一项评估 Presatovir 治疗造血干细胞移植受者呼吸道合胞病毒上呼吸道感染的 2 期、随机、双盲、安慰剂对照研究。
A Phase 2, Randomized, Double-blind, Placebo-Controlled Trial of Presatovir for the Treatment of Respiratory Syncytial Virus Upper Respiratory Tract Infection in Hematopoietic-Cell Transplant Recipients.
机构信息
Department of Infectious Diseases, Infection Control and Employee Health, University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
Division of Infectious Disease, City of Hope National Medical Center, Duarte, California, USA.
出版信息
Clin Infect Dis. 2020 Dec 31;71(11):2777-2786. doi: 10.1093/cid/ciz1166.
BACKGROUND
Hematopoietic-cell transplant (HCT) recipients are at risk for severe respiratory syncytial virus (RSV) infection. We evaluated the RSV fusion inhibitor presatovir in a randomized, double-blind, Phase II trial in HCT recipients with RSV upper respiratory tract infections.
METHODS
Patients were stratified by lymphopenia (<200/µL) and ribavirin use; were randomized, stratified by lymphopenia (<200/μL) and ribavirin use, to receive oral presatovir at 200 mg or a placebo on Days 1, 5, 9, 13, and 17, and were followed through Day 28. The coprimary efficacy endpoints were the time-weighted average change in the nasal RSV viral load between Days 1 and 9 and the proportion of patients developing lower respiratory tract complications (LRTCs) through Day 28.
RESULTS
From 23 January 2015 to 16 June 2017, 189 patients were randomly assigned to treatment (96 to presatovir and 93 to the placebo). Presatovir treatment, compared with the placebo treatment, did not significantly affect (prespecified α = 0.01) a time-weighted average decline in the RSV viral load from Day 1 to 9 (treatment difference, -0.33 log10 copies/mL; 95% confidence interval [CI] -.64 to -.02 log10 copies/mL; P = .040) or the progression to LRTC (11.2% vs 19.5%, respectively; odds ratio, 0.50; 95% CI, .22-1.18; P = .11). In a post hoc analysis among patients with lymphopenia, presatovir decreased LRTC development by Day 28 (2/15 [13.3%] vs 9/14 [64.3%], respectively; P = .008), compared with the placebo. Adverse events were similar for patients receiving presatovir and the placebo.
CONCLUSIONS
Presatovir had a favorable safety profile in adult HCT recipients with RSV but did not achieve the coprimary endpoints. Exploratory analyses suggest an antiviral effect among patients with lymphopenia.
CLINICAL TRIALS REGISTRATION
NCT02254408; EUDRA-CT#2014-002474-36.
背景
造血细胞移植（HCT）受者存在严重呼吸道合胞病毒（RSV）感染的风险。我们在一项接受 HCT 治疗且伴有 RSV 上呼吸道感染的患者中，评估了 RSV 融合抑制剂 presatovir 的随机、双盲、Ⅱ期临床试验结果。
方法
患者按淋巴细胞减少症（<200/μL）和利巴韦林的使用情况进行分层；按淋巴细胞减少症（<200/μL）和利巴韦林的使用情况进行分层，随机分组，分别接受 200mg 口服 presatovir 或安慰剂，于第 1、5、9、13 和 17 天给药，并随访至第 28 天。主要疗效终点是第 1 天至第 9 天鼻 RSV 病毒载量的时间加权平均变化，以及第 28 天前发展为下呼吸道并发症（LRTCs）的患者比例。
结果
2015 年 1 月 23 日至 2017 年 6 月 16 日，189 名患者被随机分配至治疗组（96 名患者接受 presatovir 治疗，93 名患者接受安慰剂治疗）。与安慰剂组相比，presatovir 治疗并未显著影响（预先设定的 α = 0.01）第 1 天至第 9 天 RSV 病毒载量的时间加权平均下降（治疗差异为 -0.33 log10 拷贝/mL；95%置信区间[CI]：-0.64 至 -0.02 log10 拷贝/mL；P =.040），也未显著影响至第 28 天前进展为 LRTC（分别为 11.2%和 19.5%，比值比[OR]为 0.50；95%CI：0.22-1.18；P =.11）。在一项淋巴细胞减少症患者的事后分析中，presatovir 降低了至第 28 天的 LRTC 发展率（分别为 2/15 [13.3%]和 9/14 [64.3%]；P =.008），优于安慰剂。接受 presatovir 和安慰剂的患者的不良反应相似。
结论
presatovir 在伴有 RSV 的成人 HCT 受者中具有良好的安全性，但未达到主要终点。探索性分析表明，淋巴细胞减少症患者具有抗病毒作用。
临床试验注册
NCT02254408；EUDRA-CT#2014-002474-36。
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