, Seriu T, Omata M, Sakaguchi K, Shiratori Y. Efficacy and safety of entecavir in nucleoside-naive, chronic hepatitis B patients: phase II clinical study in Japan. J Gastroenterol Hepatol. 2009 Feb;24(2):255-61. doi: 10.1111/j.1440-1746.2008.05593.x.
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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
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Entecavir in people with Chronic Hepatitis B, run by Bristol-Myers Squibb.
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 0 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: finished, as of the sponsor's last update on 6 Aug 2010. Status can change between updates, so confirm with the study contact before making plans.
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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of clinical adverse events and discontinuations due to adverse events of entecavir at doses of 0.5 and 1 mg (time frame: Week 52 (end of dosing) plus 5 days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01020565, which also lists 1 linked publication.
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 6 Aug 2010.