Clinical Trials Register

Summary
EudraCT Number:	2017-000596-87
Sponsor's Protocol Code Number:	ACTIVATE
National Competent Authority:	Greece - EOF
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2017-03-23
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

Greece - EOF

A.2

EudraCT number

2017-000596-87

A.3

Full title of the trial

A RANDOMIZED CLINICAL TRIAL FOR ENHANCED TRAINED IMMUNE RESPONSES THROUGH BACILLUS CALMETTE-GUÉRIN VACCINATION TO PREVENT INFECTIONS OF THE ELDERLY: THE ACTIVATE TRIAL

ΜΙΑ ΤΥΧΑΙΟΠΟIΗΜΕΝΗ ΚΛΙΝΙΚΗ ΜΕΛΕΤΗ ΓΙΑ ΤΗΝ ΑΞΙΟΛΟΓΗΣΗ ΤΟΥ ΕΜΒΟΛΙΑΣΜΟΥ ΜΕ BACILLUS CALMETTE-GUÉRIN ΓΙΑ ΤΗΝ ΕΝΙΣΧΥΣΗ ΤΗΣ ΜΗ ΕΙΔΙΚΗΣ ΑΝΟΣΙΑΚΗΣ ΑΠΟΚΚΡΙΣΗΣ ΚΑΙ ΤΗΝ ΠΡΟΛΗΨΗ ΛΟΙΜΩΞΕΩΝ ΣΤΟΥΣ ΥΠΕΡΗΛΙΚΕΣ: ΜΕΛΕΤΗ ACTIVATE

A.3.1

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

INFECTION PREVENTION IN THE ELDERLY WITH VACCINATION

ΠΡΟΛΗΨΗ ΛΟΙΜΩΞΕΩΝ ΤΝΩ ΕΝΗΛΙΚΩΝ ΜΕ ΕΜΒΟΛΙΑΣΜΟ

A.3.2

Name or abbreviated title of the trial where available

BACILLUS CALMETTE-GUÉRIN VACCINATION TO PREVENT INFECTIONS OF THE ELDERLY

Ο ΕΜΒΟΛΙΑΣΜΟΣ ΜΕ BACILLUS CALMETTE-GUÉRIN ΣΤΗΝ ΠΡΟΛΗΨΗ ΛΟΙΜΩΞΕΩΝ ΤΩΝ ΕΝΗΛΙΚΩΝ

A.4.1

Sponsor's protocol code number

ACTIVATE

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	Hellenic Institute for the Study of Sepsis
B.1.3.4	Country	Greece
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	Hellenic Institute for the Study of Sepsis
B.4.2	Country	Greece
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Hellenic Institute for the Study of Sepsis
B.5.2	Functional name of contact point	President of the Board
B.5.3	Address:
B.5.3.1	Street Address	88 Michalakopoulou Street
B.5.3.2	Town/ city	Athens
B.5.3.3	Post code	11528
B.5.3.4	Country	Greece
B.5.4	Telephone number	00302107480662
B.5.5	Fax number	00302107480662
B.5.6	E-mail	insepsis@otenet.gr

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	BCG Vaccine
D.2.1.1.2	Name of the Marketing Authorisation holder	BB-NCIPD Ltd.
D.2.1.2	Country which granted the Marketing Authorisation	Bulgaria
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	Bacillus Calmette Guerin
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intradermal use
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	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

Vaccination for infection prevention

Εμβολιασμός για πρόληψη λοιμώξεων

E.1.1.1

Medical condition in easily understood language

Vaccination

Εμβολιασμός

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10036897
E.1.2	Term	Prophylactic vaccination
E.1.2	System Organ Class	100000004865

E.1.2 Medical condition or disease under investigation

E.1.2	Version	19.1
E.1.2	Level	LLT
E.1.2	Classification code	10046859
E.1.2	Term	Vaccination
E.1.2	System Organ Class	100000004865

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

The aim of the study is to demonstrate in a double-blind, placebo-controlled approach if vaccination of elderly patients with BCG vaccine may modulate their disease susceptibility for bacterial diseases. This will be validated using both clinical and immunological criteria.

Σκοπός της μελέτης είναι να αξιολογήσει με μια διπλή-τυφλή, ελεγχόμενη με εικονικό φάρμακο κλινική μελέτη αν ο εμβολιασμός ηλικιωμένων με BCG μπορεί να τροποποιήσει την ευπάθεια τους για βακτηριακές λοιμώξεις. Το παραπάνω ερώτημα θα αξιολογηθεί βάση κλινικών και ανοσολογικών κριτηρίων.

E.2.2

Secondary objectives of the trial

Not applicable

Δεν εφαρμόζεται

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Male or female
• Age more than or equal to 65 years based on the precise date of birth
• Discharge from hospital after hospitalization for a medical cause. All medical causes make patients eligible for enrolment with the only exception of medical causes mentioned in the exclusion criteria

• Άρρεν ή θήλυ
• Ηλικία μεγαλύτερη ή ίση των 65 ετών βασιζόμενη στην ακριβή ημερομηνία γέννησης
• Έξοδος από το νοσοκομείο μετά νοσηλεία για παθολογικό αίτιο. Όλα τα παθολογικά αίτια δύνανται να συμπεριληφθούν με εξαίρεση αυτά που αποτελούν κριτήρια αποκλεισμού.

E.4

Principal exclusion criteria

• Failure to obtain written informed consent
• Solid organ malignancy or lymphoma diagnosed the last five years
• Treatment with oral or intravenous steroids defined as daily doses of 10mg prednisone or equivalent for longer than 3 months
• Severely immunocompromised patients. This exclusion category comprises: a) patients with known infection by the human immunodeficiency virus (HIV-1); b) neutropenic patients with less than 500 neutrophils/mm3; c) patients with solid organ transplantation; d) patients with bone marrow transplantation; e) patients under chemotherapy; f) patients with primary immunodeficiency; g) severe lymphopenia with less than 400 lymphocytes/mm3; h) treatment with any anti-cytokine therapies.
• Positive Interferon-gamma Release Assay (IGRA)

• Απουσία γραπτής συγκατάθεσης
• Νεοπλασία συμπαγούς οργάνου ή λέμφωμα διαγνωσμένα τα τελευταία 5 έτη
• Θεραπεία με από του στόματος η ενδοφλέβια κορτικοστεροειδή οριζόμενα ως ημερήσιες δοσολογίες 10mg πρεδνιζόνης ή ισοδύναμου για χρονικό διάστημα μεγαλύτερο των 3 μηνών
• Ανοσοκατασταλμένοι ασθενείς. Αυτή η κατηγορία περιλαμβάνει: α) ασθενείς με γνωστή λοίμωξη από τον ιό της ανθρώπινης επίκτητης ανοσολογικής ανεπάρκειας (HIV-1), β) ουδετεροπενικοί ασθενείς με λιγότερα από 500 ουδετερόφιλα/mm3, γ) ασθενείς με μεταμόσχευση συμπαγούς οργάνου, δ) ασθενείς με μεταμόσχευση μυελού των οστών, ε) ασθενείς υπό χημειοθεραπεία, στ) ασθενείς με πρωτοπαθή ανοσοανεπάρκεια, ζ) σοβαρή λεμφοπενία με λιγότερα από 400 λεμφοκύτταρα/mm3 και η) θεραπεία με παράγοντες έναντι κυτταροκινών.
• Θετική δοκιμασία έμμεσης αντίχνευση Mycobacterium tuberculosis με προσδιορισμό ιντερφερόνης-γ (IFNγ) έπειτα από διέγερση CD4-/CD8-κυττάρων από ειδικά πεπτίδια

E.5 End points

E.5.1

Primary end point(s)

The primary study endpoint will be the time interval to the first infection post hospital discharge between the two groups of treatment.

Το πρωτογενές καταληκτικό σημείο θα είναι το χρονικό διάστημα μέχρι την πρώτη λοίμωξη μετά την έξοδο του ασθενούς από το νοσοκομείο μεταξύ των δύο ομάδων μελέτης.

E.5.1.1

Timepoint(s) of evaluation of this end point

12 months

12 μήνες

E.5.2

Secondary end point(s)

• Rate of hospitalizations until month 12
• Time to first infection or sepsis episode
• Total number of infections
• Time to first hospitalization
• Number of antibiotic administrations
• One-year mortality
• Cytokine stimulation after 3 months
• Epigenetic changes after 3 months
• Effect of BCG vaccination on cost of treatment for infections after 12 months

• Αριθμός νοσηλειών μέχρι το μήνα 12
• Χρόνος μέχρι την πρώτη λοίμωξη ή επεισόδιο σήψης
• Συνολικός αριθμός λοιμώξεων
• Χρόνος μέχρι την πρώτη νοσηλεία
• Αριθμός αντιμικροβιακών αγωγών που χορηγήθηκαν
• Θνητότητα στο ένα έτος
• Διέγερση κυτταροκινών μετά από 3 μήνες
• Επιγενετικές αλλαγές μετά από 3 μήνες
• Αποτέλεσμα του εμβολιασμού με BCG στο κόστος αγωγής για τις λοιμώξεις μετά από 12 μήνες

E.5.2.1

Timepoint(s) of evaluation of this end point

12 months

12 μήνες

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

E.6.4

Safety

E.6.5

Efficacy

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

Yes

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)

E.7.4

Therapeutic use (Phase IV)

Yes

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

E.8.1.4

Double blind

Yes

E.8.1.5

Parallel group

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

Yes

E.8.4

The trial involves multiple sites in the 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

12 months

12 μήνες

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 years

E.8.9.2

In all countries concerned by the trial months

E.8.9.2

In all countries concerned by the trial days

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

F.1.1.1

In Utero

F.1.1.2

Preterm newborn infants (up to gestational age < 37 weeks)

F.1.1.3

Newborns (0-27 days)

F.1.1.4

Infants and toddlers (28 days-23 months)

F.1.1.5

Children (2-11years)

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

Yes

F.1.3.1

Number of subjects for this age range:

200

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

F.3.2

Patients

Yes

F.3.3

Specific vulnerable populations

F.3.3.1

Women of childbearing potential not using contraception

F.3.3.2

Women of child-bearing potential using contraception

F.3.3.3

Pregnant women

F.3.3.4

Nursing women

F.3.3.5

Emergency situation

F.3.3.6

Subjects incapable of giving consent personally

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

200

F.5

Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)

None

Κανένα

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

2017-05-15

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2017-05-26

P. End of Trial
P.	End of Trial Status	Ongoing

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