Clinical Trials Register

Summary
EudraCT Number:	2012-000657-30
Sponsor's Protocol Code Number:	V72_28E1
National Competent Authority:	Spain - AEMPS
Clinical Trial Type:	EEA CTA
Trial Status:	Completed
Date on which this record was first entered in the EudraCT database:	2013-04-09
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

Spain - AEMPS

A.2

EudraCT number

2012-000657-30

A.3

Full title of the trial

A Phase IIIB, Open Label, Multi-Center Extension Study of V72_28 to assess antibody persistence, and the safety and tolerability of a booster dose after the completion of the vaccination course in study V72_28.

Estudio de extensión del V72_28 de fase IIIB, abierto, multicéntrico para evaluar la persistencia de anticuerpos y la seguridad y tolerabilidad de una dosis de refuerzo después de finalizar el programa de vacunación del estudio V72_28

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

No disponible

A.4.1

Sponsor's protocol code number

V72_28E1

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.L.
B.5.2	Functional name of contact point	Regional Clinical Research Associat
B.5.3	Address:
B.5.3.1	Street Address	Gran Via de les Cortes Catalanes 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	E-08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	+34933064200
B.5.5	Fax number	+34933064241
B.5.6	E-mail	beatriz.torralbo@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	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	N. meningitidis 961c purified antigen
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.3	Other descriptive name	N. meningitidis 936-741 purified antigen
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.3	Other descriptive name	N. meningitidis 287-953 purified antigen
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.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Not applicable
D.3.9.3	Other descriptive name	N. meningitidis Outer Membrane Vesicles (OMV) from NZ strain
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.3.11 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

A phase IIIB, Open Label, Multi Center extension study of V72_28 to assess antibody persistence, and the safety and tolerability of a booster dose after the completion of the vaccination course in study V72_28.

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	14.1
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 evaluate the antibody persistence 24 to 36 months after the completion of the vaccination course, in subjects who participated in the V72_28 study in Groups I to IV.

Evaluar la persistencia de anticuerpos entre 24 y 36 meses después de la finalización del programa de vacunación en sujetos que hayan participado en el estudio V72_28 en los grupos I a IV.

E.2.2

Secondary objectives of the trial

Secondary Immunogenicity Objectives
-To evaluate the immune response at one month after a booster dose administered 24 to 36 months after completion of the vaccination course in the parent study (Groups A, C, E, G and I).
-To evaluate the immune response of two catch-up doses of rMenB+OMV NZ administered 1 month apart to naïve children (Group K, L and M).
Safety Objectives:
To assess the safety and tolerability of rMenB+OMV NZ when given as a booster dose administered 24 to 36 months after completion of the vaccination course in the parent study, and to assess the safety and tolerability of rMenB+OMV NZ when given as a two dose regimen (0, 1 month schedule) to naïve subjects.

Objetivos de inmunogenicidad secundarios
-Evaluar la respuesta inmunitaria un mes después de la administración de una dosis de refuerzo administrada entre 24 y 36 meses después de la finalización del programa de vacunación en el estudio principal (grupos A, C, E, G e I).
- Evaluar la respuesta inmunitaria de dos dosis de rescate de rMenB+OMV NZ administradas con un intervalo de 1 mes a niños que no la hayan recibido nunca (grupo K, L y M).

Objetivos de seguridad:
Evaluar la seguridad y tolerabilidad de rMenB+OMV NZ administrado como dosis de refuerzo entre 24 y 36 meses después de la finalización del programa de vacunación en el estudio principal, y evaluar la seguridad y tolerabilidad de rMenB+OMV NZ administrado en régimen de dos dosis (calendario de 0, 1 mes) a sujetos que no la hayan recibido nunca.

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Subject eligible to be enrolled in this study are healthy subjects who previously participated to the parental trial V72_28.
Naïve subjects eligible to participate in this trial should not have a history of any meningococcal B vaccine administration.

Los sujetos elegibles para este estudio son sujetos sanos que hayan participado anteriormente en el ensayo principal V72_28.
Los sujetos que no hayan recibido nunca la vacuna y que sean elegibles para participar en este ensayo no deben presentar un historial de administración de la vacuna meningocócica B.

E.4

Principal exclusion criteria

Exclusion Criteria for naïve subjects newly enrolled:
1. History of any serogroup B meningococcal vaccine administration;
2. Previous known or suspected disease caused by N. meningitidis;
3. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis infection or colonization;
4. History of severe allergic reaction after previous vaccinations or hypersensitivity to any component of the vaccine;
5. Pregnancy or nursing (breastfeeding) mothers;
6. Females of childbearing age who have not used or do not plan to use acceptable birth control measures, for the duration of the study. Oral, injected or implanted hormonal contraceptive, barrier methods (condom or diaphragm with spermicide), intrauterine device, surgical sterilization, transdermal delivery, congenital sterility or sexual abstinence are considered acceptable forms of birth control. If sexually active the subject must have been using one of the accepted birth control methods at least two months prior to study entry;
7. Known or suspected autoimmune disease or impairment/alteration of the immune system resulting from (for example):
- Receipt of any chronic immunosuppressive therapy
- Receipt of any chronic immunostimulants
- Immune deficiency disorder, or known HIV infection
8. History of seizure, any progressive neurological disease or Guillain Barré Syndrome (exception: one self-limited febrile seizure is acceptable).
9. Known bleeding diathesis or any condition that may be associated with a prolonged bleeding time.
10. Subject' s parent(s) or legal guardian(s) are not able to comprehend and to follow all required study procedures for the whole period of the study.
11. Intent to participate in another clinical study during this study.
12. Family members and household members of study staff;
13. History or any illness/condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives or pose additional risk to the subjects due to participation in the study.
14. Any significant chronic infection.
15. Any serious chronic or progressive disease according to judgment of the investigator (e.g. neoplasm, insulin dependent diabetes, cardiac, renal or hepatic disease).
Exclusion Criteria for Subjects who participated in the V72_28 study (Follow-on Subjects):
Exclusion criteria are the same as for naïve subjects, with the exception of criterion 1.

Criterios de exclusión para sujetos nuevos que no hayan recibido nunca la vacuna:
1. Antecedentes de administración de una vacuna meningocócica del serogrupo B.
2. Enfermedad anterior conocida causada por N. meningitidis o sospecha de la misma.
3. Contacto doméstico y/o exposición íntima con una persona con infección o colonización de N. meningitidis confirmada por laboratorio.
4. Antecedentes de reacción alérgica severa después de vacunaciones previas o hipersensibilidad a cualquier componente de una vacuna.
5. Mujeres embarazadas o en periodo de lactancia.
6. Mujeres en edad fértil que no hayan utilizado ni tengan previsto utilizar métodos anticonceptivos aceptables durante el estudio. Se consideran métodos anticonceptivos aceptables los anticonceptivos hormonales orales, inyectados o implantados, métodos de barrera (preservativo o diafragma con espermicida), dispositivo intrauterino, esterilización quirúrgica, parches transdérmicos, esterilidad congénita o abstinencia sexual. Si los sujetos son sexualmente activos, deben haber utilizado uno de los métodos anticonceptivos aceptados al menos dos meses antes de la inclusión en el estudio.
7. Enfermedades autoinmunes conocidas o sospecha de las mismas o deterioro/alteración del sistema inmunitario como resultado de (por ejemplo):
- Haber recibido un tratamiento inmunosupresor crónico.
- Haber recibido inmunoestimulantes crónicos.
- Enfermedad por inmunodeficiencia o infección de VIH conocida.
8. Historial de crisis convulsivas, cualquier enfermedad neurológica progresiva o síndrome de Guillain Barré (excepción: una crisis convulsiva febril que remita espontáneamente es aceptable).
9. Diátesis hemorrágica conocida o cualquier enfermedad que pueda estar relacionada con un tiempo prolongado de hemorragia.
10. Los sujetos cuyos padres o tutores legales no puedan comprender ni seguir todos los procedimientos necesarios del estudio para el periodo completo del estudio.
11. Intención de participar en otro estudio clínico durante este estudio.
12. Familiares y convivientes del personal del estudio.
13. Antecedentes o enfermedades/estados que, según el criterio del investigador, puedan interferir con la evaluación de los objetivos del estudio o representar un riesgo adicional para los sujetos debido a su participación en el estudio.
14. Cualquier infección crónica significativa.
15. Cualquier enfermedad crónica o progresiva grave según el criterio del investigador (p. ej., neoplasia, diabetes insulinodependiente, enfermedad cardiaca, renal o hepática).
Criterios de exclusión para sujetos que hayan participado en el estudio V72_28 (sujetos de seguimiento):
Los criterios de exclusión son los mismos que para los sujetos que nunca hayan recibido la vacuna, con excepción del criterio 1.

E.5 End points

E.5.1

Primary end point(s)

- Percentage of subjects with hSBA titers ? 5 directed against strains of N. meningitidis serogroup B.
- Percentage of subjects with hSBA titers ? 8 against strains of N. meningitidis serogroup B.
- hSBA GMTs directed against N. meningitidis serogroup B.
- GMCs (ELISA) for vaccine antigen 287-953.
- hSBA GMRs directed against N. meningitidis serogroup B:
-Groups A to F: from 1 month to 24 - 36 months after the completion of the vaccination course in the parent study (Group A and B: Visit 6, Groups C, D, E and F: Visit 5).
-Group G to J: from 1 month to 24 - 36 months after the completion of the vaccination course in the parent study (Visit 3).

- Porcentaje de sujetos con títulos hSBA ? 5 dirigidos contra cepas de N. meningitidis serogrupo B.
- Porcentaje de sujetos con títulos hSBA ? 8 dirigidos contra cepas de N. meningitidis serogrupo B.
- MGT de hSBA dirigidos contra N. meningitidis serogrupo B.
- CMG (ELISA) para el antígeno de la vacuna 287-953.
- PMG de hSBA dirigidos contra N. meningitidis serogrupo B:
-Grupos de A a F: desde 1 mes hasta 24 - 36 meses después de la finalización del programa de vacunación en el estudio principal (grupos A y B: visita 6, grupos C, D, E y F: visita 5).
-Grupos de G a J: desde 1 mes hasta 24 - 36 meses después de la finalización del programa de vacunación en el estudio principal (visita 3).

E.5.1.1

Timepoint(s) of evaluation of this end point

Study Day 1 (Visit 1) - Groups A to J

Día 1 del estudio (visita 1) - Grupos A a J

E.5.2

Secondary end point(s)

As per protocol (refer to protocol section 7.1.2)

Según protocolo (véase sección 7.1.2 del protocolo)

E.5.2.1

Timepoint(s) of evaluation of this end point

As per protocol (refer to protocol section 7.1.2)

Según protocolo (véase sección 7.1.2 del protocolo)

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

Persistency

Persistencia

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

Yes

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

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

Según protocolo

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:

1350

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:

1280

F.1.1.6

Adolescents (12-17 years)

Yes

F.1.1.6.1

Number of subjects for this age range:

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

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

507

F.4.2

For a multinational trial

F.4.2.1

In the EEA

764

F.4.2.2

In the whole clinical trial

1350

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

2013-05-31

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2013-04-24

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2016-08-11

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