PDF(Pubmed)
Abstract：
Hyper-inflammatory immune response, a hallmark of severe COVID-19, is associated with increased mortality. Acute respiratory distress syndrome (ARDS) is a common manifestation. We undertook two phase I/II studies in five and then 16 subjects with severe/critical COVID-19 to assess the safety and preliminary efficacy of apoptotic cells (Allocetra™-OTS, Enlivex Therapeutics), a cellular immunomodulatory therapy that reprograms macrophages to reduce hyper-inflammatory response severity.
Eligible patients presenting to the Emergency Room with severe COVID-19 and respiratory dysfunction received one intravenous administration of Allocetra™-OTS and were monitored for adverse events (AEs) for 28 days. The primary aim was to determine the safety profile of treatment; secondary aims were recovery from ARDS, intensive care unit (ICU) and hospital length-of-stay, and mortality. Immune modulator markers were measured to elucidate the mechanism of action of Allocetra™-OTS.
21 patients with severe-critical COVID-19 of Gamma, Alpha and Delta variants, were treated with a single dose of apoptotic cells. 19/21 patients had mild-to-severe ARDS at presentation. Median age was 53 years, 16/21 were males, 16/21 were overweight/obese. No serious related adverse events (SAEs) were reported. All 21 study subjects survived to day 28 (end of study); 19/21 recovered completely. Comparable mortality rates at the hospital were 3.8%-8.9% for age- and gender-matched patients, and 39%-55% for critical patients. Recovering patients exhibited rapid ARDS resolution and parallel resolution of inflammation markers and elevated cytokines/chemokines.
In patients with severe/critical COVID-19 associated with ARDS, Allocetra™-OTS was safe, well-tolerated, and showed promising results for resolution of respiratory failure and inflammation.
https://clinicaltrials.gov/ct2/show/study/NCT04513470, https://clinicaltrials.gov/ct2/show/study/NCT04590053, Identifiers NCT04513470, NCT04590053.
Eligible patients presenting to the Emergency Room with severe COVID-19 and respiratory dysfunction received one intravenous administration of Allocetra™-OTS and were monitored for adverse events (AEs) for 28 days. The primary aim was to determine the safety profile of treatment; secondary aims were recovery from ARDS, intensive care unit (ICU) and hospital length-of-stay, and mortality. Immune modulator markers were measured to elucidate the mechanism of action of Allocetra™-OTS.
21 patients with severe-critical COVID-19 of Gamma, Alpha and Delta variants, were treated with a single dose of apoptotic cells. 19/21 patients had mild-to-severe ARDS at presentation. Median age was 53 years, 16/21 were males, 16/21 were overweight/obese. No serious related adverse events (SAEs) were reported. All 21 study subjects survived to day 28 (end of study); 19/21 recovered completely. Comparable mortality rates at the hospital were 3.8%-8.9% for age- and gender-matched patients, and 39%-55% for critical patients. Recovering patients exhibited rapid ARDS resolution and parallel resolution of inflammation markers and elevated cytokines/chemokines.
In patients with severe/critical COVID-19 associated with ARDS, Allocetra™-OTS was safe, well-tolerated, and showed promising results for resolution of respiratory failure and inflammation.
https://clinicaltrials.gov/ct2/show/study/NCT04513470, https://clinicaltrials.gov/ct2/show/study/NCT04590053, Identifiers NCT04513470, NCT04590053.
摘要：
■超炎性免疫反应，严重COVID-19的一个标志与死亡率增加有关。急性呼吸窘迫综合征（ARDS）是一种常见的表现。我们在5名和16名患有严重/严重COVID-19的受试者中进行了两项I/II期研究，以评估凋亡细胞的安全性和初步疗效(Allocetra™-OTS，EnlivexTherapeutics)，一种细胞免疫调节疗法，可重新编程巨噬细胞以减轻过度炎症反应的严重程度。
■到急诊室就诊的患有严重COVID-19和呼吸功能障碍的符合条件的患者接受了一次Allocetra™-OTS的静脉给药，并监测不良事件（AE）28天。主要目的是确定治疗的安全性；次要目的是从ARDS中恢复，重症监护病房（ICU）和住院时间，和死亡率。测量免疫调节剂标记以阐明Allocetra™-OTS的作用机制。
■21例重症患者，Alpha和Delta变体,用单剂量的凋亡细胞处理。19/21患者在就诊时出现轻度至重度ARDS。中位年龄为53岁,16/21是男性，16/21为超重/肥胖。未报告严重相关不良事件（SAE）。所有21名研究受试者存活至第28天(研究结束);19/21完全恢复。年龄和性别匹配的患者在医院的死亡率为3.8%-8.9%，危重患者为39%-55%。康复患者表现出快速的ARDS消退和炎症标志物和升高的细胞因子/趋化因子的平行消退。
■在与ARDS相关的重症/危重症COVID-19患者中，Allocetra™-OTS是安全的,耐受性良好,并显示出解决呼吸衰竭和炎症的有希望的结果。
■https://clinicaltrials.gov/ct2/show/study/NCT04513470,https://clinicaltrials.gov/ct2/show/study/NCT04590053,标识符NCT04513470,NCT04590053。
■到急诊室就诊的患有严重COVID-19和呼吸功能障碍的符合条件的患者接受了一次Allocetra™-OTS的静脉给药，并监测不良事件（AE）28天。主要目的是确定治疗的安全性；次要目的是从ARDS中恢复，重症监护病房（ICU）和住院时间，和死亡率。测量免疫调节剂标记以阐明Allocetra™-OTS的作用机制。
■21例重症患者，Alpha和Delta变体,用单剂量的凋亡细胞处理。19/21患者在就诊时出现轻度至重度ARDS。中位年龄为53岁,16/21是男性，16/21为超重/肥胖。未报告严重相关不良事件（SAE）。所有21名研究受试者存活至第28天(研究结束);19/21完全恢复。年龄和性别匹配的患者在医院的死亡率为3.8%-8.9%，危重患者为39%-55%。康复患者表现出快速的ARDS消退和炎症标志物和升高的细胞因子/趋化因子的平行消退。
■在与ARDS相关的重症/危重症COVID-19患者中，Allocetra™-OTS是安全的,耐受性良好,并显示出解决呼吸衰竭和炎症的有希望的结果。
■https://clinicaltrials.gov/ct2/show/study/NCT04513470,https://clinicaltrials.gov/ct2/show/study/NCT04590053,标识符NCT04513470,NCT04590053。
