Clinical Trials Register

Summary
EudraCT Number:	2006-005558-63
Sponsor's Protocol Code Number:	V70P3
National Competent Authority:	Italy - Italian Medicines Agency
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2016-03-24
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

Italy - Italian Medicines Agency

A.2

EudraCT number

2006-005558-63

A.3

Full title of the trial

A phase III, randomized, controlled, observer-blind, single-center study to compare immunogenicity and safety of an MF59-adjuvanted inactivated subunit influenza vaccine (FLUAD™) to those of a nonadjuvanted inactivated subunit influenza vaccine, when administered to adults affected by chronic diseases

A.3.1

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

A.4.1

Sponsor's protocol code number

V70P3

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 S.r.l.
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 S.r.l.
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 S.r.l.
B.5.2	Functional name of contact point	Adele Longanella
B.5.3	Address:
B.5.3.1	Street Address	Via Fiorentina, 1
B.5.3.2	Town/ city	Siena
B.5.3.3	Post code	53100
B.5.3.4	Country	Italy
B.5.6	E-mail	adele.longanella@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	FLUAD
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Vaccines and Diagnostics S.r.l.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	FLUAD
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	A/ (H1N1)-LIKE VIRUS ANTIGEN
D.3.9.3	Other descriptive name	A/ (H1N1)-LIKE VIRUS ANTIGEN
D.3.9.4	EV Substance Code	SUB117552
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.3.8	INN - Proposed INN	A/ (H3N2)-LIKE VIRUS ANTIGEN
D.3.9.3	Other descriptive name	A/ (H3N2)-LIKE VIRUS ANTIGEN
D.3.9.4	EV Substance Code	SUB117553
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.3.8	INN - Proposed INN	B/ -LIKE VIRUS ANTIGEN
D.3.9.3	Other descriptive name	B/ -LIKE VIRUS ANTIGEN
D.3.9.4	EV Substance Code	SUB117554
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.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	Agrippal
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Vaccines and Diagnostics S.r.l.
D.2.1.2	Country which granted the Marketing Authorisation	Italy
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	Agrippal
D.3.4	Pharmaceutical form	Solution 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	A/ (H1N1)-LIKE VIRUS ANTIGEN
D.3.9.3	Other descriptive name	A/ (H1N1)-LIKE VIRUS ANTIGEN
D.3.9.4	EV Substance Code	SUB117552
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.3.8	INN - Proposed INN	A/ (H3N2)-LIKE VIRUS ANTIGEN
D.3.9.3	Other descriptive name	A/ (H3N2)-LIKE VIRUS ANTIGEN
D.3.9.4	EV Substance Code	SUB117553
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.3.8	INN - Proposed INN	B/ -LIKE VIRUS ANTIGEN
D.3.9.3	Other descriptive name	B/ -LIKE VIRUS ANTIGEN
D.3.9.4	EV Substance Code	SUB117554
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

Influenza

E.1.1.1

Medical condition in easily understood language

Influenza

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	18.1
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

Immunogenicity Objective
To compare the immunogenicity of a single intramuscular (IM) injection of FLUAD™ (FLUAD) vs. inactivated subunit virus influenza vaccine, with regards to A/H3N2 antigen, when administered to adult subjects with underlying chronic disease(s), as measured by Hemagglutination Inhibition (HI) test at day 22.
Safety Objective
To evaluate the safety of a single IM injection of the two influenza vaccines, when administered to adult subjects with underlying chronic disease(s).

E.2.2

Secondary objectives of the trial

• To compare the immunogenicity of a single IM injection of FLUAD vs. inactivated subunit virus influenza vaccine, with regards to B antigen, when administered to adult subjects with underlying chronic disease(s), as measured by HI test at day 22.
• To evaluate the immunogenicity of a single IM injection of FLUAD vs. inactivated subunit virus influenza vaccine, with regards to A/H1N1 antigen, when administered to adult subjects with underlying chronic disease(s), as measured by HI test at day 22.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. 18 to 60 years of age adult volunteers, mentally competent, willing and able to give written informed consent prior to study entry;
2. able to comply with all the study requirements;
3. suffering from at least one of these chronic diseases:
• moderate to severe hypertension
• moderate to severe congestive heart failure
• COPD or moderate to severe asthma
• moderate to severe hepatic or renal insufficiency
• arteriosclerotic disease or insulin dependent diabetes mellitus

E.4

Principal exclusion criteria

1. hypersensitivity to ovalbumin, chicken protein, chicken feathers, influenza viral protein, neomycin or polymyxin or any other component of the vaccine;
2. history of neurological symptoms or signs, or anaphylactic shock following administration of any vaccine;
3. 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 cortical steroid or cancer chemotherapy/radiotherapy) within 60 days prior to enrollment and for the full length of the study;
• receipt of immunostimulants;
• receipt of parenteral immunoglobulin preparation, blood products and/or plasma derivates within 3 months prior to enrollment and for the full length of the study;
• suspected or known HIV infection or HIV-related disease;
4. known or suspected history of drug or alcohol abuse;
5. women who were pregnant, or women able to bear children but not willing to practice acceptable contraception for the first 3 weeks of the duration of the trial;
6. within the 12 months prior to enrollment, the individual had:
• received more than one injection of influenza vaccine;
7. within the 6 months prior to enrollment, the individual had:
• laboratory confirmed influenza disease;
• received influenza vaccine;
8. within the 4 weeks prior to enrollment the individual had received:
• another vaccine;
• any investigational agent;
9. within the 7 days prior to enrollment, the individual had experienced:
• any acute disease;
• infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis was acceptable);
10. had experienced an acute exacerbation of a COPD within the 14 days prior to enrollment;
11. within the 3 days prior to enrollment, individuals had experienced:
• fever (i.e., body temperature ≥ 38°C);
12. were taking part in another clinical study;
13. had any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objective.

E.5 End points

E.5.1

Primary end point(s)

Immunogenicity
The immunogenicity of the two vaccines was evaluated considering the following measurements according to the CPMP/BWP/214/96 guideline:
• percentage of seroconversions or significant increase (seroconversion rate) in HI antibody titer
• mean geometric increase (i.e., GMR) in HI antibody and ratio of postvaccination GMTs between vaccines
• percentage of subjects achieving an HI titer ≥40 (seroprotection)
Safety
Number of subjects with reported local and systemic reactions as well as the number of subjects with reported SAEs and/or AEs per vaccination group.
Local reactions included: ecchymosis, erythema, induration, swelling, and pain at injection site.
Systemic reactions included: chills, malaise, myalgia, arthralgia, headache, sweating, fatigue and fever (derived from axillary temperature ≥38°C).

E.5.1.1

Timepoint(s) of evaluation of this end point

• Immunogenicity 21 days after vaccination
• AEs will be assessed for 6 days post the day of vaccination
• All adverse events (AEs) necessitating a physician’s visit or consultation and/or leading to premature study discontinuation will be collected for 3 weeks following vaccination.
• All serious adverse events (SAEs) will be collected during a 6 months follow-up, i.e., until day 181 (window: day 177- day 185).

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

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

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)

Yes

E.7.3

Therapeutic confirmatory (Phase III)

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

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

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

Last Subject Last Visit

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

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:

330

F.1.3

Elderly (>=65 years)

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

330

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

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

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2006-11-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2006-11-23

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

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