Faculty, Staff and Student Publications
Publication Date
10-13-2023
Journal
Clinical and Experimental Immunology
Abstract
MAS825, a bispecific IL-1β/IL-18 monoclonal antibody, could improve clinical outcomes in COVID-19 pneumonia by reducing inflammasome-mediated inflammation. Hospitalized non-ventilated patients with COVID-19 pneumonia (n = 138) were randomized (1:1) to receive MAS825 (10 mg/kg single i.v.) or placebo in addition to standard of care (SoC). The primary endpoint was the composite Acute Physiology and Chronic Health Evaluation II (APACHE II) score on Day 15 or on the day of discharge (whichever was earlier) with worst-case imputation for death. Other study endpoints included safety, C-reactive protein (CRP), SARS-CoV-2 presence, and inflammatory markers. On Day 15, the APACHE II score was 14.5 ± 1.87 and 13.5 ± 1.8 in the MAS825 and placebo groups, respectively (P = 0.33). MAS825 + SoC led to 33% relative reduction in intensive care unit (ICU) admissions, ~1 day reduction in ICU stay, reduction in mean duration of oxygen support (13.5 versus 14.3 days), and earlier clearance of virus on Day 15 versus placebo + SoC group. On Day 15, compared with placebo group, patients treated with MAS825 + SoC showed a 51% decrease in CRP levels, 42% lower IL-6 levels, 19% decrease in neutrophil levels, and 16% lower interferon-γ levels, indicative of IL-1β and IL-18 pathway engagement. MAS825 + SoC did not improve APACHE II score in hospitalized patients with severe COVID-19 pneumonia; however, it inhibited relevant clinical and inflammatory pathway biomarkers and resulted in faster virus clearance versus placebo + SoC. MAS825 used in conjunction with SoC was well tolerated. None of the adverse events (AEs) or serious AEs were treatment-related.
Trial registration: ClinicalTrials.gov NCT04382651.
Keywords
Humans, COVID-19, SARS-CoV-2, Interleukin-18, Inflammation, Hospitalization, Treatment Outcome, MAS825, COVID-19, pneumonia, impaired respiratory function, efficacy and safety
DOI
10.1093/cei/uxad065
PMID
37338154
PMCID
PMC10570997
PubMedCentral® Posted Date
6-20-2023
PubMedCentral® Full Text Version
Post-print
Graphical Abstract
Published Open-Access
yes
Included in
COVID-19 Commons, Epidemiology Commons, Internal Medicine Commons, Medical Immunology Commons