Phase 3, Multicenter Open-Label study to investigate the efficacy of elbasvir and grazoprevir fixed-dose combination for 8 weeks in treatment-naïve, HCV GT1b-infected patients, with non-severe fibrosis.

التفاصيل البيبلوغرافية
العنوان:	Phase 3, Multicenter Open-Label study to investigate the efficacy of elbasvir and grazoprevir fixed-dose combination for 8 weeks in treatment-naïve, HCV GT1b-infected patients, with non-severe fibrosis.
المؤلفون:	Abergel A; Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France.; UMR 6602 CNRS-Sigma-Université Clermont Auvergne, Clermont-Ferrand, France., Asselah T; Department of Hepatology, Université Paris Diderot, Sorbonne Paris Cité, CRI, UMR 1149, Inserm, Paris, France.; Department of Hepatology, AP-HP Hôpital Beaujon, Clichy, France., Mallat A; Department of Hepatology and Gastroenterology, Hôpital Henri Mondor, AP-HP, INSERM, Créteil, France.; Faculté de Médecine, Université Paris-Est, Créteil, France., Chanteranne B; Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France., Faure F; Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France., Larrey D; Department of Hepatology, Hôpital Saint Eloi, INSERM1183, Montpellier University, Montpellier, France., Gournay J; Gastroenterology and Hepatology Department, Institut des Maladies de l'Appareil Digestif, University Hospital Nantes, Nantes, France., Loustaud-Ratti V; Department of Hepatology and Gastroenterology, CHU Limoges, INSERM U1248, Université de Limoges, Limoges, France., Di Martino V; Service d'Hépatologie, CHRU Jean Minjoz and Université de Franche-Comté, Besançon, France., Fouchard-Hubert I; Hepato-Gastroenterology Department, Angers University Hospital, Angers, France.; HIFIH Laboratory, UPRES 3859, SFR 4208, Angers University, Angers, France., Pol S; Department of Hepatology, APHP Hôpital Cochin, Université Paris Descartes/INSERM U1223, Institut Pasteur, Paris, France., Bailly F; Service d'Hépatologie et Gastroentérologie, Hôpital de la Croix-Rousse, Lyon, France.; INSERM U1052, Centre de Recherche en Cancérologie de Lyon, Lyon, France., Samuel D; AP-HP Hôpital Paul-Brousse, Centre Hépato-Biliaire, Université Paris-Sud, UMR-S1193, Université Paris-Saclay, and Hepatinov, Villejuif, France., Tran A; Department of Gastroenterology, Université Côte d'Azur, CHU de Nice, INSERM, Centre Digestif, Nice, France., Dodel M; Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France., Andant N; Biostatistics Unit, Délégation Recherche Clinique & Innovation (DRCI), CHU Clermont-Ferrand, Clermont-Ferrand, France., Lamblin G; Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France., Muti L; Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France., Reymond M; Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France., Teilhet C; Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France., Pereira B; Biostatistics Unit, Délégation Recherche Clinique & Innovation (DRCI), CHU Clermont-Ferrand, Clermont-Ferrand, France., Buchard B; Service de médecine digestive et hépato-biliaire CHU Estaing, Clermont-Ferrand, France.
المصدر:	Liver international : official journal of the International Association for the Study of the Liver [Liver Int] 2020 Aug; Vol. 40 (8), pp. 1853-1859. Date of Electronic Publication: 2020 Jun 01.
نوع المنشور:	Clinical Trial, Phase III; Journal Article; Multicenter Study; Research Support, Non-U.S. Gov't
اللغة:	English
بيانات الدورية:	Publisher: Wiley-Blackwell Country of Publication: United States NLM ID: 101160857 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1478-3231 (Electronic) Linking ISSN: 14783223 NLM ISO Abbreviation: Liver Int Subsets: MEDLINE
أسماء مطبوعة:	Publication: Malden, MA : Wiley-Blackwell Original Publication: Oxford, UK : Blackwell Munksgaard, c2003-
مواضيع طبية MeSH:	Hepatitis C/drug therapy , Ribavirin, Adult ; Aged ; Amides ; Antiviral Agents/therapeutic use ; Asia ; Benzofurans ; Carbamates ; Cyclopropanes ; Drug Therapy, Combination ; Europe ; Female ; Fibrosis ; Genotype ; Hepacivirus/genetics ; Humans ; Imidazoles ; Male ; Middle Aged ; Quinoxalines/therapeutic use ; Sulfonamides
مستخلص:	Background: Genotype 1b is the most common HCV genotype worldwide, accounting for the largest proportion of infections in Europe, Russia, Latin America and Asia. Reducing treatment duration can improve adherence, reduce drug exposure and cost. Accordingly, we evaluated the efficacy of 8 weeks fixed-dose combination of grazoprevir-elbasvir in treatment-naïve patients, with non-severe fibrosis. Methods: HCV mono-infected and treatment naïve patients with non-severe fibrosis (Fibroscan ^® <9.5 kPa and Fibrotest ^® < 0.59) were enrolled in a study which included 117 patients. Genotyping by sequencing identified five patients with non-1b genotype (two GT1a, one GT1h, one GT1e and one GT1l). Thus, we included in the final analysis 112 GT1b patients. The primary end point was the proportion of patients with HCVRNA below the lower limit of quantification 12 weeks after treatment (SVR12). Findings: Mean age was 54 ± 13 years, 31% were men and viral load was higher than 800.000 IU/mL in 70 of 112 patients (63%). Using Fibroscan ^® , 100 had F0-1 fibrosis score. FIB-4 lower than 1.45 and APRI less than 1 was found in 74/112 (66%) and 107/112 (95%) patients respectively. Relapse occurred in three patients by week 12. These three patients had a viral load higher than 6 million IU/mL and NS5A Y93H RAS (resistance-associated substitution). Then, modified intention-to-treat SVR12 for patients with genotype 1b was 109/112 (97%). By week 24; five relapses were observed and all had the Y93H RAS at relapse. SVR12 was achieved in 100% of patients with a baseline viral load below 6 million and decreased to 98% (98/100) by follow-up week 24. Interpretation: Naïve patients with genotype 1b and non-severe fibrosis can achieve an SVR12 of 97% and an SVR24 of 95%. Then, these patients can be treated with grazoprevir-elbasvir for 8 weeks. (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)
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المشرفين على المادة:	0 (Amides) 0 (Antiviral Agents) 0 (Benzofurans) 0 (Carbamates) 0 (Cyclopropanes) 0 (Imidazoles) 0 (Quinoxalines) 0 (Sulfonamides) 49717AWG6K (Ribavirin) 4O2AB118LA (grazoprevir) 632L571YDK (elbasvir)
تواريخ الأحداث:	Date Created: 20200509 Date Completed: 20210621 Latest Revision: 20220909
رمز التحديث:	20240628
DOI:	10.1111/liv.14502
PMID:	32383275
قاعدة البيانات:	MEDLINE

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تدمد:	1478-3231
DOI:	10.1111/liv.14502