A Phase 1/2 interventional study of Bromelains and Acetylcysteine in COVID-19 Pneumonia, COVID-19 and Ventilator Associated Pneumonia, sponsored by Mucpharm Pty Ltd. Status unknown. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2022-02-28.
Sponsored by Mucpharm Pty Ltd · Phase 1/2, Interventional, and Treatment
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.
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.
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's planned enrollment of 30 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →Mucpharm Pty Ltd is the lead sponsor of 3 studies on the registry; none are open to participants now.
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Exclusion Criteria:
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
Bromelain combined with Acetylcysteine (BromAc), administered simultaneously.
Also known as: Bromelain
Bromelain combined with Acetylcysteine (BromAc), administered simultaneously.
Also known as: N-Acetylcysteine
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
Time frame: Following each nebulisation on days 1 to 5 and during follow up on days 6-15, 21, 28 and 60
Proportion of participants that proceed to invasive ventilation for deterioration of COVID-19 (need for mechanical ventilation)
To assess the proportion of patients following commencement of BromAc that proceed to mechanical ventilation for COVID-19
Time frame: Daily for 60 days
World Health Organisation (WHO) modified ordinal scale clinical score
Determine the clinical score by improvement or deterioration based on World Health Organisation Modified Ordinal Scale for COVID-19 over 28-days
Time frame: Daily for 28 days
Improvement or deterioration in oxygenation
Assess the improvement or deterioration in percentage of oxygen saturation (SpO2) whilst hospitalised vs the fraction of inspired oxygen (SpO2/FiO2 ratio)
Time frame: Daily for up to 14 days
All-cause mortality
Determine the all-cause mortality of patients enrolled over 28 days
Time frame: Daily for 28 days
Dose related toxicities
Determine the tolerated dose of BromAc within the therapeutic range for COVID-19 sputum mucolysis delivered by nebuliser
Time frame: 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)
Assess the proportion of participants with treatment-emergent serious adverse events (SAEs) by Common Toxicity Criteria for Adverse Events (CTCAE) v4.0
Time frame: Following each nebulisation on days 1 to 5 and during follow up on days 6-15, 21, 28 and 60
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Plan to share: No
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Mucpharm Pty Ltd