Article Figures & Data
Figures
- Figure 1
Three stages of COVID-19 disease.
- Figure 2
(A) Granulocyte-macrophage colony-stimulating factor (GM-CSF) is produced by hematopoietic cells (top) with inflammatory monocytes and activated TH1 and TH17 being among the richest sources, as well as by a variety of viscerosomatic cells including Type 2 pulmonary epithelial cells. (B) A schematic where GM-CSF plays a central role in alveolar damage in COVID-19. Depicted is the virus (SARS-CoV-2) infecting alveolar epithelial cells and upregulating inflammatory cytokine production including GM-CSF. Excess GM-CSF in concert with other cytokines may further upregulate activated alveolar macrophages, which further stimulates release of GM-CSF. Activated T cells and polarized monocytes from peripheral blood may now contribute locally and systemically by responding with release of downstream cytokines such as interleukin 1 (IL-1), tumor necrosis factor (TNF), IL-6, and chemokines, which may then attract polymorphonuclear leukocytes causing further tissue damage and release of damage-associated molecular patterns (DAMPS) further driving inflammatory signaling.
Tables
Mechanism of action Drug Study population Phase Humanized immunoglobulin G1 (IgG1) monoclonal antibody targeting granulocyte-macrophage colony-stimulating factor (GM-CSF) TJ003234 Healthy individuals 1 COVID-19 1b/2 Gimsilumab Ankylosing spondylitis 1 COVID-19 2 Lenzilumab Chronic myelomonocytic leukemia 1 Relapsed or refractory large B-cell lymphoma 1/2 COVID-19 3 Otilimab Rheumatoid arthritis 2b Inflammatory arthritis 2 COVID-19 2 Namilumab Rheumatoid arthritis 2 Chronic plaque psoriasis 2 Spondyloarthritis 2 Humanized IgG4 monoclonal antibody targeting GM-CSF receptor alpha Mavrilimumab Rheumatoid arthritis 2b Giant cell arthritis 2 COVID-19 2 Betac-receptor-specific, fully human IgG4 monoclonal antibody (inhibitor of IL-3-, GM-CSF-, and IL-5-mediated functions) CSL311 Asthma 1 Mechanism of action Molecule Trial Trial name Drugs Phase Primary end point TJ003234 NCT04341116 A Phase 1b/2, Randomized, Double-Blind, Placebo-Controlled, Multi-Center Study to Evaluate the Safety and Efficacy of TJ003234 in Subjects With Severe Coronavirus Disease 2019 (COVID-19) TJ003234 (3 or 6 mg/kg, single infusion) vs placebo 1b/2 Proportion (%) of patients experiencing deterioration in clinical status (changes from baseline on day 14) Gimsilumab NCT04351243 A Multi-Center, Adaptive, Randomized, Double-blind, Placebo-controlled Study to Assess the Efficacy and Safety of Gimsilumab in Subjects With Lung Injury or Acute Respiratory Distress Syndrome Secondary to COVID-19 (BREATHE) Gimsilumab (high dose day 1 + gimsilumab low dose day 8) vs placebo 2 Mortality at day 43 Immunoglobulin G1 (IgG1) monoclonal antibody targeting granulocyte-macrophage colony-stimulating factor (GM-CSF) Lenzilumab NCT04351152 A Phase 3 Randomized, Placebo-Controlled Study of Lenzilumab in Hospitalized Patients With COVID-19 Pneumonia Lenzilumab vs standard of care 3 Incidence of invasive mechanical ventilation and/or mortality (up to 28 days) Namilumab EudraCT 2020-001684-89; ISRCTN40580903 CATALYST - A randomised phase II proof of principle multi-arm multi-stage trial designed to guide the selection of interventions for phase III trials in hospitalised patients with COVID-19 infection Namilumab vs gemtuzumab vs infliximab 2 SpO2, measured from /FiO2 randomization to day 14, hospital discharge, death Otilimab NCT04376684 A Randomized, Double-blind, Placebo-controlled, Study Evaluating the Efficacy and Safety of Otilimab IV in Patients With Severe Pulmonary COVID-19-Related Disease Otilimab as an IV infusion + standard of care vs placebo as IV infusion + standard of care 2 Proportion of participants alive and free of respiratory failure at day 28 IgG4 monoclonal antibody targeting GM-CSF receptor alpha Mavrilimumab NCT04447469 Study of Mavrilimumab (KPL-301) in Participants Hospitalized With Severe Corona Virus Disease 2019 (COVID-19) Pneumonia and Hyper-inflammation Mavrilimumab vs placebo 2/3 Proportion of participants alive and without respiratory failure at day 15 NCT04399980 Mavrilimumab to Reduce Progression of Acute Respiratory Failure in Patients With Severe COVID-19 Pneumonia and Systemic Hyper-inflammation (RCT) Mavrilimumab vs placebo 2 Proportion of patients alive and off of oxygen at day 14 NCT04397497 A Randomized, Double Blind, Placebo-controlled Trial of Mavrilimumab for Acute Respiratory Failure Due to COVID-19 Pneumonia With Hyper-inflammation (the COMBAT-19 Trial) Mavrilimumab (single-dose IV) vs placebo 2 Reduction in the dependency on oxygen supplementation (within day 14 of treatment)
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