A Randomized, Double-Blind, Placebo-Controlled Study to Evaluate the Safety and Efficacy of EB05 + SOC vs. Placebo + SOC in Adult Hospitalized Patients With COVID-19

a study on COVID-19 Acute Respiratory Distress Syndrome

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCSF
Dates
study started
estimated completion

Description

Summary

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.

Keywords

COVID-19, ARDS, TLR4, SOC plus 15mg/kg EB05 IV

Eligibility

You can join if…

Open to people ages 18 years and up

  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.

You CAN'T join if...

  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.

Locations

  • UCSF Fresno accepting new patients
    Fresno California 93701 United States
  • St. Joseph Hospital, Orange - Providence accepting new patients
    Orange California 92868 United States
  • St. Jude Medical Center/ Providence accepting new patients
    Fullerton California 92835 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Edesa Biotech Inc.
ID
NCT04401475
Phase
Phase 2 research study
Study Type
Interventional
Participants
Expecting 396 study participants
Last Updated