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

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(s): 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. Result(s): 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(s): 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.

Glenzocimab, a Novel Antithrombotic, Shows Favorable Safety Profile in a Systematic Review of Data within the Clinical Development Program

Background and Aims: Platelets are involved in inflammatory thrombosis in acute ischemic stroke (AIS) and severe Covid-19 infection. Glenzocimab, a humanized antibody fragment targeting platelet glycoprotein VI, has been assessed in two different indications. In AIS, with a single IV dose of 1000 mg to improve the efficacy of reperfusion therapies, in Covid-19, with 1000 mg over 3 consecutive days for acute respiratory distress syndrome (ARDS) treatment. Method(s): ACTIMIS (NCT03803007) was a safety and efficacy, dose-finding clinical study. Patients were randomly assigned to placebo or glenzocimab in an initial escalating dosage scheme from 125 to 1000 mg, then to 1000 mg or placebo in 1:1 parallel groups. The primary endpoint was safety focusing on intracranial hemorrhages (ICHs). GARDEN (NCT04659109) was an exploratory efficacy and safety clinical trial. Patients randomized 1:1 to glenzocimab or placebo. Safety was a key secondary endpoint. Result(s): Within ACTIMIS, 166 patients were enrolled, 66 (40%) reported as ICH;6 were symptomatic ICH: on glenzocimab 1/102 patients (1%), on placebo 5/64 (8%);60 displayed non-symptomatic ICHs, on glenzocimab 30/102 (29%), on placebo 30/64 (47%). Twenty all-cause deaths were reported, 8/102 (8%) on glenzocimab and 12/64 (19%) on placebo. In GARDEN, safety analysis in 61 patients confirmed the favorable profile of glenzocimab with no mortality, no serious drug-related adverse event, no major bleeding. All results are consistent with those from phase I in healthy volunteers (Arterioscler Thromb Vasc Biol. 2019;39). Conclusion(s): This favorable safety profile within three clinical studies allowed glenzocimab, a novel antithrombotic, to enter a larger ongoing phase II/III study,.