Clinical Trial Details
— Status: Not yet recruiting
Administrative data
NCT number |
NCT05258682 |
Other study ID # |
MUC-COV-003 |
Secondary ID |
|
Status |
Not yet recruiting |
Phase |
Phase 1/Phase 2
|
First received |
|
Last updated |
|
Start date |
May 1, 2022 |
Est. completion date |
October 30, 2022 |
Study information
Verified date |
February 2022 |
Source |
Mucpharm Pty Ltd |
Contact |
Sarah J Valle, BN |
Phone |
61291132070 |
Email |
sarah[@]mucpharm.com |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial 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.
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 BromAcĀ® rapidly dissolved and removed
tumour mucin, making it a potent mucolytic. BromAcĀ® 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.