Department of Medicine, J.W. Goethe University Hospital, Frankfurt am Main, Germany.
Department of Gastroenterology and Hepatology, ZNA Antwerp, Antwerp, Belgium.
Hepatology. 2019 Jun;69(6):2349-2363. doi: 10.1002/hep.30527. Epub 2019 Mar 14.
The combination of three direct-acting antiviral agents (AL-335, odalasvir, and simeprevir: JNJ-4178 regimen) for 6 or 8 weeks demonstrated good efficacy and safety in a phase IIa study in chronic hepatitis C virus (HCV) genotype (GT)-1-infected patients without cirrhosis and has now been evaluated in a larger phase IIb study, OMEGA-1. This multicenter, randomized, open-label study (NCT02765490) enrolled treatment-naïve and interferon (±ribavirin) treatment-experienced patients with HCV GT1, 2, 4, 5, or 6 infection. Patients with HCV GT3 infection and/or liver cirrhosis were excluded. Patients received AL-335 800 mg, odalasvir 25 mg, and simeprevir 75 mg once daily for 6 or 8 weeks. The primary endpoint was sustained virologic response 12 weeks after the end of treatment (SVR12). In total, 365 patients (GT1a, 29.3%; GT1b, 42.5%; GT2, 12.3%; GT4, 14.2%; GT5, 1.4%; GT6, 0%) were randomized to receive 6 weeks (n = 183) or 8 weeks (n = 182) of treatment. SVR12 rates after 6 weeks (98.9%) or 8 weeks (97.8%) of treatment were noninferior to a historical control (98%). Viral relapse occurred in 5 patients (1.4%; 4 with HCV GT2c; 1 with GT1a). With the exception of 4 patients in the 8-week group, including 3 patients with missing data at the SVR24 timepoint, all patients who achieved SVR12 also achieved SVR24. One GT1a-infected patient experienced late viral relapse after achieving SVR18. Most adverse events (AEs) were mild with no treatment-related serious AEs. All randomized patients completed treatment. Conclusion: In HCV-infected patients, 6 and 8 weeks of treatment with JNJ-4178 resulted in SVR12 rates of 98.9% and 97.8%, respectively, and was well tolerated.
三种直接作用抗病毒药物（AL-335、奥达拉斯维尔和simeprevir：JNJ-4178 方案）联合治疗 6 或 8 周，在慢性丙型肝炎病毒（HCV）基因型（GT）-1 感染且无肝硬化的患者的 IIa 期研究中显示出良好的疗效和安全性，现已在更大的 IIb 期 OMEGA-1 研究中进行了评估。这项多中心、随机、开放性研究（NCT02765490）纳入了初治和干扰素（±利巴韦林）治疗后慢性丙型肝炎 GT1、2、4、5 或 6 感染的患者。排除了 HCV GT3 感染和/或肝硬化患者。患者接受 AL-335 800mg、奥达拉斯维尔 25mg 和simeprevir 75mg 每日一次治疗 6 或 8 周。主要终点是治疗结束后 12 周的持续病毒学应答（SVR12）。共有 365 名患者（GT1a，29.3%；GT1b，42.5%；GT2，12.3%；GT4，14.2%；GT5，1.4%；GT6，0%）被随机分为 6 周（n=183）或 8 周（n=182）治疗组。6 周（98.9%）或 8 周（97.8%）治疗后的 SVR12 率与历史对照（98%）非劣效。5 名患者（1.4%；4 名 GT2c 感染；1 名 GT1a 感染）发生病毒复发。除了 8 周组的 4 名患者（包括 3 名在 SVR24 时间点缺失数据的患者）外，所有达到 SVR12 的患者均达到 SVR24。1 名 GT1a 感染患者在达到 SVR18 后出现晚期病毒复发。大多数不良事件（AE）轻微，无治疗相关严重 AE。所有随机患者均完成治疗。结论：在 HCV 感染患者中，JNJ-4178 治疗 6 周和 8 周的 SVR12 率分别为 98.9%和 97.8%，耐受性良好。
