Study of Grazoprevir (MK-5172) and Elbasvir (MK-8742) in Japanese Participants With Chronic Hepatitis C (MK-5172-058)
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis; Hepatitis, Chronic
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      This is a two-part study of grazoprevir (MK-5172) + elbasvir (MK-8742) in Japanese
      participants with chronic hepatitis C virus (HCV) genotype 1 (GT1). Part I is a dose-finding
      study; in Part II, participants will be randomly assigned to receive grazoprevir at the dose
      determined in Part I in combination with elbasvir. The primary study hypothesis is that the
      percentage of treatment-naïve participants in the Immediate Treatment Arm of Part II who
      achieve sustained viral response at 12 weeks after the end of all treatment (SVR12) will be
      greater than the reference rate of 75%. A separate study arm for cirrhotic participants will
      also be included in Part II; these participants will receive grazoprevir at the determined
      dose in combination with elbasvir.
    

Detailed description: 
      In Part 1, HCV GT1 participants are randomized into one of two arms: 50 mg grazoprevir plus
      50 mg elbasvir for 12 weeks during the double blinded (DB) period followed by 24 weeks of
      follow-up (FU) during an open-label (OL) period [Arm 1]; or 100 mg grazoprevir plus 50 mg
      elbasvir for 12 weeks during the DB followed by 24 weeks of FU during the OL [Arm 2].
      Unblinding will occur after all participants complete FU Week 4 at which time the grazoprevir
      dose will be selected.

      In Part 2, non-cirrhotic HCV GT1 participants and GT1 participants with compensated liver
      cirrhosis all receive the selected dose of grazoprevir (50 mg or 100 mg from Part 1) with 50
      mg elbasvir for 12 weeks. Non-cirrhotic GT1 participants are randomized to receive either a)
      12 weeks of active treatment immediately during the DB with 24 weeks of FU in the OL [Arm
      1/Immediate Arm] or b) placebo for 12 weeks with 4 weeks of follow-up during the DB followed
      by 12 weeks of active treatment and 24 weeks of follow-up during the OL [Arm 2/Deferred Arm].
      All cirrhotic participants [Arm 3/Cirrhotic] receive the selected dose immediately for 12
      weeks during the DB with 24 weeks of FU during the OL.

      Safety analyses for Part 1 and Part 2 arms will focus on the 12 week treatment phase plus the
      first 4 FU weeks. For the Part 2 Deferred Arm this will include the initial 12 week placebo
      treatment and first 4 weeks of FU. Efficacy analyses for Parts 1 and 2 will evaluate active
      treatment only (Weeks 1-12 for all arms except for Part 2 Deferred Arm which is weeks 16-28).

      Part 1:

      50 mg grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 1) 100 mg
      grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 2)

      Part 2:

      Selected dose of grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm
      1/Immediate) Placebo treatment for 12 weeks, 4 weeks follow-up, selected dose of grazoprevir
      + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 2/Deferred) Selected dose of
      grazoprevir + 50 mg elbasvir treatment for 12 weeks, 24 weeks follow-up (Arm 3/Cirrhotic)
    

Intervention name(s): Grazoprevir; Elbasvir; Placebo to Grazoprevir; Placebo to Elbasvir
Intervention type(s): Drug; Drug; Drug; Drug
Intervention description(s): One or two 50 mg tablets (depending on randomization) taken orally once daily for 12 weeks.; One 50 mg tablet taken orally once daily for 12 weeks.; One tablet of placebo matched to grazoprevir, taken orally once daily for 12 weeks.; One tablet of placebo matched to elbasvir, taken orally once daily for 12 weeks.
Intervention MeSH terms: Grazoprevir
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment