Clinical Trials Register

Summary
EudraCT Number:	2011-006277-25
Sponsor's Protocol Code Number:	V58_32S
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:	2012-03-12
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

2011-006277-25

A.3

Full title of the trial

A Phase III Open Label, Uncontrolled, Multi Center Study to Evaluate Safety and
Immunogenicity of a Surface, Antigen, Inactivated, Influenza Vaccine Produced in
Mammalian Cell Culture (Optaflu®), Formulation 2012/2013, when Administered
to adult and elderly subjects.

A.3.1

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

Seasonal Optaflu trial 2012/13

A.3.2

Name or abbreviated title of the trial where available

Optaflu

A.4.1

Sponsor's protocol code number

V58_32S

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	Novartis Vaccines and Diagnostics GmbH
B.1.3.4	Country	Italy
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	Novartis Vaccines and Diagnostics Srl
B.4.2	Country	Italy
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation	Novartis vaccines and Diagnostics GmbH
B.5.2	Functional name of contact point	Head of Central and Northern Europe
B.5.3	Address:
B.5.3.1	Street Address	Industrie Straße 25
B.5.3.2	Town/ city	Holzkirchen
B.5.3.3	Post code	83607
B.5.3.4	Country	Germany
B.5.4	Telephone number	+49080246465401
B.5.5	Fax number	+49080246465480
B.5.6	E-mail	dietrich.bosse@novartis.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	Optaflu
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Vaccines and Diagnostics GmbH
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	Optaflu
D.3.2	Product code	V58
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.3.9.3	Other descriptive name	INFLUENZA TYPE A
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	15
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	INFLUENZA TYPE A
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
D.3.10.3	Concentration number	15
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.9.3	Other descriptive name	INFLUENZA TYPE B
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	not less then
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.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

no medical condition, healthy volunteers will be recruited into the clincial trial for annual approval of influenza vaccine with the new strain composition according WHO and EMEA recommendation and CHMP critieria (CPMP/BWP/214/96)

E.1.1.1

Medical condition in easily understood language

seasonal vaccination with Optaflu, strains 2012/13 in heathly subjects

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	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

Safety Objectives: To evaluate the safety of a single intramuscular (IM) injection of
Optaflu in adult and elderly subjects in compliance with the requirements of the current
EU recommendations for clinical trials related to yearly licensing of influenza vaccines
(CPMP/BWP/214/96).
Immunogenicity Objectives:
Primary
To evaluate the antibody response to each influenza vaccine antigen, as measured by hemagglutination inhibition (HI) at 21 days post-immunization in adult and elderly
subjects in compliance with the requirements of the current EU recommendations for
clinical trials related to yearly licensing of influenza vaccines.
Antibodies maybe additionally quantified using the Single Radial Hemolysis (SRH) test
for confirmation purposes. (Note for Guidance on Harmonization of Requirements for
Influenza Vaccines. CPMP/BWP/214/96: 12 March 1997).

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males and females volunteers of 18 years of age or older, mentally competent, willing
and able to give written informed consent prior to study entry;
2. Individuals able to comply with all the study requirements;
3. Individuals in good health as determined by the outcome of medical history, physical
examination and clinical judgment of the investigator.

E.4

Principal exclusion criteria

1. Individuals with behavioral or cognitive impairment or psychiatric disease that, in the
opinion of the investigator, may interfere with the subject's ability to participate in the
study.
2. Individuals with any serious chronic or acute disease (in the judgment of the
investigator), including but not limited to:
Medically significant Cancer (except for benign or localized skin cancer, cancer in
remission for ≥10 years or localized prostate cancer that has been clinically stable for
more than 2 years without treatment)
Medically significant advanced congestive heart failure (ie. NYHA class III and IV)
Chronic obstructive pulmonary disease (COPD);
Autoimmune disease (including rheumatoid arthritis, except for Hashimoto's
thyroiditis that has been clinically stable for ≥ 5 years)
Diabetes mellitus type I;
Poorly controlled diabetes mellitus type II;
Advanced arteriosclerotic disease;
History of underlying medical condition such as major congenital abnormalities
requiring surgery, chronic treatment, or associated with developmental delay (e.g.,Down’s syndrome);
Acute or progressive hepatic disease;
Acute or progressive renal disease;
Severe neurological (es. Guillain–Barré syndrome) or psychiatric disorder;
Severe asthma
3. Individuals with history of any anaphylactic reaction and/or serious allergic reaction
following a vaccination, a proven hypersensitivity to any component of the study
vaccine (e.g. influenza viral protein, and exipients);
4. Individuals with known or suspected (or have a high risk of developing)
impairment/alteration of immune function (excluding that normally associated with
advanced age) resulting, for example, from:
receipt of immunosuppressive therapy (any parenteral or oral corticosteroid or cancer
chemotherapy/radiotherapy) within the past 60 days and for the full length of the
study;
receipt of immunostimulants;
receipt of parenteral immunoglobulin preparation, blood products and/or plasma
derivates within the past 3 months and for the full length of the study;
suspected or known HIV infection or HIV-related disease;
5. Individuals with known or suspected history of drug or alcohol abuse
6. Individuals with a bleeding diathesis or conditions associated with prolonged bleeding
time that in the investigator’s opinion would interfere with the safety of the subject
7. Female who are pregnant or nursing (breastfeeding) mothers or females of
childbearing potential do not plan to use acceptable birth control measures, for the
whole duration of the study. Adequate contraception is defined as hormonal (e.g.,
oral, injection, transdermal patch, implant, cervical ring), barrier (e.g., condom with
spermicide or diaphragm with spermicide), intrauterine device (IUD), or
monogamous relationship with vasectomized partner who has been vasectomized for
6 months or more prior to the subject’s study entry
8. Individuals who are not able to comprehend and to follow all required study
procedures for the whole period of the study
9. Individuals with history or any illness that, in the opinion of the investigator, might
interfere with the results of the study or pose additional risk to the subjects due to
participation in the study.
10. Individuals Within the past 6 months, they have:
had any seasonal or pandemic laboratory confirmed influenza disease;
received any seasonal or pandemic influenza vaccine;
11. Individuals with any acute or chronic infections requiring systemic antibiotic
treatment or antiviral therapy within the last 7 days
12. Individuals that have experienced fever (i.e., axillary temperature ≥ 38°C) within the
last 3 days of intended study vaccination
13. Individuals with history of any illness that, in the opinion of the investigator, might
interfere with the results of the study or pose additional risk to the subject due to
participation in the study
14. Individuals participating in any clinical trial with another investigational product 4
weeks prior to first study visit or intent to participate in another clinical study at any
time during the conduct of this study.
15. Individuals who received any other vaccines within 4 weeks prior to enrollment in
this study or who are planning to receive any vaccine within 4 weeks from the study
vaccines
16. Individuals who have ever received blood, blood products and/or plasma derivatives
or any parenteral immunoglobulin preparation in the past 12 weeks and for the full
length of the study.
17. Individuals who are part of study personnel or close family members conducting this
study.
18. BMI > 35 kg/m2.

E.5 End points

E.5.1

Primary end point(s)

Immunogenicity Endpoints
The following serological assessments will be considered for each strain in non-elderly
adult subjects, aged between 18 and 60, and at least one of the assessments should meet
the indicated requirements:
- The proportion of subjects achieving seroconversion or significant increase in HI
titer or SRH area > 40%
- Mean geometric increase > 2.5
- The proportion of subjects achieving an HI titer ≥ 40 or SRH area ≥ 25 mm2
should be > 70%
The following serological assessments will be considered for each strain in elderly
subjects, aged 61 years and over, and at least one of the assessments should meet the
indicated requirements:
- Proportion of seroconversion or significant increase in HI titer or SRH area >
30%
- Mean geometric increase > 2.0
- The proportion of subjects achieving an HI titer ≥ 40 or SRH area ≥ 25 mm2
should be > 60%
Circulating anti-HA antibodies will be measured by HI and possibly SRH assay just
prior to vaccination (Day 1) and approximately 3 weeks after the vaccination (Day 22).
For the purposes of calculation, any HI result < 10 (i.e. undetectable) will be expressed
as 5, and any negative SRH result will be expressed as 4 mm2.
In HI tests, seroconversion or significant increase in antibody titer corresponds to:
 negative pre-vaccination serum / post-vaccination serum titer ≥ 40 or
 at least a four-fold increase in titer from positive pre-vaccination serum
In SRH tests, seroconversion or significant increase in antibody titer corresponds to:
 negative pre-vaccination serum / post-vaccination serum area ≥ 25 mm2
 at least a 50% increase in area from positive pre-vaccination serum

Safety Endpoints
Safety will be assessed in accordance with available safety data on influenza vaccines:
 Local and systemic reactions will be assessed for 3 days post the day of
vaccination
AEs Days 1 to 4. All AEs necessitating a physician’s visit or consultation and/or leading
to premature study discontinuation and all SAEs until Day 22 of until resolution.

E.5.1.1

Timepoint(s) of evaluation of this end point

End of the trial, after LSLV

E.5.2

Secondary end point(s)

Not applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

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

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

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.8.2.4

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

please refer to the protocol

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:

F.1.3

Elderly (>=65 years)

Yes

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

126

F.4.2

For a multinational trial

F.4.2.1

In the EEA

126

F.4.2.2

In the whole clinical trial

126

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)

Since only healthy volunteers will be recruited, no treatment or special care is applicable.

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

2012-06-27

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2012-04-10

P. End of Trial
P.	End of Trial Status	Completed

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