<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT04496245</url>
  </required_header>
  <id_info>
    <org_study_id>BV-2020/19</org_study_id>
    <nct_id>NCT04496245</nct_id>
  </id_info>
  <brief_title>Reducing Acute Severe Respiratory Events in Health Care Workers During the Covid-19 Pandemic With OM85</brief_title>
  <acronym>COVIDRASP</acronym>
  <official_title>Reducing Acute Severe Respiratory Events in Health Care Workers During the Covid-19 Pandemic With OM85</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>The University of Queensland</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Griffith University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>The Prince Charles Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Princess Alexandra Hospital, Brisbane, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Telethon Kids Institute</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Queensland Children's Hospital, South Brisbane, Queensland, Australia</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>The University of Queensland</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Parallel group, Wait-list design, with treatment delayed for 3 months. Participants will be&#xD;
      randomized on a 1:1 ratio with 500 participants per group in Australia.&#xD;
&#xD;
      Group 1: Wait-list control. One capsule OM85 (7.0 mg) will be given daily for 3 months,&#xD;
      commencing in Month 3, with 3 months follow-up off treatment.&#xD;
&#xD;
      Group 2: Initial treatment. One capsule OM85 (7.0 mg) will be given daily for 3 months,&#xD;
      commencing on day 0, with 3 months follow-up off treatment.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The Covid-19 pandemic has been characterised by acute respiratory distress syndrome (ARDS)&#xD;
      accompanied by a systemic cytokine-storm resulting in severe illness, respiratory failure and&#xD;
      death in some. Severe Acute Respiratory Syndrome (SARS)- Coronavirus (Cov-2) (COV) infection&#xD;
      per se is not the only underlying issue here, as it is becoming evident that ARDS is&#xD;
      relatively rare amongst infected subjects, and appears to be associated with gross&#xD;
      dysregulation of ensuing host-anti-viral responses resulting in collateral&#xD;
      immune-inflammatory-mediated damage to host tissues. Rather than waiting for susceptible&#xD;
      subjects to present with COV-associated ARDS, the investigators propose treatment of healthy&#xD;
      health care workers (HCW) with a therapeutic agent which simultaneously targets front-line&#xD;
      innate anti-viral immune defences, together with the core mechanism that controls immune&#xD;
      response intensity in the airways. This research addresses the hypothesis that resistance to&#xD;
      development of severe COV-associated respiratory disease in front-line HCW, even in those who&#xD;
      develop a primary infection, can be boosted via a regimen of daily dosing with the&#xD;
      bacterial-derived immunomodulatory agent OM85.&#xD;
&#xD;
      Aims&#xD;
&#xD;
        1. To demonstrate that daily treatment with OM85 will prevent HCW developing acute&#xD;
           respiratory infections (ARI) necessitating removal from the workforce.&#xD;
&#xD;
        2. To elucidate the mechanism of action by which OM85 regulates host immune responses&#xD;
           against COV.&#xD;
&#xD;
      Mechanistic studies will primarily test the hypothesis that OM85 pre-treatment modulates the&#xD;
      systemic immunoinflammatory response to COV, selectively attenuating potentially pathogenic&#xD;
      pro-inflammatory pathways without compromising activation of innate immune pathways central&#xD;
      to pathogen clearance. The investigators will additionally collect samples to test the&#xD;
      secondary hypothesis that the host response to COV displays uniquely aggressive&#xD;
      pro-inflammatory features that differ from those observed with non-COV respiratory&#xD;
      infections.&#xD;
&#xD;
      Experimental design: participants will be randomised into two groups; Immediate treatment&#xD;
      with OM85 (n=500) or wait-list control with OM85 commencing three months later (n=500).&#xD;
      Venous blood samples will be collected from each subject at four time points. Sera will be&#xD;
      stored from each time point for assay of COV-specific antibody. For the mechanistic studies&#xD;
      the investigators will focus on two groups of subjects who test respectively positive or&#xD;
      negative to COV during a defined respiratory illness. These will be further stratified by&#xD;
      treatment (OM85 treated (OM+) versus non-treated (OM-) prior to ARI, yielding 4 sets (each&#xD;
      n=50) of test samples collected at acute infection which will be utilized for two discrete&#xD;
      cross-comparisons: (i) COV+/OM+ versus COV+/OM-, and (ii) COV-/OM+ versus COV-/OM-. Analyses&#xD;
      in (i) will be prioritised as they relate exclusively to host-responses to COV and effects of&#xD;
      treatment thereon; those in (ii) which will contrast COV-associated response with those&#xD;
      elicited by conventional respiratory pathogens and compare respective susceptibility to OM85.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">August 24, 2020</start_date>
  <completion_date type="Actual">September 30, 2021</completion_date>
  <primary_completion_date type="Actual">June 30, 2021</primary_completion_date>
  <phase>Phase 3</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <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</intervention_model_description>
    <primary_purpose>Prevention</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>Participants will be randomised to the wait list group (Group 1) or the initial intervention group (Group 2) using a one-to-one ratio, stratified by hospital and department [High risk, lower risk].</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Acute Respiratory Infection necessitating workforce removal</measure>
    <time_frame>3 months</time_frame>
    <description>The proportion of Health Care Workers contracting an Acute Respiratory Infection necessitating workforce removal in the initial treatment and wait-list control groups assessed at the end of 3 months.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Time to ARI necessitating workforce removal.</measure>
    <time_frame>12 months</time_frame>
    <description>The time to the first ARI necessitating workforce removal in the initial treatment and wait-list control groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of Health Care Workers contracting an Acute Respiratory Infection necessitating workforce removal</measure>
    <time_frame>12 months</time_frame>
    <description>The proportion of Health Care Workers contracting an Acute Respiratory Infection necessitating workforce removal in the initial treatment and wait-list control groups assessed at the end of 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of HCW with documented Cov infection.</measure>
    <time_frame>12 months</time_frame>
    <description>The proportion of HCW in the initial treatment and wait-list control group with Cov infection documented by molecular techniques of seroconversion</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Time to Lower respiratory infection (LRI) necessitating workforce removal.</measure>
    <time_frame>12 months</time_frame>
    <description>The time to the first LRI necessitating workforce removal in the initial treatment and wait-list control groups.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of Health Care Workers contracting a LRI necessitating workforce removal</measure>
    <time_frame>12 months</time_frame>
    <description>The proportion of Health Care Workers contracting LRI necessitating workforce removal in the initial treatment and wait-list control groups assessed at the end of 3, 6 and 12 months</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>The proportion of HCW with documented Cov LRI.</measure>
    <time_frame>12 months</time_frame>
    <description>The proportion of HCW in the initial treatment and wait-list control group with LRI due to Cov infection documented by molecular techniques of seroconversion</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">59</enrollment>
  <condition>Respiratory Viral Infection</condition>
  <condition>Covid19</condition>
  <arm_group>
    <arm_group_label>Wait-list control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing in Month 3, with 3 months follow-up off treatment.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Initial treatment wtih OM85</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing on day 0, with 3 months follow-up off treatment.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Broncho-Vaxom®</intervention_name>
    <description>Broncho-Vaxom adult capsules® (OM85)</description>
    <arm_group_label>Initial treatment wtih OM85</arm_group_label>
    <arm_group_label>Wait-list control</arm_group_label>
    <other_name>OM85</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Participants who meet all of the following criteria are eligible for enrolment:&#xD;
&#xD;
          1. HCW in front line clinical departments assessing or caring for patients with suspected&#xD;
             or verified COV infection in one of the recruiting hospitals in Brisbane&#xD;
&#xD;
          2. Participants who, in the opinion of the investigator, are able to comply with the&#xD;
             protocol for its duration,&#xD;
&#xD;
          3. Written informed consent signed and dated according to local regulations.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Participants who meet any of these criteria are not eligible for enrolment:&#xD;
&#xD;
          -  Staff with prior COV infection necessitating workforce removal&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>100 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>PETER D SLY, DSc</last_name>
    <role>Principal Investigator</role>
    <affiliation>The University of Queensland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>The Prince Charles Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4032</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Princess Alexandra Hospital</name>
      <address>
        <city>Brisbane</city>
        <state>Queensland</state>
        <zip>4102</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Queensland Children's Hospital</name>
      <address>
        <city>South Brisbane</city>
        <state>Queensland</state>
        <zip>4101</zip>
        <country>Australia</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Australia</country>
  </location_countries>
  <reference>
    <citation>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.</citation>
    <PMID>31185221</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>29561355</PMID>
  </reference>
  <reference>
    <citation>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.</citation>
    <PMID>32199474</PMID>
  </reference>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>July 26, 2020</study_first_submitted>
  <study_first_submitted_qc>July 31, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 3, 2020</study_first_posted>
  <last_update_submitted>February 21, 2022</last_update_submitted>
  <last_update_submitted_qc>February 21, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">March 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>COVID-19</mesh_term>
    <mesh_term>Virus Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Broncho-Vaxom</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>July 23, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT04496245/Prot_SAP_001.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>July 23, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT04496245/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT04496245
org study id: BV-2020/19
nct id: NCT04496245
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
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.
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.
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
primary purpose: Prevention
masking: None (Open Label)
masking description: Participants will be randomised to the wait list group (Group 1) or the initial intervention group (Group 2) using a one-to-one ratio, stratified by hospital and department [High risk, lower risk].
measure: Acute Respiratory Infection necessitating workforce removal
time frame: 3 months
description: The proportion of Health Care Workers contracting an Acute Respiratory Infection necessitating workforce removal in the initial treatment and wait-list control groups assessed at the end of 3 months.
measure: Time to ARI necessitating workforce removal.
time frame: 12 months
description: The time to the first ARI necessitating workforce removal in the initial treatment and wait-list control groups.
measure: The proportion of Health Care Workers contracting an Acute Respiratory Infection necessitating workforce removal
time frame: 12 months
description: The proportion of Health Care Workers contracting an Acute Respiratory Infection necessitating workforce removal in the initial treatment and wait-list control groups assessed at the end of 6 and 12 months
measure: The proportion of HCW with documented Cov infection.
time frame: 12 months
description: The proportion of HCW in the initial treatment and wait-list control group with Cov infection documented by molecular techniques of seroconversion
measure: Time to Lower respiratory infection (LRI) necessitating workforce removal.
time frame: 12 months
description: The time to the first LRI necessitating workforce removal in the initial treatment and wait-list control groups.
measure: The proportion of Health Care Workers contracting a LRI necessitating workforce removal
time frame: 12 months
description: The proportion of Health Care Workers contracting LRI necessitating workforce removal in the initial treatment and wait-list control groups assessed at the end of 3, 6 and 12 months
measure: The proportion of HCW with documented Cov LRI.
time frame: 12 months
description: The proportion of HCW in the initial treatment and wait-list control group with LRI due to Cov infection documented by molecular techniques of seroconversion
arm group label: Wait-list control
arm group type: Active Comparator
description: One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing in Month 3, with 3 months follow-up off treatment.
arm group label: Initial treatment wtih OM85
arm group type: Experimental
description: One capsule OM85 (7.0 mg) will be given daily for 3 months, commencing on day 0, with 3 months follow-up off treatment.
intervention type: Drug
intervention name: Broncho-Vaxom®
description: Broncho-Vaxom adult capsules® (OM85)
arm group label: Initial treatment wtih OM85
arm group label: Wait-list control
other name: OM85
criteria: 
gender: All
minimum age: 18 Years
maximum age: 100 Years
healthy volunteers: Accepts Healthy Volunteers
last name: PETER D SLY, DSc
role: Principal Investigator
affiliation: The University of Queensland
facility: 
facility: 
facility: 
country: Australia
citation: 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.
PMID: 31185221
citation: 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.
PMID: 29561355
citation: 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.
PMID: 32199474
responsible party type: Sponsor
mesh term: COVID-19
mesh term: Virus Diseases
mesh term: Broncho-Vaxom
sharing ipd: No
provided document: 
provided document: 