Using GM-CSF as a Host Directed Therapeutic Against COVID-19

• Status: Recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Singapore General Hospital
• Treatments: Molgramostim; Sargramostim

Criteria

Inclusion Criteria:

• SARS-CoV-2 PCR-confirmed COVID-19 infection

• Presence of acute hypoxic respiratory failure defined as (either or both)

• Saturation < 94% on room air or requiring supplemental oxygen

• PaO2/FiO2 below 350

• Age 21-80

• Able and willing to provide informed consent

Exclusion Criteria:

• Patients who are already on supplemental oxygen of FiO2 ≥ 0.4

• Patients with known history of serious allergic reactions, including anaphylaxis, to human GM-CSF such as Leukine®, yeast-derived products, or any component of the product.

• Mechanical ventilation before start of study

• Patients enrolled in another investigational drug study

• Pregnant or breastfeeding females (all female subjects of childbearing potential status must have negative pregnancy test at screening)

• Patients with peripheral white blood cell count above 25,000 per microliter and/or active myeloid malignancy

• Patients on high dose systemic steroids (> 20mg methylprednisolone or equivalent)

• Patients on lithium carbonate therapy

• Patients with serum ferritin >2000 mcg/ml (which will exclude ongoing HLH)