Safety of Nebulized Combination Therapy BromAc® in COVID-19 Respiratory Disease

NCT05258682 | Unknown Phase 1 DMC FDA Drug

• 1 other identifier: MUC-COV-003
• Study Type: interventional
• Target: 30
• Locations: 0 countries
• Sites: N/A

Brief Summary

COVID-19 has multiple facets including cytokine storm, thromboembolism and gelatinous secretions. It is known that oxygen exchange is the main problem in patients with COVID-19 and hypoxia is one of the most serious, in which patients succumb to acute respiratory distress syndrome (ARDS). In other severe respiratory disease such as ventilator associated pneumonia (VAP), formation of biofilm in the endotracheal tube causes infection to spread to the lungs, resulting in respiratory decline and high mortality. The development of gelatinous sputum plugs correlates with negative outcome. Both groups of patients still have limited therapy options. BromAc is a potent mucolytic, biofilm degrader, cleaves the glycoproteins of the SARS-CoV-2 virus (antiviral), and down regulates cytokines and chemokine in COVID-19 sputum. The investigators seek to examine the safety and attempt to gain preliminary efficacy of nebulised BromAc in moderate to severe COVID-19 and other mucus producing, severe, respiratory diseases.

Conditions

COVID-19 Pneumonia; COVID-19; Ventilator Associated Pneumonia; COVID-19 Acute Respiratory Distress Syndrome

Keywords

mucolytic; COVID-19; COVID-19 pneumonia; Ventilator associated pneumonia; Secondary bacterial infections

Outcome Measures

Primary Outcomes (1)

• Evaluate the treatment-emergent adverse events (AEs) of BromAc therapy following nebulised delivery

  The safety and tolerability of BromAc will be assessed by characterising the symptoms or side effects of treatment (treatment-emergent adverse events) by the Common Toxicity Criteria for Adverse Events (CTCAE) v4.0

  Following each nebulisation on days 1 to 5 and during follow up on days 6-15, 21, 28 and 60

Secondary Outcomes (6)

• Proportion of participants that proceed to invasive ventilation for deterioration of COVID-19 (need for mechanical ventilation)

  Daily for 60 days

• World Health Organisation (WHO) modified ordinal scale clinical score

  Daily for 28 days

• Improvement or deterioration in oxygenation

  Daily for up to 14 days

• All-cause mortality

  Daily for 28 days

• Dose related toxicities

  Following each nebulisation on days 1 to 5 and during follow up on days 6-15, 21, 28 and 60

Study Arms (1)

BromAc

EXPERIMENTAL

BromAc (Bromelain and Acetylcysteine combination) will be administered three times (3x) per day for five (5) days in a dose escalation format via inhalation using an approved vibrating mesh nebuliser (Aerogen Pro). Dose escalation concentration levels are BromAc 125ug/20mg/ml, 250ug/20mg/ml, 375ug/20mg/ml. All levels will receive 5ml of BromAc.

Drug: Bromelains; Drug: Acetylcysteine

Interventions

Bromelains DRUG

Bromelain combined with Acetylcysteine (BromAc), administered simultaneously.

Also known as: Bromelain

BromAc

Acetylcysteine DRUG

Bromelain combined with Acetylcysteine (BromAc), administered simultaneously.

Also known as: N-Acetylcysteine

BromAc

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 years to 75 years old
• Admitted to hospital for management of COVID-19 with moderate or severe disease
• Positive testing by virologic test (i.e. SARS-CoV-2 based qRT-PCR)
• Clinical signs suggestive of moderate or severe disease such as oxygen saturation (SpO2) less than 93% on room air or where the participant requires oxygen support such as nasal cannulas, mask, non-rebreather mask, high flow nasal cannulas

You may not qualify if:

• Patients that have critical disease and are mechanically ventilated
• Undergoing other airway administered mucolytic therapy for e.g. dornase alfa within 24 hours, or are enrolled in another clinical trial for COVID-19
• Have known allergy, anaphylaxis or intolerance to pineapples, papain, bromeliads, sulphur, eggs or Acetylcysteine or any other serious allergy or intolerance to fruits or food products or any other serious allergy or allergen triggered asthma, such as dust or pollen
• Pregnant women are excluded from this study because BromAc has unknown but a potential risk for adverse events in nursing infants secondary to treatment of the mother
• Participants with psychiatric illness/social situations that would limit compliance with study requirements.
• Are unable to give fully informed and educated consent or are unable to comply with the standard follow up procedures of a clinical trial

Sponsors & Collaborators

• Mucpharm Pty Ltd: lead
• St George Hospital, Australia: collaborator

MeSH Terms

Conditions

COVID-19; Pneumonia, Ventilator-Associated

Interventions

Bromelains; Acetylcysteine

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; Healthcare-Associated Pneumonia; Cross Infection; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Cysteine Endopeptidases; Cysteine Proteases; Peptide Hydrolases; Hydrolases; Enzymes; Enzymes and Coenzymes; Endopeptidases; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Frank MP van Haren, MD, PhD

  St George Hospital, Director of Intensive Care

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Sarah J Valle, BN

CONTACT

61291132070; sarah@mucpharm.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 22, 2022
• First Posted: February 28, 2022
• Study Start: May 1, 2022
• Primary Completion: September 30, 2022
• Study Completion: October 30, 2022
• Last Updated: February 28, 2022

Record last verified: 2022-02

Data Sharing

• IPD Sharing: Will not share