Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial.
Efficacy and safety of an inhaled pan-Janus kinase inhibitor, nezulcitinib, in hospitalised patients with COVID-19: results from a phase 2 clinical trial.
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DOI：
10.1136/bmjresp-2023-001627
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发表时间：
2023-07
影响因子：
4.1
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中科院分区：
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吸入性肺选择性泛Janus激酶抑制剂nezulcitinib在重度COVID-19患者的II期试验的第1部分中具有有利的安全性和潜在疗效信号，支持进展至第2部分。第2部分是一项随机、双盲、II期研究（NCT 04402866）。年龄18-80岁、确诊为症状性COVID-19、需要辅助供氧（不包括基线有创机械通气）的住院患者以1：1的比例随机分配至雾化奈珠西替尼3 mg或安慰剂组，持续7天，并接受背景标准治疗（包括皮质类固醇）。疗效终点包括至第28天的无呼吸衰竭（RFF）天数作为主要终点。次要终点包括安全性和第7天血氧饱和度（SaO 2）/吸入氧分数（FiO 2）比值较基线的变化，28天死亡率是预先规定的探索性终点。在2020年6月至2021年4月期间，205名患者接受了治疗（nezulcitinib，103人;安慰剂，102人）。在主要终点（RFF天数;中位数，21.0 vs 21.0; p=0.6137）或次要疗效终点方面，奈珠西替尼与安慰剂之间无统计学显著差异。Nezulcitinib通常耐受性良好，安全性特征良好。尽管未达到预先规定的主要、次要和探索性疗效终点，包括第28天的RFF、第7天SaO 2/FiO 2比值较基线的变化和第28天死亡率，但奈珠西替尼总体耐受性良好，安全性特征良好。需要进一步的研究来确定奈珠西替尼治疗是否在特定的炎症生物标志物定义的COVID-19患者人群中具有临床获益。
The inhaled lung-selective pan-Janus kinase inhibitor nezulcitinib had favourable safety and potential efficacy signals in part 1 of a phase 2 trial in patients with severe COVID-19, supporting progression to part 2. Part 2 was a randomised, double-blind phase 2 study (NCT04402866). Hospitalised patients aged 18–80 years with confirmed symptomatic COVID-19 requiring supplemental oxygen (excluding baseline invasive mechanical ventilation) were randomised 1:1 to nebulised nezulcitinib 3 mg or placebo for up to 7 days with background standard-of-care therapy (including corticosteroids). Efficacy endpoints included respiratory failure-free (RFF) days through day 28 as the primary endpoint. Secondary endpoints included safety and change from baseline oxygen saturation (SaO2)/fraction of inspired oxygen (FiO2) ratio on day 7, and 28-day mortality rate was a prespecified exploratory endpoint. Between June 2020 and April 2021, 205 patients were treated (nezulcitinib, 103; placebo, 102). There was no statistically significant difference between nezulcitinib versus placebo in the primary endpoint (RFF days; median, 21.0 vs 21.0; p=0.6137) or secondary efficacy endpoints. Nezulcitinib was generally well tolerated with a favourable safety profile. Although the prespecified primary, secondary and exploratory efficacy endpoints, including RFF through day 28, change from baseline SaO2/FiO2 ratio on day 7, and 28-day mortality rate, were not met, nezulcitinib was generally well tolerated and had a favourable safety profile. Further studies are required to determine if treatment with nezulcitinib confers clinical benefit in specific inflammatory biomarker-defined populations of patients with COVID-19.
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