Journal article
Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19
Lung, v 201(2), pp 159-170
01 Apr 2023
PMID: 37000214
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Garadacimab, a fully human IgG4 monoclonal antibody, inhibits the kallikrein-kinin pathway at a key initiator, activated coagulation factor XII (FXIIa), and may play a protective role in preventing the progression of COVID-19. This phase 2 study evaluated the efficacy and safety of garadacimab plus standard of care (SOC) versus placebo plus SOC in patients with severe COVID-19.
Patients hospitalised with COVID-19 were randomised (1:1) to a single intravenous dose of garadacimab (700 mg) plus SOC or placebo plus SOC. Co-primary endpoint was incidence of endotracheal intubation or death between randomisation and Day 28. All-cause mortality, safety and pharmacokinetic/pharmacodynamic parameters were assessed.
No difference in incidence of tracheal intubation or death (p = 0.274) or all-cause mortality was observed (p = 0.382). Garadacimab was associated with a lower incidence of treatment-emergent adverse events (60.3% vs 67.8%) and fewer serious adverse events (34 vs 45 events) versus placebo. No garadacimab-related deaths or bleeding events were reported, including in the 45.9% (n = 28/61) of patients who received concomitant heparin. Prolonged activated partial thromboplastin time (aPTT), and increased coagulation factor XII (FXII) levels were observed with garadacimab versus placebo to Day 14, whilst FXIIa-mediated kallikrein activity (FXIIa-mKA) was suppressed to Day 28.
In patients with severe COVID-19, garadacimab did not confer a clinical benefit over placebo. Transient aPTT prolongation and suppressed FXIIa-mKA showed target engagement of garadacimab that was not associated with bleeding events even with concomitant anticoagulant use. The safety profile of garadacimab was consistent with previous studies in patients with hereditary angioedema.
NCT04409509. Date of registration: 28 May, 2020.
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Details
- Title
- Efficacy and Safety of Garadacimab in Combination with Standard of Care Treatment in Patients with Severe COVID-19
- Creators
- Alberto Papi - University of FerraraRenee D Stapleton - University of VermontPaul M Shore - CSL (United States)Mihai Alexandru Bica - Behringwerke (Germany)Younan Chen - CSL (United States)Michael Larbig - CSL (Switzerland)Tobias Welte - Medizinische Hochschule Hannover
- Publication Details
- Lung, v 201(2), pp 159-170
- Publisher
- Springer Nature
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000961173600001
- Scopus ID
- 2-s2.0-85151412789
- Other Identifier
- 991021838142704721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Respiratory System