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

Publication date: Sep 16, 2025

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. 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. 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

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