icon-folder.gif   Conference Reports for NATAP  
 
  38th Annual Meeting of the European Association for the Study of the Liver
 
Istanbul, Turkey. March 28-April 1, 2003
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Clevudine, New Drug for HBV
 
 
  A PHASE I/II DOSE ESCALATING TRIAL EVALUATING SAFETY, TOLERABILITY, PHARMACOKINETICS AND ANTIVIRAL ACTIVITY OF CLEVUDINE IN PATIENTS CHRONICALLY INFECTED WITH HBV
 
P. Marcellin, 1 G.K.K. Lau*, 2 H. Mommeja-Marin, 3 S. Sacks, 4 D. Sereni, 5 J.P. Bronowicki, 6 B. Conway, 7 C. Trepo, 8 E. Mondou, 3 A. Snow, 3 B.C. Yoo, 9 H.S. Lee, 10 F. Rousseau, 3 *Presenting Author 1Hosp Beaujon, Clichy, France 2Queen Mary Hosp, Univ of Hong Kong, SAR, China 3Triangle Pharmaceuticals, Inc, Durham, USA 4Viridae, Vancouver, BC, Canada 5Hosp Saint Louis, Paris, France 6Hosp Brabois, Nancy, France 7Univ of British Columbia, Vancouver, BC, Canada 8Hotel Dieu, Lyon, France 9Sam Sung Medical Center, Sang Kyun Kwan Univ, Sang Kyun Kwan, Korea 10Seoul National Univ Hosp, Seoul, Korea
 
Background: Clevudine (CLV, L-FMAU) is a potent inhibitor of HBV replication in vitro. In woodchucks, CLV caused a sustained viral suppression after completion of a 12 week dosing period.
 
Methods: Multicenter, open-label, dose escalation study evaluating 10, 50, 100 and 200 mg CLV QD for 28 days (n=5, 10, 10 and 7/group, respectively). Patients were followed post-treatment for 6 months. Eligible patients had baseline (BL) HBV DNA levels (VL) ≥ 3mEg/mL, were nucleoside treatment naïve and without HIV or HCV co-infection. VL was assayed using Digene Hybrid Capture II and genotype by di-deoxy sequencing.
 
Results: 32 patients were enrolled. At BL, median VLs were 7.3, 8.0, 8.8 and 8.4 log c/mL and median ALTs were 55, 119, 106 and 64 U/L in the 10, 50, 100 and 200mg QD cohorts, respectively. After 28 days of dosing, the median log VL change from BL was -2.5, -2.7, -3.0 and -2.6, in the 10, 50, 100 and 200mg groups, respectively. At 6 months post-dose sustained biochemical responses were observed and median log VL changes from BL were -1.2, -1.4, -2.7 and -1.6 in the 10, 50, 100 and 200mg arms, respectively. Seven patients (28%) lost HBeAg, 5 (19%) seroconverted to HBeAb. CLV was well tolerated, without limiting adverse events. No treatment emergent mutations in the HBV DNA polymerase domain were observed 5 months after treatment.
 
Conclusion: These results confirm in humans the antiviral activity and a unique post-treatment antiviral effect as predicted by the pre-clinical profile of clevudine.