Tania M Welzel1, Tarik Asselah2, Emily O Dumas3, Stefan Zeuzem4, David Shaw5, Rawi Hazzan6, Xavier Forns7, Tami Pilot-Matias3, Wenjing Lu3, Daniel E Cohen3, Jordan J Feld8. 1. J W Goethe University, Frankfurt, Germany. Electronic address: tania.welzel@kgu.de. 2. Centre de Recherche sur l'Inflammation, Université Paris Diderot, AP-HP Hôpital Beaujon, Clichy, France. 3. AbbVie, Chicago, IL, USA. 4. J W Goethe University, Frankfurt, Germany. 5. Royal Adelaide Hospital, Adelaide, SA, Australia. 6. Ha'emek Medical Center, Afula, Israel. 7. Liver Unit, Hospital Clinic, CIBEREHD, IDIBAPS, University of Barcelona, Barcelona, Spain. 8. Toronto Centre for Liver Disease, University of Toronto, Toronto, ON, Canada.
Abstract
BACKGROUND: Clinical studies have shown high rates of sustained virological response (hepatitis C virus [HCV] RNA <15 IU/mL) at post-treatment week 12 (SVR12) in patients with genotype 1b infection with and without cirrhosis who received coformulated ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without ribavirin, for 12 weeks. In this study, we aimed to assess 8-week treatment with ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without ribavirin in patients infected with HCV genotype 1b without cirrhosis. METHODS: We did a multicentre, open-label, single-arm, phase 3b study (GARNET) in 20 hospitals or clinics in Australia, Canada, France, Germany, Israel, Italy, Spain, and the UK, to assess the safety and efficacy of an 8-week treatment duration of once-daily oral ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg, plus twice-daily oral dasabuvir 250 mg in previously untreated patients with chronic HCV genotype 1b infection without cirrhosis (as assessed by liver biopsy, transient elastography, or serum markers). Eligible patients were aged at least 18 years, with more than 1000 IU/mL HCV RNA, and a laboratory result at screening indicating infection with HCV genotype 1b subtype only. Patients were excluded if they had evidence of HCV genotype or subtype other than genotype 1b, if they tested positive for hepatitis B surface antigen or anti-HIV antibody at screening, or if they had previously been treated for HCV. The primary endpoint was the proportion of patients with SVR12; the primary endpoint and safety were assessed in all patients who received at least one dose of study drugs. This trial is registered with ClinicalTrials.gov, number NCT02582632. FINDINGS: Patients were screened between Nov 24, 2015, and March 1, 2016, and 166 patients were enrolled. 163 (98%) of 166 enrolled patients had HCV genotype 1b infection, and three (2%) of 166 had other genotypes or subtypes (genotype 1a, genotype 1d, and genotype 6). All enrolled patients received at least one dose of study drugs. 162 (98% [95% CI 95·3-99·9]) of 166 patients achieved SVR12. One patient discontinued treatment on day 45 due to adverse events. Most adverse events were mild in severity, and the most common adverse events were headache (35 [21%] of 166) and fatigue (28 [17%] of 166). Two (1%) of 166 patients had serious adverse events; neither were considered related to study drug treatment. INTERPRETATION: Treatment with ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without ribavirin, for 8 weeks was efficacious and well tolerated. 8-week treatment options for previously untreated patients with HCV genotype 1b infection without cirrhosis are limited; shortening the treatment duration might reduce the burden associated with medical visits and procedures, thereby improving access to care and enabling the treatment of more patients. FUNDING: AbbVie.
BACKGROUND: Clinical studies have shown high rates of sustained virological response (hepatitis C virus [HCV] RNA <15 IU/mL) at post-treatment week 12 (SVR12) in patients with genotype 1b infection with and without cirrhosis who received coformulated ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without ribavirin, for 12 weeks. In this study, we aimed to assess 8-week treatment with ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without ribavirin in patients infected with HCV genotype 1b without cirrhosis. METHODS: We did a multicentre, open-label, single-arm, phase 3b study (GARNET) in 20 hospitals or clinics in Australia, Canada, France, Germany, Israel, Italy, Spain, and the UK, to assess the safety and efficacy of an 8-week treatment duration of once-daily oral ombitasvir 25 mg, paritaprevir 150 mg, and ritonavir 100 mg, plus twice-daily oral dasabuvir 250 mg in previously untreated patients with chronic HCV genotype 1b infection without cirrhosis (as assessed by liver biopsy, transient elastography, or serum markers). Eligible patients were aged at least 18 years, with more than 1000 IU/mL HCV RNA, and a laboratory result at screening indicating infection with HCV genotype 1b subtype only. Patients were excluded if they had evidence of HCV genotype or subtype other than genotype 1b, if they tested positive for hepatitis B surface antigen or anti-HIV antibody at screening, or if they had previously been treated for HCV. The primary endpoint was the proportion of patients with SVR12; the primary endpoint and safety were assessed in all patients who received at least one dose of study drugs. This trial is registered with ClinicalTrials.gov, number NCT02582632. FINDINGS:Patients were screened between Nov 24, 2015, and March 1, 2016, and 166 patients were enrolled. 163 (98%) of 166 enrolled patients had HCV genotype 1b infection, and three (2%) of 166 had other genotypes or subtypes (genotype 1a, genotype 1d, and genotype 6). All enrolled patients received at least one dose of study drugs. 162 (98% [95% CI 95·3-99·9]) of 166 patients achieved SVR12. One patient discontinued treatment on day 45 due to adverse events. Most adverse events were mild in severity, and the most common adverse events were headache (35 [21%] of 166) and fatigue (28 [17%] of 166). Two (1%) of 166 patients had serious adverse events; neither were considered related to study drug treatment. INTERPRETATION: Treatment with ombitasvir, paritaprevir, and ritonavir, plus dasabuvir, without ribavirin, for 8 weeks was efficacious and well tolerated. 8-week treatment options for previously untreated patients with HCV genotype 1b infection without cirrhosis are limited; shortening the treatment duration might reduce the burden associated with medical visits and procedures, thereby improving access to care and enabling the treatment of more patients. FUNDING: AbbVie.
Authors: Thomas N Kakuda; Matthew W McClure; Christopher Westland; Jennifer Vuong; Marie-Claude Homery; Gwendoline Poizat; Laure Viguerie; Caroline Denot; Alain Patat; Qingling Zhang; James Hui; David Apelian; David B Smith; Sushmita M Chanda; John Fry Journal: Pharmacol Res Perspect Date: 2018-04-30
Authors: Peter Ferenci; Stefan Bourgeois; Peter Buggisch; Suzanne Norris; Manuela Curescu; Dominique Larrey; Fiona Marra; Henning Kleine; Patrick Dorr; Mariem Charafeddine; Eric Crown; Mark Bondin; David Back; Robert Flisiak Journal: J Viral Hepat Date: 2019-03-05 Impact factor: 3.728
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