COVID-19 patients who develop severe disease often develop acute respiratory distress syndrome (ARDS) as a result of a dysregulated immune response. This in turn stimulates a pro-inflammatory cascade ("cytokine storm") as well as emergency myelopoiesis. This proinflammatory cascade is activated when viral-mediated cell damage occurs in the lungs, resulting in the release of damage-signaling alarmin molecules such as S100A8/A9 (Calprotectin), HMGB1, Resistin, and oxidized phospholipids. These damage-associated molecular patterns (DAMPs) are recognized by the pattern recognition receptor Toll-Like Receptor 4 (TLR4) found on macrophages, dendritic cells and other innate immune cells and result in additional release of pro-inflammatory molecules. Several recent studies have shown that S100A8/A9 serum levels in hospitalized COVID-19 patients positively correlate with both neutrophil count and disease severity. Taken together the DAMP-TLR4 interaction forms a central axis in the innate immune system and is a key driver of the pathological inflammation observed in COVID-19. We hypothesis that targeting the initial step in the signalling pathways of these DAMPs in innate immunity offers the best hope for controlling the exaggerated host response to SARS-CoV-2 infection. EB05 has demonstrated safety in two clinical studies (\>120 patients) and was able to block LPS-induced (TLR4 agonist) IL-6 release in humans. Given, this extensive body of evidence we believe EB05 could ameliorate ARDS due to COVID-19, significantly reducing ventilation rates and mortality.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
TRIPLE
Enrollment
644
Standard of care plus single IV infusion of 15mg/kg of EB05.
Standard of care plus a single IV infusion of placebo.
UCSF Fresno
Fresno, California, United States
St. Jude Medical Center/ Providence
Fullerton, California, United States
University of Miami Hospital
Coral Gables, Florida, United States
Baystate Medical Center
Springfield, Massachusetts, United States
Wayne State University
Detroit, Michigan, United States
Providence Portland Medical Center
Portland, Oregon, United States
West Virginia University Medicine Heart & Vascular Institute
Morgantown, West Virginia, United States
University of Alberta Hospital
Edmonton, Alberta, Canada
Vancouver Coastal Health
Vancouver, British Columbia, Canada
Vancouver General Hospital
Vancouver, British Columbia, Canada
...and 10 more locations
Mortality rate at Day 28 from IP administration.
For the current study, the primary efficacy outcome measure will be the mortality rate from IP administration. Mortality is the most clinically relevant therapeutic endpoint for this population that is on IMV. The primary endpoint will be assessed at 28-days after treatment initiation.
Time frame: 28 days
Proportion of patients with clinical improvement at Day 28
The proportion of patients with clinical improvement, defined as a decrease of two points or more on the World Health Organization (WHO) 9 - point ordinal scale at Day 28 from IP administration. The severity of COVID-19 disease is classified according to the WHO 9-point ordinal scale. The minimum value of 0 is associated with an "uninfected" stage wherein no clinical or virological evidence of infection is present. The maximum value of 8 is associated with death. A higher score reflects a worse outcome.
Time frame: 28 days
Proportion of patients with clinical improvement at Day 60
The proportion of patients with clinical improvement, defined as a decrease of two points or more on the World Health Organization (WHO) 9 - point ordinal scale at Day 60 from IP administration. The severity of COVID-19 disease is classified according to the WHO 9-point ordinal scale. The minimum value of 0 is associated with an "uninfected" stage wherein no clinical or virological evidence of infection is present. The maximum value of 8 is associated with death. A higher score reflects a worse outcome.
Time frame: 60 days
Mortality rate at Day 60
The mortality rate at Day 60 from IP administration.
Time frame: 60 days
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.