Clinical Trials Register

Summary
EudraCT Number:	2009-012385-31
Sponsor's Protocol Code Number:	V87_17
National Competent Authority:	Poland - Office for Medicinal Products
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2009-07-09
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

Poland - Office for Medicinal Products

A.2

EudraCT number

2009-012385-31

A.3

Full title of the trial

A Phase II, Randomized, Controlled, Double-blind, Multi-center, Study to Evaluate Safety and Immunogenicity of Two Doses, Administered Three Weeks Apart, of Two Monovalent H5N1 (Surface Antigen Adjuvanted with MF59C.1) Influenza Vaccines Containing 3.75 mcg or 7.5 mcg of H5N1 Influenza Antigen, in Non-elderly Adult and Elderly Subjects

A.3.2

Name or abbreviated title of the trial where available

Dose reduction

A.4.1

Sponsor's protocol code number

V87_17

A.7

Trial is part of a Paediatric Investigation Plan

Information not present in EudraCT

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
B.4.2	Country
B.5 Contact point designated by the sponsor for further information on the trial
B.5.1	Name of organisation
B.5.2	Functional name of contact point

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	FOCETRIA
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	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	Focetria
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.3.9.3	Other descriptive name	A/Vietnam/1194/2004 (H5N1) - like strain (A/Vietnam/1194/2004 NIBRG-14)
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	7.5 mcg per dose
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)	Information not present in EudraCT
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	Information not present in EudraCT
D.3.11.3.4	Combination ATIMP (i.e. one involving a medical device)	Information not present in EudraCT
D.3.11.3.5	Committee on Advanced therapies (CAT) has issued a classification for this product	Information not present in EudraCT
D.3.11.4	Combination product that includes a device, but does not involve an Advanced Therapy	Information not present in EudraCT
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	Information not present in EudraCT
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

Avian influenza

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

Primary
To demonstrate the non-inferiority of antibody responses of two 0.5 mL intramuscular (IM) injections administered 3 weeks apart of a monovalent MF59-adjuvanted H5N1 pandemic vaccine containing 3.75µg H5N1 antigen dose to a pandemic vaccine containing a 7.5µg H5N1antigen dose in terms of post-immunization geometric mean titers (GMT)
Co-Primary
Once non-inferiority has been shown as determined by SRH, subsequently non-inferiority will be assessed as determined by HI test in a stepwise procedure, thus non-inferiority can be concluded if either non-inferiority can be shown for SRH only or if it can be shown for both SRH and HI

E.2.2

Secondary objectives of the trial

A. To evaluate the immunogenicity of two 0.5 mL intramuscular (IM) injections of a monovalent MF59-adjuvanted H5N1 pandemic vaccine containing 3.75µg H5N1 antigen dose and a pandemic vaccine containing a 7.5µg H5N1antigen dose according to CHMP criteria in terms of seroprotection, seroconversion and geometric mean ratio (CPMP/BWP/214/96) as determined by single radial hemolysis (SRH) in non-elderly adult and elderly subjects separately, for all post-vaccination blood sampling days
B. To evaluate the immunogenicity according to CHMP criteria in terms of seroprotection, seroconversion and geometric mean ratio (CPMP/BWP/214/96) as determined by hemagglutination inhibition (HI)
C. To evaluate the immunogenicity according to CBER criteria in terms of hemagglutination inhibition (HI) and microneutralization (MN) test
D. To evaluate the immunogenicity as measured by microneutralization (MN) test

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

1. Males and females 18 yrs of age and above on the day of enrollment.
2. Individuals in good health as determined by medical history, physical examination and clinical judgment of the investigator
3. Documented consent obtained after the nature of the study has been explained according to local regulatory requirements
4. Individuals are able to comply with all study procedures and are available for all clinic visits scheduled in the study

E.4

Principal exclusion criteria

1. Individuals who are not able to comprehend and to follow all required study procedures for the whole period of the study or who do not consent to the retention of the subject’s serum samples after study completion.
2. Individuals who have had influenza vaccine or documented suspected influenza disease within the past 6 months.
3. Individuals Experienced any acute disease or infection requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) within the past 6 days;
4. 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
5. 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
6. History of any anaphylaxis, serious vaccine reactions, or hypersensitivity to influenza viral proteins, to any excipients, and to eggs (including ovalbumin), chicken protein.
7. History of any serious disease, such as:
a. cancer
b. history of serious chronic diseases (cardiac, renal, hepatic, metabolic (including diabetes mellitus), rheumatologic (including autoimmune disease such as rheumatoid arthritis), neurologic (including history of atypical febrile seizure or history of Guillain-Barré disease), and hematologic (including bleeding diathesis))
c. history of underlying medical condition such as major congenital abnormalities requiring surgery, chronic treatment, or associated with developmental delay (e.g., Down’s syndrome)
8. Known or suspected impairment/alteration of immune function, including:
a. Chronic use of oral steroids or any use of parenteral steroids within 60 days prior to Visit 1 (use of inhaled, intranasal, or topical corticosteroids is allowed).
b. receipt of immunostimulants within 60 days prior to Visit 1
c. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to Visit 1 or planned during the full length of the study
d. HIV infection or HIV-related disease
e. Heritable immunodeficiency
f. Abnormalities of splenic or thymic function
9. Pregnant or breast-feeding female
10. Any positive or indeterminate pregnancy test
11. If female, of childbearing potential, and has not used any of the “acceptable contraceptive methods” for at least 2 months prior to study entry
a. Of childbearing potential is defined as status post onset of menarche and not surgically sterile
b. Acceptable birth control methods are defined as one or more of the following:
i. Hormonal contraceptive (such as oral, injection, transdermal patch, implant, cervical ring)
ii. Barrier (condom with spermicide or diaphragm with spermicide) each and every time during intercourse
iii. Intrauterine device (IUD)
iv. Monogamous relationship with vasectomized partner. Partner must have been vasectomized for at least six months prior to the subject’s study entry
12. If female of childbearing potential, refusal to use an “acceptable contraceptive method” during the study including day 43.
13. If female of childbearing potential, refusal to submit for pregnancy testing prior to study vaccination
14. Laboratory-confirmed or suspected influenza disease within 6 months prior to Visit 1. “Laboratory-confirmed” includes:
a. Positive serology result
b. Positive viral culture
c. Positive rapid antigen test
d. “Suspected” influenza disease includes: subjects with influenza-like illness within the past 6 months with a household/intimate contact with “laboratory-confirmed” influenza disease
15. Receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to enrollment in this study
16. Experienced a fever (≥37.9°C Axillary or ≥38.1°C Sublingual) and/or any acute illness within 3 days prior to each study vaccination.
17. Use of antipyretic/analgesic medication within 24 hours of each study vaccination
18. Receipt of another investigational agent within 30 days prior to enrollment in the study 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 study
19. Research staff directly involved with the clinical study or family members or household members of research staff. Research staff are individuals with direct or indirect contact with study subjects, or study site personnel who have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, etc.
20. Elective surgery or hospitalization planned during the period of study participation.

E.5 End points

E.5.1

Primary end point(s)

▫ Day 43 post vaccination ratio of GMTs for group A and B (3.75µ / 7.5µg) including 2-sided 95% confidence intervals as measured by HI and SRH in the adult and elderly population combined

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

Yes

E.6.10

Pharmacogenetic

E.6.11

Pharmacogenomic

Information not present in EudraCT

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)

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

Yes

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

Multicenter (Poland and Turkey)

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

Yes

E.8.2.3.1

Comparator description

same product but double HA content

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

Yes

E.8.6.2

Trial being conducted completely outside of the EEA

Information not present in EudraCT

E.8.6.3

If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned

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

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 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	No
F.1.1.1	In Utero	No
F.1.1.2	Preterm newborn infants (up to gestational age < 37 weeks)	No
F.1.1.3	Newborns (0-27 days)	No
F.1.1.4	Infants and toddlers (28 days-23 months)	No
F.1.1.5	Children (2-11years)	No
F.1.1.6	Adolescents (12-17 years)	No
F.1.2	Adults (18-64 years)	Yes
F.1.3	Elderly (>=65 years)	Yes
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	No
F.3.3	Specific vulnerable populations	Yes
F.3.3.1	Women of childbearing potential not using contraception	No
F.3.3.2	Women of child-bearing potential using contraception	Yes
F.3.3.3	Pregnant women	No
F.3.3.4	Nursing women	No
F.3.3.5	Emergency situation	No
F.3.3.6	Subjects incapable of giving consent personally	No
F.3.3.7	Others	No
F.4 Planned number of subjects to be included
F.4.1	In the member state	385
F.4.2	For a multinational trial
F.4.2.1	In the EEA	385
F.4.2.2	In the whole clinical trial	770

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

2009-09-01

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2009-07-10

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2009-12-17

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