This is a randomized, multicenter, 2-part, open-label trial of the combination regimen of grazoprevir (GZR \[MK-5172\]; 100mg), uprifosbuvir (UPR \[MK-3682\]; 450 mg) and ruzasvir (RZR \[MK-8408\]; 60 mg) with and without Ribavirin (RBV) in cirrhotic (C) or non-cirrhotic (NC) participants infected with hepatitis C virus (HCV) previously failing a direct-acting antiviral regimen (DAA). The combination regimen, referred to as MK-3682B, will be administered as two fixed-dose combination (FDC) tablets, given once-daily. The study will evaluate the efficacy of MK-3682B with or without RBV as assessed by the proportion of participants achieving Sustained Virologic Response 12 weeks (SVR12) after the end of all study therapy.
This trial was divided into Part A and Part B. In Part A, comprised of 4 treatment arms, C or NC participants with HCV genotype (GT) 1 infection previously failing a DAA regimen of either sofosbuvir (SOF)/ledipasvir (LDV) \[Arms 1 and 2\] or elbasvir (EBR)/GZR \[Arms 3 and 4\] were randomized to receive either one of the following: 1) MK-3682B + RBV for 16 weeks \[Arms 1 and 3\]; or 2) MK-3682B for 24 weeks \[Arms 2 and 4\]. Study Part A was completed as planned per study protocol. In Part B, C or NC participants with GT1 through GT6 infection previously failing any all-oral DAA regimen (GT1-6) or SOF/pegylated interferon and ribavirin (PR) regimen (GT 3 only) were to receive MK-3682B for 16 weeks. However, the trial was terminated prior to participant enrollment for study Part B. Participants in MK-5172-017 (NCT01667081) were eligible for enrollment in the study.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
94
Two MK- 3682B 1,136 mg FDC tablets each containing 50 mg MK-5172 (GZR), 225 mg MK-3682 (UPR, formerly IDX21437), and 30 mg MK-8408 (RZR) taken once daily by mouth.
Ribavirin 200 mg capsules, taken twice daily by mouth as part of a weight-based dosing regimen. Depending on participant body weight, total daily dose of Ribavirin may be 800, 1000, 1200 or 1400 mg per day.
Percentage of Participants Achieving Sustained Virologic Response 12 Weeks After The End of Study Therapy (SVR12)
The percentage of participants achieving SVR12 was determined, defined as having a plasma HCV ribonucleic acid (RNA) level below the lower limit of quantification (LLOQ) 12 weeks after the end of study therapy. Plasma HCV RNA level was measured using the Roche COBAS™ AmpliPrep/COBAS™ Taqman™ HCV Test, v2.0 ® assay with a LLOQ of 15 IU/mL.
Time frame: 12 weeks following final dose of study treatment ([MK-3682B + RBV Groups]: Study Week 28; [MK-3682B Groups]: Study Week 36)
Number of Participants Who Experienced an Adverse Event
The number of participants experiencing an adverse event (AE) was assessed. An AE is any unfavorable and unintended medical occurrence, symptom, or disease witnessed in a participant, regardless of whether or not a causal relationship with the study treatment can be demonstrated. Further, any worsening of a preexisting condition that is temporally associated with the use of the study treatment is also considered an AE.
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Discontinued Study Drug Due to an Adverse Event
The number of participants discontinuing study drug due to an AE was assessed.
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced a Serious Adverse Event
The number of participants experiencing a serious adverse event (SAE) was assessed. An SAE is an adverse event that: results in death; is life threatening; results in persistent or significant disability or incapacity; results in or prolongs a hospitalization; is a congenital anomaly or birth defect; is a cancer; or may jeopardize the participant, potentially require medical or surgical intervention.
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced a Drug-Related Adverse Event
The number of participants experiencing a drug-related AE was assessed. A drug-related AE was an AE thought to be possibly, probably, or definitely related to the study drug as determined by the investigator.
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced a Serious and Drug-Related Adverse Event
The number of participants experiencing a serious and drug-related AE was assessed.
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced an Accidental or Intentional Overdose Without Adverse Effect
The number of participants experiencing an accidental or intentional overdose without adverse effect was determined. Per study protocol, any occurrence of a participant receiving either MK-3682B or RBV at any dose higher than prescribed was considered an overdose. If this definition of overdose was met without any associated clinical symptoms or abnormal laboratory results, this occurrence of overdose was reported as an accidental or intentional overdose without adverse effect.
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced a Non-Overdose Event of Clinical Interest
The number of participants experiencing a non-overdose event of clinical interest (ECI) was determined. Non-overdose ECIs, assessed from initiation of study therapy through 14 days following study treatment cessation, included the following: 1) aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>500 IU/L; or 2) AST or ALT \>3x nadir value and \>3X upper limit normal (ULN).
Time frame: Up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
Number of Participants Who Experienced AST/ALT >5x Upper Limit Normal (ULN)
The number of participants experiencing AST / ALT \>5 times ULN from study week 4 until 2 weeks following completion of study therapy was determined.
Time frame: From Study Week 4 up to 2 weeks following cessation of study treatment ([MK-3682B + RBV Groups]: Up to Week 18; [MK-3682B Groups]: Up to Week 26)
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