摘要
AIM To assess daclatasvir plus asunaprevir(d UAL)in treatment-na?ve patients from China's Mainland,Russia and South Korea with hepatitis C virus(HCV)genotype 1 b infection.METHODS Patients were randomly assigned(3:1)to receive 24 wk of treatment with d UAL(daclatasvir 60 mg once daily and asunaprevir 100 mg twice daily)beginning on day 1 of the treatment period(immediate treatment arm)or following 12 wk of matching placebo(placebodeferred treatment arm).The primary endpoint was a comparison of sustained virologic response at posttreatment week 12(SVR12)compared with the historical SVR rate for peg-interferon plus ribavirin(70%)among patients in the immediate treatment arm.The first 12 wk of the study were blinded.Safety was assessed in d UAL-treated patients compared with placebo patients during the first 12 wk(doubleblind phase),and during 24 wk of d UAL in both arms combined.RESULTS In total,207 patients were randomly assigned to immediate(n=155)or placebo-deferred(n=52)treatment.Most patients were Asian(86%),female(59%)and aged<65 years(90%).Among them,13%had cirrhosis,32%had IL28 B non-CC genotypes and 53%had baseline HCV RNA levels of≥6 million IU/m L.Among patients in the immediate treatment arm,SVR12 was achieved by 92%(95%confidence interval:87.2-96.0),which was significantly higher than the historical comparator rate(70%).SVR12 was largely unaffected by cirrhosis(89%),age≥65 years(92%),male sex(90%),baseline HCV RNA≥6 million(89%)or IL28 B non-CC genotypes(96%),although SVR12 was higher among patients without(96%)than among those with(53%)baseline NS5 A resistanceassociated polymorphisms(at L31 or Y93 H).during the double-blind phase,aminotransferase elevations were more common among placebo recipients than among patients receiving d UAL.during 24 wk of d UAL therapy(combined arms),the most common adverse events(≥10%)were elevated alanine aminotransferase and upper respiratory tract infection;emergent grade 3-4 laboratory abnormalities were infrequently observed,and all grade 3-4 aminotransferase abnormalities(alanine aminotransferase,n=9;aspartate transaminase,n=6)reversed within 8-11 d.Two patients discontinued d UAL treatment;one due to aminotransferase elevations,nausea,and jaundice and the other due to a fatal adverse event unrelated to treatment.There were no treatment-related deaths.CONCLUSION d UAL was well-tolerated during this phase 3 study,and SVR12 with d UAL treatment(92%)exceeded thehistorical SVR rate for peg-interferon plus ribavirin of 70%.
基金
Bristol-Myers Squibb
作者简介
Correspondence to:Jun Deng,MD,daniel.deng@bms.com.Telephone:+86-21-23218405,Fax:+86-21-32303705.(0000-0002-6390-7430);Lai Wei(0000-0003-2326-1257);Fu-Sheng Wang(0000-0002-8043-6685);Ming-Xiang Zhang(0000-0001-6519-3497);Ji-Dong Jia(0000-0002-4673-8890);Alexey A Yakovlev(0000-0003-4163-5769);Wen Xie(0000-0002-7314-8175);Eduard Burnevich(0000-0002-7251-4284);Jun-Qi Niu(0000-0002-9857-6520);Yong Jin Jung(0000-0001-8785-2254);Xiang-Jun Jiang(0000-0001-8786-9654);Min Xu(0000-0003-0099-9101);Xin-Yue Chen(0000-0003-0099-2398);Qing Xie(0000-0002-2582-8803);Jun Li(0000-0002-1961-7188);Jin-Lin Hou(0000-0001-8230-8583);Hong Tang(0000-0002-9790-6225);Xiao-Guang Dou(0000-0002-5293-6009);Yash Gandhi(0000-0001-7637-9617);Wenhua Hu(0000-0002-8763-609X);Fiona McPhee(0000-0002-9321-4483);Stephanie Noviello(0000-0003-2705-1097);Michelle Treitel(0000-0001-9488-7113);Ling Mo(0000-0001-8272-4210).
