Work

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

Year: 2025

Type: article

Study designs: Randomized Controlled Trial, Clinical Trial

Abstract: 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 < 60 mL/min) as comorbidity. 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. EudraCT 2022–000714-33, DRKS00031463. In patients, suffering from COVID-19, excessive activity of the enzyme neutrophil elastase can cause tissue injury during inflammation and contribute to progression to severe illness. Tiprelestat, recombinant human Elafin, reversibly inhibits this enzyme and may provide anti-inflammatory benefits in respiratory disease. This trial was the first to investigate Tiprelestat in patients hospitalized due to COVID-19. A multicentre, randomized, double-blind, placebo-controlled study was conducted in seven hospitals in Germany between May 2023 and May 2024. Adults with moderate COVID-19 received either 100 mg Tiprelestat or placebo as 30-minute infusions twice daily for up to 7 days. Safety, tolerability, and drug concentrations in blood were assessed over 29 days. Although 296 patients were planned, recruitment slowed at the end of the pandemic and only 17 were included (9 Tiprelestat, 8 placebo). Tiprelestat was well tolerated, and no drug safety concerns were identified. Stable plasma trough levels were observed with repeated dosing, even in patients with poor kidney function (eGFR 31 to 60 mL/min). None of the patients treated with Tiprelestat progressed to severe COVID-19 disease. Patients who received Tiprelestat required oxygen support for an average of 2.4 days, compared with 4.0 days in the placebo group. In summary, Tiprelestat appears safe and well tolerated in patients with moderate COVID-19. Larger studies are required to confirm potential benefits and to explore its role in treating other severe inflammatory lung diseases.

Source: Advances in Therapy

DOI: 10.1007/s12325-025-03362-w