Chronic Hepatitis BPhase 1/2NCT00895596
Safety and Efficacy Study of LB80380 in the Patients With Lamivudine-Refractory Chronic Hepatitis B
A Phase 1/2 study testing LB80380 in people with Chronic Hepatitis B, run by LG Life Sciences at 4 sites in 2 countries.
Trial summary
The purpose of the study is to investigate the safety and the antiviral activity of ascending multiple oral doses of LB80380 for 12 weeks in adults with lamivudine-refractory chronic hepatitis B infection. Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Chronic Hepatitis B
- What is being tested?
- LB80380
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 65 participants
- Where
- 4 sitesin 2 countries
- Study dates
- Mar 2004to Dec 2007
- Phase
- Phase 1/2
- 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 18 to 65 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Compensated chronic hepatitis B patient
- Presence of serum HBsAg for more than 6 months.
- Presence of HBeAg for more than 1 month with compensated liver disease
- Confirmation of YMDD mutants (M552V, M552I and its related double mutant at L528M) by genotyping of the YMDD motif using line probe assay (INNO-LiPA HBV DR assay)
- Screening HBV DNA value higher than or equal to 1,000,000 copies/mL (measured by the COBAS Amplicor HBV Monitor™ assay)
- Screening ALT value between 1.5 and 10 x ULN
Who cannot join
- Co-infection with hepatitis C or D virus (HCV or HDV) or HIV
- Pregnancy or breast-feeding
- Previous treatment with nucleoside analogue or any other treatment for HBV except for lamivudine within 6 months prior to study entry
- Treatment with immunomodulatory agent or corticosteroids within 6 months prior to study entry.
- De-compensated liver disease
- Screening alpha-fetoprotein (AFP) value > 20 ng/mL, and a follow-up ultrasonography performed prior to baseline shows findings indicative of HCC.
- Presence of anti-HBs at screening
Trial locations and contacts
4 sites in 2 countries.
4 sites in 2 countries
South Korea3 sites
Korea University Medical Center
Seoul
Severance Hospital of Yonsei University
Seoul
The Catholic University of Korea, Kangnam St. Mary's Hospital
Seoul
About this study
Official title: A PhaseII, Open-Label, Multinational, Multi-Centre, Sequential Group, Dose-Escalation Study to Assess the Safety and Antiviral Activity of LB80380 for 12 Weeks in Patients With Lamivudine-Refractory Chronic Hepatitis B
The purpose of the study is to investigate the safety and the antiviral activity of ascending multiple oral doses of LB80380 for 12 weeks in adults with lamivudine-refractory chronic hepatitis B infection.
Read the detailed description
LB80380, an oral prodrug, is a promising candidate nucleoside analogue with antiviral activity against wild-type HBV. LB80380 is undergoing clinical development by LG Life Sciences for use in the treatment of chronic HBV infection and for treatment of lamivudine-resistant disease.
In this study, the treatment period was divided into two parts: a 4-week treatment period with dose escalation assessment (Part 1), followed by an 8-week extension period (Part 2).
During Part 1, patients received LB80380 and LVD 100 mg once daily for 4 weeks. Each patient was then given only LB80380 for an additional 8 weeks (Part 2) unless dose-limiting toxicity (DLT) was observed during Part 1. At each dose level, all patients were to complete at least Part 1 of the treatment period before enrolment into the next Dose Group could commence. Dose escalation to the next group was not to be initiated if more than two patients experienced DLT during Part 1 in the previous Dose Group. Additionally, patients enrolled in LB80380 150mg and 240mg groups who agreed to participate in the pharmacokinetic (PK) analyses visited the study site the day before Week 12 for blood sampling. Follow-up period was 24 weeks, and patients were treated with adefovir dipivoxil during the follow-up period. During the study, patients were evaluated for changes from baseline in serum HBV DNA. Safety was evaluated on the basis of occurrence of AEs and changes from baseline in clinical laboratory parameters, physical examination findings, and vital signs.
- Conditions
- Chronic Hepatitis B
- Being tested
- LB80380
- Keywords
- Chronic hepatitis B, Lamivudine resistant, YMDD mutant type
- 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.
LB80380Drug
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg
| Study group | Role | What they receive |
|---|---|---|
| LB80380 30mg | Experimental | LB80380 30mg Receives: Drug: LB80380 |
| LB80380 60mg | Experimental | LB80380 60mg Receives: Drug: LB80380 |
| LB80380 90mg, | Experimental | LB80380 90mg Receives: Drug: LB80380 |
| LB80380 150mg | Experimental | LB80380 150mg Receives: Drug: LB80380 |
| LB80380 240mg | Experimental | LB80380 240mg Receives: Drug: LB80380 |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mean serum HBV DNA level (log10) reduction from the baseline at Week 12
Measured: Week 12
Secondary outcomes (1)
Proportion of patients with HBeAg seroconversion at 12 weeks Proportion of patients with HBsAg seroconversion at 12 weeks Proportion of patients with ALT normalization at 12 weeks Safety assessment during the whole study period
Measured: Week 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2009 (estimated)
- Study startMar 2004
- Primary completionAug 2006
- Study completionDec 2007
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.
- 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 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Enrolment
- 65 participants (actual)
Sponsor and investigators
- Lead sponsor
- LG Life Sciences
- Sponsor type
- Industry (pharma, biotech, devices)
- Investigators
- Ching-Lung Lai, Dr, Principal investigator, Queen Mary Hospital, Hong Kong
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00895596
- Sponsor's protocol ID
- BVCL004
- Status last verified
- May 2009
- First submitted
- 7 May 2009
- Last updated
- 8 May 2009
- Results posted
- No
- Data monitoring committee
- No
Publications
Yuen MF, Han KH, Um SH, Yoon SK, Kim HR, Kim J, Kim CR, Lai CL. Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease. Hepatology. 2010 Mar;51(3):767-76. doi: 10.1002/hep.23462.
PubMed 20091678
Study at a glance
From the registry record, last updated by the sponsor on 8 May 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A PhaseII, Open-Label, Multinational, Multi-Centre, Sequential Group, Dose-Escalation Study to Assess the Safety and Antiviral Activity of LB80380 for 12 Weeks in Patients With Lamivudine-Refractory Chronic Hepatitis B
- ClinicalTrials.gov ID
- NCT00895596
- Acronym / sponsor ID
- BVCL004
- Conditions
- Chronic Hepatitis B
- Keywords
- Chronic hepatitis B, Lamivudine resistant, YMDD mutant type
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 65 participants (actual)
- Lead sponsor
- LG Life SciencesIndustry (pharma, biotech, devices)
- Study start
- Mar 2004
- Primary completion
- Aug 2006 (actual)
- Study completion
- Dec 2007 (actual)
- First posted
- 8 May 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 purpose of the study is to investigate the safety and the antiviral activity of ascending multiple oral doses of LB80380 for 12 weeks in adults with lamivudine-refractory chronic hepatitis B infection.
Detailed description
LB80380, an oral prodrug, is a promising candidate nucleoside analogue with antiviral activity against wild-type HBV. LB80380 is undergoing clinical development by LG Life Sciences for use in the treatment of chronic HBV infection and for treatment of lamivudine-resistant disease.
In this study, the treatment period was divided into two parts: a 4-week treatment period with dose escalation assessment (Part 1), followed by an 8-week extension period (Part 2).
During Part 1, patients received LB80380 and LVD 100 mg once daily for 4 weeks. Each patient was then given only LB80380 for an additional 8 weeks (Part 2) unless dose-limiting toxicity (DLT) was observed during Part 1. At each dose level, all patients were to complete at least Part 1 of the treatment period before enrolment into the next Dose Group could commence. Dose escalation to the next group was not to be initiated if more than two patients experienced DLT during Part 1 in the previous Dose Group. Additionally, patients enrolled in LB80380 150mg and 240mg groups who agreed to participate in the pharmacokinetic (PK) analyses visited the study site the day before Week 12 for blood sampling. Follow-up period was 24 weeks, and patients were treated with adefovir dipivoxil during the follow-up period. During the study, patients were evaluated for changes from baseline in serum HBV DNA. Safety was evaluated on the basis of occurrence of AEs and changes from baseline in clinical laboratory parameters, physical examination findings, and vital signs.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Masking
- None (open label)
- Number of arms
- 5
| Arm | Type | Receives |
|---|---|---|
| LB80380 30mg | Experimental | Drug: LB80380LB80380 30mg |
| LB80380 60mg | Experimental | Drug: LB80380LB80380 60mg |
| LB80380 90mg, | Experimental | Drug: LB80380LB80380 90mg |
| LB80380 150mg | Experimental | Drug: LB80380LB80380 150mg |
| LB80380 240mg | Experimental | Drug: LB80380LB80380 240mg |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Compensated chronic hepatitis B patient
- Presence of serum HBsAg for more than 6 months.
- Presence of HBeAg for more than 1 month with compensated liver disease
- Confirmation of YMDD mutants (M552V, M552I and its related double mutant at L528M) by genotyping of the YMDD motif using line probe assay (INNO-LiPA HBV DR assay)
- Screening HBV DNA value higher than or equal to 1,000,000 copies/mL (measured by the COBAS Amplicor HBV Monitor™ assay)
Key exclusion criteria (7 listed)
- Co-infection with hepatitis C or D virus (HCV or HDV) or HIV
- Pregnancy or breast-feeding
- Previous treatment with nucleoside analogue or any other treatment for HBV except for lamivudine within 6 months prior to study entry
- Treatment with immunomodulatory agent or corticosteroids within 6 months prior to study entry.
- De-compensated liver disease
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 |
|---|---|---|
| LB80380Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg | Drug | LB80380 150mg, LB80380 240mg, LB80380 30mg, LB80380 60mg, LB80380 90mg, |
Primary outcome
Mean serum HBV DNA level (log10) reduction from the baseline at Week 12
Time frame: Week 12
1 secondary outcome
Proportion of patients with HBeAg seroconversion at 12 weeks Proportion of patients with HBsAg seroconversion at 12 weeks Proportion of patients with ALT normalization at 12 weeks Safety assessment during the whole study period
Time frame: Week 12
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 8 May 2009.
- Derived from this study: PubMed 20091678Yuen MF, Han KH, Um SH, Yoon SK, Kim HR, Kim J, Kim CR, Lai CL. Antiviral activity and safety of LB80380 in hepatitis B e antigen-positive chronic hepatitis B patients with lamivudine-resistant disease. Hepatology. 2010 Mar;51(3):767-76. doi: 10.1002/hep.23462.
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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.
Ching-Lung Lai, Dr principal investigator
Queen Mary Hospital, Hong Kong
4 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing LB80380 in people with Chronic Hepatitis B, run by LG Life Sciences at 4 sites in 2 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 6 inclusion and 7 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 8 May 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in South Korea, China. 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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?
Mean serum HBV DNA level (log10) reduction from the baseline at Week 12 (time frame: Week 12). 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 NCT00895596, 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 8 May 2009.