Targeting GPVI with glenzocimab in COVID-19 patients: Results from a randomized clinical trial.
PLoS One
; 19(6): e0302897, 2024.
Article
em En
| MEDLINE
| ID: mdl-38885234
ABSTRACT
BACKGROUND:
Glenzocimab is a novel antithrombotic agent which targets platelet glycoprotein VI (GPVI) and does not induce haemorrhage. SARS-CoV-2 triggers a prothrombotic state and lung injury whose mechanisms include coagulopathy, endothelial dysfunction, and inflammation with dysregulated platelets. METHODS AND PATIENTS GARDEN was a randomised double-blind, exploratory phase II study of glenzocimab in SARS-CoV-2 respiratory failure (NCT04659109). PCR+ adults in Brazil and France (7 centres) were randomized to standard-of-care (SOC) plus glenzocimab (1000 mg/dayx3 days) or placebo, followed for 40 days. Primary efficacy endpoint was clinical progression at Day 4. All analyses concerned the intention-to-treat population.RESULTS:
Between December 2020 and August 2021, 61 patients received at least one dose (30 glenzocimab vs 32 placebo) and 58 completed the study (29 vs 29). Clinical progression of COVID-19 ARDS was not statistically different between glenzocimab and placebo arms (43.3% and 29.0%, respectively; p = 0.245). Decrease in the NEWS-2 category at D4 was statistically significant (p = 0.0290) in the glenzocimab arm vs placebo. No Serious Adverse Event (SAE) was deemed related to study drug; bleeding related events were reported in 6 patients (7 events) and 4 patients (4 events) in glenzocimab and placebo arms, respectively.CONCLUSIONS:
Therapeutic GPVI inhibition assessment during COVID-19 was conducted in response to a Public Health emergency. Glenzocimab in coagulopathic patients under therapeutic heparin was neither associated with increased bleeding, nor SAE. Clinical impact of glenzocimab on COVID-19 ARDS was not demonstrated. A potential role for GPVI inhibition in other types of ARDS deserves further experimentation. Glenzocimab is currently studied in stroke (ACTISAVE NCT05070260) and cardiovascular indications.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Glicoproteínas da Membrana de Plaquetas
/
SARS-CoV-2
/
COVID-19
/
Tratamento Farmacológico da COVID-19
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Male
/
Middle aged
País como assunto:
America do sul
/
Brasil
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article