COVID-19Phase 2/3NCT04401475
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 Phase 2/3 study testing SOC plus 15mg/kg EB05 IV in people with COVID-19 and ARDS, run by Edesa Biotech Inc. at 20 sites in 2 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- What is being tested?
- SOC plus 15mg/kg EB05 IV
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 278 participants
- Where
- 20 sitesin 2 countries
- Study dates
- 25 Nov 2020to 22 Jul 2024
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Men and women ≥18 years of age at the time of consent.
- Laboratory-confirmed diagnosis of COVID-19.
- Hospitalized for COVID-19 related respiratory disease.
- Patient belongs to one of the following two categories in the nine-point COVID-19 severity scale:
- Hospitalized, requiring intubation and mechanical ventilation - Level 6 of the nine-point COVID-19 severity scale.
- Hospitalized and intubated with additional organ support - pressors, RRT, ECMO - Level 7 of the nine-point COVID-19 severity scale.
- 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.
- Signed informed consent obtained by any patient capable of giving consent, or, when the patient is not capable of giving consent, from his or her legal/authorized representatives.
Who cannot join
- The subject is a female who is breastfeeding or pregnant.
- Known hypersensitivity to EB05 or its excipients.
- In the opinion of the investigator, death is imminent and inevitable or patient will be discharged within the next 48 - 72 hours, irrespective of the provision of treatment.
- Experiencing cardiac arrest while hospitalized with COVID-19.
- Active participation in other immunomodulator or immunosuppressant drug clinical trials.
- Participation in COVID-19 antiviral, anticoagulant and convalescent plasma trials may be permitted; however, the decision to enroll a patient who is participating in other clinical trials will be dealt with on a case-by-case basis.
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- Treatment with immunomodulator or immunosuppressant drugs, including but not limited to TNF inhibitors and anti-IL-1 agents within 5 half-lives or 30 days (whichever is longer) before randomization. Except for the following, which are permitted:
- Treatment with immunomodulator, or immunosuppressant drugs, such as corticosteroids, as part of SOC for COVID-19
- Transplant patients
- Known other clinical conditions that contraindicate EB05 and cannot be treated or solved according to the judgment of the clinician.
- Patient has been intubated or mechanically ventilated for more than 72 hours prior to administration of the investigational product.
- Patient has been intubated and then extubated during the current hospitalization prior to administration of the investigational product.
- Patient has experienced meaningful clinical improvement in the severity of disease prior to administration of the investigational product.
Trial locations and contacts
20 sites in 2 countries.
20 sites in 2 countries
Canada13 sites
William Osler Health System
Brampton, Ontario, L6R 3J7
University of Alberta Hospital
Edmonton, Alberta, T6G 2B7
CISS Monteregie-Centre
Greenfield Park, Quebec, J4V 2H2
Markham Stouffville Hospital
Markham, Ontario, L3P 7P3
Hôpital Maisonneuve Rosemont
Montreal, Quebec, H1T 2M4
McGill University Health Centre
Montreal, Quebec, H4A 3J1
Southlake Regional Health Centre
Newmarket, Ontario, L3Y 2P9
Lakeridge Health
Oshawa, Ontario, L1G 2B9
Ottawa Hospital Research Institute
Ottawa, Ontario, K1Y 4E9
Hôpital Régional de Rimouski
Rimouski, Quebec, G5L 5T1
Toronto General Hospital
Toronto, Ontario, M5G 2C4
Vancouver Coastal Health
Vancouver, British Columbia, V5K 1Z9
Vancouver General Hospital
Vancouver, British Columbia, V5Z 1M9
United States7 sites
University of Miami Hospital
Coral Gables, Florida, 33146
Wayne State University
Detroit, Michigan, 48202
UCSF Fresno
Fresno, California, 93701
St. Jude Medical Center/ Providence
Fullerton, California, 92835
West Virginia University Medicine Heart & Vascular Institute
Morgantown, West Virginia, 26506-6224
Providence Portland Medical Center
Portland, Oregon, 97213
Baystate Medical Center
Springfield, Massachusetts, 01199
About this study
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.
- Being tested
- SOC plus 15mg/kg EB05 IV, SOC plus Placebo IV
- Keywords
- TLR4, ARDS, COVID-19
- Medical subject headings
- COVID-19
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SOC plus 15mg/kg EB05 IVBiological
Standard of care plus single IV infusion of 15mg/kg of EB05.
SOC plus Placebo IVOther
Standard of care plus a single IV infusion of placebo.
| Study group | Role | What they receive |
|---|---|---|
| Stage 1 | Experimental | Stage 1 (Phase II Study) For 80% power (β = 0.20), at a significance level of 5% (α =0.05) and a 1:1 randomization ratio, a total of 316 (EB05: 158, SOC: 158) evaluable patients will be required. Allowing for 20% attrition a total of 396 patients will be recruited. Receives: Biological: SOC plus 15mg/kg EB05 IV; Other: SOC plus Placebo IV |
| Stage 2 | Experimental | Stage 2 (Phase III Study) For a 1:1 ratio of patients treated with EB05 vs. Placebo, a cumulative one-sided alpha of 2.5% and 90% power, to detect an Odds Ratio of 2.00, a total of 586 evaluable patients will be required for Stage 2 (Phase III study). 293 of these will be treated with EB05 + SOC and 293 treated with Placebo + SOC. Allowing for 10% attrition, a total of 644 patients will be enrolled in this Stage. Receives: Biological: SOC plus 15mg/kg EB05 IV; Other: SOC plus Placebo IV |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mortality rate at Day 28 from IP administration. (Phase 2 and 3)
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.
Measured: 28 days
Secondary outcomes (3)
Proportion of patients with clinical improvement at Day 28 (Phase 2 and 3)
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.
Measured: 28 days
Proportion of patients with clinical improvement at Day 60 (Phase 2)
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.
Measured: 60 days
Mortality rate at Day 60 from IP adminstration (Phase 2 and 3)
The mortality rate at Day 60 from IP administration.
Measured: 60 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 May 2020
- Study start25 Nov 2020
- Primary completion22 Jul 2024
- Study completion22 Jul 2024
Why it stopped: Edesa has made the decision to terminate this study solely for business reasons. The study termination was not related to any safety concerns.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Model description
- This is a multicenter, randomized, double-blind, placebo-controlled, study to evaluate the safety and efficacy of EB05 in adult hospitalized patients with COVID-19. Following enrollment in the study, eligible subjects will be randomized at a ratio of 1:1 at baseline to receive an infusion of either EB05 or Placebo. In addition to study treatment, all patients will receive SOC treatment per routine care at each participating site. Randomization is stratified by site and baseline WHO COVID-19 severity strata defined as Levels 3-4 and Levels 5-6 for the phase 2 study and Levels 6-7 for the phase 3 study. The total follow-up duration of each patient will be until 60-days from treatment with the investigational product. All assessments will take place in-hospital except for the 28-day and 60-day follow-up assessment which will be by telephone if the patient has been discharged before this assessment.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 278 participants (actual)
Sponsor and investigators
- Lead sponsor
- Edesa Biotech Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- JSS Medical Research Inc.
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04401475
- Sponsor's protocol ID
- EB05-04-2020
- Status last verified
- Sep 2026
- First submitted
- 21 May 2020
- Last updated
- 26 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 26 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04401475
- Acronym / sponsor ID
- EB05-04-2020
- Keywords
- TLR4, ARDS, COVID-19
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Edesa has made the decision to terminate this study solely for business reasons. The study termination was not related to any safety concerns.
- Enrolment
- 278 participants (actual)
- Lead sponsor
- Edesa Biotech Inc.Industry (pharma, biotech, devices)
- Collaborators
- JSS Medical Research Inc.
- Study start
- 25 Nov 2020 (actual)
- Primary completion
- 22 Jul 2024 (actual)
- Study completion
- 22 Jul 2024 (actual)
- First posted
- 26 May 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Sequential
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- This is a multicenter, randomized, double-blind, placebo-controlled, study to evaluate the safety and efficacy of EB05 in adult hospitalized patients with COVID-19. Following enrollment in the study, eligible subjects will be randomized at a ratio of 1:1 at baseline to receive an infusion of either EB05 or Placebo. In addition to study treatment, all patients will receive SOC treatment per routine care at each participating site. Randomization is stratified by site and baseline WHO COVID-19 severity strata defined as Levels 3-4 and Levels 5-6 for the phase 2 study and Levels 6-7 for the phase 3 study. The total follow-up duration of each patient will be until 60-days from treatment with the investigational product. All assessments will take place in-hospital except for the 28-day and 60-day follow-up assessment which will be by telephone if the patient has been discharged before this assessment.
| Arm | Type | Receives |
|---|---|---|
| Stage 1 | Experimental | Biological: SOC plus 15mg/kg EB05 IV, Other: SOC plus Placebo IVStage 1 (Phase II Study) For 80% power (β = 0.20), at a significance level of 5% (α =0.05) and a 1:1 randomization ratio, a total of 316 (EB05: 158, SOC: 158) evaluable patients will be required. Allowing for 20% attrition a total of 396 patients will be recruited. |
| Stage 2 | Experimental | Biological: SOC plus 15mg/kg EB05 IV, Other: SOC plus Placebo IVStage 2 (Phase III Study) For a 1:1 ratio of patients treated with EB05 vs. Placebo, a cumulative one-sided alpha of 2.5% and 90% power, to detect an Odds Ratio of 2.00, a total of 586 evaluable patients will be required for Stage 2 (Phase III study). 293 of these will be treated with EB05 + SOC and 293 treated with Placebo + SOC. Allowing for 10% attrition, a total of 644 patients will be enrolled in this Stage. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Men and women ≥18 years of age at the time of consent.
- Laboratory-confirmed diagnosis of COVID-19.
- Hospitalized for COVID-19 related respiratory disease.
- Patient belongs to one of the following two categories in the nine-point COVID-19 severity scale:
- 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.
Key exclusion criteria (13 listed)
- The subject is a female who is breastfeeding or pregnant.
- Known hypersensitivity to EB05 or its excipients.
- In the opinion of the investigator, death is imminent and inevitable or patient will be discharged within the next 48 - 72 hours, irrespective of the provision of treatment.
- Experiencing cardiac arrest while hospitalized with COVID-19.
- Active participation in other immunomodulator or immunosuppressant drug clinical trials.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| SOC plus 15mg/kg EB05 IVStandard of care plus single IV infusion of 15mg/kg of EB05. | Biological | Stage 1, Stage 2 |
| SOC plus Placebo IVStandard of care plus a single IV infusion of placebo. | Other | Stage 1, Stage 2 |
Primary outcome
Mortality rate at Day 28 from IP administration. (Phase 2 and 3)
Time frame: 28 days
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.
3 secondary outcomes
Proportion of patients with clinical improvement at Day 28 (Phase 2 and 3)
Time frame: 28 days
Proportion of patients with clinical improvement at Day 60 (Phase 2)
Time frame: 60 days
Mortality rate at Day 60 from IP adminstration (Phase 2 and 3)
Time frame: 60 days
Results and safety
The study was stopped early (reason given: Edesa has made the decision to terminate this study solely for business reasons. The study termination was not related to any safety concerns.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Oct 2026.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
20 sites in 2 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing SOC plus 15mg/kg EB05 IV in people with COVID-19 and ARDS, run by Edesa Biotech Inc. at 20 sites in 2 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 13 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 26 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 20 sites in Canada, United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: Edesa has made the decision to terminate this study solely for business reasons. The study termination was not related to any safety concerns.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mortality rate at Day 28 from IP administration. (Phase 2 and 3) (time frame: 28 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Oct 2026.