Efficacy and Safety of Grazoprevir (MK-5172) and Uprifosbuvir (MK-3682) With Elbasvir (MK-8742) or Ruzasvir (MK-8408) for Chronic Hepatitis C Genotype (GT)1 and GT2 Infection (MK-3682-011)

This is a randomized, three-part, open-label trial of grazoprevir (GZR; MK-5172) (100 mg) and uprifosbuvir (UPR; MK-3682) (300 mg or 450 mg), with either elbasvir (EBR; MK-8742) (50 mg) or ruzasvir (RZR; MK-8408) (60 mg), and with or without ribavirin (RBV), in treatment-naïve (TN) cirrhotic (C) or non-cirrhotic (NC) hepatitis C virus (HCV) participants with chronic HCV genotype (GT) 1 or GT2 infection. Part A will consist of 8 arms to evaluate the safety of dose combinations. In Part B, participants will take 2 UPR+GZR+RZR 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 UPR+GZR+RZR 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 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg q.d. by mouth.

Eligibility Criteria:
Inclusion Criteria:

Parts A and B:

* Previously untreated chronic HCV GT1 or GT2 with no evidence of non-typeable or mixed genotype infection
* Has HCV ribonucleic acid (RNA) \>= 10,000 IU/mL in peripheral blood at the time of screening
* Is NC (Part A and B)
* Is HCV treatment naïve (defined as no prior exposure to any interferon, ribavirin, or other approved or experimental HCV-specific direct-acting antiviral agent
* 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 either 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 Part B must use 2 acceptable forms of contraception which may include oral contraceptives

Part B only:

* Has cirrhosis of the liver
* 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 (the ART regimen must contain only the following antiretroviral medications: tenofovir, abacavir, lamivudine, emtricitabine, raltegravir, dolutegravir, and rilpivirine with no dose modifications or changes in drugs in the 4 weeks prior to study entry \[Day 1\])
* Has at least one viable ART regimen alternative beyond their current regimen in the event of HIV virologic failure and the development of antiretroviral drug resistance

Exclusion Criteria:

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

* 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
* For cirrhotics (Part B only), participants who are Child-Pugh Class B or C or who have a Pugh-Turcotte (CPT) score \>5
* Is coinfected with hepatitis B virus
* Is coinfected with HIV (Part A only)
* If coinfected with HIV (Part B only), 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 has had 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
* Pregnant or breast-feeding, or expecting to conceive or donate eggs from at least 2 weeks prior to Day 1 and 90 days after the last dose of study medication, or longer if dictated by local regulations
* 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
* has a history of gastric surgery (e.g., stapling, bypass) or 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-arrhythmic agents for cardiac conditions, prolonged electrocardiogram (ECG) QTc interval (\>470 ms for males or \>480 ms for females by 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)
* a 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
* a history of stroke or transient ischemic attack
* a history of a medical/surgical condition that resulted in hospitalization within the 3 months prior to enrollment, other than for minor elective procedures
* a medical/surgical conditions that may result in a need for hospitalization during the period of the study
* 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 subject
* experiences a life-threatening serious adverse event (SAE) during the screening period
* 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
* hemoglobinopathy, including, but not limited to, thalassemia major (Parts B and C only) Parts B and C only: is a male whose female partner(s) is/are pregnant