Clinical trial NCT02332707
Conditions: Hepatitis C
Sponsor: Merck Sharp & Dohme LLC
Start date: 2015-01-22; Completion date: 2016-12-06
Enrollment: 443 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
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).

Detailed description:
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.

Arms: arm 1: In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. arm 2: In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. arm 3: In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 300 mg + EBR 50 mg q.d. by mouth for 8 weeks. arm 4: In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 300 mg + RZR 60 mg q.d. by mouth for 8 weeks. arm 5: In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. arm 6: In Part A, HCV GT1-infected NC participants will take GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. arm 7: In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 450 mg + EBR 50 mg q.d. by mouth for 8 weeks. arm 8: In Part A, HCV GT2-infected NC participants will take GZR 100 mg + UPR 450 mg + RZR 60 mg q.d. by mouth for 8 weeks. In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. arm 9: In Part B, HCV GT1-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. arm 10: In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight. arm 11: In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. arm 12: In Part B, HCV GT1-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. arm 13: In Part B, HCV GT1-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. arm 14: In Part B, HCV GT2-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. arm 15: In Part B, HCV GT2-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 12 weeks. Participants will also take RBV b.i.d. at a total daily dose of 800-1600 mg based on body weight. arm 16: In Part B, HCV GT2-infected C participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 16 weeks. arm 17: In Part B, HCV GT1-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks. arm 18: In Part B, HCV GT2-infected NC participants will take 2 FDC tablets containing UPR 225 mg + GZR 50 mg + RZR 30 mg per tablet q.d. by mouth for 8 weeks.
Interventions: intervention 1: Grazoprevir intervention 2: Uprifosbuvir intervention 3: Elbasvir intervention 4: Ruzasvir intervention 5: Uprifosbuvir (+) Grazoprevir (+) Ruzasvir intervention 6: Ribavirin
Intervention descriptions: intervention 1: One GZR 100 mg tablet (Part A), or 2 FDC tablets containing GZR 50 mg per tablet (Part B), taken q.d.by mouth. intervention 2: 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. intervention 3: One EBR 50 mg tablet (Part A), taken q.d. by mouth. intervention 4: 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. intervention 5: Two FDC tablets, each containing GZR 50 mg + UPR 225 mg + RZR 30 mg (Part B), taken q.d. by mouth. intervention 6: RBV 200 mg capsules taken b.i.d. at a total daily dose of 800-1400 mg based on participant body weight.

Protocol documents: