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

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

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.

Study Overview

• Status: Completed
• Conditions: SARS-CoV-2 Infection
• Intervention / Treatment: Other: Placebo; Biological: VPM1002

• Study Type: Interventional
• Enrollment (Actual): 122
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 2M9
      • University Health Network

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VPM1002; 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; VPM1002 is a recombinant BCG (rBCG); Other Names: Mycobacterium bovis rBCGΔureC::hly
Placebo Comparator: Placebo; A single dose of 0.1 mL of the 0.9% sodium chloride injection, administered via intradermal injection.	Other: Placebo; 0.9% sodium chloride; Other Names: sodium chloride

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of COVID-19 in Participants with Past BCG Vaccination	To compare the incidence of COVID-19 in participants who have received BCG vaccination previously vs those not previously vaccinated	7 months
Measure cardiac troponin, B-type natriuretic peptide, N-terminal pro b-type natriuretic peptide, C reactive protein, serum amyloid A, and procalcitonin as biomarkers of COVID-19	To measure cardiac troponin, B-type natriuretic peptide, N-terminal pro b-type natriuretic peptide, C reactive protein, serum amyloid A, and procalcitonin identified as potential biomarkers of COVID-19 infection using blood samples collected prior to the vaccination and at the end of the 7-month follow-up.	7 months
Adverse events following BCG vaccine	To compare adverse event profile in participants following administration of VPM1002 or placebo when used for prevention of COVID-19.	7 months
Innate Trained Immunity	Compare the priming of the innate trained immunity (i.e. induction of Th1 and Th17 responses to unrelated stimuli) in participants following administration of VPM1002 or placebo when used for prevention of COVID-19.	7 months

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Verity Pharmaceuticals Inc.; Max Planck Institute for Infection Biology; Serum Institute of India Pvt. Ltd.
• Investigators: Principal Investigator: Alexandre R Zlotta, MD PhD, University Health Network, Toronto

Study record dates

Study Major Dates

• Study Start (Actual): June 24, 2020
• Primary Completion (Actual): September 9, 2021
• Study Completion (Actual): September 9, 2021

Study Registration Dates

• First Submitted: June 3, 2020
• First Submitted That Met QC Criteria: June 18, 2020
• First Posted (Actual): June 19, 2020

Study Record Updates

• Last Update Posted (Actual): April 15, 2022
• Last Update Submitted That Met QC Criteria: April 13, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; Disease Attributes; COVID-19; Infections; Communicable Diseases
• Other Study ID Numbers: 20-5413

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No