A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035)
Condition: Hepatitis C
MeSH terms: Hepatitis A; Hepatitis C; Hepatitis C, Chronic; Hepatitis
Intervention: Grazoprevir; Elbasvir; Placebo to Elbasvir; Ribavirin
Intervention description: 100 mg tablet orally QD; Part A: 20 or 50 mg capsule orally QD Parts B, C, and D: 50 mg capsule orally QD; Placebo to Elbasvir 20 or 50 mg capsule, orally, once daily for 12 weeks to maintain blind (Part A only); Oral capsules BID at a total daily dose from 800 to 1400 mg based on participant weight
Intervention MeSH terms: Ribavirin; Grazoprevir
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 573.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This is a study of the safety and efficacy of grazoprevir (MK-5172) in combination with
      elbasvir (MK-8742) ± ribavirin (RBV). The primary efficacy endpoint will be Sustained
      Virologic Response 12 weeks after the end of all study therapy (SVR12) in each of the
      treatment arms.
    

Eligibility criteria:

        Inclusion criteria:

        All participants

          -  CHC genotype 1 (GT1) virus infection (Parts A, B, and C) or GT3 virus infection (Part
             D)

          -  Female participants of childbearing potential or male participant with female partners
             of childbearing potential, must use two acceptable methods of birth control from ≥2
             weeks prior to Day 1 until ≥6 months after last dose of study drug, or longer if
             dictated by local regulations

        Part A - Absence (no medical history or physical findings) of ascites, bleeding esophageal
        varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease, or
        cirrhosis - No evidence of advanced fibrosis, cirrhosis and/or hepatocellular carcinoma by
        biopsy or noninvasive testing (FibroScan and/or FibroTest)

        Parts B, C, and D

          -  Treatment naïve with or without cirrhosis, or

          -  Prior treatment failure to Peg-IFN/Ribavirin with or without cirrhosis, or

          -  Co-infected with human immunodeficiency virus (HIV) without cirrhosis

          -  Absence (no medical history or physical findings) of ascites, bleeding esophageal
             varices, hepatic encephalopathy, or other signs or symptoms of advanced liver disease

          -  Liver disease staging assessment by liver biopsy or noninvasive testing (FibroScan
             and/or FibroTest)

        Exclusion criteria:

        All participants

          -  Non-GT1 HCV infection (Part A, Part B, and Part C) or a non-GT3 HCV infection (Part D)
             including a mixed GT infection (with a non-GT1 [Part A, Part B, and Part C] or non-GT3
             [Part D]) or a non-typeable genotype

          -  Evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC

          -  Currently participating or participated in a study with an investigational compound
             within 30 days of signing informed consent and is not willing to refrain from
             participating in another study

          -  Diabetic and/or hypertensive with clinically significant ocular examination findings

          -  History of depression associated with hospitalization for depression,
             electroconvulsive therapy, or resulting in prolonged absence from work and/or
             significant disruption of daily functions

          -  Suicidal or homicidal ideations and/or attempt, or history of severe psychiatric
             disorders

          -  Clinical diagnosis of substance abuse

          -  Current history of seizure disorder, stroke, or transient ischemic attack

          -  Immunologically mediated disease

          -  Chronic pulmonary disease

          -  Clinically significant cardiac abnormalities/dysfunction

          -  Active clinical gout within the last year

          -  Hemoglobinopathy or myelodysplastic syndromes

          -  History of organ transplants including hematopoietic stem cell transplants

          -  Poor venous access

          -  Indwelling venous catheter

          -  History of gastric surgery or malabsorption disorders

          -  Severe concurrent disease

          -  Evidence of active or suspected malignancy, or a history of malignancy, ≤5 years
             before

          -  Pregnant, lactating, expecting to conceive or donate eggs

          -  Male participant with pregnant female partner

          -  Member/family member of the investigational study or sponsor staff directly involved
             with this study

          -  Evidence or history of chronic hepatitis not caused by HCV

        Part A

          -  Not treatment-naïve

          -  Documented to be HIV positive

          -  Taking or planning to take significant inducers or inhibitors of CYP3A4 substrates or
             herbal supplements 2 weeks prior to start of study medications

        Parts B, C, and D

          -  Previously received any HCV direct-acting antivirals

          -  Requiring, or likely to require, chronic systemic administration of corticosteroids
             during the course of the trial

          -  For participants diagnosed with diabetes mellitus, documented HbA1c >8.5%