DISmantling COvid iNduced Neutrophil ExtraCellular Traps (DISCONNECT-1)

NCT04409925 | Completed Phase 1

• 1 other identifier: DISCONNECT-1
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 2

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.

Conditions

COVID-19 Infection

Keywords

Neutrophil Extracellular Traps; NETs; Neutrophils; rhDNase1

Outcome Measures

Primary Outcomes (1)

• Safety of inhaled rhDNase1 in non-ventilated COVID-19 patients by reporting of adverse events

  Rate of all adverse events, rate of serious adverse events, rate of grade 3/4/5 adverse events, rate of drug-related adverse events.

  9 months

Secondary Outcomes (16)

• Time to first study participant enrolment

  Up to 2 weeks

• Enrolment rate

  Up to 9 months

• Eligible patient consent rate

  Up to 9 months

• Completeness of drug delivery

  Up to 9 months

• Completeness of study-specific tests or procedures

  Up to 9 months

Other Outcomes (5)

• Exploratory: NET quantification in blood, correlated to COVID-19 disease severity and complications.

  Up to 9 months

• Exploratory: Blood clotting and fibrinolysis assays, correlated to COVID-19 disease severity and complications.

  Up to 9 months

• Exploratory: Cytokine profile alterations in blood, correlated to COVID-19 disease severity and complications

  Up to 9 months

Study Arms (1)

rhDNase1 (Pulmozyme, Roche/Genentech)

EXPERIMENTAL

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

Drug: rhDNase I

Interventions

rhDNase I DRUG

Inhaled nebulisations

Also known as: Pulmozyme

rhDNase1 (Pulmozyme, Roche/Genentech)

Eligibility Criteria

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

You may qualify if:

• 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.
• Participants who are at least 18 years of age on the day of consenting to the informed consent
• COVID-19 (SARS-CoV2) positive test by nasopharyngeal swab
• Admitted to the ICU in negative pressure rooms
• 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):
• Dyspnea at rest or during minimal activity (sitting, talking, coughing, swallowing);
• Respiratory rate \> 22/minute;
• PaO2 \< 65mmHg or oxygen saturation \< 90% or PaO2/FiO2 ratio of less than 300
• 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.

You may not qualify if:

• Patients requiring mechanical ventilation at screening
• Previous or current treatment with rhDNase1
• Ongoing experimental treatment with other inhaled therapies through COVID-19-related clinical trials
• Known hypersensitivity to NET inhibitor or recombinant protein products
• Known hypersensitivity to Chinese Hamster Ovary cell products or any component of the product
• Known history of immunodeficiency, HBV, HCV, HIV (Note: No HBV, HCV or HIV testing is required unless mandated by local health authority)
• Known history of immunosuppressive disorders, such as primary/secondary immunodeficiencies, lymphoproliferative diseases
• Active pregnancy at any stage or lactation
• Patients deemed incapable and/or incompetent

Sponsors & Collaborators

• McGill University Health Centre/Research Institute of the McGill University Health Centre: lead
• Hamilton Health Sciences Corporation: collaborator
• Hoffmann-La Roche: collaborator
• Exactis Innovation: collaborator

Study Sites (2)

Hamilton General Hospital, Hamilton Health Sciences

Hamilton, Ontario, L8L 2X2, Canada

Location

McGill University Health Centre

Montreal, Quebec, H4A 3J1, Canada

Location

MeSH Terms

Conditions

COVID-19

Interventions

dornase alfa

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 Officials

• Jonathan Spicer, MD, PhD

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

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: May 13, 2020
• First Posted: June 1, 2020
• Study Start: December 25, 2020
• Primary Completion: April 1, 2021
• Study Completion: August 1, 2021
• Last Updated: March 17, 2023

Record last verified: 2023-03

Locations

CA (2)