Open-Labeled Study of PSI-7977 and RBV With and Without PEG-IFN in Treatment-Naïve Patients With HCV GT2 or GT3

• Safety and Tolerability [ Time Frame: 8 or 12 weeks ] [ Designated as safety issue: Yes ]
  To assess the safety and tolerability of sofosbuvir 400 mg for 8 or 12 weeks, administered with and without ribavirin and/or pegylated interferon alfa-2a (PEG-IFN) in subjects with HCV genotypes 1, 2 or 3, with and without GS-5885 or GS-9669 in subjects with genotype 1 and also of sofosbuvir/GS-5885 FDC for 6 or 12 weeks, administered with and without ribavirin, in subjects with HCV genotype 1, 2 or 3.
  
  

• HCV RNA [ Time Frame: 6, 8, or 12 weeks ] [ Designated as safety issue: No ]
  To evaluate the change in circulating HCV RNA in subjects over 6, 8, or 12 weeks of dosing with sofosbuvir or sofosbuvir/GS-5885 administered with or without ribavirin and/or PEG-IFN or GS-5885 or GS-9669
  
  
• HCV RNA [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  To evaluate the proportion of subjects who have HCV RNA below the lower limit of quantitation (LLOQ) and below the limit of detection (LOD) at various time points in the study
  
  
• Sustained Virologic Response (SVR) [ Time Frame: SVR 12 ] [ Designated as safety issue: No ]
  To evaluate the sustained virologic response at 12 weeks (SVR12) following completion of all treatment
  
  
• Resistance [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  To evaluate the emergence of HCV resistance against sofosbuvir, GS-5885 or GS-9669
  
  
• Duration of PEG-IFN therapy [ Time Frame: SVR 12 ] [ Designated as safety issue: No ]
  To explore the effects of the duration of PEG-IFN therapy on safety, tolerability, emergence of resistance, viral kinetics, and SVR12
  
  
• Pharmacokinetics [ Time Frame: Ongoing ] [ Designated as safety issue: No ]
  To characterize the steady-state plasma pharmacokinetics of the GS-331007 metabolite of sofosbuvir
  
  

Part 1: PSI-7977 400 mg QD with weight-based RBV for 12 weeks. Subjects will be randomized in equal proportions to: no PEG-IFN (Arm 1), PEG-IFN for 4 weeks (Arm 2), PEG-IFN for 8 weeks (Arm 3), or PEG-IFN for 12 weeks (Arm 4); Part 2: HCV GT 2/3 patients receive PSI-7977 400 mg QD monotherapy for 12 weeks (Arm 5), or PSI-7977 400 mg QD with PEG-IFN and weight-based RBV for 8 weeks (Arm 6), and HCV GT1 null-responders receive PSI-7977 400 mg QD with weight-based RBV for 12 weeks (Arm 7); Part 3: HCV GT-1 treatment naive (Arm 8) or HCV GT 2/3 treatment experienced subjects (Arm 9) receive PSI-7977 400 mg QD in combination with weight-based RBV for 12 weeks; Part 4: HCV GT-2/3 treatment naive subjects receive PSI-7977 400 mg QD with weight-based RBV for 8 weeks (Arm 10) or PSI-7977 400 mg QD and 800 mg RBV for 12 weeks (Arm 11). HCV GT-1 "null response" subjects receive PSI-7977 400 mg QD, GS-5885, and weight based RBV for 12 weeks (Arm 12). HCV GT-1 treatment naive subjects receive PSI-7977 400 mg QD with weight-based RBV and GS-5885 for 12 weeks (Arm 13); Part 5: HCV GT 1 "null response" subjects receive PSI-7977 400 mg QD with GS-9669 500 mg QD and weight-based RBV for 12 weeks (Arm 14). HCV GT-1 treatment naive subjects receive PSI-7977 400 mg QD with GS-9669 500 mg QD and weight-based RBV for 12 weeks (Arm 15).

Part 6: HCV GT-1 "null response" subjects with fibrosis stage F4 receive sofosbuvir/GS-5885 FDC for 12 weeks (Arm 16) or sofosbuvir/GS-5885 FDC with weight-based RBV for 12 weeks (Arm 17). HCV GT-2/3 treatment naive subjects receive sofosbuvir/GS-5885 FDC for 12 weeks (Arm 18). HCV GT-2/3 treatment-experienced subjects receive sofosbuvir/GS-5885 FDC for 12 weeks (Arm 19). HCV GT-1 hemophiliacs receive sofosbuvir/GS-5885 FDC with weight-based RBV for 12 weeks (Arm 20). HCV GT-1 treatment-naive subjects receive sofosbuvir/GS-5885 FDC with weight-based RBV for 6 weeks (Arm 21). HCV GT-1 treatment-naive subjects receive sofosbuvir/GS-5885 FDC for 6 weeks (Arm 22).