- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT05258682
Safety of Nebulized Combination Therapy BromAc® in COVID-19 Respiratory Disease
Safety of Nebulized Combination Therapy BromAc® in COVID-19 Respiratory Disease: a Phase 1 Study
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
It is well known that oxygen exchange is a major problem in patients with COVID-19 and hypoxia is one of the most serious effects, where patients succumb from acute respiratory distress syndrome (ARDS). The development of mucinous sputum plugs in individuals infected with SARS-CoV-2 is variable in the early stages of the disease. In addition, 30-40% of patients who are in hospital have expectoration production, and in a recent study on pulmonary pathology in patients with COVID-19, subsequent tests revealed markedly increased levels of MUC1 and MUC5AC in sputum and tracheal aspirates.
Currently, there are few therapeutic agents of limited efficacy to treat or avoid the complications of COVID-19 and none directed against airway mucus. An Australian pharmaceutical company has developed BromAc for the palliative treatment of highly mucinous tumors of the appendix and lung. This drug is composed of bromelain and acetylcysteine. During pre-clinical development, the sponsor found that BromAc® rapidly dissolved and removed tumour mucin, making it a potent mucolytic. BromAc® in combination have the ability, as shown in pre-clinical studies, to remove the mucin protective framework expressed by cancer including MUC1, MUC2, MUC4, MUC5AC and MUC16. The sponsor has shown the mechanism of action of BromAc - to break peptide and glycosidic linkages and disulphide bonds in tumour produced and respiratory mucin.
In an in vitro study by the sponsor with Vero and CALU-3 cells infected by SARS-CoV-2 (MOI 1 to -4) and treated with BromAc, it was found that the drug was able to reduce the virus's ability to infect cells, demonstrating an antiviral potential for SARS-CoV-2, with 99.99% reduction in viral infectivity at low concentrations. In addition to the anti-viral effect, BromAc is a potent mucolytic. In laboratory studies, BromAc (125ug or 250ug/ml plus 20mg/ml Acetylcysteine) resulted in complete dissolution of severe COVID-19 sputum after a single application within 30 minutes. BromAc significantly down-regulated cytokines and chemokines in comparison to Acetylcysteine alone or control, specifically those important to COVID-19 cytokine storm CCL2, CCL3, IL-6, CXCL10. In vivo safety models in two species have received nebulised and intranasal BromAc up to 500ug/20mg/ml three times daily for five days, with no evidence of respiratory or systemic toxicity clinically or on histology.
This project will evaluate the mucolytic and anti-inflammatory effect of BromAc in patients with moderate to severe COVID-19 that are not on mechanical ventilation. The investigators believe that BromAc may have a role clinically in removing the proteinaceous material from the bronchi and alveoli allowing improved ventilation, gas exchange and transfer and aim to study whether this is a potential treatment for these patients.
This therapy if safe may reduce the need for ventilation or improve the outcome of ventilation (reduced pressure, faster time to extubation, reduced secondary lung injury, reduced deaths), which will be assessed in future studies.
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Contact
- Name: Sarah J Valle, BN
- Phone Number: 61291132070
- Email: sarah@mucpharm.com
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
- Have other serious comorbidities where inclusion in the trial will subject the participant to a higher risk of adverse events, including participants with asthma (existing severe lung disease such as COPD, bronchiectasis and cystic fibrosis are not exclusion criteria)
- 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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: BromAc
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.
|
Bromelain combined with Acetylcysteine (BromAc), administered simultaneously.
Other Names:
Bromelain combined with Acetylcysteine (BromAc), administered simultaneously.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Evaluate the treatment-emergent adverse events (AEs) of BromAc therapy following nebulised delivery
Time Frame: Following each nebulisation on days 1 to 5 and during follow up on days 6-15, 21, 28 and 60
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Proportion of participants that proceed to invasive ventilation for deterioration of COVID-19 (need for mechanical ventilation)
Time Frame: Daily for 60 days
|
To assess the proportion of patients following commencement of BromAc that proceed to mechanical ventilation for COVID-19
|
Daily for 60 days
|
World Health Organisation (WHO) modified ordinal scale clinical score
Time Frame: Daily for 28 days
|
Determine the clinical score by improvement or deterioration based on World Health Organisation Modified Ordinal Scale for COVID-19 over 28-days
|
Daily for 28 days
|
Improvement or deterioration in oxygenation
Time Frame: Daily for up to 14 days
|
Assess the improvement or deterioration in percentage of oxygen saturation (SpO2) whilst hospitalised vs the fraction of inspired oxygen (SpO2/FiO2 ratio)
|
Daily for up to 14 days
|
All-cause mortality
Time Frame: Daily for 28 days
|
Determine the all-cause mortality of patients enrolled over 28 days
|
Daily for 28 days
|
Dose related toxicities
Time Frame: Following each nebulisation on days 1 to 5 and during follow up on days 6-15, 21, 28 and 60
|
Determine the tolerated dose of BromAc within the therapeutic range for COVID-19 sputum mucolysis delivered by nebuliser
|
Following each nebulisation on days 1 to 5 and during follow up on days 6-15, 21, 28 and 60
|
Treatment-emergent serious adverse events (SAEs)
Time Frame: Following each nebulisation on days 1 to 5 and during follow up on days 6-15, 21, 28 and 60
|
Assess the proportion of participants with treatment-emergent serious adverse events (SAEs) by 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
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Frank MP van Haren, MD, PhD, St George Hospital, Director of Intensive Care
Study record dates
Study Major Dates
Study Start (Anticipated)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Coronavirus Infections
- Coronaviridae Infections
- Nidovirales Infections
- RNA Virus Infections
- Virus Diseases
- Infections
- Respiratory Tract Infections
- Pneumonia, Viral
- Lung Diseases
- Disease Attributes
- Infant, Newborn, Diseases
- Cross Infection
- Iatrogenic Disease
- Lung Injury
- Infant, Premature, Diseases
- Healthcare-Associated Pneumonia
- COVID-19
- Pneumonia
- Respiratory Distress Syndrome
- Respiratory Distress Syndrome, Newborn
- Acute Lung Injury
- Pneumonia, Ventilator-Associated
- Respiration Disorders
- Respiratory Tract Diseases
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Protective Agents
- Respiratory System Agents
- Antioxidants
- Antidotes
- Free Radical Scavengers
- Expectorants
- Acetylcysteine
- N-monoacetylcystine
Other Study ID Numbers
- MUC-COV-003
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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