在2013年欧洲肝病学会(European Association for the Study of the Liver,EASL)主办的国际肝病大会(the International Liver Congress,ILC)上,一项2期随机研究发现,无干扰素和利巴韦林的三联方案——DCV+ASV+BMS-791325有较高的丙型肝炎病毒(HCV)治愈率和安全性。
Interim analysis of an interferon (ifn)- and ribavirin (rbv)-free regimen of daclatasvir (dcv), asunaprevir (asv), and bms-791325 in treatment-naive, hepatitis c virus genotype 1-infected patients
Background and Aims: The IFN- and RBV-free regimen of DCV(NS5A inhibitor), ASV (protease inhibitor) and BMS-791325 (nonnucleoside NS5B inhibitor, 75mg BID) for 24 or 12 weeks was well tolerated and achieved SVR4 and SVR12 >90% in treatment-naive,hepatitis C virus (HCV) genotype (GT) 1 patients. We present safety and SVR following 24 or 12 weeks of this treatment using two BMS-791325 doses (75 vs 150mg BID).
Methods: This phase 2 study randomized treatment-naive, HCV GT1, non-cirrhotic patients (N = 32) 1:1 to DCV 60mg QD, ASV 200mg BID, and BMS-791325 75mg BID for 24 (Group 1) or 12 (Group 2) weeks. Following safety evaluation, 34 additional
patients were randomized to DCV, ASV, and BMS-791325 150mg BID for 24 (Group 3) or 12 (Group 4) weeks. The primary end
point was HCVRNA< 25 IU/mL at 12 weeks post-treatment (SVR12). Safety and SVR from Groups 1 (SVR12), 2 (SVR24) and 4 (SVR4) are described, Groups 3 (SVR4) and 4 (SVR12) will be presented.
Results: Patients were mainly GT1a (74%), white race (79%), and IL28B non-CC (70%). 64 of 66 patients had HCVRNA < 25 IU/mL by Week 4 (Table). In this interim analysis, there was no difference in virologic responses between 12 and 24 weeks of treatment. Overall, patients achieved SVR4 92% (46/50), SVR12 94% (30/32), and SVR24 94% (15/16) (Table). Three failures (Groups 3–4) were observed in patients receiving BMS-791325 150mg (2-viral breakthrough,1-relapse). No patients discontinued due to adverse events (AEs) related to DCV+ASV+BMS-791325. Most common AEs (≥10% total) were headache, asthenia, and gastrointestinal. Two serious AEs have been reported, both unrelated to DCV+ASV+BMS-791325. No hepatotoxicity or Grade 3/4 elevations of ALT/AST or bilirubin were reported.
Conclusion: DCV+ASV+BMS-791325 achieved high rates of SVR4, SVR12, and SVR24 in treatment-naive GT1 patients, characterized by GT1a and IL28B non-CC. This regimen was well tolerated with no apparent safety signals. Expansion of the current study is underway to better define the efficacy and safety of this regimen.作者: hao.k.h 时间: 2013-5-3 11:46