Efficacy and Safety of VPM1002 in Reducing SARS-CoV-2 (COVID-19) Infection Rate and Severity

Study Overview
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Brief Summary
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Bacille Calmette-Guerin (BCG) is a live attenuated vaccine administered for prevention of tuberculosis. Recently, several groups have hypothesized that BCG may train the immune system to respond to a variety of unrelated infections, including viruses and in particular the coronavirus responsible for COVID-19. Trials are currently being conducted in Australia, Netherlands, Germany and the United Kingdom to evaluate its effectiveness. Front line workers includes members of municipal and provincial police services, emergency medical personnel, firefighters, public transport employees, health service workers and food manufacturing employees. They are at high risk of infection from COVID-19, with potentially high infection rate. The investigators propose an interventional trial to evaluate the effectiveness of BCG vaccination to prevent COVID-19 infection and reduce its severity in front-line employees in Ontario.

Official Title
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A Randomized, Double-blind, Placebo-controlled Phase 3 Study: Efficacy and Safety of VPM1002 in Reducing SARS-CoV-2 Infection Rate and COVID-19 Severity

Conditions
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SARS-CoV-2 Infection

Intervention / Treatment
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* Biological: VPM1002
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eighteen years of age or older Employee/member of: municipal or provincial police service, emergency medical services, fire services, public transport service, health service, food manufacturing facility Exclusion Criteria: Prior intravesical BCG or intradermal BCG, with the exception of tuberculosis vaccination in childhood. Previous known history of latent or active tuberculosis Known kidney, liver or blood disorders which impairs organ and marrow function Chronic administration of steroids (>10 mg prednisone) at the time of randomization Current or planned concomitant biologic therapy in the next 7 months. Known hypersensitivity or allergy to components of VPM1002 Pregnant or planning to become pregnant in the future 7 months. Breastfeeding. Current suspected viral or bacterial infection. Body temperature > 38° C Participation in another interventional study with potentially conflicting medication within 30 days before screening. The presence of an impaired immune response irrespective of whether this impairment is congenital or caused by disease, drugs or other therapy (e.g., anti-TNF therapy, methotrexate, azathioprine, antimalarials). Active malignancy requiring treatment. Known positive HIV serology. History of allergic reactions attributed to compounds of similar chemical or biologic composition to BCG vaccine. Previous positive COVID-19 confirmed infection. Uncontrolled intercurrent illness. Psychiatric illness/social situations that would limit compliance with study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: VPM1002<br>A single dose of 0.1 mL of the reconstituted vaccine containing VPM1002 (Mycobacterium bovis rBCGΔureC::hly, live 2-8 × 105 CFU), administered via intradermal injection. | Biological: VPM1002<br>* VPM1002 is a recombinant BCG (rBCG)<br>* Other names: Mycobacterium bovis rBCGΔureC::hly;|
| Placebo Comparator: Placebo<br>A single dose of 0.1 mL of the 0.9% sodium chloride injection, administered via intradermal injection. | Other: Placebo<br>* 0.9% sodium chloride<br>* Other names: sodium chloride;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19 infection | To compare the self-reported incidence of SARS-CoV-2 infection (confirmed by positive test) following vaccination with either VPM1002 or placebo. | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of hospitalization for COVID-19 | To compare the incidence of hospitalization in participants with positive COVID-19 test treated with either VPM1002 or placebo | 7 months | 
| Incidence of ICU admission for COVID-19 | To compare the incidence of hospitalization requiring intensive care (ICU admission) in participants with positive COVID-19 test treated with either VPM1002 or placebo | 7 months | 
| Incidence of ARDS | To compare the incidence of acute respiratory distress syndrome (ARDS) in participants with positive COVID-19 test treated with either VPM1002 or placebo. | 7 months | 
| Mechanical ventilation for COVID-19 | To compare the incidence of the need for mechanical ventilation in participants with positive COVID-19 test treated with either VPM1002 or placebo. | 7 months | 
| Secondary infection in COVID-19 | To compare the incidence of secondary infection in participants with positive COVID-19 test treated with either VPM1002 or placebo. | 7 months | 
| COVID-19-related Mortality | To compare the mortality in participants with positive COVID-19 test treated with either VPM1002 or placebo. | 7 months | 
| Incidence of DVT | To compare the incidence of deep vein thrombosis, pulmonary embolism, or stroke in participants with positive COVID-19 test treated with either VPM1002 or placebo. | 7 months |