Clinical Trials Register

Summary
EudraCT Number:	2020-001678-31
Sponsor's Protocol Code Number:	APHP200462
National Competent Authority:	France - ANSM
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2020-04-17
Trial results

Index
A. PROTOCOL INFORMATION
B. SPONSOR INFORMATION
C. APPLICANT IDENTIFICATION
D. IMP IDENTIFICATION
D.8 INFORMATION ON PLACEBO
E. GENERAL INFORMATION ON THE TRIAL
F. POPULATION OF TRIAL SUBJECTS
G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
P. END OF TRIAL

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A. Protocol Information

A.1

Member State Concerned

France - ANSM

A.2

EudraCT number

2020-001678-31

A.3

Full title of the trial

Randomized controlled trial evaluating the efficacy of vaccination with Bacillus Calmette and Guérin (BCG) in the Prevention of COVID-19 via the strengthening of innate immunity in Health Care Workers.”
COVID-BCG

Essai prospectif randomisé évaluant l’efficacité d’une vaccination BCG dans la prévention du COVID 19 via le renforcement de l’immunité innée chez le personnel soignant

A.3.1

Title of the trial for lay people, in easily understood, i.e. non-technical, language

Essai prospectif randomisé évaluant l’efficacité d’une vaccination BCG dans la prévention du COVID 19 via le renforcement de l’immunité innée chez le personnel soignant

A.3.2

Name or abbreviated title of the trial where available

COVID BCG

A.4.1

Sponsor's protocol code number

APHP200462

A.7

Trial is part of a Paediatric Investigation Plan

A.8

EMA Decision number of Paediatric Investigation Plan

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	Assistance Publique Hopitaux de Paris
B.1.3.4	Country	France
B.3.1 and B.3.2	Status of the sponsor	Non-Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	Ministère de la Santé
B.4.2	Country	France
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Assistance Publique Hopitaux de Paris
B.5.2	Functional name of contact point	moufida.dabbech@aphp.fr
B.5.3	Address:
B.5.3.1	Street Address	1 avenue Claude Vellefaux, Hopital Saint Louis
B.5.3.2	Town/ city	Paris
B.5.3.3	Post code	75010
B.5.3.4	Country	France
B.5.4	Telephone number	3301 44 84 17 37
B.5.5	Fax number	3301 44 84 17 01
B.5.6	E-mail	moufida.dabbech@aphp.fr

D. IMP Identification
D.IMP: 1
D.1.2 and D.1.3	IMP Role	Test
D.2	Status of the IMP to be used in the clinical trial
D.2.1	IMP to be used in the trial has a marketing authorisation	Yes
D.2.1.1.1	Trade name	VACCIN BCG AJVaccines
D.2.1.1.2	Name of the Marketing Authorisation holder	AJVACCINES
D.2.1.2	Country which granted the Marketing Authorisation	France
D.2.5	The IMP has been designated in this indication as an orphan drug in the Community	No
D.2.5.1	Orphan drug designation number
D.3 Description of the IMP
D.3.1	Product name	VACCIN BCG AJVaccines
D.3.4	Pharmaceutical form	Powder and solvent for dispersion for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	BCG VACCINE, FREEZE-DRIED
D.3.9.4	EV Substance Code	SUB11734MIG
D.3.10	Strength
D.3.10.1	Concentration unit	CFU/ml colony forming unit(s)/millilitre
D.3.10.2	Concentration type	range
D.3.10.3	Concentration number	2 to 8
D.3.11 The IMP contains an:
D.3.11.1	Active substance of chemical origin	No
D.3.11.2	Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP)	Yes
	The IMP is a:
D.3.11.3	Advanced Therapy IMP (ATIMP)	No
D.3.11.3.1	Somatic cell therapy medicinal product	No
D.3.11.3.2	Gene therapy medical product	No
D.3.11.3.3	Tissue Engineered Product	No
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	No
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	No
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	No
D.3.11.5	Radiopharmaceutical medicinal product	No
D.3.11.6	Immunological medicinal product (such as vaccine, allergen, immune serum)	Yes
D.3.11.7	Plasma derived medicinal product	No
D.3.11.8	Extractive medicinal product	No
D.3.11.9	Recombinant medicinal product	No
D.3.11.10	Medicinal product containing genetically modified organisms	No
D.3.11.11	Herbal medicinal product	No
D.3.11.12	Homeopathic medicinal product	No
D.3.11.13	Another type of medicinal product	No

D.8 Information on Placebo
D.8 Placebo: 1
D.8.1	Is a Placebo used in this Trial?	Yes
D.8.3	Pharmaceutical form of the placebo	Solution for injection
D.8.4	Route of administration of the placebo	Intradermal use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

COVID 19
Health care workers (medical or non-medical) in French hospitals in direct contact with COVID-19 patients, including nurses, medical doctors and other personnel working in wards in charge of COVID-19 patients (emergency, intensive care units, infectious diseases, pneumology, geriatrics …).

Personnel soignant (médical ou non médical) des hôpitaux de France en contact direct avec les patients COVID-19, incluant des aide soignants, infirmières/infirmiers, médecins, étudiants en santé et autres personnes travaillant dans les services prenant en charge ces patients (urgence, réanimation, soins intensifs, maladies infectieuses, pneumologie, gériatrie……) accueillant des patients COVID-19.

E.1.1.1

Medical condition in easily understood language

COVID19

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate among health care workers exposed to SARS CoV2 protection mediated by BCG against documented COVID-19.

Evaluer chez des personnels de santé exposés au SARS CoV-2 la protection conférée par une revaccination BCG contre le COVID-19 documentée.

E.2.2

Secondary objectives of the trial

- To evaluate protection mediated by BCG revaccination against :
a. Severe forms of COVID-19
b. Asymptomatic forms of SARS CoV2 infection
c. Respiratory infections
d. Absenteeism.
- To evaluate safety of BCG revaccination among health care workers.
- To evaluate the impact of COVID-19 on innate immunity in the context of BCG revaccination versus controls.

- Evaluer la protection conférée par la revaccination BCG sur :
a. les formes sévères de COVID -19
b. les formes asymptomatiques d’infection à SARS COV-2
c. les infections respiratoires
d. l’absentéisme des personnels de santé
- Evaluer la sécurité de la revaccination BCG parmi le personnel soignants
- Evaluer l’impact du COVID-19 sur l’immunité innée dans le contexte de revaccination BCG vs contrôles.

E.2.3

Trial contains a sub-study

Yes

E.2.3.1

Full title, date and version of each sub-study and their related objectives

A nested study will be carried out on blood samples of 72 study subjects in order to evaluate the impact of COVID-19 on innate immunity. These blood samples will be collected at M6 among 6 groups, each containing 12 study subjects:
- One group of subjects vaccinated with BCG that have remained sero-negative for SARS CoV2
- One group of subjects having received placebo that have remained sero-negative for SARS CoV2
- One group of symptomatic subjects vaccinated with BCG
- One group of symptomatic subjects having received placebo.
- One group without symptoms but sero-positive for SARS CoV2 vaccinated with BCG
- One group without symptoms but sero-positive for SARS CoV2 vaccinated with placebo

Une sous étude de prélèvements sanguins sera réalisée sur 72 sujets pour évaluer l’impact du COVID-19 sur l’immunité innée. Ces prélèvements seront effectués dans 6 groupes de 12 sujets chacun:
- 1 groupe vacciné avec le BCG et qui est resté séronégatifs au SRAS-CoV-2
- 1 groupe ayant reçu le placebo et qui est resté séronégatifs au SRAS-CoV-2
- 1 groupe symptomatique vacciné avec le BCG
- 1 groupe symptomatique vacciné avec le placebo
- 1 groupe sans symptômes mais séro-positif au SARS CoV-2 vacciné avec le BCG
- 1 groupe sans symptômes mais séro-positif au SARS CoV-2 ayant reçu le placebo

E.3

Principal inclusion criteria

-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.

1. Homme ou femme âgé(e) de 18 ans ou plus
2. Personnel soignant (médical ou non médical) en contact direct avec les patients COVID-19
3. Ayant donné leur consentement écrit avant toute procédure d'essai.
4. Couverture par un régime de sécurité sociale ou équivalent.
5. En bonne santé selon l’opinion de l’investigateur

E.4

Principal exclusion criteria

-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 therapeutic clinical trials assessing treatment
-Pregnant or breastfeeding 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).
-Another vaccine administered in the month prior to inclusion and randomization.
- Fever > 38°C within the past 24 hours
- People under legal protection measure (tutorship)

1. Antécédents de contre-indication au BCG, allergie connue au BCG ou EIG à une vaccination BCG préalable.
2. ATCD de tuberculose.
3. Personnes présentant une immuno-déficience acquise ou innée
4. Personnes ayant déjà été infectées par le SARS Cov-2 (documentation virologique ou TDM ou sérologie positive quand la sérologie sera faisable)
5. Personnes qui ne pourraient pas s’engager sur le suivi de 6 mois
6. Personnes n’étant pas en bonne condition générale, jugé par l’investigateur
7. Personnes incluses dans d’autres essais cliniques évaluant des traitements
8. Grossesse, allaitement ou test de grossesse positif le jour de l'inclusion.
9. Vacciné avec le BCG dans l’année précédente
10. Vacciné avec un autre vaccin vivant dans le mois avant la randomisation
11. Antécédents d'anaphylaxie après une vaccination.
12. Ayant reçu un traitement médical qui affecte la réponse immune ou autre thérapie immunosuppressive dans l’année précédente. Ces thérapies incluent des corticostéroïdes systémiques (supérieurs ou égaux à 10 mg pendant 2 semaines ou plus), des immunosuppresseurs, des agents biologiques (tels que des anticorps monoclonaux contre le facteur de nécrose tumorale (TNF) -alpha).
13. Ayant reçu un autre vaccin dans les 4 semaines précédentes
14. Fièvre> 38 ° C au cours des dernières 24 heures.
15. Personne sous mesure de protection juridique (tutelle)

E.5 End points

E.5.1

Primary end point(s)

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.

Proportion des participants ayant un diagnostic de COVID 19 cliniquement symptomatique et confirmé par prélèvement nasopharyngé positif pour le SARS Cov-2 et/ou un prélèvement sanguin positif et /ou un TDM thorax compatible avec le diagnostic et/ou une séroconversion SARS Cov-2 durant la période de suivi de 6 mois.

E.5.1.1

Timepoint(s) of evaluation of this end point

6 months

6 mois

E.5.2

Secondary end point(s)

-participants having developed a severe form of COVID-19, as defined by the necessity for hospitalization in ICU and O2 or artificial ventilation, or extracorporeal membrane oxygenation, or death;
-Participants with seroconversion during the study, without symptoms related to COVID-19
-participants presenting any kind of respiratory infection due to any cause;
-local and general events following BCG revaccination up to 30 days after BCG revaccination
-Numbers of sick days and number of sick leaves
-Identify and measure potentially modified markers of innate immunity upon SARS CoV2 infection by comparing BCG vaccinated and non-vaccinated controls.

- Proportion des participants ayant une forme sévère de COVID-19 définie par la nécessite d’une hospitalisation en réanimation avec recours à l’O2 ou ventilation artificielle ou ECMO ou le décès ;
- Participants avec séroconversion au cours de l'étude, sans symptômes liés à COVID-19
- Proportion des participants ayant présenté une infection respiratoire toutes causes confondues ;
- Proportion des effets locaux et généraux survenus dans les 30 jours suivant la revaccination par le BCG ;
- Nombre de jours d’arrêts de travail dans les deux groupes.
- Identifier et mesurer les marqueurs modifiés de l’immunité innée

E.5.2.1

Timepoint(s) of evaluation of this end point

6 months

6 mois

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

Yes

E.6.3

Therapy

Yes

E.6.4

Safety

Yes

E.6.5

Efficacy

Yes

E.6.6

Pharmacokinetic

E.6.7

Pharmacodynamic

E.6.8

Bioequivalence

E.6.9

Dose response

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

E.6.12

Pharmacoeconomic

E.6.13

Others

E.7

Trial type and phase

E.7.1

Human pharmacology (Phase I)

E.7.1.1

First administration to humans

E.7.1.2

Bioequivalence study

E.7.1.3

Other

E.7.1.3.1

Other trial type description

E.7.2

Therapeutic exploratory (Phase II)

E.7.3

Therapeutic confirmatory (Phase III)

Yes

E.7.4

Therapeutic use (Phase IV)

E.8 Design of the trial

E.8.1

Controlled

Yes

E.8.1.1

Randomised

Yes

E.8.1.2

Open

E.8.1.3

Single blind

Yes

E.8.1.4

Double blind

E.8.1.5

Parallel group

Yes

E.8.1.6

Cross over

E.8.1.7

Other

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

Yes

E.8.2.3

Other

E.8.2.4

Number of treatment arms in the trial

E.8.3

The trial involves single site in the Member State concerned

E.8.4

The trial involves multiple sites in the Member State concerned

Yes

E.8.4.1

Number of sites anticipated in Member State concerned

E.8.5

The trial involves multiple Member States

E.8.6 Trial involving sites outside the EEA

E.8.6.1

Trial being conducted both within and outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.7

Trial has a data monitoring committee

E.8.8

Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial

LVLS

E.8.9 Initial estimate of the duration of the trial

E.8.9.1

In the Member State concerned years

E.8.9.1

In the Member State concerned months

E.8.9.1

In the Member State concerned days

E.8.9.2

In all countries concerned by the trial months

F. Population of Trial Subjects
F.1 Age Range
F.1.1	Trial has subjects under 18	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
F.2 Gender
F.2.1	Female	Yes
F.2.2	Male	Yes
F.3 Group of trial subjects
F.3.1	Healthy volunteers	No
F.3.2	Patients	Yes
F.3.3	Specific vulnerable populations	No
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	1120

G. Investigator Networks to be involved in the Trial

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2020-04-22

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2020-04-28

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2021-08-04

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