Reducing Acute Severe Respiratory Events in Health Care Workers During the Covid-19 Pandemic With OM85

NCT ID: NCT04496245

Last Updated: 2022-03-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 59 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-08-24
• Study Completion Date: 2021-09-30

Brief Summary

Parallel group, Wait-list design, with treatment delayed for 3 months. Participants will be randomized on a 1:1 ratio with 500 participants per group in Australia.

Group 1: Wait-list control. One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing in Month 3, with 3 months follow-up off treatment.

Group 2: Initial treatment. One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing on day 0, with 3 months follow-up off treatment.

Detailed Description

The Covid-19 pandemic has been characterised by acute respiratory distress syndrome (ARDS) accompanied by a systemic cytokine-storm resulting in severe illness, respiratory failure and death in some. Severe Acute Respiratory Syndrome (SARS)- Coronavirus (Cov-2) (COV) infection per se is not the only underlying issue here, as it is becoming evident that ARDS is relatively rare amongst infected subjects, and appears to be associated with gross dysregulation of ensuing host-anti-viral responses resulting in collateral immune-inflammatory-mediated damage to host tissues. Rather than waiting for susceptible subjects to present with COV-associated ARDS, the investigators propose treatment of healthy health care workers (HCW) with a therapeutic agent which simultaneously targets front-line innate anti-viral immune defences, together with the core mechanism that controls immune response intensity in the airways. This research addresses the hypothesis that resistance to development of severe COV-associated respiratory disease in front-line HCW, even in those who develop a primary infection, can be boosted via a regimen of daily dosing with the bacterial-derived immunomodulatory agent OM85.

Aims

1. To demonstrate that daily treatment with OM85 will prevent HCW developing acute respiratory infections (ARI) necessitating removal from the workforce.

2. To elucidate the mechanism of action by which OM85 regulates host immune responses against COV.

Mechanistic studies will primarily test the hypothesis that OM85 pre-treatment modulates the systemic immunoinflammatory response to COV, selectively attenuating potentially pathogenic pro-inflammatory pathways without compromising activation of innate immune pathways central to pathogen clearance. The investigators will additionally collect samples to test the secondary hypothesis that the host response to COV displays uniquely aggressive pro-inflammatory features that differ from those observed with non-COV respiratory infections.

Experimental design: participants will be randomised into two groups; Immediate treatment with OM85 (n=500) or wait-list control with OM85 commencing three months later (n=500). Venous blood samples will be collected from each subject at four time points. Sera will be stored from each time point for assay of COV-specific antibody. For the mechanistic studies the investigators will focus on two groups of subjects who test respectively positive or negative to COV during a defined respiratory illness. These will be further stratified by treatment (OM85 treated (OM+) versus non-treated (OM-) prior to ARI, yielding 4 sets (each n=50) of test samples collected at acute infection which will be utilized for two discrete cross-comparisons: (i) COV+/OM+ versus COV+/OM-, and (ii) COV-/OM+ versus COV-/OM-. Analyses in (i) will be prioritised as they relate exclusively to host-responses to COV and effects of treatment thereon; those in (ii) which will contrast COV-associated response with those elicited by conventional respiratory pathogens and compare respective susceptibility to OM85.

Conditions

Respiratory Viral Infection; Covid19

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

Wait-list control

One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing in Month 3, with 3 months follow-up off treatment.

Group Type: ACTIVE_COMPARATOR

Broncho-Vaxom®

Intervention Type: DRUG

Broncho-Vaxom adult capsules® (OM85)

Initial treatment wtih OM85

One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing on day 0, with 3 months follow-up off treatment.

Group Type: EXPERIMENTAL

Broncho-Vaxom®

Intervention Type: DRUG

Broncho-Vaxom adult capsules® (OM85)

Interventions

Broncho-Vaxom®

Broncho-Vaxom adult capsules® (OM85)

Intervention Type: DRUG

Other Intervention Names

OM85

Eligibility Criteria

Inclusion Criteria

Participants who meet all of the following criteria are eligible for enrolment:

1. HCW in front line clinical departments assessing or caring for patients with suspected or verified COV infection in one of the recruiting hospitals in Brisbane

2. Participants who, in the opinion of the investigator, are able to comply with the protocol for its duration,

3. Written informed consent signed and dated according to local regulations.

Exclusion Criteria

Participants who meet any of these criteria are not eligible for enrolment:

• Staff with prior COV infection necessitating workforce removal

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Griffith University

OTHER

Sponsor Role: collaborator

The Prince Charles Hospital

OTHER_GOV

Sponsor Role: collaborator

Princess Alexandra Hospital, Brisbane, Australia

OTHER

Sponsor Role: collaborator

Telethon Kids Institute

OTHER

Sponsor Role: collaborator

Queensland Children's Hospital

OTHER_GOV

Sponsor Role: collaborator

The University of Queensland

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

PETER D SLY, DSc

Role: PRINCIPAL_INVESTIGATOR

The University of Queensland

Locations

The Prince Charles Hospital

Brisbane, Queensland, Australia

The Princess Alexandra Hospital

Brisbane, Queensland, Australia

Queensland Children's Hospital

South Brisbane, Queensland, Australia

Countries

Australia

References

Sly PD, Galbraith S, Islam Z, Holt B, Troy N, Holt PG. Primary prevention of severe lower respiratory illnesses in at-risk infants using the immunomodulator OM-85. J Allergy Clin Immunol. 2019 Sep;144(3):870-872.e11. doi: 10.1016/j.jaci.2019.05.032. Epub 2019 Jun 8. No abstract available.

Reference Type: BACKGROUND

PMID: 31185221 (View on PubMed)

Esposito S, Soto-Martinez ME, Feleszko W, Jones MH, Shen KL, Schaad UB. Nonspecific immunomodulators for recurrent respiratory tract infections, wheezing and asthma in children: a systematic review of mechanistic and clinical evidence. Curr Opin Allergy Clin Immunol. 2018 Jun;18(3):198-209. doi: 10.1097/ACI.0000000000000433.

Reference Type: BACKGROUND

PMID: 29561355 (View on PubMed)

The Lancet. COVID-19: protecting health-care workers. Lancet. 2020 Mar 21;395(10228):922. doi: 10.1016/S0140-6736(20)30644-9. No abstract available.

Reference Type: BACKGROUND

PMID: 32199474 (View on PubMed)

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

BV-2020/19

Identifier Type: -

Identifier Source: org_study_id