Clinical Trials Register

Summary
EudraCT Number:	2011-004931-30
Sponsor's Protocol Code Number:	V72P12E2
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:	2012-07-09
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

Spain - AEMPS

A.2

EudraCT number

2011-004931-30

A.3

Full title of the trial

A Phase 3, Open Label, Multi-Center, Extension Study to Assess Antibody Persistence and Response to a Third or Fift Dose of Novartis Meningococcal B Recombinant Vaccine in 4-Year-Old Children Who Previously Participated in Study V72P12E1

Estudio de extensión fase 3, abierto y multicéntrico para evaluar la persistencia de anticuerpos y la respuesta a una tercera o quinta dosis de la vacuna meningocócica recombinante B de Novartis en niños de 4 años de edad que hayan participado previamente en el estudio V72P12E1

A.3.1

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

Persistence of Antibody Levels and Response to Fifth or Third Meningococcal B Recombinant Vaccine in 4-year old Healthy Children who Previously Participated in Study V72P12E1

Persistencia de anticuerpos y respuesta a una tercera o quinta dosis de la vacuna meningocócica recombinante B de Novartis en niños de 4 años de edad que hayan participado previamente en el estudio V72P12E1

A.3.2

Name or abbreviated title of the trial where available

Not applicable

A.4.1

Sponsor's protocol code number

V72P12E2

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	s Clinical Research Associate
B.5.3	Address:
B.5.3.1	Street Address	Gran Via de Las Cortes Catalanas 764
B.5.3.2	Town/ city	Barcelona
B.5.3.3	Post code	08013
B.5.3.4	Country	Spain
B.5.4	Telephone number	0034NA600455797-
B.5.5	Fax number	0034933064572-
B.5.6	E-mail	beatriz.olivas_lopez-mora@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	No
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	rMenB+OMV NZ
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.3.9.3	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.3.9.3	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.3.9.3	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.3.9.3	Other descriptive name	N. meningitidis Outer Membrane Vescicles
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	Yes
D.3.11.13.1	Other medicinal product type	vaccine

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

Prevention of meningococcal disease caused by serogroup B Neisseria meningitidis by evaluating the Antibody persistence in 4-year old healthy children who previously received the Novartis meningococcal B Recombinant vaccine (rMenB+OMV NZ) as infants in study V72P12 and received a booster dose in study V72P12E1 and characterizing the antibody response to a fifth or a third booster dose or two catch-up doses of the rMenB+OMV NZ vaccine at 4 years of age.

Prevención de la enfermedad causada por el serogrupo B de N. meningitidis evaluando la persistencia de anticuerpos en niños sanos de 4 años de
edad que previamente recivieron la vacuna meningocócica recombinante B de Novartis (rMen+OMV NZ) en el estudio V72P12 y que recivieron dosis de refuerzo en el estudio V72P12E1 y caracterizando la respuesta de anticuerpos a una 5ª o 3ª dosis de la vacuna rMenB+OMV NZ en niños de 4 años.

E.1.1.1

Medical condition in easily understood language

Prevention of meningococcal disease caused by serogroup B N.meningitidis.Antibody persistence and response to meningococcal B recombinant vaccine will be evaluated in 4-years old healthy children.

Prevención de la enfermedad meningocócica causada por el serogrupo B de N. meningitidis.
Persistencia de anticuerpos y respuesta a la vacuna recombinante meningococca en niños sanos de 4 años.

E.1.1.2

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

MedDRA Classification

E.1.3

Condition being studied is a rare disease

Yes

E.2 Objective of the trial

E.2.1

Main objective of the trial

To explore antibody persistence in 4-year-old children after a fourth dose boost of rMenB+OMV administered at either 12, 18, or 24 months of age in study V72P12E1, in toddlers who previously received a three-dose primary series of rMenB+OMV (at 2, 3, 4 or 2, 4, 6 months of age) as infants in the original parent study V72P12.

Explorar la persistencia de anticuerpos en niños de 4 años de edad
después de una cuarta dosis de recuerdo de rMenB+OMV NZ administrada a los 12, 18 o 24 meses de edad en el estudio V72P12E1, en niños que previamente recibieron una serie primaria de tres dosis de rMenB+OMV NZ (a los 2, 3, 4 o 2, 4, 6 meses de edad) en el estudio original V72P12.

E.2.2

Secondary objectives of the trial

To explore antibody persistence in 4-year-old children after two catch-up doses of rMenB+OMV administered to toddlers at 12 and 14, 18 and 20, or 24 and 26 months of age in study V72P12E1.
To characterize the antibody response to a fifth dose boost of rMenB+OMV administered to 4-year-old children after a fourth dose boost of rMenB+OMV,
previously given to toddlers at 12, 18, or 24 months of age in study V72P12E1.
To characterize the antibody response to a third dose boost of rMenB+OMV
administered to 4-year-old children after two catch-up doses of rMenB+OMV,
previously administered to toddlers at either 12 and 14, 18 and 20, or 24 and 26
months of age in study V72P12E1.
To characterize the antibody response to two catch-up doses of rMenB+OMV administered 2 months apart to naïve 4-year-old children.

Evaluar la persistencia de anticuerpos en niños de 4 años de edad después de dos dosis de puesta al día de rMenB+OMV NZ administradas a niños de 12 y 14, 18 y 20, o 24 y 26 meses de edad en el estudio V72P12E1.
Caracterizar la respuesta de los anticuerpos a una quinta dosis de recuerdo de rMenB+OMV NZ administrada a niños de 4 años de edad después de una cuarta dosis de recuerdo de rMenB+OMV NZ previamente administrada a niños de 12, 18 o 24 meses de edad en el estudio V72P12E1.
Caracterizar la respuesta de los anticuerpos a una tercera dosis de recuerdo de rMenB+OMV NZ administrada a niños de 4 años de edad después de dos dosis de puesta al día de rMenB+OMV NZ previamente administrada a niños de 12 y 14, 18 y 20, o 24 y 26 meses de edad en el estudio V72P12E1.
POR FAVOR, REMITANSE AL PROTOCOLO PÁG 3

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

Informed consent must be obtained for all the subjects before enrollment into the study after the nature of the study has been explained. Subjects eligible to be enrolled in the study should comply with the following criteria. A) Inclusion Criteria for naive subjects, newly enrolled (Group 7): 1. 4 years old (48 months ± 180 days window) healthy male and female subjects will be recruited from the same sites as in study V72P12E1. 2. for whom a parent/legal guardian(s) has given written informed consent after the nature of the study has been explained; 3. for whom a parent/legal guardian(s) confirmed availability for the visit scheduled in the study; 4. in good health as determined by medical history, physical examination, clinical judgment of the investigator. B) Inclusion Criteria for follow-on participants (Groups 1, 2, 3, 4, 5, and 6): Inclusion criteria are the same as for Groups 7, with the addition that they are subjects who completed the vaccination course of V72P12E1 study, who are 4 years old and above (preferably closer to 4 years of age).

Todos los sujetos deberán otorgar su consentimiento informado antes de su inclusión en el estudio y una vez explicada la naturaleza del mismo.
Los sujetos elegibles para participar en el estudio deberán cumplir todos los criterios siguientes.
A. Criterios de inclusión para los nuevos sujetos que no hayan recibido nunca la vacuna (grupo 7):
1. los sujetos sanos de ambos sexos y 4 años de edad (ventana de 48 meses ± 180 días) se reclutarán de los mismos centros que en el estudio V72P12E1.
2. aquellos cuyopadre(s) o tutor(es) legal(es) hayan otorgado el consentimiento informado por escrito una vez explicada la naturaleza del estudio;
3. aquellos cuyopadre(s) o tutor(es) legal(es) hayan confirmado la disponibilidad para el programa de visita(s) del estudio;
4. con buena salud determinada mediante el historial médico, el examen físico y el criterio clínico del investigador
POR FAVOR, REMITANSE AL PROTOCOLO PAG 7

E.4

Principal exclusion criteria

A)Exclusion Criteria for naïve subjects, newly enrolled (Group 7):1. subjects whose parents/legal guardians are unwilling or unable to give written informed consent to participate in the study;2.history of any meningococcal B vaccine administration;
3.previous ascertained or suspected disease caused by N.meningitidis;4.household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis;5.history of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component;
6.significant acute or chronic infection within the previous 7 days or axillary
temperature >=38°C within the day before Visit 1;7. systemic use of antibiotics for treatment of significant acute or chronic infections within 7 days prior to Visit 1;
8.any serious chronic or progressive disease according to the judgment of the
investigator (e.g., neoplasm, diabetes mellitus Type I, cardiac disease, hepatic
disease, progressive 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);9. known or suspected impairment/alteration of the immune system, immunosuppressive therapy, use of systemic corticosteroids or chronic use of
inhaled high-potency corticosteroids within 30 days prior to Visit 1;10. receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation within 90 days prior to Visit 1; 11. receipt of, or intent to immunize with any other vaccine(s), within 30 days prior to Visit 1 (with the exception of licensed flu vaccine, which can be administered at any time during the study period, but not within 14 days of vaccination with rMenB+OMV NZ);12. participation in another clinical trial (except V72P12E1) within 90 days prior to
enrolment or planned for during study;
13. family members and household members of research staff. 14. any condition which, in the opinion of the investigator, might interfere with the
evaluation of the study objectives.
B. Exclusion Criteria for follow-on participants (Groups 1, 2, 3, 4, 5, and 6):
Exclusion criteria are the same as for Group 7, with the exception of criterion 2.

A. Criterios de exclusión para los nuevos sujetos que no hayan recibido nunca la vacuna (grupo 7):
1. sujetos cuyos padres o tutores legales no deseen o no puedan otorgar el consentimiento informado por escrito para participar en el estudio;
2. antecedentes de administración de una vacuna meningocócica B;
3. enfermedad anterior diagnosticada causada por N. meningitidis o sospecha de la misma;
4. contacto doméstico y/o exposición íntima con una persona con N. meningitidis confirmado por laboratorio;
5. antecedentes de reacción alérgica grave después de vacunaciones previas o hipersensibilidad a cualquier componente de una vacuna;
6. infección importante aguda o crónica durante los 7 días previos, o temperatura axilar ? 38ºC el día anterior a la visita 1;
7. uso sistémico de antibióticos para el tratamiento de infecciones importantes agudas o crónicas durante los 7 días previos a la visita 1;
8. cualquier enfermedad grave crónica o progresiva según el criterio del investigador (por ejemplo, neoplasmas, diabetes mellitus tipo I, enfermedad cardíaca, enfermedad hepática, enfermedad neurológica progresiva o ataque epiléptico, ya sea asociado a fiebre o como parte de un síndrome o trastorno neurológico subyacente, enfermedad autoinmune, infección de VIH o SIDA, o discrasia o diátesis sanguínea, signos de fallo cardíaco o renal, o desnutrición grave;
POR FAVOR, REMITANSE AL PROTOCOLO PÁG 8

E.5 End points

E.5.1

Primary end point(s)

For Groups 1 to 3: The persistence of serum bactericidal activity at 4 years of age will be measured against N. meningitidis serogroup B indicator strains H44/76, 5/99, NZ98/254 and M10713. Data will be summarized by calculating percentage of subjects with hSBA? 1:5, hSBA ? 1:8, hSBA geometric mean titers (GMTs), and geometric mean ratio (GMRs) over baselines at 4 years of age after the last rMenB+OMV NZ vaccination in the V72P12E1 study), to each of the four indicator strains. All immunogenicity analyses will be erformed on the MITT population.

? Para los grupos 1 a 3: La persistencia de la actividad bactericida sérica a los 4 años de edad se medirá frente a las cepas indicadoras H44/76, 5/99, NZ98/254 y M10713 de N. meningitidis del serogrupo B. Los datos se resumirán calculando el porcentaje de sujetos con hSBA ? 1:5, hSBA ? 1:8, la media geométrica de los títulos (MGT) hSBA y la proporción de las medias geométricas (PMG) basada en MGT un mes después de la última vacunación rMenB+OMV NZ de recuerdo en el estudio V72P12E1 a cada una de las cuatro cepas indicadoras. Todos los análisis de inmunogenicidad se llevarán a cabo en la población IDTM.
POR FAVOR, REMITANSE AL PROTOCOLO PÁG 10

E.5.1.1

Timepoint(s) of evaluation of this end point

E.5.2

Secondary end point(s)

For Groups 4 to 6: The persistence of serum bactericidal activity at 4 years of age will be measured against N. meningitidis serogroup B indicator strains H44/76, 5/99, NZ98/254 and M10713. Data will be summarized by calculating percentage of subjects with hSBA? 1:5, hSBA ? 1:8, hSBA geometric mean titers (GMTs), and geometric mean ratio (GMRs) over baselines at 4 years of age after the last rMenB+OMV vaccination in the V72P12E1 study), to each of the four indicator strains. All immunogenicity analyses will be performed on the ITT population. For subset#2 of groups 1 and 2 (1/3 of each sub-group) and for all group 3:induction of bactericidal antibodies at 1 month following a fifth dose boost of rMenB+OMV vaccination will be characterized by calculating SBA GMTs, percentage of subjects with hSBA titers ? 1:5 and ? 1:8, and fourfold increase to each of the four indicator strains.
For Groups 4 to 6: induction of bactericidal antibodies at 1 month following a third dose boost of rMenB+OMV vaccination will be characterized by calculating SBA GMTs, percentage of subjects with SBA titers ? 1:5 and ? 1:8, and fourfold increase to each of the four indicator strains.
Baseline antibody levels measured in naïve subjects at approximately 4 years of age (Group 7) will serve as a descriptive comparator to evaluate antibody persistence at 4 years of age after the fourth rMenB+OMV dose in Groups 1 to 3, and after second dose in Groups 4 to 6, in V72P12E1 study. The immune response following the first dose will also serve as a comparator for the booster responses in the above mentioned vaccine groups. These naive subjects will also serve to gain experience with catch-up immunizations with rMenB+OMV in this older age group.

? Para los grupos 4 a 6: La persistencia de la actividad bactericida sérica a los 4 años de edad se medirá frente a las cepas indicadoras H44/76, 5/99, NZ98/254 y M10713 de N. meningitidis del serogrupo B. Los datos se resumirán calculando el porcentaje de sujetos con hSBA? 1:5, hSBA ? 1:8, la media geométrica de los títulos (MGT) hSBA y la proporción de las medias geométricas (PMG) basada en MGT un mes después de la última vacunación rMenB+OMV NZ en el estudio V72P12E1) a cada una de las cuatro cepas indicadoras. Todos los análisis de inmunogenicidad se llevarán a cabo en la población IDTM.
POR FAVOR, REMITANSE AL PROTOCOLO PÁG 10

E.5.2.1

Timepoint(s) of evaluation of this end point

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

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

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)

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