GS-7977 and Ribavirin in Treatment Naive and Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection

• Efficacy 12 weeks after discontinuation of therapy. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  •To determine the efficacy of treatment with GS 7977+ ribavirin (RBV) as measured by the proportion of subjects with sustained viral response 12 weeks after discontinuation of therapy (SVR12)
• Safety and tolerability of GS-7977 + RBV. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  •To assess the safety and tolerability of GS-7977+RBV as measured by review of the accumulated safety data.

• Efficacy 12 weeks after discontinuation of therapy. [ Time Frame: 24 weeks ] [ Designated as safety issue: No ]
  To determine the efficacy of treatment with GS-7977 + Ribavarin (RBV) compared to treatment with GS-7977 placebo + RBV placebo as measured by the proportion of subjects with sustained viral response 12 weeks after discontinuation of therapy (SVR 12).
• Safety and tolerability of GS-7977 + RBV. [ Time Frame: 12 weeks ] [ Designated as safety issue: Yes ]
  To assess the safety and tolerability of GS-7977 + RBV compared to placebo control as measured by review of the accumulated safety data.

• Efficacy 4 and 24 weeks after discontinuation of therapy. [ Time Frame: 16 weeks and 36 weeks ] [ Designated as safety issue: No ]
  To determine the proportion of subjects who attain SVR at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24).
• Efficacy of treatment with GS-7977 + RBV based on prior treatment history. [ Time Frame: 12 weeks ] [ Designated as safety issue: No ]
  To determine the efficacy of treatment with GS-7977 + RBV based on prior treatment history.
• Kinetics of circulating HCV RNA during and after treatment discontinuation. [ Time Frame: 12 weeks and 36 weeks ] [ Designated as safety issue: No ]
  To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation.
• Viral resistance to GS-7977 during and after treatment discontinuation. [ Time Frame: 12 weeks and 36 weeks ] [ Designated as safety issue: No ]
  To evaluate the emergence of viral resistance to GS-7977 during treatment and after treatment discontinuation.

The purpose of this study is to determine if GS-7977 and Ribavirin is effective and safe in the treatment of Genotype 2 or 3 HCV infection.

• Drug: GS-7977 + RBV
  GS-7977 400 mg QD + RBV (1000 or 1200 mg.day) BID for 12 weeks.
  Other Names:

  • -Sofosbuvir
  • -PSI-7977
  • -GS-7977
  • -Ribavirin
  • -RBV
• Drug: GS-7977 placebo + RBV placebo
  GS-7977 placebo QD + RBV placebo BID
  Other Names:

  • -Sofosbuvir
  • -PSI-7977
  • -GS-7977
  • -Ribavirin
  • -RBV

• Experimental: GS-7977
  Approximately 320 subjects will be randomized to Arm 1.
  Intervention: Drug: GS-7977 + RBV
• Placebo Comparator: Placebo
  Approximately 80 subjects will be randomized to Arm 2.
  Intervention: Drug: GS-7977 placebo + RBV placebo

Inclusion Criteria:

• Age > 18 with chronic genotype 2 or 3 HCV infection.
• HCV RNA > 10,000 IU/mL at Screening.
• Subjects must be treatment naïve or treatment experienced.
• Presence or absence of cirrhosis; a liver biopsy may be required.
• Healthy according to medical history and physical examination with the exception of HCV diagnosis.
• Agree to use two forms of highly effective contraception for the duration of the study and 6 months after the last dose of study medication.

Exclusion Criteria:

• Prior use of any other inhibitor of the HCV NS5B Polymerase.
• History of any other clinically significant chronic liver disease.
• Evidence of or history of decompensated liver disease.
• HIV or chronic hepatitis B virus (HBV) infection.
• Hepatocellular carcinoma (HCC) or other malignancy (with exception of certain resolved skin cancers).
• Chronic use of immunosuppressive agents or immunomodulatory agents.
• History or current evidence of any condition, therapy, laboratory abnormality or other circumstance that might confound the results of the study, or interfere with the subject's participation for the full duration of the study or not be in the best interest of the subject in the opinion of the investigator.