Targeting GPVI with glenzocimab in COVID-19 patients: Results from a randomized clinical trial
Julien Pottecher, Francois Raffi, Martine Jandrot-Perrus, Sophie Binay, Andrea Comenducci, Violaine Desort-Henin, Déborah François, Shahin Gharakhanian, Marilyn Labart, Adeline Meilhoc, Elie Toledano, Yannick Pletan, Gilles Avenard, Victor H Sato
PLOS ONE, doi:10.1371/journal.pone.0302897
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.
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'abstract': '<jats:sec id="sec001">\n'
'<jats:title>Background</jats:title>\n'
'<jats:p>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.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec002">\n'
'<jats:title>Methods and patients</jats:title>\n'
'<jats:p>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.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec003">\n'
'<jats:title>Results</jats:title>\n'
'<jats:p>Between December 2020 and August 2021, 61 patients received at least one dose (30 '
'glenzocimab vs 32 placebo) and 58 completed the study (29 <jats:italic>vs</jats:italic> 29). '
'Clinical progression of COVID-19 ARDS was not statistically different between glenzocimab and '
'placebo arms (43.3% and 29.0%, respectively; <jats:italic>p = '
'0</jats:italic>.<jats:italic>245</jats:italic>). Decrease in the NEWS-2 category at D4 was '
'statistically significant (<jats:italic>p = 0</jats:italic>.<jats:italic>0290</jats:italic>) '
'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.</jats:p>\n'
'</jats:sec>\n'
'<jats:sec id="sec004">\n'
'<jats:title>Conclusions</jats:title>\n'
'<jats:p>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.</jats:p>\n'
'</jats:sec>',
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