Clinical trial NCT02613403
Conditions: Hepatitis Hepatitis C Digestive System Diseases Flaviviridae Infections Hepatitis, Viral, Human Liver Diseases RNA Virus Infections Virus Diseases
Sponsor: Merck Sharp & Dohme LLC
Start date: 2015-12-10; Completion date: 2017-03-27
Enrollment: 94 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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.

Detailed description:
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.

Arms: arm 1: C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 \[50 mg\]) + UPR (MK-3682 \[225 mg\]) + RZR (MK-8408 \[30 mg\]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. arm 2: C or NC HCV GT1 participants previously failing a DAA regimen of SOF/LDV receive MK-3682B, an FDC of GZR (MK-5172 \[50 mg\]) + UPR (MK-3682 \[225 mg\]) + RZR (MK-8408 \[30 mg\]), administered as 2 tablets once daily for 24 weeks. arm 3: C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 \[50 mg\]) + UPR (MK-3682 \[225 mg\]) + RZR (MK-8408 \[30 mg\]), administered as 2 tablets once daily in combination with RBV twice daily for 16 weeks. arm 4: C or NC HCV GT1 participants previously failing a DAA regimen of GZR/EBR (MK-5172/MK-8742) receive MK-3682B, an FDC of GZR (MK-5172 \[50 mg\]) + UPR (MK-3682 \[225 mg\]) + RZR (MK-8408 \[30 mg\]), administered as 2 tablets once daily for 24 weeks. arm 5: C or NC HCV participants previously failing any all-oral DAA regimen (GT1-6) or SOF/PR regimen (GT 3 only) receive MK-3682B, an FDC of GZR (MK-5172 \[50 mg\]) + UPR (MK-3682 \[225 mg\]) + RZR (MK-8408 \[30 mg\]), administered as 2 tablets once daily for 16 weeks.
Interventions: intervention 1: MK-3682B intervention 2: Ribavirin
Intervention descriptions: intervention 1: 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. intervention 2: 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.

Protocol documents: