A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035)
A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035)
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.
Part A is being done in treatment-naïve (TN), genotype 1 (GT1), interferon eligible,
 non-cirrhotic (N-C) participants with chronic hepatitis C (CHC). Participants will be
 assigned randomly to 1 of 2 treatment arms in which they will receive grazoprevir 100 mg once
 daily (QD) + elbasvir 20 mg or 50 mg QD and twice daily (BID) RBV, or to a treatment arm in
 which they will receive grazoprevir 100 mg QD + elbasvir 50 mg QD without RBV. Treatment will
 last 12 weeks.

 In Part B, participants with hepatitis C virus (HCV) GT1 and HCV ribonucleic acid (RNA)
 levels of ≥10,000 IU/mL will be randomly assigned to a study arm, based on absence or
 presence of cirrhosis (C), whether they are TN or had poor response to previous antiviral
 therapy (null responders [NR]), or whether co-infected with human immunodeficiency virus
 (HIV); these participants will receive open-label grazoprevir (100 mg) in combination with
 elbasvir (50 mg) ± RBV. Treatment will last 8 to 18 weeks dependent on arm assignment.

 In Part C, TN, N-C participants with HCV GT1b and HCV RNA levels of ≥10,000 IU/mL will be
 randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50
 mg) ± RBV. Treatment will last 8 weeks.

 In Part D, TN N-C participants with HCV GT3 and HCV RNA levels of ≥10,000 IU/mL will be
 randomly assigned to receive open-label grazoprevir (100 mg) in combination with elbasvir (50
 mg) + RBV for 12 or 18 weeks.
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%