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

SARS-CoV-2 Infection Clinical Trial

— COBRA  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04439045
• Other study ID #: 20-5413
• Status: Completed
• Phase: Phase 3
• Start date: June 24, 2020
• Est. completion date: September 9, 2021

Study information

• Verified date: April 2022
• Source: University Health Network, Toronto
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 122
• Est. completion date: September 9, 2021
• Est. primary completion date: September 9, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Communicable Diseases
• COVID-19
• Infections
• SARS-CoV-2 Infection

Intervention

Biological:
• VPM1002
VPM1002 is a recombinant BCG (rBCG)

Other:
• Placebo
0.9% sodium chloride

Locations

Country	Name	City	State
Canada	University Health Network	Toronto	Ontario

Sponsors (4)

Lead Sponsor	Collaborator
University Health Network, Toronto	Max Planck Institute for Infection Biology, Serum Institute of India Pvt. Ltd., Verity Pharmaceuticals Inc.

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	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
Other	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
Other	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
Other	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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	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
Secondary	COVID-19-related Mortality	To compare the mortality in participants with positive COVID-19 test treated with either VPM1002 or placebo.	7 months
Secondary	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