Efficacy and Safety of Grazoprevir (MK-5172) and Uprifosbuvir (MK-3682) With Elbasvir (MK-8742) or Ruzasvir (MK-8408) for Chronic Hepatitis C Virus (HCV) Genotype (GT) 3, GT4, GT5, and GT6 Infection (MK-3682-012)

This is a randomized, three-part, parallel-group, open-label trial of grazoprevir (MK-5172) (100 mg) and uprifosbuvir (MK-3682) (300 mg or 450 mg) with either elbasvir (MK-8742) (50 mg) or ruzasvir (MK-8408) (60 mg), and with or without ribavirin (RBV), in treatment-naive (TN) or treatment-experienced (TE) cirrhotic (C) or non-cirrhotic (NC) participants infected with hepatitis C virus (HCV) genotype (GT) 3, GT4, GT5, or GT6. Part A will consist of 4 arms to evaluate the safety of dose combinations. In Part B, participants will take 2 uprifosbuvir (+) grazoprevir (+) ruzasvir (MK-3682B) fixed dose combination (FDC) tablets once daily (q.d.) by mouth, with or without twice-daily (b.i.d.) RBV (200 mg capsules; weight-based dosing). Participants who relapse following completion of therapy in Part A will be offered the option of retreatment with 16 weeks of uprifosbuvir (+) grazoprevir (+) ruzasvir with RBV in Part C (data obtained from Part C will not be used in the analysis of outcome measures).

In Part A, study therapy will be administered as separate products, each taken q.d. by mouth. In Part B and Part C, participants will take 2 uprifosbuvir (+) grazoprevir (+) ruzasvir FDC tablets q.d. by mouth; each uprifosbuvir (+) grazoprevir (+) ruzasvir FDC tablet contains grazoprevir 50 mg + uprifosbuvir 225 mg + ruzasvir 30 mg.

Eligibility Criteria:
Inclusion Criteria:

* Has documented chronic HCV GT3, GT4, GT5, or GT6 with no evidence of non-typeable or mixed GT infection
* Is otherwise healthy as determined by the medical history, physical examination, electrocardiogram (ECG), and clinical laboratory measurements performed at the time of screening
* Has cirrhosis of the liver (Part B only) or is non-cirrhotic (Part A and B)
* Is HCV treatment-naïve or has experienced virologic failure after completing a prior Pegylated Interferon/Ribavirin (Peg-IFN/RBV) regimen
* Is of non childbearing potential or agrees to avoid becoming pregnant or impregnating a partner beginning at least 2 weeks prior to administration of the initial dose of study drug and for 14 days after the last dose of study drug if not taking RBV, or for 6 months after the last dose of study drug if taking RBV (or longer if dictated by local regulations). If not abstinent from heterosexual activity, participants in Part A must use 2 acceptable forms of barrier contraception whereas participants in Parts B and C must use 2 acceptable forms of contraception which may include oral contraceptives

Part B only:

* If coinfected with human immunodeficiency virus (HIV) is not currently on antiretroviral therapy (ART) and has no plans to initiate ART treatment while participating in this study OR has well-controlled HIV on ART.
* Has at least 1 viable antiretroviral regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of anti-retroviral drug resistance.

Exclusion Criteria:

Parts A, B, and C (unless otherwise specified):

* Has evidence of decompensated liver disease manifested by the presence of or history of ascites, esophageal or gastric variceal bleeding, hepatic encephalopathy or other signs or symptoms of advanced liver disease.
* If cirrhotic (Part B only), is Child-Pugh Class B or C or has a Pugh-Turcotte (CPT) score \>5.
* Is coinfected with hepatitis B virus (Parts A, B, and C) or is coinfected with HIV (Part A only; HIV coinfected participants are eligible for Parts B and C).
* If coinfected with HIV, has a history of opportunistic infection in the preceding 6 months prior to screening.
* Has a history of malignancy ≤5 years prior to signing informed consent except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer or carcinoma in situ; or is under evaluation for other active or suspected malignancy.
* Has cirrhosis and liver imaging within 6 months of Day 1 showing evidence of hepatocellular carcinoma (HCC) or is under evaluation for HCC.
* Has clinically-relevant drug or alcohol abuse within 12 months of screening.
* Is female and is pregnant or breastfeeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 and 6 months after the last dose of study medication, or longer if dictated by local regulations OR a male participant who is expecting to donate sperm from at least 2 weeks prior to day 1 until 6 months after the last dose of study medication.
* Has any of the following conditions:
* Organ transplants (including hematopoietic stem cell transplants) other than cornea and hair.
* Poor venous access that precludes routine peripheral blood sampling required for this trial.
* History of gastric surgery (e.g., stapling, bypass) or a history of malabsorption disorders (e.g., celiac sprue disease).
* Current or history of any clinically significant cardiac abnormalities/dysfunction, including but not limited to: angina, congestive heart failure, myocardial infarction, pulmonary hypertension, complex congenital heart disease, cardiomyopathy, significant arrhythmia, uncontrolled hypertension, a history of use of antianginal or anti-arrythmic agents for cardiac conditions, prolonged ECG QTc interval (\>470 ms for males or \>480 ms for females by either the Fridericia formula) at the screening visit, personal or family history of Torsade de pointes.
* Chronic pulmonary disease, including but not limited to: clinically significant chronic obstructive pulmonary disease, interstitial lung disease, pulmonary fibrosis, sarcoidosis.
* Central nervous system (CNS) trauma requiring intubation, intracranial pressure monitoring, brain meningeal or skull surgery, or resulting in seizure, coma, permanent neurologic deficits, abnormal brain imaging, or cerebral spinal fluid (CSF) leak. Prior brain hemorrhage and/or intracranial aneurysms (whether adequately repaired or not).
* Current or history of seizure disorder unless seizure was \>10 years ago, a single isolated event, no history of or current use of anti-seizure medications prescribed, and a normal neurological examination is documented in trial files within 6 months of Day 1.
* Has a history of stroke or transient ischemic attack.
* Has a history of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures.
* Has medical/surgical conditions that may result in a need for hospitalization during the period of the study.
* Has any medical condition requiring, or likely to require, chronic systemic administration of corticosteroids, tumor necrosis factor (TNF) antagonists, or other immunosuppressant drugs during the course of the trial.
* Has any condition, prestudy laboratory or ECG abnormality or history of any illness, which, in the opinion of the investigator, might confound the results of the study or pose additional risk in administering the study drugs to the participant.
* Has had a life-threatening serious adverse event (SAE) during the screening period.
* Has evidence of history of chronic hepatitis not caused by HCV, including but not limited to nonalcoholic steatohepatitis (NASH), drug-induced hepatitis, hemochromatosis, Wilson's disease, α1-antitrypsin deficiency, alcoholic liver disease and autoimmune hepatitis Parts B and C only: is a male whose female partner(s) is/are pregnant