Temple University Hospital has treated the first patient in the United States in the BREATHE clinical trial evaluating the impact of intravenous treatment with gimsilumab on mortality for patients with COVID-19 and acute respiratory distress syndrome (ARDS).
Gerard J. Criner, MD, FACP, FACCP, chair and professor of thoracic medicine and Surgery at the Lewis Katz School of Medicine at Temple University and Director of the Temple Lung Center, is the principal investigator at Temple University Hospital for the adaptive, randomized, double-blind, placebo-controlled pivotal trial, which includes a planned interim analysis.
COVID-19 is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Many COVID-19 patients experience an overactive immune response that leads to lung injury, ARDS, and ultimately death.1 ARDS is a life-threatening inflammatory lung injury characterized by a lack of oxygen to the tissue and stiff lungs. It necessitates hospitalization and mechanical ventilation, and, when implementing standard of care, including mechanical ventilation, it has an overall mortality rate of 41%.6
Gimsilumab is a fully human monoclonal antibody targeting granulocyte macrophage-colony stimulating factor (GM-CSF), which is believed to be a key driver of lung hyper-inflammation. Previous evidence from SARS-CoV-1 animal models and emerging data from COVID-19 patients suggests that GM-CSF contributes to the immunopathology caused by SARS-CoV-2 infection in patients with or at risk of developing ARDS.2-5 GM-CSF has been found to be up-regulated in the serum of COVID-19 patients according to recent data from patients in China.2
"Emerging evidence suggests that GM-CSF may contribute to clinical worsening in COVID-19," Dr. Criner said. "We are proud to participate in this clinical trial testing gimsilumab in this vulnerable patient population."
Gimsilumab has been tested in numerous non-clinical studies and two prior clinical studies, including a four-week Phase 1 study in healthy volunteers which completed dosing in February. It has demonstrated a favorable safety and tolerability profile based on data collected to date.
The multi-site clinical trial will enroll up to 270 patients with a confirmed diagnosis of COVID-19 and clinical evidence of acute lung injury or ARDS. Subjects will be randomized 1:1 to receive either gimsilumab or placebo. The primary endpoint of the study is incidence of mortality by Day 43. Key secondary endpoints include the incidence and duration of mechanical ventilation use during the study, number of days in the intensive care unit, and number of days of inpatient hospitalization.
The trial is sponsored by Roivant Sciences.
1. Siddiqi HK and Mehra MR. COVID-19 illness in native and immunosuppressed states: a clinical-therapeutic staging proposal, J Heart Lung Transpl. 2020. https://doi.org/10.1016/j.healun.2020.03.012.
2. Huang C, Wang Y, Li X, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. doi:10.1016/s0140-6736(20)30183-5.
3. Zhou Y, Fu B, Zheng X, et al. Aberrant pathogenic GM-CSF+ T cells and inflammatory CD14+CD16+ monocytes in severe pulmonary syndrome patients of a new coronavirus. Pre-Print. 2020. https://doi.org/10.1101/2020.02.12.945576.
4. Shiomi A, Usui T. Pivotal roles of GM-CSF in autoimmunity and inflammation. Mediators Inflamm. 2015;2015:568543. doi:10.1155/2015/568543.
5. Channappanavar R, Fehr AR, Vijay R, et al. Dysregulated type I interferon and inflammatory monocyte-macrophage responses cause lethal pneumonia in SARS-CoV-infected mice. Cell Host Microbe. 2016;19(2):181-193. doi:10.1016/j.chom.2016.01.007.
6. Rubenfeld GD, Caldwell E, Peabody E, et al. Incidence and outcomes of acute lung injury. New England Journal of Medicine. 2005 Oct 20;353(16):1685-93.