RecruitingPhase 1ACTRN12620000788976

Safety and efficacy of intranasal delivery of BromAc® (Bromelain & Acetylcysteine) in swab positive SARS-CoV-2 COVID-19 patients

Safety and efficacy of intranasal delivery of BromAc® (Bromelain & Acetylcysteine) in swab positive SARS-CoV-2 patients – a phase I, single-arm, dose escalation study

Sponsor

Mucpharm Pty Ltd

Enrollment

40 participants

Start Date

Jan 4, 2021

Study Type

Interventional

Conditions

COVID19

Summary

Since December 2019, we have been facing our third severe acute respiratory syndrome (SARS) due to a coronavirus in 18 years, known as SARS-CoV-2. There are currently few therapeutic agents and of only limited efficacy. The large majority of patients are diagnosed with a mild form of the virus. The SARS-CoV-2 virus, with its clinical syndrome known as COVID-19, is made up of spike protein (S), nucleocapsid protein (N) that contains the RNA, membrane protein (M) and the envelope protein (E). The spike protein that is responsible for initiating internalization of the virus genome into human lung cells protrudes on the outer surface and is a number of amino acids and glycoproteins. Recent insights strongly support the theory that the nose is the primary site of infection, from where the infection is prone to progress to the lung, suggesting the potential for early nasal-directed treatment. Bromelain and Acetylcysteine (BromAc®) is a palliative treatment for highly mucinous tumours of the appendix due to its ability to remove glycosidic linkages and disulphide bonds. Bromelain is already known to remove the spike protein and haemagglutinin of similar viruses, including Semliki Forest virus, Sindbis virus, mouse gastrointestinal coronavirus, hemagglutinating encephalomyelitis virus and H1i1 influenza viruses, rendering these non-infective, Acetylcysteine has already been used as an anti-viral. It inhibits influenza A and induced production of pro-inflammatory molecules in lung epithelial cells. In a murine model of lethal influenza infection, an increased survival was seen in the acetylcysteine combination with oseltamivir group (100% vs 60%). We predicted and have now shown that BromAc® can disrupt and completely cleave the glycoproteins of the SARS-CoV-2 virus, which have a detrimental effect on the virus, rendering it non-infective. We believe that BromAc® may be suitable in clinical application with delivery intranasally in swab PCR positive SARS-CoV-2 outpatients. This drug has the potential to reduce infectivity of those with SARS-CoV-2, potentially reducing exposure to close contacts and progression of the disease into COVID19 syndrome, and act as a prophylactic to prevent the virus from binding to host cells.

Eligibility

Sex: Both males and femalesMin Age: 18 Yearss

Inclusion Criteria7

Aged 18 years or older
Swab positive for SARS-CoV-2 based on RT-PCR (patients must be identified and commence treatment within 3 days of the positive result)
Diagnostic PCR or pre-treatment PCR must have viral load titre measurement
Swabbed within 48 hours of symptom onset
Remain generally well and as an outpatient in isolation in their home
Are considered suitable for the trial based on ability to follow protocol and provide informed consent
Are within a 50km radius of a study centre for ensuring adherence to trial procedures and follow up

Exclusion Criteria10

Have symptoms from SARS-CoV-2 that warrant admission to hospital, require supplemental oxygen therapy or are an inpatient in a hospital for SARS-CoV-2
Are unwilling to undergo repeat swab for PCR viral load
On anti-viral therapy for SARS-CoV-2 (for e.g. Remdesivir, Interferon-beta1alpha) or are enrolled in another clinical trial for SARS-CoV-2
Have known allergy (anaphylaxis) to pineapples, papain, bromeliads, sulphur, eggs or Acetylcysteine that cannot be managed with steroids or antihistamine prophylaxis or any other serious unrelated allergy
Have a coagulation disorder of any kind or are on anticoagulant or anti-platelet therapy that cannot be withheld for the treatment period
ECOG >2
Have other serious comorbidities where inclusion in the trial will subject the patient to a higher risk of adverse events, including patients with uncontrolled intercurrent illness
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

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Interventions

This is a phase I study on the safety of a combination of Bromelain and Acetylcysteine (BromAc®), where 40 patients who are PCR-positive for SARS-CoV-2 that are otherwise well and remain in the outpatient setting will receive BromAc® as an intranasal spray. This drug is a product that combines these two existing products (Bromelain and Acetylcysteine), along with 5% glucose to be delivered into the nose via spray bottle delivery. The dose of the nose spray will vary based on dose escalation with Bromelain 25, 50, 75, 100 and 125ug/ml. The dose of Acetylcysteine will be 20mg/ml. Doses will be increased after every 10 patients with the first patient receiving dose level 2 (50ug Bromelain) if safe based on the number of dose limiting toxicities. Cohorts will commence one week apart. The nose spray will be administered four times per day for five days. The participant will be asked to electronically log administration of the drug and any symptoms or side effects. In addition, the patient will be assessed for symptoms and side effects on daily follow up phone calls as well as preliminary evidence of efficacy with daily RT-PCR for viral load.