一项针对初治丙型肝炎病毒（HCV）基因1型（GT1）患者的12周simeprevir联合聚乙二醇干扰素/利巴韦林（PR）的开放标签试验。
An Open-Label Trial of 12-Week Simeprevir plus Peginterferon/Ribavirin (PR) in Treatment-Naïve Patients with Hepatitis C Virus (HCV) Genotype 1 (GT1).
作者信息
Asselah Tarik, Moreno Christophe, Sarrazin Christoph, Gschwantler Michael, Foster Graham R, Craxí Antonio, Buggisch Peter, Ryan Robert, Lenz Oliver, Scott Jane, Van Dooren Gino, Lonjon-Domanec Isabelle, Schlag Michael, Buti Maria
机构信息
Service d'Hépatologie, Beaujon Hospital, INSERM UMR 1149, Université Paris Diderot, Paris, France.
CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium.
出版信息
PLoS One. 2016 Jul 18;11(7):e0158526. doi: 10.1371/journal.pone.0158526. eCollection 2016.
BACKGROUND
Shortening duration of peginterferon-based HCV treatment reduces associated burden for patients. Primary objectives of this study were to assess the efficacy against the minimally acceptable response rate 12 weeks post-treatment (SVR12) and safety of simeprevir plus PR in treatment-naïve HCV GT1 patients treated for 12 weeks. Additional objectives included the investigation of potential associations of rapid viral response and baseline factors with SVR12.
METHODS
In this Phase III, open-label study in treatment-naïve HCV GT1 patients with F0-F2 fibrosis, patients with HCV-RNA <25 IU/mL (detectable/undetectable) at Week 2, and undetectable HCV-RNA at Weeks 4 and 8, stopped all treatment at Week 12. All other patients continued PR for a further 12 weeks. Baseline factors significantly associated with SVR12 were identified through logistic regression.
RESULTS
Of 163 patients who participated in the study, 123 (75%) qualified for 12-week treatment; of these, 81 (66%) achieved SVR12. Baseline factors positively associated with SVR12 rates in patients receiving the 12-week regimen were: IL28B CC genotype: (94% SVR12); HCV RNA ≤800,000 IU/mL (82%); F0-F1 fibrosis (74%). Among all 163 patients, 94% experienced ≥1 adverse event (AE), 4% a serious AE, and 2.5% discontinued due to an AE. Reduced impairment in patient-reported outcomes was observed in the 12-week vs >12-week regimen.
CONCLUSIONS
Overall SVR12 rate (66%) was below the target of 80%, indicating that shortening of treatment with simeprevir plus PR to 12 weeks based on very early response is not effective. However, baseline factors associated with higher SVR12 rates were identified. Therefore, while Week 2 response alone is insufficient to predict efficacy, GT1 patients with favourable baseline factors may benefit from a shortened simeprevir plus PR regimen.
TRIAL REGISTRATION
ClinicalTrials.gov NCT01846832.
背景
缩短基于聚乙二醇干扰素的丙型肝炎病毒（HCV）治疗疗程可减轻患者的相关负担。本研究的主要目的是评估simeprevir联合聚乙二醇化干扰素（PR）对初治HCV基因1型（GT1）患者治疗12周后达到最低可接受应答率（治疗结束后12周持续病毒学应答，SVR12）的疗效及安全性。其他目的包括研究快速病毒学应答及基线因素与SVR12之间的潜在关联。
方法
在这项针对初治、F0-F2纤维化的HCV GT1患者的III期开放标签研究中，第2周时HCV-RNA <25 IU/mL（可检测/不可检测）且第4周和第8周时HCV-RNA不可检测的患者在第12周停止所有治疗。所有其他患者继续PR治疗12周。通过逻辑回归确定与SVR12显著相关的基线因素。
结果
参与研究的163例患者中，123例（75%）符合12周治疗标准；其中，81例（66%）实现了SVR12。接受12周治疗方案的患者中，与SVR12率呈正相关的基线因素为：IL28B CC基因型（SVR12率为94%）；HCV RNA≤800,000 IU/mL（82%）；F0-F1纤维化（74%）。在所有163例患者中，94%经历了≥1次不良事件（AE），4%经历了严重AE，2.5%因AE停药。与治疗时间>12周的方案相比，12周治疗方案中患者报告结局的损害有所减轻。
结论
总体SVR12率（66%）低于80%的目标，表明基于非常早期的应答将simeprevir联合PR治疗缩短至12周无效。然而，确定了与较高SVR12率相关的基线因素。因此，虽然仅第2周的应答不足以预测疗效，但具有有利基线因素的GT1患者可能从缩短的simeprevir联合PR方案中获益。
试验注册
ClinicalTrials.gov NCT01846832。
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