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.
Biological: SOC plus 15mg/kg EB05 IV
Standard of care plus single IV infusion of 15mg/kg of EB05.
Other: SOC plus Placebo IV
Standard of care plus a single IV infusion of placebo.
Inclusion Criteria:
1. Men and women ≥18 years of age at the time of consent.
2. Laboratory-confirmed diagnosis of COVID-19.
3. Hospitalized for COVID-19 related respiratory disease.
4. Patient belongs to one of the following four categories in the nine-point COVID-19
severity scale:
1. Hospitalized, not requiring supplemental oxygen - Level 3 of the nine-point
COVID-19 severity scale.
2. Hospitalized, requiring supplemental oxygen - Level 4 of the nine-point COVID-19
severity scale.
3. Hospitalized, requiring nasal high-flow oxygen therapy, non-invasive mechanical
ventilation, or both - Level 5 of the nine-point COVID-19 severity scale.
4. Hospitalized, requiring intubation and mechanical ventilation- Level 6 of the
nine-point COVID-19 severity scale.
5. For women of childbearing potential involved in any sexual intercourse that could lead
to pregnancy: Negative pregnancy test and willingness to use contraceptive (consistent
with local regulations) during the study period.
6. Signed informed consent form by any patient capable of giving consent, or, when the
patient is not capable of giving consent, by his or her legal/authorized
representatives.
Exclusion Criteria:
1. The subject is a female who is breastfeeding or pregnant.
2. Known hypersensitivity to EB05 or its excipients.
3. Mechanical ventilation (including venovenous ECMO) for ≥5 days (120 hours), or any
duration of venoarterial ECMO.
4. In the opinion of the investigator, death is imminent and inevitable within the next
48 - 72 hours, irrespective of the provision of treatment.
5. Active participation in other drug clinical trials.
6. Treatment with immunomodulator or immunosuppressant drugs, including but not limited
to IL-6 inhibitors, TNF inhibitors, anti-IL-1 agents, and JAK inhibitors within 5
half-lives or 30 days (whichever is longer) before randomization. (Note treatment with
immunomodulator or immunosuppressant drugs, such as corticosteroids, as part of SOC,
is permitted).
7. Known other clinical conditions that contraindicate EB05 and cannot be treated or
solved according to the judgment of the clinician.
8. Possibility of the subject being transferred to a non-study hospital within 72h.
UCSF Fresno
Fresno, California, United States
St. Jude Medical Center/ Providence
Fullerton, California, United States
St. Joseph Hospital, Orange - Providence
Orange, California, United States
University of Miami Hospital
Coral Gables, Florida, United States
Augusta University Medical Center
Augusta, Georgia, United States
Methodist Medical Center IL
Peoria, Illinois, United States
Norton Hospital
Louisville, Kentucky, United States
Norton Brownsboro Hospital
Louisville, Kentucky, United States
Baystate Medical Center
Springfield, Massachusetts, United States
Henry Ford Hospital
Detroit, Michigan, United States
Providence Regional Medical Center - Everett
Everett, Washington, United States
UW Medicine Valley Medical Center
Renton, Washington, United States
West Virginia University Medicine Heart & Vascular Institute
Morgantown, West Virginia, United States
Royal Alexandra Hospital
Edmonton, Alberta, Canada
Misericordia Community Hospital
Edmonton, Alberta, Canada
University of Alberta Hospital
Edmonton, Alberta, Canada
Grey Nuns Community Hospital
Edmonton, Alberta, Canada
Vancouver General Hospital
Vancouver, British Columbia, Canada
University Hospital - LHSC
London, Ontario, Canada
Victoria Hospital - LHSC
London, Ontario, Canada
North York General Hospital
Toronto, Ontario, Canada
Toronto General Hospital
Toronto, Ontario, Canada
Hôpital Maisonneuve Rosemont
Montréal, Quebec, Canada
Hôpital Régional de Rimouski
Rimouski, Quebec, Canada
Clinica de las Americas
Medellín, Antioquia, Colombia
IPS de Universidad de Antioquia
Medellín, Antioquia, Colombia
FOSCAL
Bucaramanga, Santander, Colombia
Fund.Cardiovascular de Colombia-FCV
Bucaramanga, Santander, Colombia
Blair Gordon, PhD
289-800-9600 - 140
info@edesabiotech.com