Anti-C5a抗体IFX-1 (vilobelimab)治疗和最好的支持性护理患者严重COVID-19 (PANAMO):一个探索性,非盲、第二阶段的随机对照试验。

文章的细节

引用
复制到剪贴板

Vlaar已de熊先生年代,布希米,蒂默曼SAMEG, van Zeggeren即今敏R,霍斯特后L, Bulle EB, van Baarle FEHP, van de调查MCG, Kemper EM, van der霍斯特刑事法庭,舒尔茨MJ,角J,保卢斯F, Bos LD, Wiersinga WJ, Witzenrath M, Rueckinger年代,Pilz K,这MC,郭射频,Heunks L, van Paassen P, Riedemann数控,van de发现D

Anti-C5a抗体IFX-1 (vilobelimab)治疗和最好的支持性护理患者严重COVID-19 (PANAMO):一个探索性,非盲、第二阶段的随机对照试验。

柳叶刀Rheumatol。2020年12月,2 (12):e764-e773。doi: 10.1016 / s2665 - 9913 (20) 30341 - 6。Epub 2020年9月28日。

PubMed ID
33015643 (在PubMed
]
文摘

背景:严重COVID-19的特点是炎症和凝固的补体系统激活。我们旨在探讨选择性地阻断过敏毒素的潜在效益和安全与单克隆抗体和补充蛋白质C5a IFX-1 (vilobelimab) COVID-19患者严重。方法:我们进行了一次探索性、非盲、随机第二阶段试验(自适应2/3 PANAMO阶段试验的一部分)成年人患有严重的静脉IFX-1 COVID-19三个学术医院在荷兰。合格标准是18岁或以上;严重肺炎和肺浸润与肺炎一致,临床严重气短的历史在过去14天,或需要非侵入性或侵入性通风;严重的疾病定义为一个动脉氧气分压比部分的氧气浓度在吸气(PaO2 /供给)100毫米汞柱和250毫米汞柱之间的仰卧位;2、严重急性呼吸系统综合症冠状病毒感染通过rt - pcr证实。病人被随机分配接受IFX-1 1:1(7 800毫克剂量的静脉注射)+最好的支持性护理(IFX-1组)或者只最好的支持性护理(对照组)。主要结果的百分比变化PaO2 /供给基线之间的仰卧位和第五天。死亡率在28天,治疗诱发二次结果和严重不良事件是关键。 The primary analysis was done in the intention-to-treat population and safety analyses were done in all patients according to treatment received. This trial is registered at ClinicalTrials.gov (NCT04333420). Findings: Between March 31 and April 24, 2020, 30 patients were enrolled and randomly assigned to the IFX-1 group (n=15) or the control group (n=15). During the study it became clear that several patients could not be assessed regularly in the supine position because of severe hypoxaemia. It was therefore decided to focus on all PaO2/FiO2 assessments (irrespective of position). At day 5 after randomisation, the mean PaO2/FiO2 (irrespective of position) was 158 mm Hg (SD 63; range 84-265) in the IFX-1 group and 189 mm Hg (89; 71-329) in the control group. Analyses of the least squares mean relative change in PaO2/FiO2 at day 5 showed no differences between treatment groups (17% change in the IFX-1 group vs 41% in the control group; difference -24% [95% CI -58 to 9], p=0.15. Kaplan-Meier estimates of mortality by 28 days were 13% (95% CI 0-31) for the IFX-1 group and 27% (4-49) for the control group (adjusted hazard ratio for death 0.65 [95% CI 0.10-4.14]). The frequency of serious adverse events were similar between groups (nine [60%] in the IFX-1 group vs seven [47%] in the control group) and no deaths were considered related to treatment assignment. However, a smaller proportion of patients had pulmonary embolisms classed as serious in the IFX-1 group (two [13%]) than in the control group (six [40%]). Infections classed as serious were reported in three (20%) patients in the IFX-1 group versus five (33%) patients in the control group. Interpretation: In this small exploratory phase 2 part of the PANAMO trial, C5a inhibition with IFX-1 appears to be safe in patients with severe COVID-19. The secondary outcome results in favour of IFX-1 are preliminary because the study was not powered on these endpoints, but they support the investigation of C5a inhibition with IFX-1 in a phase 3 trial using 28-day mortality as the primary endpoint. Funding: InflaRx.

DrugBank数据引用了这篇文章

药物
药物靶点
药物 目标 类 生物 药理作用 行动
Vilobelimab 补充C5 蛋白质 人类
未知的
抑制剂
 细节