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Clevudine, New Drug for HBV
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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.
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