Objective: To evaluate the safety and efficacy of ombitasvir/paritaprevir/ritonavir (OBV/PTV/r) 25/150/100 mg once daily combined with dasabuvir 250mg, twice daily in non-cirrhotic Chinese adult patients with newly diagnosed and treated chronic HCV genotype 1b infection. Methods: A randomized, double-blind, placebo-controlled, multicenter phase 3 clinical trial was conducted in mainland China, Korea, and Taiwan.Safety and efficacy of OBV/PTV/r plus DSV administered for 12 weeks were evaluated in a newly diagnosed and treated (interferon alpha /pegylated interferon alpha) and ribavirin non-cirrhotic adults with chronic HCVgenotype 1b infection. Patients randomly received OBV/PTV/r plus DSV for 12 weeks (Group A), or placebo for 12 weeks (Group B) followed by an open-label phase of OBV/PTV/r plus DSV for 12 weeks. Sustained response (SVR12) rate obtained at 12 weeks and (SVR24) 24 weeks after discontinuation of treatment, and the incidence of adverse events and laboratory abnormalities after double-blind and open-label phase treatment were assessed. Results: A total of 410 cases of Chinese patients were included and randomly assigned to group A and B (with 205 cases in each group) in a 1:1 ratio. The rates of SVR12 and SVR24 were 99% (95% CI: 94.8% - 99.8%) in the newly diagnosed patients in group A (205 patients) and the rates of SVR12 and SVR24 were 100% in treated patients (95% CI: 96.3% - 100%). Different baseline characteristics had no effect on SVR12 and SVR24 rates. Most of the adverse events occurred were mild, asymptomatic, and≥ 3 laboratory abnormalities during treatment were rare, including elevation of alanine aminotransferase (2 cases in double-blind stage A group), aspartate aminotransferase (Double-blind stage A (3 cases) and total bilirubin (1 case in open-label phase B group); however, those mild adverse events could be recovered after drug withdrawal or discontinuation. only1 person discontinued drugs due to adverse events (Group B, open-label phase). Conclusion: The 12 weeks treatment course of OBV/PTV/r combined with DSV produced 99% ~ 100% rates of SVR12 and SVR24 in non-cirrhotic Asian adult patients with newly diagnosed and treated chronic HCV genotype 1b infection, and the tolerance and safety were good.
目的： 评估奥比帕利（奥比他韦/帕立瑞韦/利托那韦，OBV/PTV/r）25/150/100 mg，1次/d，联合达塞布韦250 mg，2次/d，在丙型肝炎病毒基因1b型感染的初治和经治非肝硬化中国成年患者中的有效性和安全性。 方法： 采用随机、双盲、安慰剂对照、多中心III期临床试验，在中国大陆、韩国、中国台湾地区进行。纳入基因1b型初治和普通干扰素/聚乙二醇干扰素α联合利巴韦林经治非肝硬化患者，随机分为2组，分别接受OBV/PTV/r联合达塞布韦方案立即治疗12周（A组），或接受安慰剂治疗12周后再继续接受OBV/PTV/r联合达塞布韦方案治疗12周（B组）。评估患者停药12周获得的持续病毒学应答（SVR12）及停药24周获得的持续病毒学应答（SVR24）率，及双盲阶段和开放标签阶段治疗后的不良事件和实验室异常发生率。 结果： 共纳入410例中国大陆患者资料，按1∶1比例随机分至A组和B组（每组205例）。A组（205例）中初治患者的SVR12及SVR24率均为99% (95% CI: 94.8%～99.8%)，经治患者的SVR12及SVR24率均为100% (95% CI: 96.3%～100%)，不同基线特征对SVR12及SVR24率没有影响。发生的大多数不良事件为轻度，治疗期间≥ 3级实验室异常少见，主要包括丙氨酸氨基转移酶升高（双盲阶段A组2例）、天冬氨酸氨基转移酶升高（双盲阶段A组3例）和总胆红素升高（开放标签阶段B组1例），通常无症状，用药中断或停药后可恢复。仅有1例因不良事件停药（B组，开放标签阶段）。 结论： 疗程为12周的OBV/PTV/r联合达塞布韦方案治疗中国基因1b型初治和经治非肝硬化慢性丙型肝炎患者可获得99%～100%的SVR12及SVR24率，且耐受性和安全性良好。.
Keywords: Direct-acting antiviral agent; Hepatitis C, chronic; Safety.