Nebulised BromAc in Healthy Volunteers

NCT05220605 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: MUC-COV-002
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

COVID-19 is a disease that has multiple facets including an inflammatory storm, it promotes blood clotting and causes kidney damage, mucinous secretions in the lung are of great importance to outcome. Increasingly sticky sputum is associated with critical illness, with considerably raised levels of a specific type of mucous protein (MUC5AC) in sputum in COVID-19 patients. There is a strong link between viral infection and mucus production via multiple inter-cellular signalling pathways including Interleukin (IL)6, IL10 and Tumour Necrosis Factor (TNF) whereby the inflammatory storm causes sudden secretion of high volumes of dense mucus. An Australian pharmaceutical company has developed BromAc (Bromelain \& Acetylcysteine) for the palliative treatment of highly mucinous tumors of the appendix and lung. During pre-clinical development, they found that BromAc® rapidly dissolved and removed tumour mucin, making it a potent mucolytic. In combination, bromelain and acetylcysteine disrupt the architecture of the SARS-COV-2 virus in a way that renders it non-infective, reduced cytokines and chemokines in COVID-19 sputum and is a highly effective respiratory mucolytic. The aim of this study is to assess whether BromAc delivered into the respiratory tract as a nebulised aerosol is tolerated and safe at three specific concentrations in healthy volunteer participants. The investigators will further assess the safety of nebulised BromAc and efficacy of the drug product as a mucolytic and anti-inflammatory, and whether this improves clinical outcome in participants with COVID-19. The hypothesis is that BromAc will be tolerated by patients and will result in mucus clearance, improving oxygenation and compliance in those that are ventilated. This is a phase I study on the safety of BromAc, where 12 healthy volunteers will receive BromAc as a nebulised aerosol into the respiratory tract. BromAc is a product that combines two existing products to be delivered into the respiratory tract via nebulised aerosol delivery through a mask. The participant will be assessed for symptoms and side effects. The participant will receive nebulised BromAc at the allocated dose level for a total of 3 days. The hypothesis is that nebulised airway delivery of BromAc will be safe at the concentrations assessed.

Conditions

COVID-19 Pneumonia; Bromelains Adverse Reaction; Acetylcysteine Adverse Reaction; Mucus; Plug; COVID-19 Acute Respiratory Distress Syndrome

Keywords

bromelain; BromAc; acetylcysteine; SARS-CoV-2; mucin; mucus plug; COVID-19 pneumonia; ventilator associated pneumonia; secondary bacterial infection

Outcome Measures

Primary Outcomes (6)

• To characterise and evaluate the safety of BromAc following nebulised delivery

  Clinical observations will be performed to to assess change compared to baseline in heart rate (HR) (beats per minute).

  Heart rate will be measured every 10 minutes during nebulisation, then 30 minutes after cessation of treatment and again at 1 hour and 2 hours.

• To characterise and evaluate the safety of BromAc following nebulised delivery

  Clinical observations will be performed to assess change compared to baseline in blood pressure (BP) (mmHg)

  Blood pressure will be measured every 10 minutes during nebulisation, then 30 minutes after cessation of treatment and again at 1 hour and 2 hours.

• To characterise and evaluate the safety of BromAc following nebulised delivery on oxygen saturation

  Clinical observations will be performed to assess change compared to baseline in SpO2 (oxygen saturation) to determine SpO2 to FiO2 (fraction of inspired oxygen) ratio.

  SpO2 will be measured every 10 minutes during nebulisation, then 30 minutes after cessation of treatment, and again at 1 hour and 2 hours.

• To characterise and evaluate the safety of BromAc following nebulised delivery on respiratory rate

  Clinical observations will be performed to assess change compared to baseline in respiratory rate (RR) (breaths per minute)

  Respiratory rate will be measured every 10 minutes during nebulisation, then 30 minutes after cessation of treatment, and again at 1 hour and 2 hours.

• To characterise and evaluate the safety of BromAc following nebulised delivery on mucosal parameters

  Mucosal assessment will be performed by the Total Nasal Symptom Score to determine any changes in mucosal parameters vs baseline. A higher score will mean a worse outcome in terms of nasal mucosal side effect to treatment.

  Baseline each treatment day and at the end of each nebulisation on days 1-3.

• To characterise and evaluate the safety of BromAc following nebulised delivery on blood parameters

  Biochemical analyses liver and kidney function, full blood count, coagulation and inflammatory markers will be measured and compared to baseline pretreatment results to determine if there is any change to the baseline biochemical parameters of the drug treatment.

  Blood tests will be performed at baseline (day 0), then each day of treatment (days 1-5), during follow up on day 6 and day 14.

Secondary Outcomes (2)

• Determine the proportion of patients with treatment-emergent adverse events (AEs)

  Adverse events will be monitored during and immediately post-treatment on days 1, 2 and 3; and for delayed adverse events on days 4, 5 and 10 and 14.

• Determine the maximum tolerated dose (MTD) of BromAc within he therapeutic range for COVID-19 delivered by nebuliser

  At each dose escalation and up until the end of follow up (last day of follow up for the last patient enrolled).

Study Arms (3)

Bromac (100ug/20mg)

EXPERIMENTAL

The nurse/investigator will fill the jet nebuliser canister supplied on the ward with the 5ml of BromAc (100micrograms bromelain and 20mg acetylcysteine). The cannister will be collected to the mask and attached to the wall compressed air supply, with flow of between 6-8L per minute. The mask will be placed on the participant immediately upon generating aerosol. The nebulisation will continue until the chamber is empty, estimated 15 minutes, unless otherwise indicated, such as adverse event. The nurse/investigator will undertake clinical observations including heart rate, respiratory rate, SpO2 and blood pressure, every 5 minutes during nebulisation and then at 30 minutes, 1 hour and 2 hours. Cardiorespiratory auscultation will occur at the end of nebulisation and prior to discharge. This will be repeated once daily for three consecutive days. Blood tests will be taken before the first dose is given on day 1, and two hours after the last dose is given on day 3.

Drug: BromAc

Bromac (150ug/20mg)

EXPERIMENTAL

The nurse/investigator will fill the jet nebuliser canister supplied on the ward with the 5ml of BromAc (150micrograms bromelain and 20mg acetylcysteine). The cannister will be collected to the mask and attached to the wall compressed air supply, with flow of between 6-8L per minute. The mask will be placed on the participant immediately upon generating aerosol. The nebulisation will continue until the chamber is empty, estimated 15 minutes, unless otherwise indicated, such as adverse event. The nurse/investigator will undertake clinical observations including heart rate, respiratory rate, SpO2 and blood pressure, every 5 minutes during nebulisation and then at 30 minutes, 1 hour and 2 hours. Cardiorespiratory auscultation will occur at the end of nebulisation and prior to discharge. This will be repeated once daily for three consecutive days. Blood tests will be taken before the first dose is given on day 1, and two hours after the last dose is given on day 3.

Drug: BromAc

Bromac (200ug/20mg)

EXPERIMENTAL

The nurse/investigator will fill the jet nebuliser canister supplied on the ward with the 5ml of BromAc (200 micrograms bromelain and 20mg acetylcysteine). The cannister will be collected to the mask and attached to the wall compressed air supply, with flow of between 6-8L per minute. The mask will be placed on the participant immediately upon generating aerosol. The nebulisation will continue until the chamber is empty, estimated 15 minutes, unless otherwise indicated, such as adverse event. The nurse/investigator will undertake clinical observations including heart rate, respiratory rate, SpO2 and blood pressure, every 5 minutes during nebulisation and then at 30 minutes, 1 hour and 2 hours. Cardiorespiratory auscultation will occur at the end of nebulisation and prior to discharge. This will be repeated once daily for three consecutive days. Blood tests will be taken before the first dose is given on day 1, and two hours after the last dose is given on day 3.

Drug: BromAc

Interventions

BromAc DRUG

Bromelain and acetylcysteine are combined in various concentrations (either 100ug, 150ug or 200ug of bromelain, with 20mg of acetylcysteine). This is then delivered by a nebuliser to up to 12 healthy volunteers. The primary aim is determining safety.

Bromac (100ug/20mg); Bromac (150ug/20mg); Bromac (200ug/20mg)

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Aged 18 to 70 years
• Received complete vaccination against COVID-19 over one week from trial commencement, able to adhere to 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

You may not qualify if:

• Have been in contact with a known case of COVID-19 or advised to undertake self-isolation
• 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
• ECOG \>2
• 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
• Patients 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

Sponsors & Collaborators

• Mucpharm Pty Ltd: lead
• St George Hospital, Australia: collaborator
• Mobius Medical Pty Ltd.: collaborator

Study Sites (1)

St George Hospital

Kogarah, New South Wales, 2217, Australia

Location

MeSH Terms

Conditions

Medullary cystic kidney disease 1; Pneumonia, Ventilator-Associated

Interventions

bromelain and acetylcysteine drug combination

Condition Hierarchy (Ancestors)

Healthcare-Associated Pneumonia; Cross Infection; Infections; Pneumonia; Respiratory Tract Infections; Lung Diseases; Respiratory Tract Diseases; Iatrogenic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Frank van Haren, MD, PhD

  St George Hospital, Director of Intensive Care

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 24, 2022
• First Posted: February 2, 2022
• Study Start: July 27, 2022
• Primary Completion: August 14, 2022
• Study Completion: August 25, 2022
• Last Updated: September 15, 2022

Record last verified: 2022-09

Locations

AU (1)