Phase: 1

First-in-Human Indication: Hepatitis C

Study Population: Treatment-naïve, chronically-infected HCV subjects

# of Subjects: 19 randomized and completed – highest enrolling of 13 total studysites, with 27% of total subjects

Cohorts: 6 unique dosing cohorts:

• Cohort 1: Genotype 1a
• Cohort 2: Genotype 1a
• Cohort 3: Genotype 1a
• Cohort 4: Genotype 1a
• Cohort 5: Genotype 1b
• Cohort 6: Genotype 1b

Study Duration: 5 months

In-patient Period: 5 days

Objectives

Primary

To evaluate the safety and tolerability of escalating, multiple, oral doses of XXXX in subjects with chronic genotype 1 Hepatitis C Virus (HCV) infection.

To evaluate the antiviral activity of XXXX against genotype 1 HCV following administration of multiple oral doses.

Secondary

To characterize the plasma pharmacokinetics of XXXX following administration of escalating, multiple, oral doses ingenotype 1 HCV-infected subjects.

To assess the PK/PD relationship between HCV viral load change and XXXX plasma concentrations following multiple dose administration.

To compare XXXX antiviral activity in genotype 1a versus 1b infections.

To evaluate genotypic changes from baseline in the NS5A coding region of HCV following multiple dose administration of XXXX and for up to 48 weeks thereafter.

Lab Assessments - 95 per subject

Hematology, Serum Chemistry, Lipids

HBV, HCV, and HIV Serology

HCV Genotype

Prothrombin time/INR

Serial Plasma HCV RNA

Serial Pharmacokinetic Analysis

Plasma for Resistance Surveillance

IL28B Genotyping

Plasma/Serum for Storage