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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
443
One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth.
Two or 3 UPR 150 mg (300 mg and 450 mg total daily dose) tablets (Part A), or 2 FDC tablets containing UPR 225 mg (Part B), taken q.d. by mouth.
One EBR 50 mg tablet (Part A), taken q.d. by mouth.
Six RZR 10 mg (60 mg total daily dose) capsules (Part A), or 2 FDC tablets containing RZR 30 mg per tablet (Part B), taken q.d. by mouth.
Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth.
RBV 200 mg capsules taken b.i.d. at a total daily dose of 800-1400 mg based on participant body weight.
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After Completing Treatment (SVR12)
The percentage of participants with Hepatitis C virus (HCV) ribonucleic acid (RNA) \< Lower Limit of Quantification (LLoQ) 12 weeks after completing treatment (i.e., SVR12) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL.
Time frame: Up to 28 weeks
Percentage of Participants Experiencing an Adverse Event (AE)
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 18 weeks
Percentage of Participants Discontinuing From Study Treatment Due to an AE
An AE is defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment.
Time frame: Up to 16 weeks
Percentage of Participants Achieving Sustained Virologic Response 24 Weeks After Ending Study Treatment (SVR24)
The percentage of participants with HCV RNA \< LLoQ 24 weeks after completing treatment (i.e., SVR24) in each arm was determined. Plasma levels of HCV RNA levels were measured using the Roche COBAS® AmpliPrep/COBAS® TaqMan® HCV Test, v2.0 assay, which has a LLoQ of 15 IU/mL.
Time frame: Up to 40 weeks
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