Dose Ranging of GSK2336805 in Combination Therapy
Condition: Hepatitis C, Chronic
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Study type: Interventional
Phase: Phase 2

Summary: 
      GSK2336805 is a novel hepatitis C virus (HCV) non-structural 5A (NS5A) inhibitor being
      developed for the treatment of chronic HCV infection. This Phase II, multicenter,
      parallel-group, randomized, dose-ranging study will assess the safety and tolerability,
      antiviral activity, and pharmacokinetics of GSK2336805 at 2 dose levels (40 and 60 mg) in
      combination with pegylated interferon alfa-2a (PEG) and ribavirin (RIBA) in approximately 100
      treatment-naïve subjects with chronic genotype 1 HCV infection.

      In a separate nonrandomized single-arm cohort, up to 15 treatment-naïve subjects with
      genotype 4 chronic HCV infection will be enrolled in parallel at the dose level of 60 mg of
      GSK2336805.
    

Detailed description: 
      Subjects with chronic genotype 1 hepatitis C virus (HCV) infection will be randomly assigned
      on a 2:2:1 basis to 1 of 3 treatment arms: T40 (GSK2336805 40 mg and PEG + RIBA) or T60
      (GSK2336805 60 mg and PEG + RIBA) or PEG + RIBA and telaprevir (PRT). Randomization will be
      stratified by interleukin 28B (IL28B) rs12979860 status (C/C versus carriage of the T
      allele), HCV genotype (1a vs. 1b), and plasma HCV Ribonucleic Acid (RNA) (<800,000 IU/mL
      versus ≥800,000 IU/mL).

      An additional nonrandomized single-arm cohort of subjects with chronic genotype 4 HCV
      infection will be enrolled in parallel. A maximum of 15 genotype 4 subjects will receive
      GSK2336805 60 mg and PEG + RIBA. The purpose of this cohort is to further characterize the
      antiviral activity of GSK2336805 in subjects with chronic genotype 4 HCV infection. The
      schedule of assessments for the genotype 4 subjects will be the same as for the genotype 1
      subjects. Recruitment of the genotype 4 subjects may be terminated when the target sample of
      genotype 1 subjects have been randomized.

      Subjects in a GSK2336805 treatment arm who achieve extended rapid virologic response (eRVR)
      will receive a total of 24 weeks of therapy (12 weeks GSK2336805 in combination with PEG +
      RIBA followed by 12 weeks PEG + RIBA). Subjects who are HCV detectable at Week 4 and then
      undetectable at Week 12 will receive a total of 48 weeks of therapy (12 weeks GSK2336805 in
      combination with PEG + RIBA followed by 36 weeks PEG + RIBA). Subjects in the telaprevir
      treatment control arm will be managed according to the current product label for
      treatment-naïve subjects.

      Subjects who complete treatment will undergo follow-up monitoring for 24 weeks after
      completion of therapy. At the end of the 24-week follow-up visit, subjects will have
      completed their participation in the study. The total duration of the study will be 48 weeks
      for subjects who achieve eRVR at Week 12 and up to 72 weeks for subjects who do not achieve
      eRVR at Week 12.
    

Intervention name(s): GSK2336805 40 mg; GSK2336805 60 mg; Pegylated interferon alpha-2a; Ribavirin; Telaprevir
Intervention type(s): Drug; Drug; Drug; Drug; Drug
Intervention description(s): 20 mg tablet, round, 10-mm diameter, white to off-white, no markings; 30 mg tablet, round, 10-mm diameter, white to off-white, no markings; 180 microgram per 0.5 mL prefilled syringe for single use; 200-mg tablet, capsule-shaped, light blue, film-coated, and debossed with "200" on 1 side and the logo "3RP" on the other side; 375 mg film-coated tablet
Other intervention name(s): Pegasys; Ribasphere; Incivek (United States); Incivo (European Union)
Intervention MeSH terms: Interferons; Ribavirin; Interferon-alpha; Interferon alpha-2; Peginterferon alfa-2a
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment
Keywords: Genotype 4; GSK2336805; pegylated interferon; telaprevir; Genotype 1; chronic hepatitis C; ribavirin; NS5A inhibitor; hepatitis C virus (HCV) infection