Reducing Acute Severe Respiratory Events in Health Care Workers During the Covid-19 Pandemic With OM85
Condition: Respiratory Viral Infection; Covid19
MeSH terms: COVID-19; Virus Diseases
Study type: Interventional
Phase: Phase 3

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.
    

Intervention name(s): Broncho-Vaxom®
Intervention type(s): Drug
Intervention description(s): Broncho-Vaxom adult capsules® (OM85)
Other intervention name(s): OM85
Intervention MeSH terms: Broncho-Vaxom
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Participants will be randomized to either Group 1 (waitlist control, delayed treatment group) or Group 2 (initial treatment) for treatment for a period of 3 months with 3 months follow-up off treatment
Masking: None (Open Label)
Primary purpose: Prevention