A Novel Anti-Thrombotic, Glenzocimab, in Covid-19 acute respiratory distress syndrome (Cov-ARDS).

Abstract

Background: Platelets (plt) may contribute to the inflammatory thrombosis in Cov-ARDS. Glenzocimab a humanized monoclonal antibody fragment against plt glycoprotein VI, inhibiting plt binding to the thrombus does affect physiological hemostasis, is assessed in Stroke (ph.II/II) and thrombotic diseases.

Method: GARDEN (NCT04659109) was a randomized, double -blind, multicenter, parallel group, ph.IIb trial. Patients (pts) randomized 1/1 to Glenzocimab (1000 mg/day/3days)-placebo. All had confirmed SARS-CoV2, moderate respiratory clinical signs and a prothrombotic status. Primary endpoint: day 4 severe progression.

Results: 60 pts enrolled in Brazil & France, aged median 56yrs; 75% male Caucasians with ≥ 1 comorbidity. All had thromboprophylaxis and steroids. Safety analysis confirmed good tolerance of Glenzocimab. No deaths, serious drug-related adverse event nor major bleeding. 31 SAEs in 15 pts mainly related to Cov-ARDS or infection. No difference for the primary endpoint. Insufficient power, imbalance of risk factors (within Glenzocimab group), or lesser role of GPVI in Cov-ARDS pathophysiology are possible reasons.

Conclusion: The GARDEN study was set up to tackle a global Public Health emergency. Glenzocimab was safe in doses three times higher than used in stroke. Albeit efficacy was not shown, overall, GARDEN provides insights into Cov-ARDS.