Clinical Trials Register

Summary
EudraCT Number:	2010-021528-81
Sponsor's Protocol Code Number:	V72_28
National Competent Authority:	Hungary - National Institute of Pharmacy
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2011-01-07
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
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

Hungary - National Institute of Pharmacy

A.2

EudraCT number

2010-021528-81

A.3

Full title of the trial

A Phase 3B, Open Label, Multi-Center Study to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered Alone to Healthy Infants According to Different Immunization Schedules and to Healthy Children aged 2 to 10 Years

A.3.1

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

A.3.2

Name or abbreviated title of the trial where available

Not available

A.4.1

Sponsor's protocol code number

V72_28

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	ICON Clinical Research Ltd
B.5.2	Functional name of contact point	Study Start-up Associate
B.5.3	Address:
B.5.3.1	Street Address	Szépvölgyi út 39.
B.5.3.2	Town/ city	Budapest
B.5.3.3	Post code	1037
B.5.3.4	Country	Hungary
B.5.4	Telephone number	+3628471689
B.5.5	Fax number	+36 1 7789223
B.5.6	E-mail	zsuzsanna.tribel@iconplc.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	Bexsero
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	Novartis Meningococcal B Recombinant +OMV NZ Vaccine
D.3.2	Product code	-
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	Not applicable
D.3.9.3	Other descriptive name	OUTER MEMBRANE VESICLES (OMV) FROM NEISSERIA MENINGITIDIS GROUP B STRAIN NZ98/254 MEASURED AS AMOUNT OF TOTAL PROTEIN CONTAINING THE PORA P1.4 ADSORBED ON ALUMINIUM HYDROXIDE
D.3.9.4	EV Substance Code	SUB96091
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	50
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.3	Other descriptive name	RECOMBINANT NEISSERIA MENINGITIDIS GROUP B FHBP FUSION PROTEIN PRODUCED IN E. COLI CELLS BY RECOMBINANT DNA TECHNOLOGY ADSORBED ON ALUMINIUM HYDROXIDE
D.3.9.4	EV Substance Code	SUB96090
D.3.10	Strength
D.3.10.1	Concentration unit	µg/µl microgram(s)/microlitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.3	Other descriptive name	RECOMBINANT NEISSERIA MENINGITIDIS GROUP B NADA PROTEIN PRODUCED IN E. COLI CELLS BY RECOMBINANT DNA TECHNOLOGY ADSORBED ON ALUMINIUM HYDROXIDE
D.3.9.4	EV Substance Code	SUB96089
D.3.10	Strength
D.3.10.1	Concentration unit	µl/ml microlitre(s)/millilitre
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	100
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	not applicable
D.3.9.3	Other descriptive name	RECOMBINANT NEISSERIA MENINGITIDIS GROUP B NHBA FUSION PROTEIN PRODUCED IN E. COLI CELLS BY RECOMBINANT DNA TECHNOLOGY ADSORBED ON ALUMINIUM HYDROXIDE
D.3.9.4	EV Substance Code	SUB96088
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	100
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	Yes
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

E.1.1.1

Medical condition in easily understood language

Meningitis B

E.1.1.2

Therapeutic area

Diseases [C] - Immune System Diseases [C20]

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	16.1
E.1.2	Level	PT
E.1.2	Classification code	10027202
E.1.2	Term	Meningitis bacterial
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

-To demonstrate a sufficient immune response following rMenB+OMV NZ vaccination, when given as a two dose primary series to healthy infants at 3 1/2 and 5 months of age or at 6 and 8 months of age, as measured by the percentage of subjects with serum bactericidal activity (SBA) titers of at least 4, at 1 month after the second rMenB+OMV NZ dose, directed against MenB indicator strains H44/76, 5/99 and NZ98/254.

E.2.2

Secondary objectives of the trial

-Demonstrate a sufficient immune response following rMenB+OMV NZ vaccination, when given as a three dose primary series to healthy infants, see protocol.
-Demonstrate a sufficient immune response following rMenB+OMV NZ vaccination, when given as a two dose catch series to healthy children, aged 2-10 years, see protocol.
-Demonstrate a sufficient immune response following a booster dose of rMenB+OMV, when given at 11 months of age, see protocol.
-Assess the immune response following rMenB+OMV NZ vaccination, see protocol.
-Explore bactericidal antibody persistence at 11 months of age in subjects who previously received a primary series of two or three doses, see protocol.
-Evaluate the immune responses to vaccine antigen 287-953 by ELISA following two and three dose primary immunization schedules with rMenB+OMV NZ in infants followed by a booster dose, see protocol.
Safety Objectives: see protocol
Additional objectives for Part 2 of study (Brazil): See protocol

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Male and female subjects: a)Healthy infants 2½ months of age (71 -79 days, inclusive), (only applicable to group I). b)Healthy infants 3½ months of age (101 -109 days, inclusive), (only applicable to group II). c)Healthy infants 6 months of age (only applicable to group III) (The age windowis defined as the first day the subject turns 6 months of age up to the day before the subject turns 7 months of age).
d)Healthy children 2 to 5 years of age (only applicable to group IVa) (The age window is defined as the first day the subject turns 2 years of age up to the day before the subject turns 6 years of age). e) Healthy children 6 to 10 years of age (only applicable to group IVb). (The age window is defined as the first day the subject turns 6 years of age up to the day before the subject turns 11 years of age). f) Healthy infants 3 months of age (applicable to Groups V and VI).
2.For whom parent(s)/legal guardian(s) have given written informed consent according to local regulations after the nature of the study has been explained;
3.Available for all the visits scheduled in the study;
4.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.Subjects whose parent(s)/legal guardian(s) are unwilling or unable to give written informed consent to participate in the study;
2.Children's parents or legal guardian who are not able to comprehend and to follow all required study procedures for the whole period of the study.
3.History of any meningococcal B vaccine administration;
4.Previous ascertained or suspected disease caused by N. meningitidis;
5.Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis;
6.History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component
7.Significant acute or chronic infection within the previous 7 days or temperature higher than 38 Centigrade within the previous day of receiving the study vaccine;
8.Antibiotics treatment within 6 days prior to enrollment;
9.Individuals with history of allergy to vaccine components.
10.Any serious chronic or progressive disease according to the judgment of the investigator (e.g., neoplasm, diabetes mellitus Type I, cardiac disease, hepatic disease, neurological disease or seizure, either associated with fever or as part of an underlying neurological disorder or syndrome, autoimmune disease, HIV infection or AIDS, or blood dyscrasias or diathesis, signs of cardiac or renal failure or severe malnutrition);
11.Known or suspected impairment/alteration of the immune system, immunosuppressive therapy, use of high dose systemic corticosteroids or chronic use of inhaled high-potency corticosteroids within 14 days prior to enrollment (use of low or moderate doses of inhaled steroids is not an exclusion);
See protocol

E.5 End points

E.5.1

Primary end point(s)

Immunogenicity Endpoints
Data will be summarized by calculating percentage of subjects with hSBA titers (≥ 4 and ≥ 5), percentage of subjects with hSBA titers ≥ 8, percentage of subjects with fourfold increase over baseline and hSBA geometric mean titers (GMTs) at the different time points. Antibody responses to vaccine antigen 287-953 will be determined by ELISA and summarized by geometric mean concentrations (GMCs).
In the second part of the study, the rMenB + OMV NZ immunogenicity response will be evaluated as described above, and for the MenC-CRM data will be also summarized by calculating percentage of subjects with hSBA titers ≥ 8, percentage of subjects with four-fold increase over baseline and hSBA geometric mean titers (GMTs) at the different time points, against N. meningitidis type C.
Primary: A sufficient immune response of rMenB+OMV NZ, when given as a two dose primary series to healthy infants in Group II (3½, 5 months of age) or Group III (6, 8 months of age), will be defined as ≥ 70% for the lower limit of the two-sided 97.5% CI for the percentage of subjects achieving hSBA titers of at least 4 for all 3 indicator strains.
Safety Endpoints - See protocol

E.5.1.1

Timepoint(s) of evaluation of this end point

1 month after the 3rd, 4th vaccination in group I
1 month after the 2nd, 3rd vaccination in group II
1 month after the 2nd, 3rd vaccination in group III
1 month after the 2nd vaccination in group IV
First blood draw post first vaccination- 3 1/2
months in group Ib, 5 months in group IIb, 8 months in group IIIb
1 month after the 2nd, 3rd vaccination in group V
1 month after the 2nd, 3rd vaccination in group VI

E.5.2

Secondary end point(s)

As per protocol (refer to E.5.1)

E.5.2.1

Timepoint(s) of evaluation of this end point

As per protocol (refer to E.5.1.1)

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

tolerability, 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

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

Yes

E.8.5.1

Number of sites anticipated in the EEA

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

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

Peru

Brazil

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

As per 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

Yes

F.1.1

Number of subjects for this age range:

1400

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)

Yes

F.1.1.4.1

Number of subjects for this age range:

1000

F.1.1.5

Children (2-11years)

Yes

F.1.1.5.1

Number of subjects for this age range:

400

F.1.1.6

Adolescents (12-17 years)

F.1.2

Adults (18-64 years)

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

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

F.3.3.7

Others

F.4 Planned number of subjects to be included

F.4.1

In the member state

200

F.4.2

For a multinational trial

F.4.2.1

In the EEA

750

F.4.2.2

In the whole clinical trial

1400

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

2011-02-28

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2011-02-16

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-07-01

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