Conditions: Hepatitis C, Chronic
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 368
Healthy volunteers: no

Brief summary:
This study will evaluate the safety, tolerability, and antiviral activity of grazoprevir (MK-5172) when administered in combination with peginterferon alfa-2b (Peg-IFN) and ribavirin (RBV) in treatment-naïve (TN) participants with chronic hepatitis C.

Detailed description:
Amendment 4 unblinded treatment after an interim analysis for all subsequently enrolled TN participants (the Second Cohort) who were receiving grazoprevir 400 or 800 mg daily, and they were down-dosed to 100 mg daily between Treatment Week (TW) 3 and TW12 for the remainder of the 12-week treatment course.

Amendment 5 allowed treatment-naïve participants with chronic hepatitis C and compensated cirrhosis to be enrolled and receive open-label grazoprevir 100 mg in combination with Peg-IFN and RBV, without a corresponding control arm.

Arms:
arm 1: TN non-cirrhotic (NC) participants receive Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. arm 2: TN NC participants receive Grazoprevir 200 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. arm 3: TN NC participants receive Grazoprevir 400 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. arm 4: TN NC participants receive Grazoprevir 800 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy. arm 5: TN NC participants start a 4 week lead-in with Peg-IFN + RBV, then receive Boceprevir 800 mg + Peg-IFN + RBV for 24 weeks followed by 0 or 20 weeks of Peg-IFN + RBV, based on response guided therapy. arm 6: As the result of an interim analysis, TN NC participants assigned to the 400 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study. arm 7: As the result of an interim analysis, TN NC participants assigned to the 800 mg grazoprevir group were unblinded and transitioned to 100 mg grazoprevir once daily + Peg-IFN + RBV and will remain in the study. arm 8: TN cirrhotic participants receive open-label Grazoprevir 100 mg + Peg-IFN + RBV for 12 weeks followed by 12 or 36 weeks of Peg-IFN + RBV, based on response guided therapy.

Interventions: intervention 1: Grazoprevir intervention 2: Boceprevir intervention 3: Placebo for Grazoprevir intervention 4: Placebo for Boceprevir intervention 5: Peg-interferon alfa-2b intervention 6: Ribavirin
Intervention descriptions: intervention 1: Orally once daily in AM. Blinded or open-label depending on treatment arm. intervention 2: Four 200 mg capsules orally three times daily. intervention 3: Orally once daily in AM. intervention 4: Four capsules orally three times daily. intervention 5: 1.5 μg/kg/week subcutaneous injection. intervention 6: 300 mg to 700 mg orally twice daily.

Protocol document: