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Introduction <p>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.</p> Methods <p>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&#xa0;mg Tiprelestat or placebo twice a day for 7&#xa0;days, or shorter if no longer hospitalized due to COVID-19. Data about efficacy, safety, and pharmacokinetic trough levels were collected over 29&#xa0;days.</p> Results <p>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&#xa0;±&#xa0;4.8 (SD, maximum 15) 30-min infusions with Tiprelestat and 7.8&#xa0;±&#xa0;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&#xa0;≥&#xa0;6). The number of days with any oxygen support tended to be lower in the Tiprelestat group (2.4&#xa0;±&#xa0;3.6&#xa0;days) compared to placebo (4.0&#xa0;±&#xa0;6.2&#xa0;days). Stable plasma trough levels of Tiprelestat were shown upon repeated administration for up to 7&#xa0;days, even in patients with impaired renal function (eGFR&#xa0;&gt;&#xa0;31 to&#xa0;&lt;&#xa0;60&#xa0;mL/min) as comorbidity.</p> Conclusion <p>Tiprelestat infused for 30&#xa0;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.</p> Trial registrations <p>EudraCT 2022–000714-33, DRKS00031463.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年9月16日

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  • 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

摘要

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.