Rao Huiying, Yang Xingxiang, Tan Youwen, Ning Qin, Yang Daokun, Wang Jiefei, Yang Yongfeng, Zheng Sujun, Yang Dongliang, Hou Jinlin, Xie Qing, Zhao Caiyan, Zhang Lunli, Mao Xiaorong, Sun Tong, Bai Lang, Zhang Fuchun, Jin Jinglan, Zhao Yingren, Wang Maorong, Xie Wen, Ma Yingjie, Quan Jun, Yan Xuebing, An Ping, Lin Feng, Jia Jidong, Hu Xiaoxuan, Gong Zuojiong, Wu Jie, Chen Yongping, Jia Zhansheng, Lin Minghua, Wang Guiqiang, Zhu Yueyong, Zhang Yingjun, Xie Hongming, Luo Lin, Ren Qingyun, Huang Rui, Wei Lai
Peking University People's Hospital, Peking University Hepatology Institute, National Clinical Research Center for Infectious Disease, Beijing Key Laboratory of Hepatitis C and Immunotherapy for Liver Diseases, Beijing International Cooperation Base for Science and Technology on NAFLD Diagnosis, Beijing, China.
Department of Infectious Diseases, Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.
J Clin Transl Hepatol. 2020 Sep 28;8(3):255-261. doi: 10.14218/JCTH.2020.00031. Epub 2020 Sep 11.
Emitasvir is a new type of hepatitis C virus (HCV) nonstructural protein 5A (NS5A) inhibitor, and the data of phase 2 trial has shown emitasvir-sofosbuvir to have good safety and tolerance. We conducted this phase 3 trial to further verify the efficacy and safety. We evaluated the antiviral activity and safety of a 12-week regimen of emitasvir phosphate (100 mg) combined with sofosbuvir (400 mg) once daily in non-cirrhotic patients with genotype 1 HCV infection. The primary endpoint was a sustained virological response at 12 weeks (SVR12) after the end of treatment. Of the 362 patients enrolled in the trial, 39.8% were male, 99.2% had HCV genotype 1b, 0.8% had genotype 1a and 79.8% were treatment-naïve. The average age was 47.2 years. All patients completed the treatment and follow-up. All 3 patients with genotype 1a achieved SVR. Two genotype 1b treatment-naïve patients experienced virologic relapse. The rate of SVR12 was 99.7% (358/359), and SVR24 was 99.4% (357/359) in genotype 1b. Overall, 36.2% had resistance-associated substitutions (RASs) in NS5A and 98.3% had RASs in NS5B at baseline. The RASs at baseline had no effect on the rates of response. Serious adverse events were reported in 16 patients and were not related to emitasvir-sofosbuvir. Most adverse events did not require therapy. The 12 weeks of treatment with emitasvir-sofosbuvir was a highly efficient and safe treatment for a wide range of patients with HCV genotype 1b infection without cirrhosis, who had not been treated or who had been treated with interferon-based regimen previously.
艾尔巴韦是一种新型丙型肝炎病毒（HCV）非结构蛋白5A（NS5A）抑制剂，2期试验数据表明艾尔巴韦-索磷布韦具有良好的安全性和耐受性。我们开展了这项3期试验以进一步验证其疗效和安全性。我们评估了在基因型1 HCV感染的非肝硬化患者中，每日一次给予12周疗程的磷酸艾尔巴韦（100 mg）联合索磷布韦（400 mg）的抗病毒活性和安全性。主要终点是治疗结束后12周的持续病毒学应答（SVR12）。在该试验纳入的362例患者中，39.8%为男性，99.2%为HCV基因型1b，0.8%为基因型1a，79.8%为初治患者。平均年龄为47.2岁。所有患者均完成了治疗和随访。所有3例基因型1a患者均实现了SVR。2例初治的基因型1b患者出现病毒学复发。基因型1b患者中SVR12率为99.7%（358/359），SVR24率为99.4%（357/359）。总体而言，36.2%的患者在基线时NS5A存在耐药相关置换（RASs），98.3%的患者在基线时NS5B存在RASs。基线时的RASs对应答率无影响。16例患者报告了严重不良事件，且与艾尔巴韦-索磷布韦无关。大多数不良事件无需治疗。对于广泛的未接受过治疗或既往接受过基于干扰素方案治疗的非肝硬化基因型1b HCV感染患者，12周的艾尔巴韦-索磷布韦治疗是一种高效且安全的治疗方法。
