Efficacy and Safety Study of GS-9256 and GS-9190 Alone and in Combination With Ribavirin for 28 Days in Patients With Chronic Hepatitis C Virus Infection
Condition: HCV Infection
MeSH terms: Infections; Communicable Diseases; Hepatitis C; Virus Diseases; Hepatitis
Study type: Interventional
Phase: Phase 2

Summary: 
      This a phase 2, randomized, open-label trial of GS-9256 plus GS-9190, two oral anti HCV
      drugs, for 28 days with and without ribavirin (RIBA) and with pegylated interferon (PEG)/RIBA
      in adults with chronic Hepatitis C virus (HCV). In Part A, approximately thirty (30) subjects
      18-70 years of age who meet study entry criteria will be randomized (in other words, selected
      at random, like flipping a coin) to one of the two treatment groups (GS-9256 plus GS-9190 or
      GS-9256 plus GS-9190 plus RIBA). In Part B, an additional fifteen (15) subjects will receive
      75 mg GS-9256 BID plus 40 mg GS-9190 BID in combination with PEG/RIBA. After the 28-day
      treatment period, subjects will receive PEG/RIBA as standard of care (SOC).

      Following randomization, subjects will return for a Baseline (Day 1) visit, at which time
      study medication will be dispensed and subjects will enter a 28 day treatment phase. During
      the treatment phase, subjects will receive oral study drugs twice daily for 28 days and PEG
      once weekly for Part B. Subjects then receive PEG/RIBA as local SOC starting on Day 28 (not
      provided as part of the study). Following completion of the 28-day treatment phase, subjects
      will be followed for approximately 72 weeks.
    

Detailed description: 
      GS-9256 (an HCV NS3 protease inhibitor) plus GS-9190 (non-nucleoside HCV NS5B inhibitor) will
      be administered for 28 days with and without RIBA (weight-based dosing) and with PEG/RIBA in
      treatment-naïve subjects with chronic genotype 1 HCV infection. In Part A, thirty (30)
      subjects with genotype 1 will be randomized to 75 mg GS-9256 BID plus 40 mg GS-9190 BID or 75
      mg GS-9256 BID plus 40 mg GS-9190 BID plus RIBA 1000-1200 mg/day for 28 days. In Part B, an
      additional fifteen (15) subjects with genotype 1 will receive 75 mg GS-9256 BID plus 40 mg
      GS-9190 BID in combination with PEG/RIBA for 28 days. After the 28-day treatment period,
      subjects will receive PEG/RIBA as standard of care (SOC).

      In Part A, for any subjects meeting pre-defined, individual, virologic criteria, PEG/RIBA
      standard of care will be started prior to Day 28.

      Both PEG and RIBA will be administered at their currently approved dosages for treatment of
      HCV infection in accordance with appropriate labeling. Subjects will be monitored for safety
      (including ECG monitoring), antiviral activity, pharmacokinetics, and resistance 2-3 times
      weekly through Day 28.
    

Intervention name(s): GS-9256; GS-9190; Ribavirin; Peginterferon alfa-2a
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): 75 mg BID x 28 days; 40 mg BID x 28 days; 1000-1200 mg/day given BID; 180 ug q week
Other intervention name(s): COPEGUS; Pegasys
Intervention MeSH terms: Ribavirin; Peginterferon alfa-2a
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Hepatitis C; HCV; GS-9256; GS-9190; Genotype 1