Safety and Efficacy Study of LB80380 in the Patients With Lamivudine-Refractory Chronic Hepatitis B

Chronic Hepatitis B Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00895596
• Other study ID #: BVCL004
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: May 7, 2009
• Last updated: May 7, 2009
• Start date: March 2004
• Est. completion date: December 2007

Study information

• Verified date: May 2009
• Source: LG Life Sciences
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationKorea: Food and Drug Administration
• Study type: Interventional

Clinical 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 65
• Est. completion date: December 2007
• Est. primary completion date: August 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, 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:
• LB80380
Total treatment period: 12 weeks, followed by 24 weeks of treatment with adefovir dipivoxil 10mg

Locations

Country	Name	City	State
China	Queen Mary Hospital	Hong Kong
Korea, Republic of	Korea University Medical Center	Seoul
Korea, Republic of	Severance Hospital of Yonsei University	Seoul
Korea, Republic of	The Catholic University of Korea, Kangnam St. Mary's Hospital	Seoul

Sponsors (1)

Lead Sponsor	Collaborator
LG Life Sciences

Countries where clinical trial is conducted

China,  Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mean serum HBV DNA level (log10) reduction from the baseline at Week 12		Week 12	No
Secondary	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		Week 12	Yes