Clinical Trials Register

Summary
EudraCT Number:	2014-004634-26
Sponsor's Protocol Code Number:	4896
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:	2015-04-28
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

2014-004634-26

A.3

Full title of the trial

The Effect of Live Attenuated Influenza Vaccine (LAIV) on Experimental Human Pneumococcal Colonisation (EHPC) Study

A.3.1

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

The Effect of Live Attenuated Influenza Vaccine (LAIV) on Experimental Human Pneumococcal Colonisation (EHPC) Study

A.3.2

Name or abbreviated title of the trial where available

LAIV and EHPC

A.4.1

Sponsor's protocol code number

4896

A.5.1

ISRCTN (International Standard Randomised Controlled Trial) Number

ISRCTN16993271

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	Royal Liverpool University Hospital
B.1.3.4	Country	United Kingdom
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	Bill and Melinda Gates Foundation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Royal Liverpool University Hospital
B.5.2	Functional name of contact point	Angela Wright
B.5.3	Address:
B.5.3.1	Street Address	Prescot Street
B.5.3.2	Town/ city	Liverpool
B.5.3.3	Post code	L7 8XP
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4401517064856
B.5.5	Fax number	+4401517064856
B.5.6	E-mail	adwright@liverpool.ac.uk
B.Sponsor: 2
B.1.1	Name of Sponsor	Liverpool School of Tropical Medicine
B.1.3.4	Country	United Kingdom
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	Bill and Melinda Gates Foundation
B.4.2	Country	United States
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Angela Wright
B.5.2	Functional name of contact point	LSTM
B.5.3	Address:
B.5.3.1	Street Address	Pembroke Place
B.5.3.2	Town/ city	Liverpool
B.5.3.3	Post code	L3 5QA
B.5.3.4	Country	United Kingdom
B.5.4	Telephone number	+4401517064856
B.5.5	Fax number	+4401517064856
B.5.6	E-mail	adwright@liverpool.ac.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 Tetra/ FluMist
D.2.1.1.2	Name of the Marketing Authorisation holder	MedImmune
D.2.1.2	Country which granted the Marketing Authorisation	Netherlands
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	Live Attenuated Influenza Vaccine (LAIV) Fluenz Tetra/ FluMist
D.3.4	Pharmaceutical form	Nasal spray, solution in single-dose container
D.3.4.1	Specific paediatric formulation	Yes
D.3.7	Routes of administration for this IMP	Intranasal use (Noncurrent)
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	Fluarix Tetra
D.2.1.1.2	Name of the Marketing Authorisation holder	SmithKline Beecham Limited
D.2.1.2	Country which granted the Marketing Authorisation	United Kingdom
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 Inactivated Influenza Vaccine (QIV) 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.3.11 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	Nasal spray, solution in single-dose container
D.8.4	Route of administration of the placebo	Intranasal use (Noncurrent)
D.8 Placebo: 2
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	Intramuscular use

E. General Information on the Trial

E.1 Medical condition or disease under investigation

E.1.1

Medical condition(s) being investigated

Pneumococcal colonisation post inoculation

E.1.1.1

Medical condition in easily understood language

Pneumococcal bacteria detected in nasal wash samples post inoculation with live bacteria

E.1.1.2

Therapeutic area

Body processes [G] - Microbiological Phenomena [G06]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.1
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

We will define the effect of LAIV on pneumococcal colonisation using the EHPC model in order to assess the potential effects of mass influenza vaccination. We will measure colonisation acquisition, density and duration.

E.2.2

Secondary objectives of the trial

To evaluate changes in commensal and potential pathogenic species in nasopharyngeal microbiome associated with influenza vaccination.
To evaluate inflammatory responses at the nasal mucosa using mucosal nanosampling method (lining fluid and cells).
To evaluate cellular responses in the lung after LAIV and EHPC co-infection.
To evaluate symptoms associated with influenza vaccination and EHPC.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

have capacity to give informed consent
aged 18-50 yrs - ages chosen to minimise the risk of pneumococcal infection
speak fluent English- to ensure a comprehensive understanding of the research project and their proposed involvement, in order to minimise any communication issues to maximise participant safety.

E.4

Principal exclusion criteria

Not currently involved in another study unless observational or in follow-up phase (non-interventional)
Not received any influenza vaccine over the last 2 years
No egg allergy (as per influenza vaccines patient leaflet)
No previous significant adverse reaction to any vaccination/immunisation
No close contact with at risk individuals (children under 5years, immunosuppressed adults, elderly, chronic ill health) – to minimise risk of pneumococcal transmission and transmission of virus for those receiving the LAIV
Not current regular smoker (smokes daily)
No significant smoking history [defined as someone who has previously smoked more than 20 cigarettes per day for 10 years or the equivalent (>10 pack yrs)] – to minimise risk of bronchoscopy or pneumococcal disease
No asthma (on regular medication) or respiratory disease – to minimise risk of bronchoscopy or pneumococcal disease
Not pregnant - to minimise the risk of pneumococcal disease
Women of child-bearing potential (WOCBP) who are not deemed to have sufficient, effective birth control in place for 1 month prior to vaccination and 1 month after the final vaccination
No allergic to penicillin/amoxicillin/gentamicin
Not taking medication that may affect the immune system in any way e.g. steroids, steroid nasal spray
Not regularly taking acetylsalicylic acid (aspirin) - as per LAIV guidance to reduce the risk of Reye’s syndrome
Not been involved in a clinical trial involving experimental human pneumococcal carriage in the last 3 years
Unable to give fully informed consent
No current acute severe febrile illness - to avoid vaccination and inoculation in participants that may have current infection
Not taking long term antibiotics eg. following splenectomy or sickle cell disease
Not been clinically diagnosed with flu in the last 2 years

E.5 End points

E.5.1

Primary end point(s)

Pneumococcal bacteria (6B) detected in nasal wash post inoculation at any point post inoculation

E.5.1.1

Timepoint(s) of evaluation of this end point

Study 1: Pneumococcal bacteria detected post inoculation day 2,7,9,14,22,29
Study 2: Pneumococcal bacteria detected post inoculation day 2,6,9,14,21,27
Experimental colonisation is defined as pneumococcal bacteria (6B) detected at ANY TIMEPOINT post inoculation

E.5.2

Secondary end point(s)

Pneumococcal density and duration post inoculation

E.5.2.1

Timepoint(s) of evaluation of this end point

Study 1: Pneumococcal bacteria detected post inoculation day 2,7,9,14,22,29
Study 2: Pneumococcal bacteria detected post inoculation day 2,6,9,14,21,27

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

Yes

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

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

Yes

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

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)

Yes

F.1.2.1

Number of subjects for this age range:

314

F.1.3

Elderly (>=65 years)

F.1.3.1

Number of subjects for this age range:

F.2 Gender

F.2.1

Female

Yes

F.2.2

Male

Yes

F.3 Group of trial subjects

F.3.1

Healthy volunteers

Yes

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

Yes

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

314

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

314

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

G. Investigator Networks to be involved in the Trial
G.4 Investigator Network to be involved in the Trial: 1
G.4.1	Name of Organisation	Local Comprehensive Research Network North West Coast
G.4.3.4	Network Country	United Kingdom

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2015-05-20

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-12-18

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2017-04-30

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