Safety, Tolerability, and Antiviral Activity of 24 or 48 Weeks of GS-9190 in Combination With Peginterferon Alfa 2a and Ribavirin for the Treatment of Genotype-1 Chronic HCV Infection
Condition: HCV Infection
MeSH terms: Infections; Communicable Diseases; Hepatitis C
Study type: Interventional
Phase: Phase 2

Summary: 
      The purpose of this study is to compare the safety, tolerability and effectiveness of the
      experimental drug GS-9190 when administered for 24 or 48 weeks with peginterferon alfa 2a and
      ribavirin for the treatment of genotype-1 chronic hepatitis C infection.
    

Detailed description: 
      The safety, tolerability and antiviral efficacy GS-9190, administered orally twice daily at
      40 mg, will be compared to placebo when used in combination with peginterferon alfa 2a (PEG)
      and ribavirin (RIBA) in treatment-naïve subjects chronically infected with HCV genotype 1
      infection. Two-hundred forty-eight (248) subjects will be randomized (ratio: 1:2:1) to one of
      three treatment arms:

      Arm 1: PEG/RIBA + placebo BID for 48 weeks + 24 weeks treatment-free follow-up (n = 62)

      Arm 2: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up (n =
      124)

      Arm 3: PEG/RIBA + GS 9190 40 mg BID for 48 weeks + 24 weeks treatment-free follow-up.
      However, subjects who achieve RVR (HCV RNA undetectable at Week 4) and maintain that response
      through Week 24 will stop all study drugs at Week 24 and be followed for an additional 48
      weeks (n = 62).

      Randomization will be stratified by plasma HCV RNA level (< or ≥ 400,000 IU/mL) at screening
      and race (of African descent or other).

      In order to ensure adequate representation of subjects with genotypes 1a and 1b in this
      trial, enrollment for either genotype will be capped at 120 subjects. Once 120 subjects of
      either genotype (e.g., genotype 1a) have been randomized, subsequent enrollment will only be
      allowed for subjects with the other genotype (e.g., genotype 1b).

      The duration of double-blind treatment is 48 weeks plus 24 weeks of treatment-free follow-up;
      however subjects in Arm 3 will stop all medication at Week 24 if they have achieved an RVR
      (defined by undetectable HCV RNA following 4 weeks on therapy) and have maintained that
      response thereafter. Subjects will only learn that they have been randomized to Arm 3 if, at
      Week 24, having achieved criteria for stopping therapy, they are instructed to stop. All
      other subjects will remain blinded to their treatment status throughout the course of the
      study.

      The standard of care treatment stopping criterion used in clinical practice when treating HCV
      with PEG/RIBA, failure to achieve EVR, will be utilized in this trial. Additionally, subjects
      with detectable plasma HCV RNA at Week 24 will discontinue all study medications no later
      than the Week 28 visit and will be followed off-treatment for 24 weeks.
    

Intervention name(s): placebo; GS-9190; Peginterferon Alfa 2a; Ribavirin
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): oral BID; 40 mg oral BID; All subjects received a fixed dose of 180 μg PEG via subcutaneous injection on a weekly basis.; Ribavirin supplied as 200 mg Copegus® tablets (1000 mg for subjects weighing < 75 kg and 1200 mg for subjects weighing ≥ 75 kg) were given in a divided daily dose.
Other intervention name(s): PEG; RBV
Intervention MeSH terms: Ribavirin; Peginterferon alfa-2a
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Hepatitis C; HCV; Rapid Virologic Response; Sustained Virologic Response; HCV RNA; Polymerase inhibitor; GS-9190