All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study.
All-oral 12-week treatment with daclatasvir plus sofosbuvir in patients with hepatitis C virus genotype 3 infection: ALLY-3 phase III study.
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DOI：
10.1002/hep.27726
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发表时间：
2015-04
期刊：
影响因子：
13.5
通讯作者：
Hughes, Eric A.
中科院分区：
文献类型：
--
作者：
Nelson, David R.;Cooper, James N.;Lalezari, Jacob P.;Lawitz, Eric;Pockros, Paul J.;Gitlin, Norman;Freilich, Bradley F.;Younes, Ziad H.;Harlan, William;Ghalib, Reetn;Oguchi, Godson;Thuluvath, Paul J.;Ortiz-Lasanta, Grisell;Rabinovitz, Mordechai.;Berastein, David;Bennett, Michael;Hawkins, Trevor;Ravendhran, Natarajan;Sheikh, Aasim M.;Varunok, Peter;Kowdley, Kris V.;Hennicken, Delphine;McPhee, Fiona;Rana, Ithurram;Hughes, Eric A.
丙型肝炎病毒(丙型肝炎病毒)3型感染患者的治疗选择有限，目前批准的全口服方案需要24周的治疗和添加利巴韦林(RBV)。这项第三阶段研究(ALLY-3；http://ClinicalTrials.gov：NCT02032901)评估了达拉塔韦(DCV；泛型非结构蛋白[NS]5A抑制剂)和索莫布韦(SOF；泛型NS5B抑制剂)对感染3型的患者为期12周的治疗方案。患者要么接受单纯治疗(n=101)，要么接受治疗(n=51)，并接受Dcv 60 mg加SOF400 mg每日一次，为期12周。核心终点是指在治疗后12周(SVR12)实现持续病毒学应答(SVR)的未接受治疗的患者和有治疗经验的患者的比例。初治患者和有治疗经验患者的≥-12发生率分别为90%(91/101)和86%(44/51)，未观察到病毒学突破，治疗结束时SVR99%的患者有病毒学应答(VR)。非肝硬化组SVR12的发生率(96%；105/109)高于肝硬化组(63%；20/32)。在之前用含SOF方案治疗失败的7名患者中，有5名患者和之前用含阿利斯匹韦方案治疗失败的2名患者中的2名患者获得了SVR12。基线特征，包括性别、年龄、丙型肝炎病毒核糖核酸水平和白介素28B基因，不影响病毒学结果。DCV加SOF耐受性良好；没有不良事件(AEs)导致停药，只有1例严重的AE仍在治疗中，这与研究药物无关。观察到的少数治疗紧急3/4级实验室异常是暂时性的。结论：DCV联合SOF治疗12周的非肝硬化3型感染者中，96%的患者获得了SVR12，且耐受性良好。目前正在进行进一步的评估，以优化3型感染的肝硬变患者的疗效。(《肝病》2015；61：1127-1135)
Treatment options for patients with hepatitis C virus (HCV) genotype 3 infection are limited, with the currently approved all-oral regimens requiring 24-week treatment and the addition of ribavirin (RBV). This phase III study (ALLY-3; http://ClinicalTrials.gov: NCT02032901) evaluated the 12-week regimen of daclatasvir (DCV; pangenotypic nonstructural protein [NS]5A inhibitor) plus sofosbuvir (SOF; pangenotypic NS5B inhibitor) in patients infected with genotype 3. Patients were either treatment naïve (n = 101) or treatment experienced (n = 51) and received DCV 60 mg plus SOF 400 mg once-daily for 12 weeks. Coprimary endpoints were the proportions of treatment-naïve and treatment-experienced patients achieving a sustained virological response (SVR) at post-treatment week 12 (SVR12). SVR12 rates were 90% (91 of 101) and 86% (44 of 51) in treatment-naïve and treatment-experienced patients, respectively; no virological breakthrough was observed, and ≥99% of patients had a virological response (VR) at the end of treatment. SVR12 rates were higher in patients without cirrhosis (96%; 105 of 109) than in those with cirrhosis (63%; 20 of 32). Five of seven patients who previously failed treatment with an SOF-containing regimen and 2 of 2 who previously failed treatment with an alisporivir-containing regimen achieved SVR12. Baseline characteristics, including gender, age, HCV-RNA levels, and interleukin-28B genotype, did not impact virological outcome. DCV plus SOF was well tolerated; there were no adverse events (AEs) leading to discontinuation and only 1 serious AE on-treatment, which was unrelated to study medications. The few treatment-emergent grade 3/4 laboratory abnormalities that were observed were transient. Conclusion: A 12-week regimen of DCV plus SOF achieved SVR12 in 96% of patients with genotype 3 infection without cirrhosis and was well tolerated. Additional evaluation to optimize efficacy in genotype 3–infected patients with cirrhosis is underway. (Hepatology 2015;61:1127–1135)
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