Stanford University Division of Gastroenterology and Hepatology, Palo Alto, CA, USA.
Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas, USA.
J Hepatol. 2017 Aug;67(2):263-271. doi: 10.1016/j.jhep.2017.03.039. Epub 2017 Apr 13.
BACKGROUND & AIMS: Hepatitis C virus (HCV) therapy that is highly efficacious, pangenotypic, with a high barrier to resistance and short treatment duration is desirable. The efficacy and safety of 8- and 12-week treatments with glecaprevir (ABT-493; NS3/4A protease inhibitor) and pibrentasvir (ABT-530; NS5A inhibitor) were evaluated in non-cirrhotic patients with chronic HCV genotype 1-6 infection.
SURVEYOR-I and SURVEYOR-II were phase II, open-label, multicenter, dose-ranging trials including patients with chronic HCV genotype 1-6 infection who were either previously untreated or treated with pegylated interferon plus ribavirin. Patients received once-daily glecaprevir plus pibrentasvir at varying doses with or without ribavirin for 8 or 12weeks. The primary efficacy endpoint was the percentage of patients with a sustained virologic response at post-treatment week 12 (SVR12).
Of the 449 patients who received varying doses of glecaprevir plus pibrentasvir, 25%, 29%, 39%, and 8% had HCV genotype 1, 2, 3, and 4-6 infection, respectively. Twelve-week treatment achieved SVR12 in 97-100%, 96-100%, 83-94%, and 100% in genotypes 1, 2, 3, and 4-6, respectively. Eight-week treatment with 300mg glecaprevir plus 120mg pibrentasvir in genotype 1-, 2-, or 3-infected patients yielded 97-98% SVR12 with no virologic failures. Three (0.7%) patients discontinued treatment due to adverse events; most events were mild (grade 1) in severity. No post-nadir alanine aminotransferase elevations were observed.
Glecaprevir plus pibrentasvir was well tolerated and achieved high sustained virologic response rates in HCV genotypes 1-6-infected patients without cirrhosis following 8- or 12-week treatment durations.
The combination of direct-acting antivirals glecaprevir and pibrentasvir comprise a once-daily, all-oral, pangenotypic treatment for HCV genotype 1-6 infection. This article describes results from two phase II trials investigating a range of doses at treatment durations of 8 or 12weeks in 449 patients without cirrhosis. Efficacy of the optimal dose, as determined by rates of sustained virologic response at post-treatment week 12, ranged from 92%-100%; treatment was well tolerated and significant laboratory abnormalities were rare.
clinicaltrials.gov Identifiers: NCT02243280 and NCT02243293. http://www.clinicaltrials.gov/show/NCT02243280, http://www.clinicaltrials.gov/show/NCT01939197.
人们希望能有一种高效、广谱、耐药屏障高且治疗时间短的丙型肝炎病毒（HCV）治疗药物。本文评估了非肝硬化慢性丙型肝炎基因型 1-6 感染患者接受 8 或 12 周 glecaprevir（ABT-493；NS3/4A 蛋白酶抑制剂）和 pibrentasvir（ABT-530；NS5A 抑制剂）治疗的疗效和安全性。
SURVEYOR-I 和 SURVEYOR-II 为 II 期、开放标签、多中心、剂量范围试验，纳入了既往未接受过治疗或接受过聚乙二醇干扰素加利巴韦林治疗的慢性丙型肝炎基因型 1-6 感染患者。患者接受了每日一次的 glecaprevir 加 pibrentasvir 治疗，剂量不同，联合或不联合利巴韦林，治疗时间为 8 或 12 周。主要疗效终点是治疗后 12 周持续病毒学应答率（SVR12）。
在接受不同剂量 glecaprevir 加 pibrentasvir 治疗的 449 例患者中，分别有 25%、29%、39%和 8%的患者感染了 HCV 基因型 1、2、3 和 4-6。12 周治疗使基因型 1、2、3 和 4-6 的 SVR12 分别达到 97-100%、96-100%、83-94%和 100%。基因型 1、2 或 3 感染患者接受 300mg glecaprevir 加 120mg pibrentasvir 治疗 8 周，SVR12 率为 97-98%，无病毒学失败病例。3 例（0.7%）患者因不良事件停药；大多数事件为轻度（1 级）。未观察到治疗后丙氨酸氨基转移酶水平升高。
glecaprevir 加 pibrentasvir 治疗无肝硬化的慢性丙型肝炎基因型 1-6 感染患者，8 或 12 周治疗后耐受性良好，持续病毒学应答率高。
直接作用抗病毒药物 glecaprevir 和 pibrentasvir 的联合治疗方案为 HCV 基因型 1-6 感染患者提供了一种每日一次、口服全药物、广谱的治疗方案。本文描述了两项 II 期临床试验的结果，该试验在 449 例无肝硬化患者中，在 8 或 12 周的治疗期间，研究了一系列剂量。根据治疗后 12 周持续病毒学应答率（SVR12）确定的最佳剂量的疗效，范围为 92%-100%；治疗耐受性良好，且显著的实验室异常情况罕见。
NCT02243280 和 NCT02243293。http://www.clinicaltrials.gov/show/NCT02243280，http://www.clinicaltrials.gov/show/NCT01939197。
