COVID-19 PneumoniaPhase 1/2NCT05258682
Safety of Nebulized Combination Therapy BromAc® in COVID-19 Respiratory Disease
A Phase 1/2 study testing Bromelains and Acetylcysteine in people with COVID-19 Pneumonia and COVID-19, run by Mucpharm Pty Ltd.
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). Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- COVID-19 Pneumonia, COVID-19, Ventilator Associated Pneumonia
- What is being tested?
- Bromelains and Acetylcysteine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2022to 30 Oct 2022
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Safety of Nebulized Combination Therapy BromAc® in COVID-19 Respiratory Disease: a Phase 1 Study
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.
Read the 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.
- Conditions
- COVID-19 Pneumonia, COVID-19, Ventilator Associated Pneumonia, COVID-19 Acute Respiratory Distress Syndrome
- Being tested
- Bromelains, Acetylcysteine
- Keywords
- mucolytic, COVID-19, COVID-19 pneumonia, Ventilator associated pneumonia, Secondary bacterial infections
- Medical subject headings
- COVID-19, Pneumonia, Ventilator-Associated
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BromelainsDrug
Also called Bromelain
Bromelain combined with Acetylcysteine (BromAc), administered simultaneously.
AcetylcysteineDrug
Also called N-Acetylcysteine
Bromelain combined with Acetylcysteine (BromAc), administered simultaneously.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Bromelains; Drug: Acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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)
To assess the proportion of patients following commencement of BromAc that proceed to mechanical ventilation for COVID-19
Measured: 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
Measured: 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)
Measured: Daily for up to 14 days
All-cause mortality
Determine the all-cause mortality of patients enrolled over 28 days
Measured: 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
Measured: 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
Measured: Following each nebulisation on days 1 to 5 and during follow up on days 6-15, 21, 28 and 60
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Feb 2022
- Study start1 May 2022 (estimated)
- Primary completion30 Sep 2022 (estimated)
- Study completion30 Oct 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for COVID-19 PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mucpharm Pty Ltd
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- St George Hospital, Australia
- Responsible party
- Sponsor
- Investigators
- Frank MP van Haren, MD, PhD, Principal investigator, St George Hospital, Director of Intensive Care
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05258682
- Sponsor's protocol ID
- MUC-COV-003
- Status last verified
- Feb 2022
- First submitted
- 22 Feb 2022
- Last updated
- 28 Feb 2022
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety of Nebulized Combination Therapy BromAc® in COVID-19 Respiratory Disease: a Phase 1 Study
- ClinicalTrials.gov ID
- NCT05258682
- Acronym / sponsor ID
- MUC-COV-003
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Mucpharm Pty LtdIndustry (pharma, biotech, devices)
- Collaborators
- St George Hospital, Australia
- Study start
- 1 May 2022 (estimated)
- Primary completion
- 30 Sep 2022 (estimated)
- Study completion
- 30 Oct 2022 (estimated)
- First posted
- 28 Feb 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| BromAc | Experimental | Drug: Bromelains, Drug: AcetylcysteineBromAc (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. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (7 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BromelainsAlso: BromelainBromelain combined with Acetylcysteine (BromAc), administered simultaneously. | Drug | BromAc |
| AcetylcysteineAlso: N-AcetylcysteineBromelain combined with Acetylcysteine (BromAc), administered simultaneously. | Drug | BromAc |
Primary outcome
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
6 secondary outcomes
Proportion of participants that proceed to invasive ventilation for deterioration of COVID-19 (need for mechanical ventilation)
Time frame: Daily for 60 days
World Health Organisation (WHO) modified ordinal scale clinical score
Time frame: Daily for 28 days
Improvement or deterioration in oxygenation
Time frame: Daily for up to 14 days
All-cause mortality
Time frame: 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
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
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Feb 2022.
- Individual participant dataSharing planned: No
Related trials for COVID-19 Pneumonia
Not yet recruitingPhase 1
Phase I Open-Label Safety Trial of Pembrolizumab for Neurological Post- Acute Sequelae of SARS-CoV-2 (PD1-PASC I)
Post-Acute COVID-19 Syndrome
Active, not recruitingPhase 1
A Safety and Immunogenicity Trial of OCU500, ChAd36 Vector Encoding SARS-CoV-2 Spike Vaccine Via Intranasal and Inhalational Routes in Previously Vaccinated Adults
COVID-19
Recruiting
Home-Based Exercise Tele-Rehabilitation After COVID-19
Post SARS-CoV2 (COVID-19)
Not yet recruitingPhase 1
A Safety, Reactogenicity and Immunogenicity Trial of RVX-sCPD9 Booster Intranasal COVID-19 Vaccine
COVID -19
RecruitingObservational study
Cardiovascular Disease Progression in Survivors of Community Acquired Pneumonia and Lung Infection by Covid-19.
Pneumonia, Community-Acquired, COVID-19 Pneumonia
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Frank MP van Haren, MD, PhD principal investigator
St George Hospital, Director of Intensive Care
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Bromelains and Acetylcysteine in people with COVID-19 Pneumonia and COVID-19, run by Mucpharm Pty Ltd.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 4 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 28 Feb 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Sarah J Valle, BN (61291132070, sarah@mucpharm.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Feb 2022.