Clinical Trials Register

Summary
EudraCT Number:	2013-003592-35
Sponsor's Protocol Code Number:	LAIVImmuno
National Competent Authority:	UK - MHRA
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-12-10
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
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

UK - MHRA

A.2

EudraCT number

2013-003592-35

A.3

Full title of the trial

A phase III/IV open-label study of the immunogenicity and safety of a single dose of a Live Attenuated Influenza Vaccine (LAIV) (FluenzTM) for each of three successive years in children naïve to, or in previous receipt of the AS03B adjuvanted H1N1 (2009) influenza vaccine (Pandemrix ™).

A.3.1

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

Assessing responses to annual nasal flu vaccine in children who have or have not previously been given pandemic flu vaccine.

A.3.2

Name or abbreviated title of the trial where available

LAIV Immuno

A.4.1

Sponsor's protocol code number

LAIVImmuno

A.5.4

Other Identifiers

Name:

LAIV IMMUNO

Number:

LAIN IMMUNO

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	Public Health England
B.1.3.4	Country
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	Department of Health
B.4.2	Country	United Kingdom
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Health Protection Agency
B.5.2	Functional name of contact point	Southern
B.5.3	Address:
B.5.3.1	Street Address	61 Colindale Ave
B.5.3.2	Town/ city	London
B.5.3.3	Post code	NW9 5EQ
B.5.4	Telephone number	0208 327 6084
B.5.5	Fax number	0208 200 7868
B.5.6	E-mail	jo.southern@hpa.org.uk

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	FLUENZ▼ nasal spray suspension
D.2.1.1.2	Name of the Marketing Authorisation holder	MedImmune, LLC
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	Fluenz
D.3.4	Pharmaceutical form	Nasal spray, suspension
D.3.4.1	Specific paediatric formulation	No
D.3.7	Routes of administration for this IMP	Intranasal use (Noncurrent)
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	A/California/7/2009 (H1N1)pdm09-like strain (A/California/7/2009, MEDI 228029
D.3.9.4	EV Substance Code	AS1
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10 to the 7.0±0.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	A/Victoria/361/2011 (H3N2)-like strain (A/Victoria/361/2011, MEDI 231411)
D.3.9.4	EV Substance Code	AS2
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10 to the 7.0±0.5
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	B/Wisconsin/1/2010-like strain (B/Wisconsin/1/2010, MEDI 028507)
D.3.9.4	EV Substance Code	AS3
D.3.10	Strength
D.3.10.1	Concentration unit	Other
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	10 to the 7.0±0.5
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

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Protection against influenza in healthy children

E.1.1.1

Medical condition in easily understood language

Protection against influenza in healthy children

E.1.1.2

Therapeutic area

Body processes [G] - Immune system processes [G12]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10059430
E.1.2	Term	Influenza immunization
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10046859
E.1.2	Term	Vaccination
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

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	10059429
E.1.2	Term	Influenza immunisation
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10039244
E.1.2	Term	Routine vaccination
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.2 Medical condition or disease under investigation

E.1.2	Version	14.1
E.1.2	Level	LLT
E.1.2	Classification code	10016794
E.1.2	Term	Flu vaccination
E.1.2	System Organ Class	10042613 - Surgical and medical procedures

E.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

Technical version:
To compare the immune response to homologous and heterologous strains before and after to annual doses of LAIV over three consecutive years in children aged 4-9(+364days) years at enrollment in naïve children vs those in previous receipt of the AS03B adjuvanted pandemic influenza vaccine to homologous vaccine strains .

Lay version:
To compare the immune system responses to various strains of flu after having the nasal influenza vaccine (LAIV) for each of three consecutive years in children aged 4-8 when they join the study and who have either previously had a dose of Pandemirix (a pandemic flu vaccine) or have never had any pandemic flu vaccine.

E.2.2

Secondary objectives of the trial

To document the incidence of laboratory confirmed influenza and other respiratory viruses in the naïve and Pandemrix™ primed children over the three seasons.

To compare the safety and tolerability of annual doses of LAIV in naïve compared to Panemrix™ vaccinated children.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Parent/legal guardian gives written informed consent for participation of their child in the study.
• Male or female aged 4 years (+364 days) to 8 years (+364 days) on the day of consent.
• Documented prior receipt of Pandemrix, or no evidence in the medical notes of never having had pandemic influenza vaccine.

E.4

Principal exclusion criteria

*Absolute exclusion criteria - The participant may not enter the study if ANY of the following apply:

From Fluenz Summary of Product Characterstics (SPC):
• Hypersensitivity to the active substances, to any of the excipients (e.g. gelatin; see appendix 1), to gentamicin (a possible trace residue), to eggs or to egg proteins (e.g. ovalbumin).
• Children and adolescents who are clinically immunodeficient due to conditions or immunosuppressive therapy such as: acute and chronic leukaemias; lymphoma; symptomatic HIV infection; cellular immune deficiencies; and high-dose corticosteroids. FLUENZ is not contraindicated for use in individuals with asymptomatic HIV infection; or individuals who are receiving topical/inhaled corticosteroids or low-dose systemic corticosteroids or those receiving corticosteroids as replacement therapy, e.g. for adrenal insufficiency.
• Children and adolescents younger than 18 years of age receiving salicylate therapy because of the association of Reye's syndrome with salicylates and wild-type influenza infection.

Study specific exclusions:
• Any contraindication to vaccination as specified in the “Green Book”- Immunisation against Infectious Disease, HMSO.
• known bleeding diathesis (or any condition that may be associated with a prolonged bleeding time).
• Any other significant condition or circumstance which, in the opinion of the investigator, may either put the participant at risk because of participation in the study, or may influence the result of the study, or the participant’s ability to participate in the study.

*Temporary Exclusion Criteria
From the SPC:
• The concurrent use of FLUENZ with antiviral agents that are active against influenza A and/or B viruses has not been evaluated. However, based upon the potential for influenza antiviral agents to reduce the effectiveness of FLUENZ, it is recommended not to administer the vaccine until 48 hours after the cessation of influenza antiviral therapy. Administration of influenza antiviral agents within two weeks of vaccination may affect the response of the vaccine.

Because of this information in the SPC, should any child be given these medications the administration of LAIV would be delayed as specified.

Study specific:
• Fever (sublingual temperature ≥ 38°C)
• Received any blood or blood products within the past 12 weeks.

E.5 End points

E.5.1

Primary end point(s)

The measures of immunogenicity, collected for all evaluable subjects include:

Geometric mean titre. Least squares GMTs for HI (H3N2, H1N1, H7N9, B) and MN (H1N1 and H7N9) data associated 95% confidence interval and median, minimal, and maximal titre values for study Days 0 and 21 +/- 7 (pre and post bleed).

Geometric Mean Ratio. Least squares GMRs will be calculated for the HI, MN results (for all viruses) for Day 21/day0

Percentages of Subjects with Seroconversion or Significant Increase in HI and MN Titre. Seroconversions or significant increase (negative titres at D0; <10 and ≥ 40 at D21 or at least 4-fold increase in titre) in HI titres or MN (for all viruses) from pre-immunization to days 21, will be tabulated for both vaccine groups;

Percentages of Subjects achieving each of the following thresholds: HI ≥ 40, MN ≥ 40; MN ≥ 80, four-fold rise in MN titres: The number and proportion of subjects achieving each threshold at study at Days 0, 21will be tabulated for all viruses for both vaccine groups.

E.5.1.1

Timepoint(s) of evaluation of this end point

Blood samples will be collected prior to and at three weeks after each of the three annual vaccinations. The measures described above will be applied at each timepoint.

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

Yes

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

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

E.8.1.1

Randomised

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

E.8.2

Comparator of controlled trial

E.8.2.1

Other medicinal product(s)

E.8.2.2

Placebo

E.8.2.3

Other

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 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