Efficacy and Safety of 12-week Interferon-based Danoprevir Regimen in Patients with Genotype 1 Chronic Hepatitis C
Open Access
- 22 July 2019
- journal article
- research article
- Published by Xia & He Publishing in Journal of Clinical and Translational Hepatology
- Vol. 7 (X), 1-5
- https://doi.org/10.14218/jcth.2019.00018
Abstract
Background and Aims: Genotype (GT) 1 remains the predominant hepatitis c virus (HCV) GT in Chinese patients. Over 80% of those Chinese patients harbor the interferon-sensitive CC allele of IFNL4rs12979860, which is favorable for interferon-based treatment regimens. This phase III clinical trial aimed to evaluate the efficacy and safety of the ritonavir-boosted danoprevir plus pegylated-interferon alpha-2a and ribavirin regimen for 12 weeks in treatment-naive mainland Chinese patients infected with HCV GT1 without cirrhosis. Methods: One hundred and forty-one treatment-naive, non-cirrhotic HCV GT1 Chinese patients (age >= 18 years) were enrolled for this single-arm, multicenter, phase III MAN-ASA study (NCT03020082). Patients received a combination of ritonavir-boosted danoprevir (100 mg/100 mg) twice a day plus subcutaneous injection of weekly pegylated-interferon alpha-2a (180 mu g) and oral ribavirin (1000/1200 mg/day body weight = 75 kg) for 12 weeks. The primary end-point was sustained virologic response rate at 12 weeks after the end of treatment. The secondary end-points were safety outcomes, tolerability, virologic response over time and relapse rate. Results: All enrolled patients were HCV GT1-infected, and most among them (97.9%, 123/141) had the HCV GT1b subtype. Single-nucleotide polymorphism test showed that the majority of patients were of the IFNL4 rs12979860 CC genotype (87.2%, 123/141). Overall, 140 patients completed the 12-week treatment, and 97.1% (136/140) patients achieved sustained virologic response at 12 weeks (per protocol population group, 95% confidence interval: 92.9-99.2%). Only drug-related serious adverse event occurred. Most of the adverse events were grade 1 and grade 2 alanine aminotransferase elevation or liver dysfunction. One patient discontinued treatment because of severe head injury in a car accident. Conclusions: The triple regimen of ritonavir-boosted danoprevir plus pegylated-interferon a-2a and ribavirin produced a sustained virologic response rate of 97.1% after 12 weeks treatment in noncirrhotic HCV GT1-infected Chinese patients, and was safe and well tolerated.Keywords
This publication has 13 references indexed in Scilit:
- Global prevalence and genotype distribution of hepatitis C virus infection in 2015: a modelling studyThe Lancet Gastroenterology & Hepatology, 2016
- Ritonavir‐boosted danoprevir plus peginterferon alfa‐2a and ribavirin in Asian chronic hepatitis C patients with or without cirrhosisJournal of Gastroenterology and Hepatology, 2016
- Real‐world treatment patterns and clinical outcomes of HCV treatment‐naive patients in China: an interim analysis from the CCgenos studyJournal of Gastroenterology and Hepatology, 2016
- Current Challenges and the Management of Chronic Hepatitis C in Mainland ChinaJournal of Clinical Gastroenterology, 2014
- Impact of New Hepatitis C Treatments in Different Regions of the WorldGastroenterology, 2014
- DAUPHINE: a randomized phase II study of danoprevir/ritonavir plus peginterferon alpha‐2a/ribavirin in HCV genotypes 1 or 4Liver International, 2014
- Distribution and clinical correlates of viral and host genotypes in Chinese patients with chronic hepatitis C virus infectionJournal of Gastroenterology and Hepatology, 2013
- Discovery of Danoprevir (ITMN-191/R7227), a Highly Selective and Potent Inhibitor of Hepatitis C Virus (HCV) NS3/4A ProteaseJournal of Medicinal Chemistry, 2013
- Differential Efficacy of Protease Inhibitors Against HCV Genotypes 2a, 3a, 5a, and 6a NS3/4A Protease Recombinant VirusesGastroenterology, 2011
- Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trialThe Lancet, 2001