DISmantling COvid iNduced Neutrophil ExtraCellular Traps (DISCONNECT-1)

NCT ID: NCT04409925

Last Updated: 2023-03-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-25
• Study Completion Date: 2021-08-01

Brief Summary

This is a pilot study to investigate the safety and feasibility of rhDNase1 and its impact on neutrophil extracellular traps (NETs) in COVID-19 infected patients.

Detailed Description

It has been reported that elevated numbers of neutrophils (PMNs) in the blood predicts poor outcomes and severity in patients with COVID-19 infections. Acute inflammation results in formation of neutrophil extracellular traps (NETs) by PMNs and NK cells. Pre-clinical studies showed that NETs are critically involved in the pathophysiology of ARDS and increased capacity of PMNs to form NETs was shown to correlated with increased severity and mortality in patients with ARDS after community-acquired pneumonia. In early reports, patients with severe COVID-19 infections were also found to have radiological and clinical findings of Acute Respiratory Distress Syndrome (ARDS). NETs can be degraded by DNase1 for which there is a human recombinant equivalent rhDNase1.

This study proposes:

1. to evaluate the safety and feasibility of inhaled rhDNase1 in severely ill COVID-19 patients requiring admission;

2. to evaluate the impact of rhDNase1 in limiting progression of disease and COVID-19 related complications in these patients;

3. and to investigate NETs as possible therapeutic targets in severe COVID-19 patients by quantifying levels of circulating NETs in the blood and sputum and correlating these with oxygen requirements, need for mechanical ventilation, duration of mechanical ventilation, radiological progression of ARDS, secondary bacterial infections (pneumonia, bacteremia and other), renal dysfunction, duration of ICU admission, and time to discharge or mortality.

Conditions

COVID-19 Infection

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

rhDNase1 (Pulmozyme, Roche/Genentech)

Single Arm: rhDNase1 (Pulmozyme, Roche/Genentech) 2.5 mg inhaled nebulisations BID, for a maximum of 14 consecutive days.

Group Type: EXPERIMENTAL

rhDNase I

Intervention Type: DRUG

Inhaled nebulisations

Interventions

rhDNase I

Inhaled nebulisations

Intervention Type: DRUG

Other Intervention Names

Pulmozyme

Eligibility Criteria

Inclusion Criteria

1. Verbal informed consent by patient (or legal representative), done in the presence of an impartial witness. The consent is signed by the Principal Investigator (or Co-Investigator) and the impartial witness.

2. Participants who are at least 18 years of age on the day of consenting to the informed consent

3. COVID-19 (SARS-CoV2) positive test by nasopharyngeal swab

4. Admitted to the ICU in negative pressure rooms

5. Mild to severe respiratory illness (defined as requiring admission* and/or supplemental oxygen), not intubated or on mechanical ventilation at screening and enrolment.

• Admission respiratory criteria (1 of the following):

1. Dyspnea at rest or during minimal activity (sitting, talking, coughing, swallowing);

2. Respiratory rate > 22/minute;

3. PaO2 < 65mmHg or oxygen saturation < 90% or PaO2/FiO2 ratio of less than 300

4. Infiltrate on CXR (or worsening CXR, if baseline CXR at admission was already abnormal)

• Mild disease with hospitalization:

• No oxygen therapy;
• Oxygen by mask or nasal prongs.
• Severe disease with hospitalization (requiring greater than 40% oxygen):

• Oxygen by non-invasive ventilation or high flow oxygen/Optiflow.

Exclusion Criteria

1. Patients requiring mechanical ventilation at screening

2. Previous or current treatment with rhDNase1

3. Ongoing experimental treatment with other inhaled therapies through COVID-19-related clinical trials

4. Known hypersensitivity to NET inhibitor or recombinant protein products

5. Known hypersensitivity to Chinese Hamster Ovary cell products or any component of the product

6. Known history of immunodeficiency, HBV, HCV, HIV (Note: No HBV, HCV or HIV testing is required unless mandated by local health authority)

7. Known history of immunosuppressive disorders, such as primary/secondary immunodeficiencies, lymphoproliferative diseases

8. Active pregnancy at any stage or lactation

9. Patients deemed incapable and/or incompetent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Hamilton Health Sciences Corporation

OTHER

Sponsor Role: collaborator

Hoffmann-La Roche

INDUSTRY

Sponsor Role: collaborator

Exactis Innovation

OTHER

Sponsor Role: collaborator

McGill University Health Centre/Research Institute of the McGill University Health Centre

OTHER

Sponsor Role: lead

Responsible Party

Jonathan Spicer

Principal Investigator

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jonathan Spicer, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

McGill University Health Centre/Research Institute of the McGill University Health Centre

Locations

Hamilton General Hospital, Hamilton Health Sciences

Hamilton, Ontario, Canada

McGill University Health Centre

Montreal, Quebec, Canada

Countries

Canada

Other Identifiers

DISCONNECT-1

Identifier Type: -

Identifier Source: org_study_id