Clinical Trials Register

Summary
EudraCT Number:	2011-000758-41
Sponsor's Protocol Code Number:	115345
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2013-10-11
Trial results	View 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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2011-000758-41

A.3

Full title of the trial

A phase III, observer-blind, randomized, multi-country, non-influenza vaccine comparator-controlled study to demonstrate the efficacy of GlaxoSmithKline Biologicals’ quadrivalent seasonal influenza candidate vaccine GSK2321138A (FLU D-QIV), administered intramuscularly in children 6 to 35 months of age

A.3.1

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

An efficacy study of GSK Biologicals’ quadrivalent influenza vaccine GSK2321138A in children

A.3.2

Name or abbreviated title of the trial where available

FLU D-QIV-004 PRI

A.4.1

Sponsor's protocol code number

115345

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/287/2011

B. Sponsor Information
B.Sponsor: 1
B.1.1	Name of Sponsor	GlaxoSmithKline Biologicals
B.1.3.4	Country	Belgium
B.3.1 and B.3.2	Status of the sponsor	Commercial
B.4 Source(s) of Monetary or Material Support for the clinical trial:
B.4.1	Name of organisation providing support	GlaxoSmithKline Biologicals
B.4.2	Country	Belgium
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	GlaxoSmithKline Biologicals
B.5.2	Functional name of contact point	Clinical Disclosure Advisor
B.5.3	Address:
B.5.3.1	Street Address	Rue de l’Institut, 89
B.5.3.2	Town/ city	Rixensart
B.5.3.3	Post code	1330
B.5.3.4	Country	Belgium
B.5.4	Telephone number	442089904466
B.5.5	Fax number	------------
B.5.6	E-mail	GSKClinicalSupportHD@gsk.com

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	Influsplit Tetra/Fluarix Tetra
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKlineGmbH & Co.KG
D.2.1.2	Country which granted the Marketing Authorisation	Germany
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	quadrivalent seasonal influenza vaccine (Flu D-QIV)
D.3.2	Product code	GSK2321138A
D.3.4	Pharmaceutical form	Suspension for 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	ANTIGENS OF THE INFLUENZA VIRUS A/CALIFORNIA/7/2009 (H1N1)-LIKE VIRUS PDM09
D.3.9.3	Other descriptive name	ANTIGENS OF THE INFLUENZA VIRUS A/CALIFORNIA/7/2009 (H1N1)-LIKE VIRUS PDM09
D.3.9.4	EV Substance Code	SUB75743
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	ANTIGENS OF THE INFLUENZA VIRUS A/VICTORIA/361/2011 (H3N2)-LIKE VIRUS
D.3.9.3	Other descriptive name	ANTIGENS OF THE INFLUENZA VIRUS A/VICTORIA/361/2011 (H3N2)-LIKE VIRUS
D.3.9.4	EV Substance Code	SUB88544
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	B/MASSACHUSETTS/2/2012 -DERIVED STRAIN USED (NYMC BX-51B)
D.3.9.3	Other descriptive name	B/MASSACHUSETTS/2/2012 -DERIVED STRAIN USED (NYMC BX-51B)
D.3.9.4	EV Substance Code	SUB121431
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	B/BRISBANE/60/2008
D.3.9.3	Other descriptive name	B/BRISBANE/60/2008
D.3.9.4	EV Substance Code	SUB38710
D.3.10	Strength
D.3.10.1	Concentration unit	µg/ml microgram(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	30
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	Prevenar 13
D.2.1.1.2	Name of the Marketing Authorisation holder	Wyeth
D.2.1.2	Country which granted the Marketing Authorisation	European Union
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	Prevenar 13
D.3.4	Pharmaceutical form	Suspension for 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	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 5 CONJUGATED TO CRM197
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 5 CONJUGATED TO CRM197
D.3.9.4	EV Substance Code	SUB30927
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1 CONJUGATED TO CRM197
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 1 CONJUGATED TO CRM197
D.3.9.4	EV Substance Code	SUB30925
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3 CONJUGATED TO CRM197
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 3 CONJUGATED TO CRM197
D.3.9.4	EV Substance Code	SUB30926
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 4 CONJUGATED TO CRM197
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 4 CONJUGATED TO CRM197
D.3.9.4	EV Substance Code	SUB25336
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6A CONJUGATED TO CRM197
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6A CONJUGATED TO CRM197
D.3.9.4	EV Substance Code	SUB30928
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6B CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 6B CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.4	EV Substance Code	SUB25344
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	4.4
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 7F CONJUGATED TO CRM197
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 7F CONJUGATED TO CRM197
D.3.9.4	EV Substance Code	SUB30929
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 9V CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 9V CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.4	EV Substance Code	SUB25342
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 14 CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 14 CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.4	EV Substance Code	SUB25340
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 18C
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 18C
D.3.9.4	EV Substance Code	SUB20580
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 19A CONJUGATED TO CRM197
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 19A CONJUGATED TO CRM197
D.3.9.4	EV Substance Code	SUB30930
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 19F CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 19F CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.4	EV Substance Code	SUB25366
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	2.2
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 23F CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.3	Other descriptive name	PNEUMOCOCCAL POLYSACCHARIDE SEROTYPE 23F CONJUGATED TO CRM197 ADSORBED ON ALUMINIUM PHOSPHATE
D.3.9.4	EV Substance Code	SUB25347
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	2.2
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: 3
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	Varivax/ProVarivax
D.2.1.1.2	Name of the Marketing Authorisation holder	Sanofi Pasteur MSD
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	Varivax/ProVarivax
D.3.4	Pharmaceutical form	Powder and solvent for suspension for 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	VARICELLA VIRUS OKA/MERCK STRAIN, (LIVE, ATTENUATED) PRODUCED IN HUMAN DIPLOID (MRC-5) CELLS
D.3.9.3	Other descriptive name	VARICELLA VIRUS OKA/MERCK STRAIN, (LIVE, ATTENUATED) PRODUCED IN HUMAN DIPLOID (MRC-5) CELLS
D.3.9.4	EV Substance Code	SUB25312
D.3.10	Strength
D.3.10.1	Concentration unit	PFU/dose plaque forming unit(s)/dose
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	1350
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: 4
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	Varilrix
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline
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	Varilrix
D.3.4	Pharmaceutical form	Powder and solvent for solution for injection
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Subcutaneous use
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	VARICELLA VIRUS
D.3.9.3	Other descriptive name	VARICELLA VIRUS
D.3.9.4	EV Substance Code	SUB20954
D.3.10	Strength
D.3.10.1	Concentration unit	PFU plaque forming unit
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	1995.26
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: 5
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 Junior
D.2.1.1.2	Name of the Marketing Authorisation holder	GlaxoSmithKline
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	Havrix Junior
D.3.4	Pharmaceutical form	Suspension for 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 (INACTIVATED ) ADSORBED ON ALUMINIUM HYDROXIDE HYDRATED PRODUCED ON HUMAN DIPLOID (MRC-5) CELLS
D.3.9.3	Other descriptive name	HEPATITIS A VIRUS (INACTIVATED ) ADSORBED ON ALUMINIUM HYDROXIDE HYDRATED PRODUCED ON HUMAN DIPLOID (MRC-5) CELLS
D.3.9.4	EV Substance Code	SUB25294
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

Healthy volunteers (Immunization against influenza A and/or B in children aged 6 months to 35 months).

E.1.1.1

Medical condition in easily understood language

Seasonal flu

E.1.1.2

Therapeutic area

Diseases [C] - Virus Diseases [C02]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	PT
E.1.2	Classification code	10022000
E.1.2	Term	Influenza
E.1.2	System Organ Class	10021881 - Infections and infestations

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 the efficacy of FLU D-QIV in the prevention of RT-PCR confirmed moderate to severe influenza A and/or B disease due to any seasonal influenza strain, when compared to non-influenza vaccine controls in children aged 6 to 35 months.
• To evaluate the efficacy of FLU D-QIV in the prevention of RT-PCR confirmed influenza A and/or B disease due to any seasonal influenza strain, when compared to non-influenza vaccine controls in children aged 6 to 35 months.

E.2.2

Secondary objectives of the trial

-To evaluate the efficacy of FLU D-QIV when compared to non-influenza vaccine controls in the prevention of:
• lower respiratory illness (LRI) and acute otitis media (AOM) associated with RT-PCR confirmed influenza A and/or B (at any time starting 7 days before the onset of LRI and ending 7 days after end of LRI)
• culture confirmed moderate to severe and of any severity influenza A and/or B disease due to antigenically-matching influenza strains and any seasonal influenza strain.
• RT-PCR confirmed severe influenza A and/or B disease.
-To evaluate the immunogenicity of FLU D-QIV in terms of HI antibody response 28 days after completion of vaccination, in an immuno sub-cohort of subjects
-To evaluate the reactogenicity of FLU D-QIV and non-influenza vaccine controls in terms of:
• solicited local and general adverse events (AEs) and unsolicited symptoms during 7 days and 28 days respectively after each vaccination
• AEs with MAV, SAEs and pIMDs during the entire study period

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

•Subjects who the investigator believes that their parents/ LAR(s) can and will comply with the requirements of the protocol (e.g., completion of the diary cards, reporting an ILI or MAV using internet access, being available for follow-up phone contacts).
•A male or female between, and including, 6 and 35 months of age at the time of first vaccination; children are eligible regardless of history of influenza vaccination.
•Written informed consent obtained from the parent(s) /LAR(s) of the subject.
•Subjects in stable health as determined by medical history and clinical examination before entering into the study.

E.4

Principal exclusion criteria

•Participation in a previous FLU-D-QIV-004 study (115345) cohort.
•Child in care
•Use of any investigational or non-registered product (drug or vaccine) other than the study vaccines within 30 days preceding the first dose of study vaccine, or planned use during the study period.
•Prior receipt of any influenza vaccine (registered or investigational) within 6 months preceding the first dose of study vaccine, or planned use of such vaccines during the study period.
•Children with underlying illness who are at risk of complications of influenza and for whom yearly (seasonal) influenza vaccination is recommended in their respective country.
•Any confirmed or suspected immunosuppressive or immunodeficient condition (including HIV), based on medical history and physical examination (no laboratory testing required).
•Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune modifying drugs within six months prior to the first vaccine dose. For corticosteroids, this will mean a dose equivalent to either >= 0.5 mg/kg of body weight or maximum of 10 mg/day of prednisone or equivalent. Inhaled and topical steroids are allowed.
•Administration of immunoglobulins and/ or any blood products within 3 months preceding the first dose of study vaccine or planned administration during the study period
•Any known or suspected allergy to any constituent of influenza vaccines (including egg proteins), non-influenza vaccine comparators (including neomycin) and latex; a history of anaphylactic-type reaction to consumption of eggs; or a history of severe adverse reaction to a previous vaccination
•Any contraindication to intramuscular injection
•Acute disease and/or fever at the time of enrolment.
Fever is defined as temperature ≥37.5°C by any route. Subjects with a minor illness (such as mild diarrhoea, mild upper respiratory infection) without fever may, be enrolled at the discretion of the investigator.
•Any other condition which, in the opinion of the Investigator, prevents the subject from participating in the study
Additional criteria for children >= 12 months of age:
•Prior receipt of any licensed varicella vaccine* or any licensed hepatitis A vaccine or planned use of these vaccines during the study period. Other routine registered childhood vaccinations are permitted.
* For countries with varicella vaccine administered as 2-dose schedule, prior receipt of a single dose of a varicella vaccine is allowed if administered at least 2 weeks before the first study vaccination.
•Any history of hepatitis A or varicella diseases.
Additional criteria for children 6 - 11 months of age in countries without universal mass vaccination recommendation for pneumococcal vaccine:
•Prior receipt of any pneumococcal conjugated vaccine or planned use of this vaccine during the study period. Other routine registered childhood vaccinations are permitted.

E.5 End points

E.5.1

Primary end point(s)

•First occurrence of RT-PCR confirmed moderate to severe influenza A and/or B disease due to any seasonal influenza strain
•First occurrence of RT-PCR confirmed influenza A and/or B disease of any severity due to any seasonal influenza strain

E.5.1.1

Timepoint(s) of evaluation of this end point

during the surveillance period (approximately 6 to 8 months)

E.5.2

Secondary end point(s)

Efficacy:
•First occurrence of Lower respiratory illness (LRI) with RT-PCR confirmed influenza A and/or B infection due to any seasonal influenza strain identified at any time starting 7 days before the onset of LRI and ending 7 days after end of LRI
•First occurrence of culture-confirmed moderate to severe influenza A and/or B disease due to antigenically-matching influenza strains.
•First occurrence of culture-confirmed influenza A and/or B disease of any severity due to antigenically-matching influenza strains.
•First occurrence of culture-confirmed moderate to severe influenza A and/or B disease due to any seasonal influenza strain.
•First occurrence of culture-confirmed influenza A and/or B disease of any severity due to any seasonal influenza strain.
•First occurrence of acute otitis media (AOM) with RT-PCR confirmed influenza A and/or B infection due to any seasonal influenza strain identified at any time starting 7 days before the onset of AOM and ending 7 days after end of AOM
•First occurrence of RT-PCR confirmed severe influenza A and/or B due to any seasonal influenza strain.

Immunogenicity:
•Humoral immune response in terms of haemagglutination-inhibition (HI) antibody titres against each of four vaccine strains contained in FLU D-QIV (in immuno sub-cohort of subjects only).
Derived variables:
- Geometric Mean Titres (GMTs) of HI antibody titres
- Seropositivity rates
- Seroconversion rates (SCR)*
- Mean geometric increase (MGI) **
- Seroprotection rates (SPR) ***
*SCR is defined as the percentage of vaccinees that have either a pre-vaccination titre < 1:10 and a post-vaccination titre ≥1:40 or a pre-vaccination titre ≥1:10 and at least a four-fold increase in post-vaccination titre.
**MGI is defined as the fold increase in serum HI GMTs post-vaccination compared to prevaccination.
***SPR is defined as the percentage of vaccinees with a serum HI titre ≥1:40 that usually is accepted as indicating protection in adults. SPR will be also presented as the percentage of vaccinees with a serum HI titre ≥1:80 and ≥1:160.

Safety:
•Solicited local and general symptoms
•Unsolicited adverse events (AEs)
•AEs with MAV
•SAEs and pIMDs

E.5.2.1

Timepoint(s) of evaluation of this end point

Efficacy:
•during the surveillance period (approximately 6 to 8 months)

Immunogenicity
•Geometric Mean Titers (GMTs) of HI antibody titres at Days 0 and 28/56.
•Seropositivity rates at Days 0 and 28/56.
•Seroconversion rates (SCR) at Day 28/56.
•Mean geometric increase (MGI) at Day 28/56.
•Seroprotection rates (SPR) at Days 0 and 28/56.

Safety
•Solicited local and general symptoms within 7 days (Day 0-Day 6) after each vaccination
•Unsolicited AEs within 28 days (Day 0-Day 27) after each vaccination
•AEs with medically attended visits (MAV), Seriouse adverse events (SAEs), potential immune-mediated diseases (pIMDs): during the entire study period (6 to 8 months).

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

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

E.8.1.4

Double blind

E.8.1.5

Parallel group

E.8.1.6

Cross over

E.8.1.7

Other

Yes

E.8.1.7.1

Other trial design description

observer-blind

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

E.8.2.4

Number of treatment arms in the trial

E.8.3

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Bangladesh

Dominican Republic

Honduras

India

Lebanon

Philippines

Thailand

Turkey

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

LSLV

E.8.9 Initial estimate of the duration of the trial

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

Yes

F.1.1