Clinical Trials Register

Summary
EudraCT Number:	2019-001186-33
Sponsor's Protocol Code Number:	AIV_FLU_2019_01_VIGIRA_JDD
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Ongoing
Date on which this record was first entered in the EudraCT database:	2019-06-11
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

Spain - AEMPS

A.2

EudraCT number

2019-001186-33

A.3

Full title of the trial

Clinical trial, phase IV, randomized, double-blind, controlled, in children aged 12 to 35 months, of the vaccine against seasonal influenza to estimate efficacy against influenza and other respiratory infections

Ensayo clínico de fase IV, aleatorizado, doble ciego, controlado, en niños de 12 a 35 meses, de la vacuna contra la gripe estacional para estimar la eficacia frente a la gripe y frente a otras infecciones respiratorias

A.3.1

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

Clinical trial in children from 12 to 35 months of the flu vaccine to estimate efficacy against influenza and other respiratory infections

Ensayo clínico en niños de 12 a 35 meses de la vacuna contra la gripe para estimar la eficacia frente a la gripe y frente a otras infecciones respiratorias

A.3.2

Name or abbreviated title of the trial where available

VIGIRA

A.4.1

Sponsor's protocol code number

AIV_FLU_2019_01_VIGIRA_JDD

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	FISABIO
B.1.3.4	Country	Spain
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	Fondo de Investigación en Salud - Instituto de Salud Carlos III
B.4.2	Country	Spain
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	FISABIO
B.5.2	Functional name of contact point	AIV
B.5.3	Address:
B.5.3.1	Street Address	Av. Cataluña, 21
B.5.3.2	Town/ city	Valencia
B.5.3.3	Post code	46020
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34961925968
B.5.5	Fax number	+34961925938
B.5.6	E-mail	vacunas_fisabio@gva.es

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	Fluarix tetra
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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	Fluarix Tetra
D.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	A/MICHIGAN/45/2015 (H1N1)PDM09-LIKE STRAIN (A/SINGAPORE/GP1908/2015, IVR-180)
D.3.9.3	Other descriptive name	A/MICHIGAN/45/2015 (H1N1)PDM09-LIKE STRAIN (A/SINGAPORE/GP1908/2015, IVR-180)
D.3.9.4	EV Substance Code	SUB187226
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	A/SINGAPORE/INFIMH-16-0019/2016 (H3N2)-LIKE STRAIN (A/SINGAPORE/INFIMH-16-0019/2016, NIB-104)
D.3.9.3	Other descriptive name	A/SINGAPORE/INFIMH-16-0019/2016 (H3N2)-LIKE STRAIN (A/SINGAPORE/INFIMH-16-0019/2016, NIB-104)
D.3.9.4	EV Substance Code	SUB191971
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	B/COLORADO/06/2017-LIKE STRAIN (B/VICTORIA/2/87 LINEAGE) (B/MARYLAND/15/2016, NYMC BX-69A)
D.3.9.3	Other descriptive name	B/COLORADO/06/2017-LIKE STRAIN (B/VICTORIA/2/87 LINEAGE) (B/MARYLAND/15/2016, NYMC BX-69A)
D.3.9.4	EV Substance Code	SUB191972
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	B/PHUKET/3073/2013-LIKE STRAIN (B/PHUKET/3073/2013, WILD TYPE)
D.3.9.3	Other descriptive name	B/PHUKET/3073/2013-LIKE STRAIN (B/PHUKET/3073/2013, WILD TYPE)
D.3.9.4	EV Substance Code	SUB178474
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	15
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.IMP: 2
D.1.2 and D.1.3	IMP Role	Comparator
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	Havrix 720
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline
D.2.1.2	Country which granted the Marketing Authorisation	Spain
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.3.4	Pharmaceutical form	Injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intramuscular use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	HEPATITIS A VIRUS ANTIGEN (INACTIVATED)
D.3.9.3	Other descriptive name	HEPATITIS A VIRUS ANTIGEN (INACTIVATED)
D.3.9.4	EV Substance Code	SUB38555
D.3.10	Strength
D.3.10.1	Concentration unit	ELISA unit enzyme-linked immunosorbent assay unit
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	720
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Flu and acute respiratory infections

Gripe e infecciones respiratorias agudas

E.1.1.1

Medical condition in easily understood language

Flu and respiratory infeccions

Gripe e infecciones respiratorias

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 estimate the effectiveness of the inactivated flu vaccine with the number of episodes of acute respiratory infections, its severity and its complications in children with risk.

Estimar la eficacia de la VIG frente al número de episodios de IRA, su gravedad y sus complicaciones en niños con riesgo.

E.2.2

Secondary objectives of the trial

To estimate the effectiveness of the inactivated flu vaccine against the number of episodes of acute respiratory infections, its severity and its complications in children at risk by sex.
To estimate the effectiveness of the inactivated flu vaccine against the number of flu infections confirmed by laboratory.
To estimate the effectiveness of the inactivated flu vaccine against the number of episodes of acute respiratory infections with non-influenza virus isolation.
To estimate the effectiveness of the inactivated flu vaccine against the number of episodes of acute respiratory infections with detection of respiratory viruses (influenza and not influenza).
To analyze the consumption of resources in vaccinated and unvaccinated children with acute respiratory infections.

Estimar la eficacia de la VIG frente al número de episodios de IRA, su gravedad y sus complicaciones en niños con riesgo por sexo.
Estimar la eficacia de la VIG frente al número gripes confirmadas por laboratorio.
Estimar la eficacia de la VIG frente al número de episodios de IRA con aislamiento de virus no gripe.
Estimar la eficacia de la VIG frente al número de episodios de IRA con detección de virus respiratorios (gripe y no gripe).
Analizar el consumo de recursos por cuadros de IRA en niños vacunados y no vacunados.

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

To compare the understanding of traditional informed consent against an informed consent following the iConsent guidelines, as well as its quality as an information document.

Comparar la comprensión del CI tradicional frente a un CI elaborado siguiendo las guías iConsent, así como su calidad como documento de información.

E.3

Principal inclusion criteria

1. Subjects of both sexes who are between 12 to 35 months of age (both inclusive) with a history of recurrent or severe ARI defined as:
a. three or more acute respiratory infections diagnosed in primary care (rhinitis, acute otitis media, pharyngitis, bronchitis, bronchiolitis or pneumonia) in the previous 6 months or four or more in the last 12 months; or
b. a recurrent acute respiratory infection referral to the emergency department or the otorhinolaryngology specialist in the last 12 months; or
c. an hospitalization by acute respiratory infection in the last 12 months.
2. Informed consent of the parents or legal representatives of the subject.
3. Subject and parent or other legally authorized representative, can and are willing to attend scheduled visits and accept all trial procedures.
4. Willingness to use the mobile tracking application while the participation in the study lasts.

1. Sujetos de ambos sexos que tengan entre 12 a 35 meses de edad (ambos inclusive) con antecedentes de IRA recurrente o grave definida como:
a. tres o más IRA diagnosticadas en AP (rinitis, OMA, faringitis, bronquitis, bronquiolitis o neumonía) en los 6 meses previos o cuatro o más en los últimos 12 meses; o
b. una derivación de IRA recurrente a urgencias o al especialista en otorrinolaringología en los últimos 12 meses; o
c. una hospitalización por IRA en los últimos 12 meses.
2. Consentimiento informado por escrito de los padres o representantes legales del sujeto.
3. Sujeto y progenitor u otro representante legalmente autorizado, pueden y están dispuestos a asistir a las visitas programadas y aceptar todos los procedimientos del ensayo.
4. Disposición a utilizar la aplicación móvil de seguimiento mientras dure la participación en el estudio.

E.4

Principal exclusion criteria

1. Child in foster care, without legal tutor.
2. Planned administration of any influenza vaccine (other than the study vaccine) during the entire study period, according to the official immunization schedule.
3. Anaphylaxis known to the active ingredients or to any of the excipients included in the influenza vaccine data sheet or to any component that may be present in trace amounts, such as egg (ovalbumin, etc.).
4. Anaphylaxis known to the active ingredients or to any of the excipients included in the hepatitis A vaccine data sheet.
5. Any immunological disorder or medical condition that at the discretion of the pediatrician contraindicates vaccination against influenza or hepatitis A.
6. Any treatment with chronic immunosuppressants (defined as more than 14 days) or other immunological treatment in the three months prior to the first dose of the vaccine or during the study. Topical use of corticosteroids (for example, cream, drops or aerosols), within the dose indicated on the product label, is allowed.
7. Administration of immunoglobulins and / or any blood product (transfusion) within 3 months before the first dose of the study vaccine or planned administration during the study period.
8. Have received any influenza vaccine or have been diagnosed with influenza in the same season (confirmed by laboratory diagnostic tests or rapid influenza).
9. Have been previously vaccinated against hepatitis A.
10. Have a fever and / or an acute illness or infection on the day of vaccination, defining fever as an axillary temperature ≥38.0°C. Immunization will be postponed until fever disappears.
11. Planned surgery that requires a general anesthetic or planned surgery that requires hospitalization for at least 24 hours during the entire study period.
12. Have participated in the first year of this study.
13. Do not authorize the laboratory results to be recorded in the clinical record.

1. Niño en acogida, sin tutor legal.
2. Administración planificada de cualquier vacuna antigripal (que no sea la vacuna del estudio) durante todo el período de estudio, según el calendario oficial de vacunación.
3. Anafilaxia conocida a los principios activos o a alguno de los excipientes incluidos en la ficha técnica de la vacuna de la gripe o a cualquier componente que pueda estar presente en cantidad de traza, tales como huevo (ovoalbúmina, etc.).
4. Anafilaxia conocida a los principios activos o a alguno de los excipientes incluidos en la ficha técnica de la vacuna de la hepatitis A.
5. Cualquier trastorno inmunológico o condición médica que a criterio del pediatra contraindique la vacunación contra la gripe o la hepatitis A.
6. Cualquier tratamiento con inmunosupresores crónico (definido como más de 14 días) u otro tratamiento inmunológico en los tres meses anteriores a la primera dosis de la vacuna o durante el estudio. El uso tópico de corticosteroides (por ejemplo, crema, gotas o aerosoles), dentro de la dosis indicada en la etiqueta del producto, está permitido.
7. Administración de inmunoglobulinas y/o de cualquier producto sanguíneo (transfusión) dentro de los 3 meses antes de la primera dosis de la vacuna del estudio o la administración planificada durante el período de estudio.
8. Haber recibido alguna vacuna antigripal o que hayan sido diagnosticados de gripe en la misma temporada (confirmado por pruebas de diagnóstico de laboratorio o de influenza rápida).
9. Haber sido vacunados previamente frente a la hepatitis A.
10. Tener fiebre y /o una enfermedad o infección aguda el día de la vacunación, definiendo fiebre como una temperatura axilar ≥38,0°C.
11. Cirugía planificada que requiera un anestésico general o cirugía planificada que requiera hospitalización durante al menos 24 horas durante todo el período de estudio.
12. Haber participado en el primer año de este estudio.
13. No autorizar que los resultados de laboratorio sean registrados en la historia clínica.

E.5 End points

E.5.1

Primary end point(s)

To estimate the efficacy of the influenza vaccine against the number of episodes of acute respiratory infection, its severity and its complications in children at risk. These are chosen as measures of net health effects and to analyze whether the vaccine causes viral interference.

Estimar la eficacia de la vacuna contra la influenza contra el número de episodios de infección respiratoria aguda, su gravedad y sus complicaciones en niños en riesgo. Estos se eligen como medidas de los efectos netos para la salud y para analizar si la vacuna causa interferencia viral.

E.5.1.1

Timepoint(s) of evaluation of this end point

After each flu season (2020 and 2021), for two consecutive seasons.

Después de cada temporada gripal (2020 y 2021), durante dos temporadas consecutivas.

E.5.2

Secondary end point(s)

E.5.2.1

Timepoint(s) of evaluation of this end point

September 2021

Septiembre de 2021

E.6 and E.7 Scope of the trial

E.6

Scope of the trial

E.6.1

Diagnosis

E.6.2

Prophylaxis

E.6.3

Therapy

E.6.4

Safety

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)

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)

Yes

E.8.2.2

Placebo

E.8.2.3

Other

Yes

E.8.2.3.1

Comparator description

Havrix 720

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

September 2021

Septiembre de 2021

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

F. Population of Trial Subjects

F.1 Age Range

F.1.1

Trial has subjects under 18

Yes

F.1.1

Number of subjects for this age range:

400

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

400

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

400

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

F.1.3

Elderly (>=65 years)

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

F.3.3

Specific vulnerable populations

Yes

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

The study is about children (12-35 months). The consent will be giving by the parents or legal guardians.

El estudio trata sobre niños (12-35 meses). El consentimiento será otorgado por los padres o tutores legales.

F.3.3.7

Others

Yes

F.3.3.7.1

Details of other specific vulnerable populations

Children (12-35 months)

Niños (12-35 meses)

F.4 Planned number of subjects to be included

F.4.1

In the member state

400

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)

Those patients who, once the blind has been opened, have been vaccinated with the hepatitis A vaccine, will have an additional dose to complete this regimen in a period established between 6 and 12 months after the last dose.

Aquellos pacientes que, una vez abierto el ciego, hayan sido vacunados con la vacuna contra la hepatitis A, tendrán una dosis adicional para completar esta pauta en un periodo establecido entre los 6 y 12 meses después de la última dosis.

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

2019-09-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2019-09-25

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

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