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

COVID-19 Clinical Trial

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04401475
• Other study ID #: EB05-04-2020
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: November 25, 2020
• Est. completion date: December 2024

Study information

• Verified date: July 2023
• Source: Edesa Biotech Inc.
• Contact: Blair Gordon, PhD
• Phone: 289-800-9600
• Email: info[@]edesabiotech.com
• Is FDA regulated: No
• Study type: Interventional

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 644
• Est. completion date: December 2024
• Est. primary completion date: December 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

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 two categories in the nine-point COVID-19 severity scale:

1. Hospitalized, requiring intubation and mechanical ventilation - Level 6 of the nine-point COVID-19 severity scale.

2. Hospitalized and intubated with additional organ support - pressors, RRT, ECMO - Level 7 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 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.

Exclusion Criteria:

1. The subject is a female who is breastfeeding or pregnant.

2. Known hypersensitivity to EB05 or its excipients.

3. 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.

4. Experiencing cardiac arrest while hospitalized with COVID-19.

5. Active participation in other immunomodulator or immunosuppressant drug clinical trials.

a. 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.

6. 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:

1. Treatment with immunomodulator, or immunosuppressant drugs, such as corticosteroids, as part of SOC for COVID-19

2. Transplant patients

7. Known other clinical conditions that contraindicate EB05 and cannot be treated or solved according to the judgment of the clinician.

8. Patient has been intubated or mechanically ventilated for more than 72 hours prior to administration of the investigational product.

9. Patient has been intubated and then extubated during the current hospitalization prior to administration of the investigational product.

10. Patient has experienced meaningful clinical improvement in the severity of disease prior to administration of the investigational product.

Related Conditions & MeSH terms

• ARDS
• COVID-19

Intervention

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.

Locations

Country	Name	City	State
Canada	William Osler Health System	Brampton	Ontario
Canada	University of Alberta Hospital	Edmonton	Alberta
Canada	CISS Monteregie-Centre	Greenfield Park	Quebec
Canada	Markham Stouffville Hospital	Markham	Ontario
Canada	Hôpital Maisonneuve Rosemont	Montréal	Quebec
Canada	McGill University Health Centre	Montréal	Quebec
Canada	Southlake Regional Health Centre	Newmarket	Ontario
Canada	Lakeridge Health	Oshawa	Ontario
Canada	Ottawa Hospital Research Institute	Ottawa	Ontario
Canada	Hôpital Régional de Rimouski	Rimouski	Quebec
Canada	Toronto General Hospital	Toronto	Ontario
Canada	Vancouver Coastal Health	Vancouver	British Columbia
Canada	Vancouver General Hospital	Vancouver	British Columbia
United States	University of Miami Hospital	Coral Gables	Florida
United States	Wayne State University	Detroit	Michigan
United States	UCSF Fresno	Fresno	California
United States	St. Jude Medical Center/ Providence	Fullerton	California
United States	West Virginia University Medicine Heart & Vascular Institute	Morgantown	West Virginia
United States	Providence Portland Medical Center	Portland	Oregon
United States	Baystate Medical Center	Springfield	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Edesa Biotech Inc.	JSS Medical Research Inc.

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of treatment-emergent adverse events (TEAEs) and serious TEAEs.	Safety Endpoint: Number of treatment-emergent adverse events (TEAEs) and serious TEAEs.	28 and 60 days
Primary	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.	28 days
Secondary	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.	28 days
Secondary	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.	60 days
Secondary	Mortality rate at Day 60	The mortality rate at Day 60 from IP administration.	60 days