876 ACH-3102, A SECOND GENERATION NS5A INHIBITOR, DEMONSTRATES POTENT ANTIVIRAL ACTIVITY IN PATIENTS WITH GENOTYPE 1a HCV INFECTION DESPITE THE PRESENCE OF BASELINE NS5A-RESISTANT VARIANTS

Abstract

The primary objective(s) of this study were: Results: ACH-3102 was safe and well tolerated in patients with GT-1 chronic HCV infection at doses of 25 mg, 50 mg, 150 mg and 300 mg. There were no serious adverse events, and no discontinuations for safety concerns in subjects adminis- tered ACH-3102. The systemic exposure increased in a dose-proportional manner across the doses studied. At the 25, 50, 150 and 300 mg doses, mean maximum reductions in plasma HCV RNA were 4.04, 3.78, 3.52 and 3.93 log10 (IU/ml), respec- tively. Mean plasma HCV RNA levels did not return to baseline until Day 15. Geno- typic analyses revealed the presence of baseline NS5A-resistant viral variants in the majority of patients. Viral kinetic modeling indicated inhibition of HCV RNA production and virion secretion with estimated efficiencies of 0.9831± 0.0429 and 0.9941 ± 0.0156, respectively, for the doses studied. Conclusions: ACH-3102 was safe and well-tolerated in GT-1 HCV chronically infected subjects at all tested doses. Robust, rapid and sustained suppression of plasma HCV RNA levels was observed after all tested single doses of ACH-3102. Viral kinetics parameters estimated from modeling of ACH-3102 monotherapy dem- onstrated high drug efficiency. These data provide evidence that ACH-3102 is a safe and well-tolerated second-generation NS5A inhibitor with potent anti-viral activity against both wild-type HCV virus and NS5A-resistant viral variants, making it a promising candidate for future use in the treatment of chronic HCV infection. RESULTS 6.60 (0.5) 6.94 (0.3) 6.48 (0.2) 6.77(0.3) 6.76 (0.3) 6.76 (0.3) 6.49 7.06 6.48 6.74 6.78 6.77 5.87, 7.26 6.29, 7.24 6.26, 6.69 6.38, 7.20 6.37, 7.09 6.26, 7.24 Mean (SD) Sex, n (%)