PMID- 30693573 OWN - NLM STAT- MEDLINE DCOM- 20200615 LR - 20201210 IS - 1527-3350 (Electronic) IS - 0270-9139 (Linking) VI - 69 IP - 6 DP - 2019 Jun TI - JNJ-4178 (AL-335, Odalasvir, and Simeprevir) for 6 or 8 Weeks in Hepatitis C Virus-Infected Patients Without Cirrhosis: OMEGA-1. PG - 2349-2363 LID - 10.1002/hep.30527 [doi] AB - The combination of three direct-acting antiviral agents (AL-335, odalasvir, and simeprevir: JNJ-4178 regimen) for 6 or 8 weeks demonstrated good efficacy and safety in a phase IIa study in chronic hepatitis C virus (HCV) genotype (GT)-1-infected patients without cirrhosis and has now been evaluated in a larger phase IIb study, OMEGA-1. This multicenter, randomized, open-label study (NCT02765490) enrolled treatment-naive and interferon (+/-ribavirin) treatment-experienced patients with HCV GT1, 2, 4, 5, or 6 infection. Patients with HCV GT3 infection and/or liver cirrhosis were excluded. Patients received AL-335 800 mg, odalasvir 25 mg, and simeprevir 75 mg once daily for 6 or 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). In total, 365 patients (GT1a, 29.3%; GT1b, 42.5%; GT2, 12.3%; GT4, 14.2%; GT5, 1.4%; GT6, 0%) were randomized to receive 6 weeks (n = 183) or 8 weeks (n = 182) of treatment. SVR12 rates after 6 weeks (98.9%) or 8 weeks (97.8%) of treatment were noninferior to a historical control (98%). Viral relapse occurred in 5 patients (1.4%; 4 with HCV GT2c; 1 with GT1a). With the exception of 4 patients in the 8-week group, including 3 patients with missing data at the SVR24 timepoint, all patients who achieved SVR12 also achieved SVR24. One GT1a-infected patient experienced late viral relapse after achieving SVR18. Most adverse events (AEs) were mild with no treatment-related serious AEs. All randomized patients completed treatment. Conclusion: In HCV-infected patients, 6 and 8 weeks of treatment with JNJ-4178 resulted in SVR12 rates of 98.9% and 97.8%, respectively, and was well tolerated. CI - (c) 2019 by the American Association for the Study of Liver Diseases. FAU - Zeuzem, Stefan AU - Zeuzem S AD - Department of Medicine, J.W. Goethe University Hospital, Frankfurt am Main, Germany. FAU - Bourgeois, Stefan AU - Bourgeois S AD - Department of Gastroenterology and Hepatology, ZNA Antwerp, Antwerp, Belgium. FAU - Greenbloom, Susan AU - Greenbloom S AD - Toronto Digestive Disease Associates, Inc., Vaughan, ON, Canada. FAU - Buti, Maria AU - Buti M AD - Hospital Vall d'Hebron and Centro de Investigacion Biomedica en Red en Enfermedades Hepaticas y Digestivas (CIBERehd), Barcelona, Spain. FAU - Aghemo, Alessio AU - Aghemo A AD - Humanitas University and Research Hospital, Rozzano, Italy. FAU - Lampertico, Pietro AU - Lampertico P AUID- ORCID: 0000-0002-1026-7476 AD - CRC "AM e A Migliavacca," Division of Gastroenterology and Hepatology, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Universita di Milano, Milan, Italy. FAU - Janczewska, Ewa AU - Janczewska E AD - Outpatients Clinic for Hepatology, ID Clinic, Myslowice, Poland. AD - Medical University of Silesia, School of Public Health in Bytom, Department of Basic Medical Sciences, Bytom, Poland. FAU - Lim, Seng Gee AU - Lim SG AD - Division of Gastroenterology and Hepatology, Department of Medicine, Yong Loo Lin School of Medicine, National University Health System, Singapore. FAU - Moreno, Christophe AU - Moreno C AD - CUB Hopital Erasme, Universite Libre de Bruxelles, Brussels, Belgium. FAU - Buggisch, Peter AU - Buggisch P AD - Institute for Interdisciplinary Medicine, Hamburg, Germany. FAU - Tam, Edward AU - Tam E AD - LAIR Centre, Vancouver, BC, Canada. FAU - Corbett, Chris AU - Corbett C AD - Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Willems, Wouter AU - Willems W AD - Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Vijgen, Leen AU - Vijgen L AD - Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Fevery, Bart AU - Fevery B AD - Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Ouwerkerk-Mahadevan, Sivi AU - Ouwerkerk-Mahadevan S AD - Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Ackaert, Oliver AU - Ackaert O AD - Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Beumont, Maria AU - Beumont M AD - Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. FAU - Kalmeijer, Ronald AU - Kalmeijer R AD - Janssen Research & Development, LLC, Titusville, NJ. FAU - Sinha, Rekha AU - Sinha R AD - Janssen Research & Development, LLC, Titusville, NJ. FAU - Biermer, Michael AU - Biermer M AD - Janssen Research & Development, Janssen Pharmaceutica NV, Beerse, Belgium. CN - OMEGA-1 study team LA - eng GR - Janssen Research & Development/International PT - Clinical Trial, Phase II PT - Comparative Study PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20190314 PL - United States TA - Hepatology JT - Hepatology (Baltimore, Md.) JID - 8302946 RN - 0 (Antiviral Agents) RN - 0 (Benzimidazoles) RN - 0 (Carbamates) RN - 0 (Indoles) RN - 0 (Phosphoramides) RN - 9WS5RD66HZ (Simeprevir) RN - OF5P57N2ZX (Alanine) RN - OVR52K7BDW (odalasvir) RN - S83770Y75R (adafosbuvir) RN - WHI7HQ7H85 (Uridine) SB - IM MH - Adult MH - Aged MH - Alanine/adverse effects/*analogs & derivatives/therapeutic use MH - Antiviral Agents/therapeutic use MH - Benzimidazoles/adverse effects/*therapeutic use MH - Carbamates/adverse effects/*therapeutic use MH - Dose-Response Relationship, Drug MH - Drug Administration Schedule MH - Drug Therapy, Combination MH - Female MH - Follow-Up Studies MH - Hepacivirus/*genetics MH - Hepatitis C, Chronic/*drug therapy/genetics/pathology MH - Humans MH - Indoles/adverse effects/*therapeutic use MH - Internationality MH - Liver Cirrhosis MH - Male MH - Middle Aged MH - *Patient Reported Outcome Measures MH - Patient Selection MH - Phosphoramides MH - Severity of Illness Index MH - Simeprevir/adverse effects/*therapeutic use MH - Sustained Virologic Response MH - Time Factors MH - Treatment Outcome MH - Uridine/adverse effects/*analogs & derivatives/therapeutic use MH - Young Adult EDAT- 2019/01/30 06:00 MHDA- 2020/06/17 06:00 CRDT- 2019/01/30 06:00 PHST- 2018/09/28 00:00 [received] PHST- 2019/01/10 00:00 [accepted] PHST- 2019/01/30 06:00 [pubmed] PHST- 2020/06/17 06:00 [medline] PHST- 2019/01/30 06:00 [entrez] AID - 10.1002/hep.30527 [doi] PST - ppublish SO - Hepatology. 2019 Jun;69(6):2349-2363. doi: 10.1002/hep.30527. Epub 2019 Mar 14.