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.

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%