Clinical Trials Register

Summary
EudraCT Number:	2013-001094-25
Sponsor's Protocol Code Number:	200188
National Competent Authority:	Germany - PEI
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-04-26
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

Germany - PEI

A.2

EudraCT number

2013-001094-25

A.3

Full title of the trial

A Phase III, open-label, non-randomised, multi-centre, single dose study to assess the immunogenicity and safety of GSK Biologicals' Quadrivalent Split Virion Influenza Vaccine (GSK2321138A) Influsplit Tetra (Fluarix Tetra) (2013/2014 season) injected intramuscularly in adults (18 to 60 years) and in the elderly (over 60 years)

A.3.1

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

Immunogenicity and safety study of GSK Biologicals' Quadrivalent Split Virion Influenza Vaccine (GSK2321138A) Influsplit Tetra (Fluarix Tetra) (2013/2014 season) in adults 18 years of age and older.

A.3.2

Name or abbreviated title of the trial where available

FLU D-QIV-011

A.4.1

Sponsor's protocol code number

200188

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	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.5.6	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	GlaxoSmithKline BIiologicals s.a.
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.3.4	Pharmaceutical form	Suspension for injection in pre-filled syringe
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	ANTIGENS OF THE INFLUENZA VIRUS B/MASSACHUSETTS/02/2012-LIKE VIRUS
D.3.9.3	Other descriptive name	ANTIGENS OF THE INFLUENZA VIRUS B/MASSACHUSETTS/02/2012-LIKE VIRUS
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 B/BRISBANE/60/2008-LIKE VIRUS
D.3.9.3	Other descriptive name	ANTIGENS OF THE INFLUENZA VIRUS B/BRISBANE/60/2008-LIKE VIRUS
D.3.9.4	EV Substance Code	SUB75745
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.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

Immunization of healthy adults against influenza

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	LLT
E.1.2	Classification code	10059430
E.1.2	Term	Influenza immunization
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

To evaluate the humoral response [(anti- Haemagglutinin (HA) antibodies tested by Haemagglutination Inhibition (HI)] against each vaccine strain in adults 18-60 years and >60 years of age, 21 days after vaccination with Fluarix/Influsplit Tetra 2013/2014.

E.2.2

Secondary objectives of the trial

1) To describe the reactogenicity and safety of Fluarix/Influsplit Tetra 2013/2014 in adults 18-60 years and >60 years of age, in terms of solicited adverse events (AEs), unsolicited AEs, and serious adverse events (SAEs).

2) To evaluate the humoral response (anti-HA antibodies tested by HI) against each vaccine strain, 21 days after vaccination, in adults 18-60 years and >60 years of age who have and who have not received an influenza vaccine during the 2 influenza seasons prior to season 2012/2013.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

• Subjects who the investigator believes can and will comply with the
requirements of the protocol
• A male or female aged 18 years or above at the time of vaccination.
• Written informed consent obtained from the subject.
• Healthy subjects or subjects with well-controlled chronic diseases as
established by medical history and clinical examination before entering
the study.
• Female subjects of non-childbearing potential may be enrolled in the
study
- Non-childbearing potential is defined as pre-menarche, current tubal
ligation, hysterectomy, ovariectomy or post-menopause
• Female subjects of childbearing potential may be enrolled in the study,
if the subject:
- has practiced adequate contraception for 30 days prior to vaccination,
and
- has a negative pregnancy test on the day of vaccination, and
- has agreed to continue adequate contraception during the entire
treatment period and for 2 months after completion of vaccination

E.4

Principal exclusion criteria

• Participation in previous year's Fluarix registration study (116663)
• Use of any investigational or non-registered product (drug or vaccine)
other than the study vaccine within 30 days preceding the dose of study
vaccine, or planned use during the study period.
• Chronic administration of immunosuppressants or other immunemodifying
drugs within the six months prior to vaccination. Inhaled and
topical steroids are allowed.
• Any administration of a long-acting immune-modifying drug within 6
months before study start, or planned administration during the study
period.
• Administration of immunoglobulins and/or any blood products within
the three months preceding the administration of the study vaccine or
planned administration during the study period.
• Administration of an influenza vaccine within the twelve months
preceding the study vaccination.
• Receipt of a vaccine other than the study vaccine within 30 days before
study vaccination and/or plan to receive any vaccine other than the
study vaccine during the entire study period.
• Clinically or virologically confirmed influenza infection within the six
months preceding the study vaccination.
• Acute disease and/or fever at the time of enrolment.
- Fever is defined as temperature ≥ 37.5°C/99.5°F on oral, axillary or
tympanic setting, or ≥ 38.0°C/100.4°F on rectal setting. The preferred
route for recording temperature in this study will be axillary.
- Subjects with a minor illness (such as mild diarrhoea, mild upper
respiratory infection) without fever may be enrolled at the discretion of
the investigator.
• Acute, clinically significant pulmonary, cardiovascular, hepatic or renal
functional abnormality, as determined by physical examination or
laboratory screening tests.
• Chronic underlying disease (such as cancer, chronic obstructive
pulmonary disease under oxygen therapy, insulin-dependent diabetes
mellitus), not stabilized or clinically serious.
• History of chronic alcohol consumption and/or drug abuse.
• Any confirmed or suspected immunosuppressive or immunodeficient
condition, based on medical history and physical examination (no
laboratory testing required).
• History of Guillain-Barré syndrome.
• History of allergic disease or reactions likely to be exacerbated by any
component of the vaccine including latex.
• Anaphylaxis following the administration of vaccine(s).
• Pregnant or lactating female.
• Female planning to become pregnant or planning to discontinue
contraceptive precautions.
• Any condition which, in the opinion of the investigator, prevents the
subject from participating in the study or would make intramuscular
injection unsafe.

E.5 End points

E.5.1

Primary end point(s)

Humoral immune response in terms of anti-HA antibodies against each of the four vaccine influenza strains.

The following parameters will be calculated with 95% confidence
intervals (CIs):
- Geometric mean titres (GMT) of anti-HA antibody titres
- Seroprotection rates (SPR)*

*SPR is defined as the percentage of vaccinees with serum HI titre ≥
1:40; usually accepted as indicating protection in at least 50% of the
vaccinees.

The following parameters will be calculated with 95% confidence
intervals (CIs):
- Seroconversion rates (SCR)*
- Mean geometric increase ([MGI] also known as the Seroconversion
factor [SCF])**
- Seroprotection power (SPP)***

*SCR is defined as the percentage of vaccinees with either a pre-vaccination
titre < 1:10 and a post-vaccination titre ≥ 1:40 or a pre-vaccination
titre ≥ 1:10 and at least 4-fold increase in post-vaccination
titre.
**MGI or SCF is defined as the fold increase in serum HI geometric mean
titres post-vaccination compared to Day 0.
***SPP is defined as the percentage of subjects who have a pre-vaccination
titre < 1:40 and a post-vaccination titre ≥ 1:40

E.5.1.1

Timepoint(s) of evaluation of this end point

At Day 0 and Day 21 post-vaccination for Geometric Mean Titres and
Seroprotection Rates.

At Day 21 post-vaccination for Seroconversion Rates, Mean Geometric
Increases (Seroconversion Factors), and Seroprotection Powers.

E.5.2

Secondary end point(s)

1) Reactogenicity:
• Occurrence of solicited local and general symptoms
- Percentage, intensity and duration of solicited local symptoms
- Percentage, intensity, duration and relationship to vaccination of
solicited general symptoms
• Occurrence of unsolicited symptoms
- Percentage, intensity and relationship to vaccination of unsolicited
symptoms
• Occurrence of serious adverse events (SAEs)
- Percentage, intensity and relationship to vaccination of SAEs

2) Humoral immune response in terms of anti-HA antibodies against
each of the four vaccine influenza strains, in subjects aged 18-60 years
and >60 years who have and who have not received an influenza vaccine
during the 2 influenza seasons prior to season 2012/2013.

• The following parameters will be calculated with 95% CIs:
- GMTs of anti-HA antibody titres and SPRs, in subjects who have
and who have not received an influenza vaccine during the 2 influenza
seasons prior to season 2012/2013.

E.5.2.1

Timepoint(s) of evaluation of this end point

• Solicited local and general symptoms: During a 4-day follow-up period
after vaccination (Days 0-3) (i.e. day of vaccination and 3 subsequent
days).
• Unsolicited symptoms: During a 21-day follow-up period after
vaccination (Days 0-20) (i.e. day of vaccination and 20 subsequent days.
• Serious adverse events: During the entire study period (Day 0-Day 21)

• Humoral immune response in subjects who have and who have not
received an influenza vaccine during the 2 influenza seasons prior to
season 2012/2013: At Day 0 and Day 21 post-vaccination

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

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenicity

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

E.8.1.1

Randomised

E.8.1.2

Open