Clevudine re-administered to the patients with previous 12-weeks clevudine experience is as active as to the naive patients in terms of virological and biochemical responses.

Abstract

Introduction: Clevudine(CLV, L-FMAU) is a pyrimidine analogue that is a potent inhibitor of HBV replication in vitro. In woodchucks and in a phase I/II clinical study (L-FMAU-102), CLV produced a potent and durable post-treatment viral suppression. In a phase II clinical study (L-FMAU-201), CLV showed potent antiviral activities during 12-week dosing period and prolonged antiviral activities after discontinuation of treatment, which was associated with sustained normalization of ALT.

Aims: The primary objectives of this study were to evaluate the safety and efficacy of CLV, when re-administered to the patients who had been treated with CLV in L-FMAU-201 study.

Methods: CLV was re-administered 30mg/day, orally for 24 weeks to the patients who had been previously treated for 12 weeks, and then antiviral activities and the safety were evaluated. The study was conducted at a total of 7 sites in South Korea. Eligible patients were chronic hepatitis B patients who were treated with CLV in L-FMAU-201 study, whose HBV DNA were not negative (below 4,700 copies/mL) consecutively at the last 2 visits. A total of 50 patients were enrolled and among them, 17 patients have completed 24-week treatment period, the data of which were analyzed for this interim report.

Results: Median HBV DNA level at baseline was 7.12 log10 copies/ml, and the median changes in HBV DNA levels from baseline were -3.13, -3.07 log10 copies/ml, at week 12 and week 24, respectively. In contrast, the rates of patients with HBV DNA levels below the lower limit of detection of Supersensitive Digene II assay (LOD, 4.7 X 10^3 copies/ml) were as high as 71% and 76% at week 12 and 24, respectively. The rate of patients with HBV DNA levels below LOD in Amplicor PCR assay (400 copies/ml) at week 12 and 24 were as remarkable as 35% and 65% respectively. Normalization rates of alanine transaminase (ALT) level at week 12 and 24 were 65% and 71%, respectively. No serious or severe adverse events relevant to CLV were reported during the study and no adverse events led to treatment discontinuation.

Conclusion: CLV re-administered is as active to the patients with previous 12-week CLV experience as to the naive patients in terms of potent antiviral activity and normalization rates of ALT.