A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part.
A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part.
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DOI：
10.1128/aac.00697-22
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发表时间：
2022-10-18
影响因子：
4.9
通讯作者：
中科院分区：
文献类型：
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作者：
这项多中心、双盲、2/3期研究的2a期部分评估了恩西瑞韦（一种新型严重急性呼吸综合征冠状病毒2型（SARS-CoV-2）3C样蛋白酶抑制剂）在日本轻中度冠状病毒病2019（COVID-19）或无症状SARS-CoV-2感染患者中的疗效和安全性。69名患者随机（1：1：1）接受5天恩西曲韦富马酸（第1天375 mg，随后每日125 mg，或第1天750 mg，随后每日250 mg）或安慰剂口服，并随访至第28天。主要结局是SARS-CoV-2病毒滴度较基线的变化。恩西瑞韦125 mg、恩西瑞韦250 mg和安慰剂组分别有16、14和17名患者被纳入意向治疗人群（平均年龄：38.0至40.4岁）。第4天，SARS-CoV-2病毒滴度较基线的变化在基线时病毒滴度和病毒RNA阳性的患者中，恩西瑞韦125 mg组的感染率（log 10 50%组织培养感染剂量/mL）更高（平均值[标准差]，-2.42 [1.42]; P = 0.0712）和250 mg（-2.81 [1.21]; P = 0.0083）与安慰剂（-1.54 [0.74]）相比;与安慰剂相比，恩西瑞韦治疗使SARS-CoV-2 RNA减少了-1.4至-1.5 log 10拷贝/mL。在第6天和之后，各组的病毒滴度和病毒RNA相似。恩西瑞韦治疗后，感染性病毒清除的中位时间缩短了约50小时。所有不良事件均为轻度至中度。恩西瑞韦治疗显示出快速的SARS-CoV-2清除和良好的耐受性（日本临床试验注册处标识符：jRCT 2031210350）。
This multicenter, double-blind, phase 2a part of a phase 2/3 study assessed the efficacy and safety of ensitrelvir, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor, in Japanese patients with mild-to-moderate coronavirus disease 2019 (COVID-19) or asymptomatic SARS-CoV-2 infection. Sixty-nine patients were randomized (1:1:1) to orally receive 5-day ensitrelvir fumaric acid (375 mg on day 1 followed by 125 mg daily, or 750 mg on day 1 followed by 250 mg daily) or placebo and followed up until day 28. The primary outcome was the change from baseline in the SARS-CoV-2 viral titer. A total of 16, 14, and 17 patients in the ensitrelvir 125 mg, ensitrelvir 250 mg, and placebo groups, respectively, were included in the intention-to-treat population (mean age: 38.0 to 40.4 years). On day 4, the change from baseline in SARS-CoV-2 viral titer (log10 50% tissue culture infectious dose/mL) in patients with positive viral titer and viral RNA at baseline was greater with ensitrelvir 125 mg (mean [standard deviation], –2.42 [1.42]; P = 0.0712) and 250 mg (–2.81 [1.21]; P = 0.0083) versus placebo (–1.54 [0.74]); ensitrelvir treatment reduced SARS-CoV-2 RNA by –1.4 to –1.5 log10 copies/mL versus placebo. The viral titer and viral RNA were similar across groups on and after day 6. The median time to infectious viral clearance decreased by approximately 50 h with ensitrelvir treatment. All adverse events were mild to moderate. Ensitrelvir treatment demonstrated rapid SARS-CoV-2 clearance and was well tolerated (Japan Registry of Clinical Trials identifier: jRCT2031210350).
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影响因子：
19
作者：
Singanayagam, Anika;Patel, Monika;Gopal, Robin
通讯作者：
Gopal, Robin
影响因子：
64.8
作者：
通讯作者：
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影响因子：
13.8
作者：
通讯作者：
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DOI：
10.1016/j.cmi.2021.02.014
发表时间：
2021-06
期刊：
Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases
影响因子：
--
作者：
Folgueira MD;Luczkowiak J;Lasala F;Pérez-Rivilla A;Delgado R
通讯作者：
Delgado R
DOI：
10.1016/j.ijid.2021.12.312
发表时间：
2022-03
期刊：
International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases
影响因子：
--
作者：
Davies M;Bramwell LR;Jeffery N;Bunce B;Lee BP;Knight B;Auckland C;Masoli JA;Harries LW
通讯作者：
Harries LW