Sofosbuvir + Ribavirin for 12 or 16 Weeks in Treatment Experienced Subjects With Chronic Genotype 2 or 3 HCV Infection (FUSION) (FUSION)

• Percentage of Participants Achieving SVR12 [ Time Frame: Posttreatment Week 12 ]

  SVR12 was defined as HCV RNA < the lower limit of quantitation (LLOQ, ie, < 25 IU/mL) 12 weeks after cessation of therapy.

  For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

• Adverse Events Leading to Permanent Discontinuation of Study Drug [ Time Frame: Baseline to Week 16 ]
  Adverse events which led to permanent discontinuation of study drug may or may not have been related to study treatment.

• Efficacy 12 weeks post dosing [ Time Frame: 12 weeks ]
  The proportion of patients with a sustained virologic response (SVR) 12 weeks after the end of treatment
• The safety and tolerability of GS-7977+RBV when given for 12 or 16 weeks [ Time Frame: 12 or 16 weeks ]
  The safety and tolerability of GS-7977+RBV when given for 12 or 16 weeks as measured by review of the accumulated safety data

• Percentage of Participants Achieving SVR4 [ Time Frame: Posttreatment Week 4 ]

  SVR4 was defined as HCV RNA < LLOQ 4 weeks after cessation of therapy.

  For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

• Percentage of Participants Achieving SVR24 [ Time Frame: Posttreatment Week 24 ]

  SVR24 was defined as HCV RNA < LLOQ 24 weeks after cessation of therapy.

  For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

• Percentage of Participants With Viral Breakthrough [ Time Frame: Up to 16 weeks ]

  Viral breakthrough was defined as HCV RNA ≥ LLOQ after having previously had HCV RNA < LLOQ while receiving treatment, confirmed with 2 consecutive values (second confirmation value could be posttreatment), or last available on-treatment measurement with no subsequent follow-up values.

  For the purposes of this efficacy analysis, assessments were made during active treatment (up to Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

• Percentage of Participants With Viral Relapse [ Time Frame: End of treatment to posttreatment Week 24 ]

  Viral relapse was defined as HCV RNA ≥ LLOQ during the posttreatment period having achieved HCV RNA < LLOQ at end of treatment, confirmed with 2 consecutive values or last available posttreatment measurement.

  For the purposes of this efficacy analysis, the posttreatment period began after the end of active treatment (following Week 12 for the SOF+RBV+placebo arm, and Week 16 for the SOF+RBV arm).

• Efficacy 4 and 24 weeks post dosing [ Time Frame: 4 weeks and 24 weeks ]
  To determine the proportion of subjects who attain SVR at 4 and 24 weeks after discontinuation of therapy (SVR4 and SVR24)
• Amount of circulating HCV RNA [ Time Frame: 12 weeks post dosing ]
  To evaluate the kinetics of circulating HCV RNA during treatment and after treatment discontinuation
• Characterization of viral resistance [ Time Frame: 12 weeks ]
  To evaluate the emergence of viral resistance to GS 7977 during treatment and after treatment discontinuation

• Drug: SOF
  Sofosbuvir (SOF) 400 mg tablet was administered orally once daily.
  Other Names:

  • Sovaldi®
  • GS-7977
  • PSI-7977
• Drug: RBV
  Ribavirin (RBV) tablets was administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg).
• Drug: Placebo to match SOF
  Placebo to match SOF was administered orally once daily.
• Drug: Placebo to match RBV
  Placebo to match RBV was administered orally twice daily.

• Experimental: SOF+RBV+placebo
  Participants were randomized to receive SOF+RBV for 12 weeks followed by placebo to match SOF plus placebo to match RBV for 4 weeks.
  Interventions:

  • Drug: SOF
  • Drug: RBV
  • Drug: Placebo to match SOF
  • Drug: Placebo to match RBV
• Experimental: SOF+RBV
  Participants were randomized to receive SOF+RBV for 16 weeks.
  Interventions:

  • Drug: SOF
  • Drug: RBV

• Younossi ZM, Stepanova M, Sulkowski M, Naggie S, Puoti M, Orkin C, Hunt SL. Sofosbuvir and Ribavirin for Treatment of Chronic Hepatitis C in Patients Coinfected With Hepatitis C Virus and HIV: The Impact on Patient-Reported Outcomes. J Infect Dis. 2015 Aug 1;212(3):367-77. doi: 10.1093/infdis/jiv005. Epub 2015 Jan 12.
• Stepanova M, Nader F, Cure S, Bourhis F, Hunt S, Younossi ZM. Patients' preferences and health utility assessment with SF-6D and EQ-5D in patients with chronic hepatitis C treated with sofosbuvir regimens. Aliment Pharmacol Ther. 2014 Sep;40(6):676-85. doi: 10.1111/apt.12880. Epub 2014 Jul 15.
• Jacobson IM, Gordon SC, Kowdley KV, Yoshida EM, Rodriguez-Torres M, Sulkowski MS, Shiffman ML, Lawitz E, Everson G, Bennett M, Schiff E, Al-Assi MT, Subramanian GM, An D, Lin M, McNally J, Brainard D, Symonds WT, McHutchison JG, Patel K, Feld J, Pianko S, Nelson DR; POSITRON Study; FUSION Study. Sofosbuvir for hepatitis C genotype 2 or 3 in patients without treatment options. N Engl J Med. 2013 May 16;368(20):1867-77. doi: 10.1056/NEJMoa1214854. Epub 2013 Apr 23.

Inclusion Criteria:

• Infection with HCV genotype 2 or 3
• Had cirrhosis determination
• Prior treatment failure
• Screening laboratory values within defined thresholds
• Subject had not been treated with any investigational drug or device within 30 days of the screening visit
• Use of highly effective contraception methods if female of childbearing potential or sexually active male

Exclusion Criteria:

• Prior exposure to an direct-acting antiviral targeting the HCV nonstructural protein (NS)5B polymerase
• Pregnant or nursing female or male with pregnant female partner
• Current or prior history of clinical hepatic decompensation
• History of clinically significant illness or any other major medical disorder that may have interfered with subject treatment, assessment or compliance with the protocol
• Excessive alcohol ingestion or significant drug abuse