Clinical Trials Register

Summary
EudraCT Number:	2014-004757-14
Sponsor's Protocol Code Number:	V71P5
Clinical Trial Type:	Outside EU/EEA
Date on which this record was first entered in the EudraCT database:	2014-11-07
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
H.4 THIRD COUNTRY IN WHICH THE TRIAL WAS FIRST AUTHORISED

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A. Protocol Information

A.2

EudraCT number

2014-004757-14

A.3

Full title of the trial

A Phase III Observer-Blind, Randomized, Controlled, Multicenter Study to Evaluate Safety, Tolerability, and Immunogenicity of Two Trivalent Subunit Inactivated Influenza Vaccines (Agrippal® and Fluvirin®) in Healthy Children Aged 3 to 8 years, in Healthy Children/Adolescents Aged 9 to 17 Years And in Healthy Adults Aged 18 to 64 Years

A.3.1

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

Safety, and Immunogenicity of Two Influenza Vaccines in Healthy Subjects 3 to 64 Years Old

A.4.1

Sponsor's protocol code number

V71P5

A.5.2

US NCT (ClinicalTrials.gov registry) number

NCT00464672

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
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
B.5.2	Functional name of contact point	Posting Director
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	RegistryContactVaccinesUS@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	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	Suspension for injection
D.3.4.1	Specific paediatric formulation	Information not present in EudraCT
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/NEW CALEDONIA/20/99 (H1N1)
D.3.9.3	Other descriptive name	A/NEW CALEDONIA/20/99 (H1N1) - LIKE STRAIN
D.3.9.4	EV Substance Code	SUB22984
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
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/CALIFORNIA/7/2004 (H3N2)
D.3.9.3	Other descriptive name	A/CALIFORNIA/7/2004 (H3N2) - LIKE STRAIN
D.3.9.4	EV Substance Code	SUB22985
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
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/SHANGHAI/361/2002
D.3.9.3	Other descriptive name	B/SHANGHAI/361/2002 - LIKE STRAIN
D.3.9.4	EV Substance Code	SUB22986
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
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	Yes
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	Fluvirin
D.2.1.1.2	Name of the Marketing Authorisation holder	Novartis Vaccines and Diagnostics
D.2.1.2	Country which granted the Marketing Authorisation	United States
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	Fluvirin
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.3.8	INN - Proposed INN	A/NEW CALEDONIA/20/99 (H1N1)
D.3.9.3	Other descriptive name	A/NEW CALEDONIA/20/99 (H1N1) - LIKE STRAIN
D.3.9.4	EV Substance Code	SUB22984
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
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/CALIFORNIA/7/2004 (H3N2)
D.3.9.3	Other descriptive name	A/CALIFORNIA/7/2004 (H3N2) - LIKE STRAIN
D.3.9.4	EV Substance Code	SUB22985
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
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/SHANGHAI/361/2002
D.3.9.3	Other descriptive name	B/SHANGHAI/361/2002 - LIKE STRAIN
D.3.9.4	EV Substance Code	SUB22986
D.3.10	Strength
D.3.10.1	Concentration unit	µg microgram(s)
D.3.10.2	Concentration type	equal
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.1.3

Condition being studied is a rare disease

E.2 Objective of the trial

E.2.1

Main objective of the trial

To evaluate immunogenicity, measured by seroprotection (defined as percentage of subjects achieving a hemagglutination inhibition [HI] titer (> or = 40) and by percentage of subjects achieving seroconversion (defined as negative pre-vaccination serum (<10)/
post-vaccination serum (> or = 40) or significant increase (defined as at least a fourfold increase in titer from non-negative pre-vaccination serum (> or = 10), of
one dose of Agrippal influenza vaccine, administered to healthy adults aged 18 to 64
years according to the CBER Guidance for Industry issued in May 2007.

To evaluate safety and tolerability of:
1. Two doses of either Agrippal or Fluvirin, administered four weeks apart to healthy children aged 3 to 8 years
2. one dose of either Agrippal or Fluvirin, administered to children/adolescents aged 9 to 17 years and adults aged 18 to 64 years.

E.2.2

Secondary objectives of the trial

To descriptively evaluate immunogenicity of:

One dose of Fluvirin® influenza vaccine, administered to healthy adults aged 18 to 64 years.
One dose of either Agrippal® or Fluvirin® influenza vaccine, administered to healthy children/adolescents aged 9 to 17 years.
Two doses of either Agrippal® or Fluvirin®influenza vaccine, administered four weeks apart to healthy children aged 3 to 8 years.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Subjects aged 3 to 8 years (age group 1), whose parents or legal guardians have given written informed consent prior to study entry

2. Subjects aged 9 to 17 years (age group 2) and 18 to 64 years (age group 3), able and willing to provide written informed consent prior to study entry

3. Available for all the visits and telephone call scheduled in the study

4. In good health as determined by:
a. medical history,
b. physical examination,
c. clinical judgment of the Investigator.

E.4

Principal exclusion criteria

1. Receipt of another investigational agent within 90 days, or before completion of the safety follow-up period in another study, whichever is longer, prior to enrollment and unwilling to refuse participation in another clinical study through the end of the present study

2. Any disease or infection, both requiring systemic antibiotic or antiviral therapy, within 30 days prior to Visit 1

3. Fever (defined as axillary temperature 􀂕38.0°C) within 7 days prior to Visit 1

4. Pregnant or nursing mothers or females of childbearing potential who do not plan to use acceptable birth control measures during the three weeks following vaccination. Oral, injected, inserted or implanted hormonal contraceptive, diaphragm or condom with spermicidal agent or intrauterine device are considered acceptable forms of birth control

5. Any serious disease, such as:
a. cancer,
b. autoimmune disease (including rheumatoid arthritis),
c. diabetes mellitus,
d. chronic pulmonary disease,
e. acute or progressive hepatic disease,
f. acute or progressive renal disease

6. Surgery planned during the study period

7. Bleeding diathesis

8. History of hypersensitivity to any component of the study vaccine or chemically related substances

9. History of any anaphylaxis, serious vaccine reactions, or allergy to eggs, egg products, or any other vaccine component

10. Known or suspected impairment/alteration of immune function, for example, resulting from
a. receipt of immunosuppressive therapy (any corticosteroid therapy or cancer
chemotherapy),
b. receipt of immunostimulants,
c. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma
derivatives within 3 months prior to Visit 1 or planned during the full length of the
study,
d. high risk for developing an immunocompromising disease

11. Laboratory confirmed influenza disease within 6 months prior to Visit 1

12. Having ever received an influenza vaccine (for subjects aged 3 to 8 years only)

13. Receipt of another vaccine within 30 days prior to Visit 1 or planned vaccination within 3 weeks following the last study vaccination

14. Any condition which, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.

E.5 End points

E.5.1

Primary end point(s)

1. Percentage of subjects achieving seroconversion1 or significant increase2 in antibody titer at Day 22 for age group 3;

2. Percentage of subjects with at least a 4-fold increase in HI titer at Day 22 for age group 3

3. Percentage of subjects achieving a titer 􀂕40 (seroprotection) at Day 1 and at Day 22 for age group 3;

4. All local and systemic reactions and any adverse events occurring within 7 days after each vaccination.

5. All AEs will be collected from day 1 to day 49 for age group 1;

6. All AEs will be collected from day 1 to day 21 for age group 2 & 3;

*Age group 1 = 3 to 8 years;
*Age group 2 = 9 to 17 years;
*Age group 3 = 18 to 64 years;

E.5.1.1

Timepoint(s) of evaluation of this end point

1.Day 22;

2.Day 22;

3.Day 1 and at Day 22;

4. Days 1 to 7 after each vaccination;

5.Day 1 to day 49;

6.Day 1 to day 21;

E.5.2

Secondary end point(s)

1. Geometric Mean Titers (GMTs) are evaluated at day 1, day 29 and day 50 for age group 1;

2. GMRs for each antigen and vaccine group calcluated against Day 29/Day 1, Day 50/Day 29 and Day 50/Day 1 for age group 1;

3. Percentages of Subjects Achieving Seroconversion at day 29 & day 50 for age group 1;

4. Percentages of Subjects Achieving at least a 4-fold increase at day 29 & day 50 for age group 1;

5. Percentages of Subjects Achieving Seroprotection at day 1, day22 and day 50; for age group 1;

6. Geometri mean titers at day 1 and day 22 for age group 2 and 3;

7. Geometric Mean ratios at day 22/ day 1 for age group 2 & 3;

8. Percentage of subjects achieving seroconversion1 or significant increase in antibody titer at Day 22 for age group 2;

9. Percentage of subjects with at least a 4-fold increase in HI titer at Day 22 for age group 2;

10. Percentage of subjects achieving a titer > or = 40 (seroprotection) at Day 1 and at Day 22 for age group 2;

*Age group 1 = 3 to 8 years;
*Age group 2 = 9 to 17 years;
*Age group 3 = 18 to 64 years;

E.5.2.1

Timepoint(s) of evaluation of this end point

1.Day 1, day 29 and day 50;

2.Day 29/Day 1, Day 50/Day 29 and Day 50/Day 1;

3.Day 29 & day 50;

4.Day 29 & day 50;

5.Day 1, day22 and day 50;

6.Day 1 and day 22;

7. Day 22/ day 1;

8.Day 22;

9.Day 22;

10.Day 1 and at Day 22;

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

Yes

E.6.13.1

Other scope of the trial description

Immunogenecity

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

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

Will this trial be conducted at a single site globally?

E.8.4

Will this trial be conducted at multiple sites globally?

Yes

E.8.6 Trial involving sites outside the EEA

E.8.6.2

Trial being conducted completely outside of the EEA

Yes

E.8.6.3

Specify the countries outside of the EEA in which trial sites are planned

Argentina

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.8.9.2

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

Number of subjects for this age range:

1200

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)

Yes

F.1.1.5.1

Number of subjects for this age range:

600

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

600

F.1.2

Adults (18-64 years)

Yes

F.1.2.1

Number of subjects for this age range:

600

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

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

Yes

F.3.3.6.1

Details of subjects incapable of giving consent

Subjects aged 3 to 8 years (age group 1), whose parents or legal guardians have given written informed consent prior to study entry;

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.2

For a multinational trial

F.4.2.2

In the whole clinical trial

1800

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)

Not applicable

G. Investigator Networks to be involved in the Trial

H.4 Third Country in which the Trial was first authorised
H.4.1	Third Country in which the trial was first authorised:	Argentina

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