Sofosbuvir With Pegylated Interferon and Ribavirin Hepatitis C Virus (HCV) Genotypes 1,4,5,6 (ATOMIC)

• Percentage of Participants With Sustained Virologic Response 24 Weeks Following Completion of Treatment (SVR24) [ Time Frame: Post-treatment Week 24 ] [ Designated as safety issue: No ]
  SVR24 was defined as HCV RNA < the limit of detection (LOD; < 15 IU/mL) 24 weeks after the last dose of study drug.
• Percentage of Participants Who Experienced Adverse Events [ Time Frame: Baseline (Day 1) to post-treatment Day 30 ] [ Designated as safety issue: Yes ]
  Adverse events (AEs) occurring from baseline (Day 1 for all groups) to 30 days following the last dose of study drug were summarized across the participant population. A participant was counted once if they had a qualifying event.

• Number of participants with adverse events as a measure of safety and tolerability [ Time Frame: 12 or 24 weeks ] [ Designated as safety issue: Yes ]
  To assess the safety of PSI-7977 in combination with PEG/RBV for 12 or 24 weeks of treatment
• Efficacy of PSI-7977 in subjects treated for 12 or 24 weeks [ Time Frame: 12 or 24 weeks ] [ Designated as safety issue: No ]
  To assess the efficacy of PSI-7977 with PEG/RBV for 12 or 24 weeks of treatment as measured by HCV RNA levels of detection.

• Percentage of Participants With Sustained Virologic Response 12 Weeks Following Completion of Treatment (SVR12) [ Time Frame: Post-treatment Week 12 ] [ Designated as safety issue: No ]
  SVR12 was defined as HCV RNA < LOD 12 weeks after the last dose of study drug.
• Change in HCV RNA at Week 2 [ Time Frame: Baseline (Day 1) to Week 2 ] [ Designated as safety issue: No ]
• Change in HCV RNA at Week 4 [ Time Frame: Baseline (Day 1) to Week 4 ] [ Designated as safety issue: No ]
• Change in HCV RNA at Week 8 [ Time Frame: Baseline (Day 1) to Week 8 ] [ Designated as safety issue: No ]
• Change in HCV RNA at Week 12 [ Time Frame: Baseline (Day 1) to Week 12 ] [ Designated as safety issue: No ]
• Percentage of Participants With HCV RNA < LOD at Week 2 [ Time Frame: Week 2 ] [ Designated as safety issue: No ]
• Percentage of Participants With HCV RNA Below < LOD at Week 4 [ Time Frame: Week 4 ] [ Designated as safety issue: No ]
• Percentage of Participants With HCV RNA Below < LOD at Week 8 [ Time Frame: Week 8 ] [ Designated as safety issue: No ]
• Percentage of Participants With HCV RNA Below < LOD at Week 12 [ Time Frame: Week 12 ] [ Designated as safety issue: No ]
• Percentage of Participants With HCV RNA Below < LOD at Week 24 [ Time Frame: Week 24 ] [ Designated as safety issue: No ]
• Percentage of Participants With ALT Normalization at Week 12 [ Time Frame: Baseline (Day 1) to Week 12 ] [ Designated as safety issue: No ]
  ALT normalization was defined as ALT > ULN at baseline and ALT ≤ ULN at Week 12.
• Percentage of Participants With ALT Normalization at Week 24 [ Time Frame: Baseline (Day 1) to Week 24 ] [ Designated as safety issue: No ]
  ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Week 24.
• Percentage of Participants With ALT Normalization at Post-treatment Week 4 [ Time Frame: Baseline (Day 1) to Post-treatment Week 4 ] [ Designated as safety issue: No ]
  ALT normalization was defined as ALT > ULN at baseline (Day 1 for all groups) and ALT ≤ ULN at Post-treatment Week 4.
• Percentage of Participants With Virologic Failure During Treatment [ Time Frame: Baseline (Day 1) to Week 24 ] [ Designated as safety issue: No ]

  Virologic failure was defined as either

  • HCV RNA ≥ 15 IU/mL after having previously had HCV RNA < 15 IU/mL while on treatment, confirmed with 2 consecutive values or last available measurement (ie, breakthrough);
  • > 1 log10 IU/mL increase in HCV RNA from nadir while on treatment, confirmed with 2 consecutive values or last available measurement (ie, rebound);or
  • HCV RNA persistently ≥ 15 IU/mL through 8 weeks of treatment (ie, nonresponse)

  Baseline was Day 1 for all groups.

• Percentage of Participants With Virologic Failure Following Treatment (Viral Relapse). [ Time Frame: End of treatment to Post-treatment Week 24 ] [ Designated as safety issue: No ]
  Viral relapse was defined as HCV RNA < 15 IU/mL at end of treatment, confirmed with 2 consecutive values or last available measurement.

• Change in circulating HCV ribonucleic acid (RNA) [ Time Frame: 12 or 24 weeks ] [ Designated as safety issue: No ]
  To assess the change in circulating HCV RNA in patients over 12 or 24 weeks of dosing.
• Number of participants with Sustained Viral Response (SVR) post-treatment [ Time Frame: Week 12 or Week 24 ] [ Designated as safety issue: No ]
  To assess the SVR at Week 12 or Week 24 after treatment.

The purpose of this study is to assess the safety, tolerability, and efficacy of sofosbuvir (GS-7977; PSI-7977) administered in combination with pegylated interferon and ribavirin (PEG/RBV) in treatment-naive patients with HCV genotypes 1,4,5,6, or indeterminate genotype.

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

  • Sovaldi®
  • GS-7977
  • PSI-7977
• Drug: RBV
  Ribavirin (RBV) tablets administered orally in a divided daily dose according to package insert weight-based dosing recommendations (< 75kg = 1000 mg and ≥ 75 kg = 1200 mg)
  Other Name: Copegus®
• Drug: PEG
  Pegylated interferon alfa-2a (PEG) 180 μg administered once weekly by subcutaneous injection
  Other Name: Pegasys®

• Experimental: SOF+PEG+RBV 12 weeks
  Participants were randomized to receive sofosbuvir+PEG+RBV for 12 weeks.
  Interventions:

  • Drug: Sofosbuvir
  • Drug: RBV
  • Drug: PEG
• Experimental: SOF+PEG+RBV 24 weeks
  Participants were randomized to receive sofosbuvir+PEG+RBV for 24 weeks.
  Interventions:

  • Drug: Sofosbuvir
  • Drug: RBV
  • Drug: PEG
• Experimental: SOF+PEG+RBV 12 week/Rerandomization Group
  Participants were randomized to receive sofosbuvir+PEG+RBV for 12 weeks, then were rerandomized to receive sofosbuvir only or sofosbuvir+RBV for 12 additional weeks.
  Interventions:

  • Drug: Sofosbuvir
  • Drug: RBV
  • Drug: PEG

Inclusion Criteria:

• Males and females with Chronic Hepatitis C (HCV) Genotype 1,4,5,6, or indeterminate
• Naive to previous HCV treatment

Exclusion Criteria:

• Positive for HBsAg, anti-HBc IgM Ab, or anti-HIV Ab
• History of any other clinically significant chronic liver disease