一项随机2a期研究，旨在调查用托佐拉单抗阻断白细胞介素-33对因新冠肺炎住院患者的影响：ACCORD-2研究。
A randomised phase 2a study to investigate the effects of blocking interleukin-33 with tozorakimab in patients hospitalised with COVID-19: ACCORD-2.
作者信息
Wilkinson Tom, De Soyza Anthony, Carroll Miles, Chalmers James D, Crooks Michael G, Griffiths Gareth, Shankar-Hari Manu, Ho Ling-Pei, Horsley Alex, Kell Chris, Lara Beatriz, Mishra Biswa, Moate Rachel, Page Clive, Pandya Hitesh, Raw Jason, Reid Fred, Saralaya Dinesh, Scott Ian C, Siddiqui Salman, Ustianowski Andy, van Zuydam Natalie, Woodcock Ashley, Singh Dave
机构信息
NIHR Southampton Biomedical Research Centre and University of Southampton, Southampton, UK.
Population Health Sciences Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.
出版信息
ERJ Open Res. 2023 Oct 2;9(5). doi: 10.1183/23120541.00249-2023. eCollection 2023 Sep.
BACKGROUND
Increased serum interleukin (IL)-33 predicts poor outcomes in patients hospitalised with coronavirus disease 2019 (COVID-19). We examined the efficacy and safety of tozorakimab, a monoclonal antibody that neutralises IL-33, in improving outcomes in ACCORD-2 (EudraCT: 2020-001736-95).
METHODS
ACCORD-2 was an open-label, phase 2a study in adults hospitalised with COVID-19. Patients were randomised 1:1 to tozorakimab 300 mg plus standard of care (SoC) or SoC alone. The primary end-point was time to clinical response (sustained clinical improvement of ≥2 points on the World Health Organization ordinal scale, discharge from hospital or fit for discharge) by day 29. Other end-points included death or respiratory failure, mortality and intensive care unit admission by day 29, and safety. Serum IL-33/soluble stimulated-2 (sST2) complex levels were measured by high-sensitivity immunoassay.
RESULTS
Efficacy analyses included 97 patients (tozorakimab+SoC, n=53; SoC, n=44). Median time to clinical response did not differ between the tozorakimab and SoC arms (8.0 and 9.5 days, respectively; HR 0.96, 80% CI 0.70-1.31; one-sided p=0.33). Tozorakimab was well tolerated and the OR for risk of death or respiratory failure with treatment SoC was 0.55 (80% CI 0.27-1.12; p=0.26), while the OR was 0.31 (80% CI 0.09-1.06) in patents with high baseline serum IL-33/sST2 complex levels.
CONCLUSIONS
Overall, ACCORD-2 results suggest that tozorakimab could be a novel therapy for patients hospitalised with COVID-19, warranting further investigation in confirmatory phase 3 studies.
背景
血清白细胞介素（IL）-33水平升高预示着2019冠状病毒病（COVID-19）住院患者预后不良。我们在ACCORD-2研究（欧洲药品管理局临床试验注册号：2020-001736-95）中检验了托扎单抗（一种可中和IL-33的单克隆抗体）改善预后的疗效和安全性。
方法
ACCORD-2是一项针对COVID-19住院成人患者的开放标签2a期研究。患者按1:1随机分组，分别接受300mg托扎单抗加标准治疗（SoC）或仅接受标准治疗。主要终点是至第29天时的临床反应时间（世界卫生组织序贯量表上持续临床改善≥2分、出院或适合出院）。其他终点包括第29天时的死亡或呼吸衰竭、死亡率和重症监护病房入院情况以及安全性。采用高敏免疫分析法检测血清IL-33/可溶性刺激因子2（sST2）复合物水平。
结果
疗效分析纳入了97例患者（托扎单抗+SoC组，n=53；SoC组，n=44）。托扎单抗组和SoC组至临床反应的中位时间无差异（分别为8.0天和9.5天；风险比0.96，80%置信区间0.70-1.31；单侧p=0.33）。托扎单抗耐受性良好，接受治疗的患者死亡或呼吸衰竭风险的比值比为0.55（80%置信区间0.27-1.12；p=0.26），而基线血清IL-33/sST2复合物水平高的患者该比值比为0.31（80%置信区间0.09-1.06）。
结论
总体而言，ACCORD-2研究结果表明，托扎单抗可能是COVID-19住院患者的一种新型治疗方法，值得在确证性3期研究中进一步探究。
Zotero 插件