Principal Investigator
Enrollment Status
Clinical Trial ID
Clinical Trial 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.
Phase
Phase 2
Funding Agency/Sponsor
Industry
Disease
Other
Enrollment Eligibility
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.