Using GM-CSF as a Host Directed Therapeutic Against COVID-19 - a Phase 2 Investigator Initiated Trial

Detailed Summary

The coronavirus disease 2019 (COVID-19) has rapidly become a pandemic. COVID-19 poses a mortality risk of 3-7%, rising to 20% in older patients with co-morbidities. Of all infected patients, 15-20% will develop severe respiratory symptoms necessitating hospital admission. Around 5% of patients will require invasive mechanical ventilation, and up to 50% will die. Evidence in severe COVID-19 suggests that these patients experience cytokine storm and progressed rapidly with acute respiratory distress syndrome and eventual multi-organ failure. Early identification and immediate treatment of hyperinflammation is thus recommended to reduce mortality. Granulocyte Macrophage Colony Stimulating Factor (GM-CSF) has been shown to be a myelopoietic growth factor that has pleiotropic effects in promoting the differentiation of immature precursors into polymorphonuclear neutrophils, monocytes/ macrophages and dendritic cells, and also in controlling the function of fully mature myeloid cells. It plays an important role in priming monocytes for production of proinflammatory cytokines under TLR and NLR stimulation. It has a broad impact on the processes driving DC differentiation and affects DC effector function at the mature state. Importantly, GM-CSF plays a critical role in host defense and stimulating antiviral immunity. Detailed studies have also shown that GM-CSF is necessary for the maturation of alveolar macrophages from foetal monocytes and the maintenance of these cells in adulthood. The known toxicology, pharmacologic and safety data also support the use of Leukine® in hypoxic respiratory failure and ARDS due to COVID-19. This study aims to recruit patients with evidence of pneumonia and hypoxia who have increased risk for severe disease and need for mechanical ventilation. The overall hypothesis is that GM-CSF has antiviral immunity, can provide the stimulus to restore immune homeostasis in the lung with acute lung injury from COVID-19, and can promote lung repair mechanisms, which would lead to improvement in lung oxygenation parameters.

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