Saturday, January 23, 2016

Simeprevir Plus Sofosbuvir (12 and 8 Weeks) in HCV Genotype 1-Infected Patients Without Cirrhosis: OPTIMIST-1, a Phase 3, Randomized Study

Abstract

Effective antiviral therapy is essential for achieving sustained virological response (SVR) in hepatitis C virus (HCV)-infected patients. The phase 2 COSMOS study reported high SVR rates in treatment-naïve and prior null-responder HCV genotype (GT)1-infected patients receiving simeprevir+sofosbuvir±ribavirin for 12/24 weeks. OPTIMIST-1 (NCT02114177) was a multicenter, randomized, open-label study assessing the efficacy and safety of 12 and 8 weeks of simeprevir+sofosbuvir in HCV GT1-infected treatment-naïve and -experienced patients without cirrhosis. Patients were randomly assigned (1:1; stratified by HCV GT/subtype and presence/absence of NS3 Q80K polymorphism [GT1b, GT1a with Q80K, GT1a without Q80K]), prior HCV treatment history, and IL28B GT [CC, non-CC]) to simeprevir 150 mg once daily (QD)+sofosbuvir 400 mg QD for 12 or 8 weeks. Primary efficacy endpoint: SVR rate 12 weeks after end of treatment (SVR12). Superiority in SVR12 was assessed for simeprevir+sofosbuvir at 12 and 8 weeks versus a composite historical control SVR rate. 310 patients were enrolled, randomized, and received treatment (n=155 in each arm). SVR12 with simeprevir+sofosbuvir for 12 weeks (97% [150/155; 95% CI 94-100%]) was superior to the historical control (87%). SVR12 with simeprevir+sofosbuvir for 8 weeks (83% [128/155; 95% CI 76-89%]) was not superior to the historical control (83%). The most frequent adverse events (AEs) were nausea, headache, and fatigue (12-week arm: 15% [23/155]), 14% [22/155], and 12% [19/155]; 8-week arm: 9% [14/155], 17% [26/155], and 15% [23/155], respectively). No patients discontinued treatment due to an AE. One (1%; 12-week arm) and three (2%; 8-week arm) patients experienced a serious AE (all unrelated to study treatment). Conclusion: Simeprevir+sofosbuvir for 12 weeks is highly effective in the treatment of HCV GT1-infected, non-cirrhotic patients, including those with Q80K. This article is protected by copyright. All rights reserved.

No comments:

Post a Comment