Glenzocimab, a novel antiplatelet therapy in COVID-19 related acute respiratory distress syndrome (ARDS): the garden study, a phase 2 clinical trial

Background : Glenzocimab is a fully-humanized fragment of monoclonal antibody directed against the human platelet glycoprotein VI (GPVI), which is involved in the formation, growth and stability of thrombi. Thrombosis mechanism in COVID-19 has not been completely elucidated. In severe COVID-19 disease, platelets may contribute to both micro and macro-thrombosis (particularly involving lung vasculature) and to the inflammatory syndrome. Furthermore, evidence involving platelets in lung fibrosis, via GPVI, have been described. In COVID-19-induced ARDS, developing new treatments aiming at reducing the contribution of platelets to uncontrolled lung inflammation and at preventing pro-thrombotic downstream complications is an unmet medical need. Such treatments should also be safe, avoiding undesirable bleeding. Aims : The primary objective of GARDEN, a phase 2 clinical trial, is to offer an additional treatment option to SARS-CoV-2 infected patients presenting with an ARDS, and beyond, preventing downstream complications due to pro-thrombotic and pro-inflammatory conditions. Methods : GARDEN (NCT04659109) is a randomized, double blind, multicenter, placebo-controlled, parallel group, fixed dose phase 2b clinical trial. Sixty evaluable patients will be randomized in a 1/1 ratio to glenzocimab (1000 mg/day for 3 days, 6h IV infusion) or to a matching placebo. Main inclusion criteria are: a symptomatic and biologically-confirmed SARS-CoV-2 infection with signs of moderate but progressive pulmonary disease;a prothrombotic status and elevated inflammation markers. Patients requiring invasive mechanical ventilation or with a disseminated intravascular coagulation are excluded. The primary objective is to evaluate the effect of glenzocimab in preventing clinical progression of disease when added to standard-of-care. Secondary safety endpoints include mortality, chest CT scan, SAEs and bleeding-related events. Results : GARDEN study has been approved in France and Brazil. To date, 16 patients have been recruited, no safety signal requiring a DSMB evaluation occurred. Conclusions : The study is expected to be completed by June 2021.