Tiprelestat for treatment of hospitalized COVID-19: results of the double-blind randomized placebo-controlled COMCOVID trial.

IF 4 3区医学 Q2 MEDICINE, RESEARCH & EXPERIMENTAL

Advances in Therapy Pub Date : 2025-09-16 DOI:10.1007/s12325-025-03362-w

Ingmar Bergs, Stephan Budweiser, Hans-Heinrich Henneicke-von Zepelin, Hagen Kelm, Tom Bollmann, Johannes-Josef Tebbe, Stephan Sorichter, Stefan Lüth, Stephan Walterspacher, Henning Wege, Oliver Wiedow, Michael Dreher

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引用次数: 0

Abstract

Introduction: Tiprelestat (recombinant human elafin) reversibly inhibits human neutrophil elastase. This can reduce overactivity of this enzyme in COVID-19-patients and might prohibit further organ damage and progression to severe disease. This protein had yet not been tested in COVID-19 patients.

Methods: This prospective, multicenter, randomized, double-blind, placebo-controlled trial investigated Tiprelestat in adult patients hospitalized for COVID-19 in 7 hospitals in Germany between May 2023 and May 2024. Patients received 100 mg Tiprelestat or placebo twice a day for 7 days, or shorter if no longer hospitalized due to COVID-19. Data about efficacy, safety, and pharmacokinetic trough levels were collected over 29 days.

Results: A total of 296 patients were planned. Due to slow recruitment during the end of the pandemic, only 17 patients were finally included. Of these, 9 received Tiprelestat and 8 placebo. The mean treatment exposition was 9.1 ± 4.8 (SD, maximum 15) 30-min infusions with Tiprelestat and 7.8 ± 3.2 (maximum 14) with placebo. No relevant abnormalities in clinical or laboratory blood parameters were suspected to be caused by Tiprelestat. None of the Tiprelestat-treated patients developed severe COVID-19 (WHO Clinical Progression Scale ≥ 6). The number of days with any oxygen support tended to be lower in the Tiprelestat group (2.4 ± 3.6 days) compared to placebo (4.0 ± 6.2 days). Stable plasma trough levels of Tiprelestat were shown upon repeated administration for up to 7 days, even in patients with impaired renal function (eGFR > 31 to < 60 mL/min) as comorbidity.

Conclusion: Tiprelestat infused for 30 min twice daily in patients with moderate COVID-19 requiring hospitalization was well tolerated and appears to be safe. Beneficially, plasma trough levels of the drug over time were high and stable. The small sample size does not facilitate reliable statements about efficacy. Further studies are necessary including other inflammatory severe respiratory diseases.

Trial registrations: EudraCT 2022-000714-33, DRKS00031463.

查看原文本刊更多论文

替普雷司他治疗住院COVID-19：双盲随机安慰剂对照COMCOVID试验结果

替普雷司他（重组人elafin）可逆性抑制人中性粒细胞弹性酶。这可以减少covid -19患者体内这种酶的过度活性，并可能阻止进一步的器官损伤和严重疾病的进展。这种蛋白质尚未在COVID-19患者中进行测试。方法：这项前瞻性、多中心、随机、双盲、安慰剂对照试验调查了2023年5月至2024年5月在德国7家医院因COVID-19住院的成年患者使用替普雷司他的情况。患者每天两次接受100毫克替普雷司他或安慰剂治疗，连续7天，如果因COVID-19不再住院，则接受更短时间的治疗。在29天内收集疗效、安全性和药代动力学谷底水平的数据。结果：共计划296例患者。由于大流行结束时招募缓慢，最终只纳入了17名患者。其中9人接受替普雷司他治疗，8人接受安慰剂治疗。替普雷司他输注30分钟平均暴露时间为9.1±4.8 (SD，最长15)，安慰剂输注30分钟平均暴露时间为7.8±3.2（最长14）。未发现替普雷司他引起的相关临床或实验室血液参数异常。替普雷司他治疗的患者中没有出现严重的COVID-19 （WHO临床进展量表≥6）。与安慰剂组（4.0±6.2天）相比，替普雷司他组（2.4±3.6天）使用任何氧支持的天数更短。反复给药长达7天的替普雷司他血浆谷水平稳定，即使在肾功能受损的患者中也是如此。结论：替普雷司他输注30分钟，每天两次，需要住院治疗的中度COVID-19患者耐受性良好，似乎是安全的。有益的是，随着时间的推移，该药物的血浆谷水平高且稳定。小样本量不能促进关于疗效的可靠陈述。需要进一步研究，包括其他炎症性严重呼吸系统疾病。试验注册：EudraCT 2022-000714-33， DRKS00031463。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Advances in Therapy 医学-药学

CiteScore

7.20

自引率

2.60%

发文量

353

审稿时长

6-12 weeks

期刊介绍： Advances in Therapy is an international, peer reviewed, rapid-publication (peer review in 2 weeks, published 3–4 weeks from acceptance) journal dedicated to the publication of high-quality clinical (all phases), observational, real-world, and health outcomes research around the discovery, development, and use of therapeutics and interventions (including devices) across all therapeutic areas. Studies relating to diagnostics and diagnosis, pharmacoeconomics, public health, epidemiology, quality of life, and patient care, management, and education are also encouraged. The journal is of interest to a broad audience of healthcare professionals and publishes original research, reviews, communications and letters. The journal is read by a global audience and receives submissions from all over the world. Advances in Therapy will consider all scientifically sound research be it positive, confirmatory or negative data. Submissions are welcomed whether they relate to an international and/or a country-specific audience, something that is crucially important when researchers are trying to target more specific patient populations. This inclusive approach allows the journal to assist in the dissemination of all scientifically and ethically sound research.