TY - JOUR
T1 - Efficacy and safety of a two-drug direct-acting antiviral agent regimen ruzasvir 180 mg and uprifosbuvir 450 mg for 12 weeks in adults with chronic hepatitis C virus genotype 1, 2, 3, 4, 5 or 6
AU - the C-BREEZE-2 Study Investigators
AU - Lawitz, Eric
AU - Gane, Edward
AU - Feld, Jordan J.
AU - Buti, Maria
AU - Foster, Graham R.
AU - Rabinovitz, Mordechai
AU - Burnevich, Eduard
AU - Katchman, Helena
AU - Tomasiewicz, Krzysztof
AU - Lahser, Fred
AU - Jackson, Beth
AU - Shaughnessy, Melissa
AU - Klopfer, Stephanie
AU - Yeh, Wendy W.
AU - Robertson, Michael N.
AU - Hanna, George J.
AU - Barr, Eliav
AU - Platt, Heather L.
AU - Gordon, Stuart C.
AU - Ruane, Peter Jerome
AU - Sahota, Amandeep
AU - Terrault, Norah A.
AU - Tsai, Naoky
AU - Kalathil, Sumodh C.
AU - Reddy, Gautham
AU - Ghesquiere, Wayne
AU - Borgia, Sergio
AU - Conway, Brian
AU - Tsoi, Keith
AU - Cooper, Curtis L.
AU - Ghali, Peter Maged
AU - Thompson, Alexander James Venn
AU - Panero, Jose Luis Calleja
AU - Ferret, Sabela Lens Maria Buti
AU - Franinan, Luis Margusino
AU - de los Angeles Castro Iglesias, Maria
AU - Brown, Ashley
AU - Agarwal, Kaushik
AU - Cramp, Matthew
AU - Zuckerman, Eli
AU - Veitsman, Ella
AU - Cohen, Michal
AU - Lurie, Yoav
AU - Ari, Ziv Ben
AU - Janczewska, Ewa
AU - Szymczak, Aleksandra
AU - Halota, Waldemar
AU - Flisiak, Robert
AU - Mahomed, Adam
AU - Sonderup, Mark Wayne
N1 - Funding Information:
We extend our gratitude to the participants, their families, investigators and site personnel who participated in these studies. The C‐ BREEZE‐2 Study Investigators were as follows: Stuart C. Gordon, Eric J. Lawitz, Mordechai Rabinovitz, Peter Jerome Ruane, Amandeep Sahota, Norah A. Terrault, Naoky Tsai, Sumodh C. Kalathil, Gautham Reddy, Wayne Ghesquiere, Sergio Borgia, Brian Conway, Jordan Feld, Keith Tsoi, Curtis L. Cooper, Peter Maged Ghali, Alexander James Venn Thompson, Edward Gane, Jose Luis Calleja Panero, Sabela Lens Maria Buti Ferret, Luis Margusino Franinan, Maria de los Angeles Castro Iglesias, Ashley Brown, Kaushik Agarwal, Graham Foster, Matthew Cramp, Eli Zuckerman, Ella Veitsman, Helena Katchman, Michal Cohen, Yoav Lurie, Ziv Ben Ari, Ewa Janczewska, Aleksandra Szymczak, Krzysztof Tomasiewicz, Waldemar Halota, Robert Flisiak, Adam Mahomed, Mark Wayne Sonderup, Zelda Erika Punt, Mpho Klaas Kgomo, David C Bernhardi, Eduard Z. Burnevich and Svetlana Kizhlo. Medical writing assistance was provided by Jennifer M. Kulak, PhD, and Tim Ibbotson, PhD, of ApotheCom (Yardley, PA, USA) and funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA.
Funding Information:
This study was funded by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Eric Lawitz reports grants from Merck, AbbVie and Gilead and personal fees from AbbVie and Gilead. Edward J. Gane has received personal fees as a member of the clinical advisory board for Merck, Gilead Sciences and AbbVie and has received personal fees as a member of the speakers bureau for Gilead Sciences and AbbVie. Jordan J. Feld has received grant and personal fees for consultant and advisory board work for AbbVie, Janssen, Gilead and Merck; consultant personal fees from Contravir and Enanta; and grant fees from Wako. Maria Buti has received personal fees from MSD, Gilead and AbbVie. Graham R. Foster has received grant and personal fees from MSD, Gilead and AbbVie. Krzysztof Tomasiewicz has received grants, personal fees and nonfinancial support from Gilead, AbbVie and BMS and personal fees and nonfinancial support from Merck. Frederick Lahser, Beth Jackson, Stephanie Klopfer, Melissa Shaughnessy, Wendy W. Yeh, Michael N. Robertson, George J. Hanna, Eliav Barr and Heather Platt are employees of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Stephanie Klopfer, Melissa Shaughnessy, Wendy W. Yeh, Michael N. Robertson, George J. Hanna, Eliav Barr and Heather Platt may own stock in Merck & Co., Inc., Kenilworth, NJ, USA. The following authors have nothing to disclose: Mordechai Rabinovitz, Eduard Z. Burnevich and Helena Katchman.
PY - 2019
Y1 - 2019
N2 - Ruzasvir (MK-8408, an NS5A inhibitor) and uprifosbuvir (MK-3682, a nonstructural protein 5B nucleotide inhibitor) are highly potent direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection. A phase III clinical trial evaluating the two-drug combination of ruzasvir 60 mg plus uprifosbuvir 450 mg suggested suboptimal efficacy in certain HCV genotypes (C-BREEZE 1; NCT02759315). The aim of the present study was to evaluate the efficacy and safety of ruzasvir in combination with uprifosbuvir administered at a higher dose than that assessed in the earlier study (C-BREEZE 2: NCT02956629/Merck protocol PN041). Treatment-naïve or interferon (with or without ribavirin)-experienced participants with or without compensated cirrhosis were enrolled. All participants received ruzasvir 180 mg plus uprifosbuvir 450 mg once daily for 12 weeks. The primary objectives were the proportion of participants with HCV RNA <15 lU/mL at 12 weeks after the end of study therapy (SVR12), and safety and tolerability of the study drug. Overall, 282 participants were enrolled. SVR12 (n/N) was 91.3% (42/46) in participants infected with HCV genotype (GT) 1a; GT1b, 96.7% (29/30); GT2, 91.5% (43/47); GT3, 73.8% (45/61); GT4, 98.2% (55/56); GT5, 100.0% (18/18); and GT6, 90.9% (20/22). Adverse events (AEs) were reported by 61.3% of participants; drug-related AEs were reported by 33.3%. The most frequent (≥5% of participants) drug-related AEs in all participants were fatigue (7.8%) and headache (7.4%). In conclusion, the two-drug combination of ruzasvir 180 mg plus uprifosbuvir 450 mg for 12 weeks was highly effective and well tolerated in participants infected with HCV GT1, GT2, GT4, GT5 and GT6, with a lower efficacy in GT3-infected persons.
AB - Ruzasvir (MK-8408, an NS5A inhibitor) and uprifosbuvir (MK-3682, a nonstructural protein 5B nucleotide inhibitor) are highly potent direct-acting antiviral agents for the treatment of hepatitis C virus (HCV) infection. A phase III clinical trial evaluating the two-drug combination of ruzasvir 60 mg plus uprifosbuvir 450 mg suggested suboptimal efficacy in certain HCV genotypes (C-BREEZE 1; NCT02759315). The aim of the present study was to evaluate the efficacy and safety of ruzasvir in combination with uprifosbuvir administered at a higher dose than that assessed in the earlier study (C-BREEZE 2: NCT02956629/Merck protocol PN041). Treatment-naïve or interferon (with or without ribavirin)-experienced participants with or without compensated cirrhosis were enrolled. All participants received ruzasvir 180 mg plus uprifosbuvir 450 mg once daily for 12 weeks. The primary objectives were the proportion of participants with HCV RNA <15 lU/mL at 12 weeks after the end of study therapy (SVR12), and safety and tolerability of the study drug. Overall, 282 participants were enrolled. SVR12 (n/N) was 91.3% (42/46) in participants infected with HCV genotype (GT) 1a; GT1b, 96.7% (29/30); GT2, 91.5% (43/47); GT3, 73.8% (45/61); GT4, 98.2% (55/56); GT5, 100.0% (18/18); and GT6, 90.9% (20/22). Adverse events (AEs) were reported by 61.3% of participants; drug-related AEs were reported by 33.3%. The most frequent (≥5% of participants) drug-related AEs in all participants were fatigue (7.8%) and headache (7.4%). In conclusion, the two-drug combination of ruzasvir 180 mg plus uprifosbuvir 450 mg for 12 weeks was highly effective and well tolerated in participants infected with HCV GT1, GT2, GT4, GT5 and GT6, with a lower efficacy in GT3-infected persons.
KW - clinical trial
KW - efficacy
KW - genotype
KW - hepatitis C virus
KW - safety
UR - http://www.scopus.com/inward/record.url?scp=85068780193&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068780193&partnerID=8YFLogxK
U2 - 10.1111/jvh.13132
DO - 10.1111/jvh.13132
M3 - Article
C2 - 31108015
AN - SCOPUS:85068780193
VL - 26
SP - 1127
EP - 1138
JO - Journal of Viral Hepatitis
JF - Journal of Viral Hepatitis
SN - 1352-0504
IS - 9
ER -