Efficacy of BCG Vaccination in the Prevention of COVID19 Via the Strengthening of Innate Immunity in Health Care Workers

NCT04384549 | Unknown Phase 3 DMC

• 2 other identifiers: APHP2004622020-001678-31
• Study Type: interventional
• Target: 1,120
• Locations: 1 country
• Sites: 1

Brief Summary

Healthcare Workers (HCW) are at high risk for COVID-19. In addition to the risk of serious forms among HCW, significant absenteeism due to illness would have dramatic consequences in our ability to fight COVID-19. No coronavirus vaccine is available today and drug treatments are only at the start of clinical evaluation. Available since 1921, the bacillus Calmette and Guérin (BCG) is the most widely used vaccine in the world (\> 3 billion doses administered) with an extremely low rate of adverse effects. BCG is indicated for the prevention of tuberculosis (TB), but more recent studies have shown that it also has nonspecific immune properties which may be interesting in the current COVID-19 epidemic. Data in mice and in humans have demonstrated protection conferred by BCG against viral respiratory infections such as influenza. In countries with high endemic TB, BCG decreases the incidence of acute respiratory infections by up to 80%, neonatal BCG vaccination has been shown to greatly reduce the risk of sepsis and of hospitalization of children for reasons other than TB. A recent study conducted in South Africa showed that re-vaccination with BCG in adults reduced the incidence of respiratory infections by 70% compared to unvaccinated controls. Beyond respiratory infections, BCG has also shown protective effects against inflammatory diseases. These non-specific beneficial effects are likely linked to the induction of "trained innate immunity", implying epigenetic and metabolic re-programming of innate immune cells. It is therefore possible that revaccination with BCG could significantly reduce the incidence and severity of COVID-19. Very recent ecological observations indeed suggest an inverse correlation between BCG vaccination coverage and the morbidity and mortality of COVID-19. In this context several trials began in Europe and Australia to evaluate the efficacy of BCG vaccination in populations at risk of exposure (HCW) or severe disease (elderly). This study is aligned with studies carried out in Australia, The Netherlands and Spain. In contrast to these latter studies, virtually all French study participants have been vaccinated in their childhood, since BCG vaccination was mandatory in France in neonates until 2007, and in HCW until recently. Therefore, the French study will be in a unique situation to evaluate the effect of re-vaccination with BCG in the context of BCG priming decades before revaccination.

Conditions

Infection; Viral, Agent as Cause of Disease Classified Elsewhere

Keywords

Vaccinology; Infectiology; COVID-19; Health Workers

Outcome Measures

Primary Outcomes (1)

• Incidence of documented COVID-19 among health care workers exposed to SARS CoV2 and vaccinated with BCG compared to placebo.

  Documented COVID-19, i.e. symptomatic COVID-19 confirmed by either * positive nasopharyngeal tests for SARS CoV2 * and/or by thoracic tomodensitometry compatible with the diagnosis. * and/or SARS CoV2 seroconversion

  during the study period of 6 months

Secondary Outcomes (6)

• Numbers of COVID-19 patients requiring hospitalization in ICU and O2, artificial ventilation or extracorporal membrane oxygenation, or deaths in BCG-vaccinated health care workers compared to placebo

  during the study period of 6 months.

• Incidence of asymptomatic SARS CoV2 seropositive subjects among BCG-vaccinated health care workers compared to placebo.

  during the study period of 6 months.

• Incidence of subjects with any respiratory infection among BCG-vaccinated health care workers compared to placebo.

  during the study period of 6 months.

• Numbers of sick days and numbers of sick leaves among BCG-vaccinated health care workers compared to placebo.

  during the study period of 6 months

• Numbers of subjects with BCG-related advers events among BCG-vaccinated health care workers compared to placebo.

  30 days after BCG revaccination

Study Arms (2)

BCG Arm

EXPERIMENTAL

One intradermal injection of 0.1 ml of BCG vaccine (AJ Vaccine).Each 0.1 ml vaccine contains between 2 to 8 x 105 colony forming units.

Biological: BCG GROUP

PLACEBO Arm

PLACEBO COMPARATOR

One intradermal placebo injection.

Other: PLACEBO GROUP

Interventions

BCG GROUP BIOLOGICAL

One intradermal injection of 0.1 ml of BCG vaccine (AJ Vaccine).Each 0.1 ml vaccine contains between 2 to 8 x 105 colony forming units.

Also known as: Experimental GROUP

BCG Arm

PLACEBO GROUP OTHER

One intradermal injection of 0.1ml NaCl

Also known as: Control GROUP

PLACEBO Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Individual (Male and female) aged 18 or over.
• Healthcare Worker (medical or non-medical) from hospitals in direct contact with COVID-19 patients.
• Participants must give their written consent before any trial procedure.
• Participants covered by social security regimen (excepting AME).
• Healthy according to the opinion of the investigator.

You may not qualify if:

• Has any BCG vaccine contraindication, known allergy to the BCG vaccine or SAE to prior BCG vaccination.
• History of tuberculosis
• People with acquired or innate immunodeficiency.
• People have already been infected with SARS Cov-2 (virological documentation or TDM or seropositive if serology available).
• People who could not commit to follow-up for 6 months.
• People not in good general condition, as assessed by the investigator.
• People included in other clinical trials assessing treatment.
• Pregnant or breastfeeding or positive urine pregnancy at enrolment visit.
• BCG vaccine given within the last year.
• Another live vaccine administered in the month prior to randomization.
• History of anaphylaxis following vaccination.
• Receiving medical treatment that affects the immune response or other immunosuppressive therapy in the last year. These therapies include systemic corticosteroids (more than or equal to 10 mg for more than or equal to 2 weeks), immunosuppressant, biological agents (such as monoclonal antibodies against tumour necrosis factor (TNF)-alpha).
• Fever \> 38°C within the past 24 hours
• People with malignancies (e.g. lymphoma, leukemia, Hodgkin's disease or other tumors of the reticuloendothelial system) or infected with HIV
• Receipt of immune globulins, blood or blood-derived products in the past 3 months

Sponsors & Collaborators

• Assistance Publique - Hôpitaux de Paris: lead

Study Sites (1)

I-REIVAC/CIC 1417 Cochin Hospital, APHP

Paris, 75014, France

RECRUITING

Related Publications (4)

• Moorlag SJCFM, Arts RJW, van Crevel R, Netea MG. Non-specific effects of BCG vaccine on viral infections. Clin Microbiol Infect. 2019 Dec;25(12):1473-1478. doi: 10.1016/j.cmi.2019.04.020. Epub 2019 May 2.

  PMID: 31055165 BACKGROUND

• Nemes E, Geldenhuys H, Rozot V, Rutkowski KT, Ratangee F, Bilek N, Mabwe S, Makhethe L, Erasmus M, Toefy A, Mulenga H, Hanekom WA, Self SG, Bekker LG, Ryall R, Gurunathan S, DiazGranados CA, Andersen P, Kromann I, Evans T, Ellis RD, Landry B, Hokey DA, Hopkins R, Ginsberg AM, Scriba TJ, Hatherill M; C-040-404 Study Team. Prevention of M. tuberculosis Infection with H4:IC31 Vaccine or BCG Revaccination. N Engl J Med. 2018 Jul 12;379(2):138-149. doi: 10.1056/NEJMoa1714021.

  PMID: 29996082 BACKGROUND

• Kowalewicz-Kulbat M, Locht C. BCG and protection against inflammatory and auto-immune diseases. Expert Rev Vaccines. 2017 Jul;16(7):1-10. doi: 10.1080/14760584.2017.1333906. Epub 2017 May 30.

  PMID: 28532186 BACKGROUND

• Netea MG, Dominguez-Andres J, Barreiro LB, Chavakis T, Divangahi M, Fuchs E, Joosten LAB, van der Meer JWM, Mhlanga MM, Mulder WJM, Riksen NP, Schlitzer A, Schultze JL, Stabell Benn C, Sun JC, Xavier RJ, Latz E. Defining trained immunity and its role in health and disease. Nat Rev Immunol. 2020 Jun;20(6):375-388. doi: 10.1038/s41577-020-0285-6. Epub 2020 Mar 4.

  PMID: 32132681 BACKGROUND

Related Links

• Miller A, et al. 2020. Correlation between universal BCG vaccination policy and reduced morbidity and mortality for COVID-19: an epidemiological study.

MeSH Terms

Conditions

Infections; COVID-19

Interventions

Control Groups

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Epidemiologic Research Design; Epidemiologic Methods; Investigative Techniques; Research Design; Methods

Study Officials

• Odile LAUNAY, Professor

  Assitance Publique-Hôpitaux de Paris

  PRINCIPAL INVESTIGATOR

• Camille LOCHT, Professor

  Institut Pasteur de Lille

  STUDY DIRECTOR

Central Study Contacts

Odile LAUNAY, Professor

CONTACT

01 58 41 28 58; odile.launay@aphp.fr

Anne RADENNE

CONTACT

01 42 16 16 99; anne.radenne@aphp.fr

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 6, 2020
• First Posted: May 12, 2020
• Study Start: May 20, 2020
• Primary Completion: February 20, 2021
• Study Completion: February 20, 2021
• Last Updated: August 18, 2020

Record last verified: 2020-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)