L-DT: an ongoing phase I/II dose escalation trial in patients with chronic HBV infection (NV-02B-001)

Abstract

Introduction: L-dT (fl-L-2'deoxythymidine) is a novel L-nucleoside shown to be a hightly specific and potent inhibitor of HBV DNA polymerase and HBV replication in vitro. Methods: NV-02B-001 is a blinded dose escalation trial to evaluate the pK, safety and efficacy of L-dT at once daily doses starting at 25 mg. 7 HBeAg(+) patients are to be enrolled in each of the sequential dose cohorts (25, 50, 100, 200 and 400 mg) at a ratio of 6:1 (L-dT: placebo). Dose limiting toxicities (DLTs) must be <2 in any given cohort in order to dose-escalate to subsequent cohorts. The primary efficacy measure is plasma HBV DNA, measured by COBAS Amplicor HBV Monitor TM Assay. Results: 7 patients have completed the 28-day active treatment phase of the 1 st dose (25 rag) cohort. The median baseline viral load (log10 C/mL) was 9.72. The median change in viral load from baseline to Day 28 was - 2.5 log[0 C/mL for the 6 actively treated patients. No serious adverse events or DLTs have been reported to date. Conclusion: Preliminary safety and antiviral activity data have shown L-dT to be active and well tolerated in patients enrolled in the 1 st and lowest dose cohort.