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

NCT04401475 | Suspended Phase 2 DMC FDA Drug

• 1 other identifier: EB05-04-2020
• Study Type: interventional
• Target: 644
• Locations: 2 countries
• Sites: 20

Brief 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.

Conditions

COVID-19; ARDS

Keywords

TLR4; ARDS; COVID-19

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Proportion of patients with clinical improvement at Day 28

  28 days

• Proportion of patients with clinical improvement at Day 60

  60 days

• Mortality rate at Day 60

  60 days

Other Outcomes (1)

• Number of treatment-emergent adverse events (TEAEs) and serious TEAEs.

  28 and 60 days

Study Arms (2)

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.

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.

Biological: SOC plus 15mg/kg EB05 IV; Other: SOC plus Placebo IV

Interventions

SOC plus 15mg/kg EB05 IV BIOLOGICAL

Standard of care plus single IV infusion of 15mg/kg of EB05.

Stage 1; Stage 2

SOC plus Placebo IV OTHER

Standard of care plus a single IV infusion of placebo.

Stage 1; Stage 2

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.
• 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.

Sponsors & Collaborators

• Edesa Biotech Inc.: lead
• JSS Medical Research Inc.: collaborator

Study Sites (20)

UCSF Fresno

Fresno, California, 93701, United States

Location

St. Jude Medical Center/ Providence

Fullerton, California, 92835, United States

Location

University of Miami Hospital

Coral Gables, Florida, 33146, United States

Location

Baystate Medical Center

Springfield, Massachusetts, 01199, United States

Location

Wayne State University

Detroit, Michigan, 48202, United States

Location

Providence Portland Medical Center

Portland, Oregon, 97213, United States

Location

West Virginia University Medicine Heart & Vascular Institute

Morgantown, West Virginia, 26506-6224, United States

Location

University of Alberta Hospital

Edmonton, Alberta, T6G 2B7, Canada

Location

Vancouver Coastal Health

Vancouver, British Columbia, V5K 1Z9, Canada

Location

Vancouver General Hospital

Vancouver, British Columbia, V5Z 1M9, Canada

Location

William Osler Health System

Brampton, Ontario, L6R 3J7, Canada

Location

Markham Stouffville Hospital

Markham, Ontario, L3P 7P3, Canada

Location

Southlake Regional Health Centre

Newmarket, Ontario, L3Y 2P9, Canada

Location

Lakeridge Health

Oshawa, Ontario, L1G 2B9, Canada

Location

Ottawa Hospital Research Institute

Ottawa, Ontario, K1Y 4E9, Canada

Location

Toronto General Hospital

Toronto, Ontario, M5G 2C4, Canada

Location

CISS Monteregie-Centre

Greenfield Park, Quebec, J4V 2H2, Canada

Location

Hôpital Maisonneuve Rosemont

Montreal, Quebec, H1T 2M4, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

Hôpital Régional de Rimouski

Rimouski, Quebec, G5L 5T1, Canada

Location

MeSH Terms

Conditions

COVID-19

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: May 21, 2020
• First Posted: May 26, 2020
• Study Start: November 25, 2020
• Primary Completion: December 1, 2024
• Study Completion: December 1, 2024
• Last Updated: November 14, 2024

Record last verified: 2024-11

Locations

CA (13); US (7)