Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial.
Safety and efficacy of inhaled nebulised interferon beta-1a (SNG001) for treatment of SARS-CoV-2 infection: a randomised, double-blind, placebo-controlled, phase 2 trial.
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雾化吸入干扰素β-1a(SNG001)治疗SARS-CoV-2感染的安全性和有效性：一项随机、双盲、安慰剂对照的2期试验。
DOI：
10.1016/s2213-2600(20)30511-7
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发表时间：
2021-03
期刊：
影响因子：
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通讯作者：
Inhaled Interferon Beta COVID-19 Study Group
中科院分区：
文献类型：
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作者：
Monk PD;Marsden RJ;Tear VJ;Brookes J;Batten TN;Mankowski M;Gabbay FJ;Davies DE;Holgate ST;Ho LP;Clark T;Djukanovic R;Wilkinson TMA;Inhaled Interferon Beta COVID-19 Study Group
严重急性呼吸综合征冠状病毒2(SARS-CoV-2)感染具有严重和长期患病的巨大风险；目前治疗选择有限。我们评估了雾化吸入干扰素β-1a(SNG001)治疗新冠肺炎入院患者的有效性和安全性。我们在英国的9个地点进行了一项随机、双盲、安慰剂对照的第二阶段试点试验。18岁或以上的成年人入院时出现新冠肺炎症状，RT-PCR法和/或护理点试验阳性，他们被随机分配(1：1)接受SNG001(6MIU)或安慰剂治疗，每天通过口罩吸入，持续14天。主要结果是在有意治疗的人群(所有接受至少一剂研究药物的随机患者)的剂量期间，世界卫生组织临床改善序贯评分(OSCI)上的临床情况发生了变化。OSCI为9分制，0分代表没有感染，8分代表死亡。进行了多项分析，以确定最适合未来临床试验的统计方法。安全性通过28天的不良事件监测进行评估。这项试验在ClinicaltrialsRegister.eu(2020-001023-14)和ClinicalTrials.gov(NCT04385095)注册；新冠肺炎住院患者的试点试验现已完成。在2020年3月30日至5月30日期间，101名患者被随机分配到SNG001组(n=50)或安慰剂组(n=51)。48人接受SNG001治疗，50人接受安慰剂治疗，并包括在意向治疗人群中。66名患者(67%)在基线时需要氧气补充：安慰剂组29名，SNG001组37名。在第15天或第16天，接受SNG001治疗的患者在OSCI量表上有更大的改善几率(优势比2·32[95%CI 1·07-5·04]；p=0.033)，并且在治疗期间比接受安慰剂治疗的患者更有可能恢复到OSCI评分1(无活动限制)(风险比2·19[95%CI 1·03-4·69]；p=0.043)。SNG001耐受性良好。报告的最常见的紧急治疗不良事件是头痛(SNG001组有7名患者[15%]，安慰剂组有5名患者[10%])。安慰剂组有3人死亡，SNG001组没有死亡。与服用安慰剂的患者相比，服用SNG001的患者改善的几率更大，从SARS-CoV-2感染中恢复得更快，这为进一步试验提供了强有力的理由。Synairgen研究公司。
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection carries a substantial risk of severe and prolonged illness; treatment options are currently limited. We assessed the efficacy and safety of inhaled nebulised interferon beta-1a (SNG001) for the treatment of patients admitted to hospital with COVID-19. We did a randomised, double-blind, placebo-controlled, phase 2 pilot trial at nine UK sites. Adults aged 18 years or older and admitted to hospital with COVID-19 symptoms, with a positive RT-PCR or point-of-care test, or both, were randomly assigned (1:1) to receive SNG001 (6 MIU) or placebo by inhalation via a mouthpiece daily for 14 days. The primary outcome was the change in clinical condition on the WHO Ordinal Scale for Clinical Improvement (OSCI) during the dosing period in the intention-to-treat population (all randomised patients who received at least one dose of the study drug). The OSCI is a 9-point scale, where 0 corresponds to no infection and 8 corresponds to death. Multiple analyses were done to identify the most suitable statistical method for future clinical trials. Safety was assessed by monitoring adverse events for 28 days. This trial is registered with Clinicaltrialsregister.eu (2020-001023-14) and ClinicalTrials.gov (NCT04385095); the pilot trial of inpatients with COVID-19 is now completed. Between March 30 and May 30, 2020, 101 patients were randomly assigned to SNG001 (n=50) or placebo (n=51). 48 received SNG001 and 50 received placebo and were included in the intention-to-treat population. 66 (67%) patients required oxygen supplementation at baseline: 29 in the placebo group and 37 in the SNG001 group. Patients receiving SNG001 had greater odds of improvement on the OSCI scale (odds ratio 2·32 [95% CI 1·07–5·04]; p=0·033) on day 15 or 16 and were more likely than those receiving placebo to recover to an OSCI score of 1 (no limitation of activities) during treatment (hazard ratio 2·19 [95% CI 1·03–4·69]; p=0·043). SNG001 was well tolerated. The most frequently reported treatment-emergent adverse event was headache (seven [15%] patients in the SNG001 group and five [10%] in the placebo group). There were three deaths in the placebo group and none in the SNG001 group. Patients who received SNG001 had greater odds of improvement and recovered more rapidly from SARS-CoV-2 infection than patients who received placebo, providing a strong rationale for further trials. Synairgen Research.