Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12622000022763
Ethics application status
Approved
Date submitted
5/09/2021
Date registered
12/01/2022
Date last updated
14/09/2022
Date data sharing statement initially provided
12/01/2022
Type of registration
Prospectively registered

Titles & IDs
Public title
Safety of nebulised delivery of BromAc® (Bromelain & Acetylcysteine) in healthy volunteers: a potential treatment for severe COVID-19
Scientific title
Safety of nebulised delivery of BromAc® (Bromelain & Acetylcysteine) in healthy volunteers: a potential treatment for severe COVID-19
Secondary ID [1] 305224 0
nil
Universal Trial Number (UTN)
U1111-1269-2328
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
COVID-19 323499 0
Condition category
Condition code
Respiratory 321063 321063 0 0
Other respiratory disorders / diseases
Infection 321113 321113 0 0
Other infectious diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This is a phase I study on the safety of BromAc, where 12 healthy volunteers who are otherwise well and remain in the outpatient setting will receive BromAc as a nebulised aerosol into the respiratory tract once daily for three days, in a dose escalation format.
Dose escalation will be Bromelain 100ug/ml, 150ug/ml or 200ug/ml in combination with Acetylcysteine 20mg/ml. Doses will be increased after every 4 patients, with the first patient receiving dose level 1 (BromAc 100ug/20mg/ml). If safe, dose escalation will occur to the next level based on the number of dose limiting toxicities. Dose escalation to the next level will occur after treatment of 4 patients at each level has been completed at the end of day 3.
BromAc is a product that combines two existing products (Bromelain and Acetylcysteine), along with 0.9% normal saline to be delivered into the respiratory tract via nebulised aerosol delivery through a mask, which will be administered by a nurse or member of the study team. The nebulisation will take approximately 20 minutes. Doses will be administered under clinic monitoring. The participant will be assessed for symptoms and side effects during nebulisation of BromAc and for 2 hours following completion of nebulisation. Clinical observations and a symptom assessment questionnaire will be completed on days 1, 2 and 3 with a blood test at the end of day 3 treatment. Follow up phone calls will occur on days 5 and 10, with a symptom assessment questionnaire.
Intervention code [1] 321622 0
Treatment: Drugs
Comparator / control treatment
no control group
Control group
Uncontrolled

Outcomes
Primary outcome [1] 328839 0
To characterise and evaluate the safety of BromAc following nebulised delivery: safety will be assessed by the number of moderate to severe adverse events. Possible adverse events include allergy/sensitivity to the drug, bronchospasm, throat dryness or nasal dripping. Participants will be monitored for adverse events in the clinic and by telephone follow up.
Timepoint [1] 328839 0
On days 1, 2, 3 during treatment and post treatment for 2 hours, and during follow up on days 5 and 10
Secondary outcome [1] 400594 0
Proportion of participants with treatment-emergent adverse events (AEs): Possible adverse events include allergy/sensitivity to the drug, bronchospasm, throat dryness or nasal dripping. Participants will be monitored for adverse events in the clinic and by telephone follow up. Participants will also complete a study specific symptom questionnaire following treatment on days 1, 2 and 3 and during follow up on days 5 and 10.
Timepoint [1] 400594 0
On days 1, 2, 3 during treatment and post treatment for 2 hours, and during follow up on days 5 and 10
Secondary outcome [2] 400595 0
Determine the maximum tolerated dose (MTD) of BromAc within the therapeutic range for COVID-19 delivered by nebuliser: toxicity will be assessed by the modified toxicity probability interval (MTPI) design and graded according to the Common Terminology Criteria for Adverse Events criteria
Timepoint [2] 400595 0
On days 1, 2, 3 during treatment and post treatment for 2 hours, and during follow up on days 5 and 10

Eligibility
Key inclusion criteria
• Aged 18 to 60 years
• Remain generally well and as an outpatient
• Received the first vaccination for COVID-19, able to adhere to NSW Health guidelines surrounding attendance to a public hospital, and completion of any hospital questionnaires
• Are considered suitable for the trial based on ability to follow protocol and provide informed consent
• Are within a 10km radius of a study centre for ensuring adherence to trial procedures and follow up
Minimum age
18 Years
Maximum age
60 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
• Have been in contact with a known case of COVID-19 or advised to undertake self-isolation in the last 14 days
• Have known allergy (anaphylaxis) or sensitivity to pineapples, papain, bromeliads, (fruit or plant) sulphur, eggs or Acetylcysteine that cannot be managed with steroids or antihistamine prophylaxis or any other serious unrelated allergy
• Have symptoms of COVID-19 such as cough or shortness of breath or evidence of pulmonary disease, other respiratory disease including asthma or chronic obstructive pulmonary disease
• Have a coagulation disorder of any kind or are on anticoagulant or anti-platelet therapy, history of nose bleeds or easy bruising
• Have any other serious comorbidities where inclusion in the trial will subject the participant to a higher risk of adverse events
• 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. Breastfeeding should be discontinued if the mother is treated with BromAc
• People 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 design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Dose escalation, phase 1, healthy volunteer study
Phase
Phase 1
Type of endpoint/s
Safety
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
1/08/2022
Actual
26/07/2022
Date of last participant enrolment
Anticipated
30/09/2022
Actual
11/08/2022
Date of last data collection
Anticipated
14/10/2022
Actual
25/08/2022
Sample size
Target
12
Accrual to date
Final
12
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 20475 0
St George Hospital - Kogarah
Recruitment postcode(s) [1] 35244 0
2217 - Kogarah

Funding & Sponsors
Funding source category [1] 309600 0
Commercial sector/Industry
Name [1] 309600 0
Mucpharm Pty Ltd
Country [1] 309600 0
Australia
Primary sponsor type
Commercial sector/Industry
Name
Mucpharm Pty Ltd
Address
1 Chapel Street
Kogarah NSW 2217
Country
Australia
Secondary sponsor category [1] 310613 0
None
Name [1] 310613 0
Address [1] 310613 0
Country [1] 310613 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 309411 0
Bellberry Ltd
Ethics committee address [1] 309411 0
123 Glen Osmond Rd
Eastwood SA 5063
Ethics committee country [1] 309411 0
Australia
Date submitted for ethics approval [1] 309411 0
04/09/2021
Approval date [1] 309411 0
25/03/2022
Ethics approval number [1] 309411 0
2021-09-1017

Summary
Brief summary
COVID-19 has multiple facets including cytokine storm, thromboembolism, renal impairment, and mucinous secretions. It is known that oxygen exchange is the main problem in patients with COVID-19 and hypoxia is one of the most serious effects, in which patients succumb to acute respiratory distress syndrome (ARDS). The development of mucinous sputum plugs in individuals infected with SARS-CoV-2 in addition to cytokine storm is of great clinical importance, correlating with negative outcome.
Bromelain and Acetylcysteine (BromAc) is a potent mucolytic applied in highly mucinous tumours of the appendix. Previous research has shown that BromAc cleaves the glycoproteins of the SARS-CoV-2 virus (antiviral), is a mucolytic, dissolving COVID-19 and other respiratory sputum in clinically relevant times, and down regulates cytokines and chemokines in sputum from ventilated COVID-19 patients. The investigators now seek to examine the safety of nebulised BromAc in healthy volunteers to assess any symptoms or side effects prior to progressing towards a potential treatment option in patients with severe COVID-19.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 113934 0
Prof Frank van Haren
Address 113934 0
St George Hospital
Intensive Care
Gary Street Kogarah NSW 2217
Country 113934 0
Australia
Phone 113934 0
+61291133285
Fax 113934 0
Email 113934 0
[email protected]
Contact person for public queries
Name 113935 0
Sarah Valle
Address 113935 0
St George Hospital
L3 Pitney Building
Short Street
Kogarah NSW 2217
Country 113935 0
Australia
Phone 113935 0
+61 291132070
Fax 113935 0
Email 113935 0
[email protected]
Contact person for scientific queries
Name 113936 0
Sarah Valle
Address 113936 0
St George Hospital
L3 Pitney Building
Short Street
Kogarah NSW 2217
Country 113936 0
Australia
Phone 113936 0
+61 291132070
Fax 113936 0
Email 113936 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Only aggregate data will be available.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.