A Study of the Combination Regimen Grazoprevir (MK-5172) and Elbasvir (MK-8742) ± Ribavirin in Participants With Chronic Hepatitis C (MK-5172-035)

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%