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

Primary Purpose

SARS-CoV-2 Infection

Status
Completed
Phase
Phase 3
Locations
Canada
Study Type
Interventional
Intervention
VPM1002
Placebo
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for SARS-CoV-2 Infection

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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.

Sites / Locations

  • University Health Network

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

VPM1002

Placebo

Arm Description

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.

A single dose of 0.1 mL of the 0.9% sodium chloride injection, administered via intradermal injection.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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
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
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.
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.
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.
COVID-19-related Mortality
To compare the mortality in participants with positive COVID-19 test treated with either VPM1002 or placebo.
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.

Full Information

First Posted
June 3, 2020
Last Updated
April 13, 2022
Sponsor
University Health Network, Toronto
Collaborators
Serum Institute of India Pvt. Ltd., Max Planck Institute for Infection Biology, Verity Pharmaceuticals Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04439045
Brief Title
Efficacy and Safety of VPM1002 in Reducing SARS-CoV-2 (COVID-19) Infection Rate and Severity
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 24, 2020 (Actual)
Primary Completion Date
September 9, 2021 (Actual)
Study Completion Date
September 9, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto
Collaborators
Serum Institute of India Pvt. Ltd., Max Planck Institute for Infection Biology, Verity Pharmaceuticals Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
SARS-CoV-2 Infection

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare Provider
Masking Description
The clinical trial is designed as a double-blind (observer blind) study. Observer-blind means that during the course of trial, the companions/parents/guardians of the subjects and the study personnel responsible for the evaluation of any study endpoint will be unaware which vaccine was administered.
Allocation
Randomized
Enrollment
122 (Actual)

8. Arms, Groups, and Interventions

Arm Title
VPM1002
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
A single dose of 0.1 mL of the 0.9% sodium chloride injection, administered via intradermal injection.
Intervention Type
Biological
Intervention Name(s)
VPM1002
Other Intervention Name(s)
Mycobacterium bovis rBCGΔureC::hly
Intervention Description
VPM1002 is a recombinant BCG (rBCG)
Intervention Type
Other
Intervention Name(s)
Placebo
Other Intervention Name(s)
sodium chloride
Intervention Description
0.9% sodium chloride
Primary Outcome Measure Information:
Title
COVID-19 infection
Description
To compare the self-reported incidence of SARS-CoV-2 infection (confirmed by positive test) following vaccination with either VPM1002 or placebo.
Time Frame
7 months
Secondary Outcome Measure Information:
Title
Incidence of hospitalization for COVID-19
Description
To compare the incidence of hospitalization in participants with positive COVID-19 test treated with either VPM1002 or placebo
Time Frame
7 months
Title
Incidence of ICU admission for COVID-19
Description
To compare the incidence of hospitalization requiring intensive care (ICU admission) in participants with positive COVID-19 test treated with either VPM1002 or placebo
Time Frame
7 months
Title
Incidence of ARDS
Description
To compare the incidence of acute respiratory distress syndrome (ARDS) in participants with positive COVID-19 test treated with either VPM1002 or placebo.
Time Frame
7 months
Title
Mechanical ventilation for COVID-19
Description
To compare the incidence of the need for mechanical ventilation in participants with positive COVID-19 test treated with either VPM1002 or placebo.
Time Frame
7 months
Title
Secondary infection in COVID-19
Description
To compare the incidence of secondary infection in participants with positive COVID-19 test treated with either VPM1002 or placebo.
Time Frame
7 months
Title
COVID-19-related Mortality
Description
To compare the mortality in participants with positive COVID-19 test treated with either VPM1002 or placebo.
Time Frame
7 months
Title
Incidence of DVT
Description
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.
Time Frame
7 months
Other Pre-specified Outcome Measures:
Title
Incidence of COVID-19 in Participants with Past BCG Vaccination
Description
To compare the incidence of COVID-19 in participants who have received BCG vaccination previously vs those not previously vaccinated
Time Frame
7 months
Title
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
Description
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.
Time Frame
7 months
Title
Adverse events following BCG vaccine
Description
To compare adverse event profile in participants following administration of VPM1002 or placebo when used for prevention of COVID-19.
Time Frame
7 months
Title
Innate Trained Immunity
Description
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.
Time Frame
7 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alexandre R Zlotta, MD PhD
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
University Health Network
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada

12. IPD Sharing Statement

Plan to Share IPD
No

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

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