Clinical Trials Register

Summary
EudraCT Number:	2013-002454-78
Sponsor's Protocol Code Number:	V72_62
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:	2014-04-15
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

2013-002454-78

A.3

Full title of the trial

A Phase IIIb, Open Label, Controlled, Multi-Center Study to Evaluate the Safety, Tolerability and Immunogenicity of Two Doses of Novartis Meningococcal Group B Vaccine when administered to Immunocompromised Patients from 2 to 17 years of age who are at Increased Risk of Meningococcal Disease because of Complement Deficiency or Asplenia compared to matched Healthy Controls

A.3.1

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

Study conducted in immunocompromized patients, 2 to 17 years of age, who are at increased risk of acquiring severe meningococcus diasease because of asplenia or deficiencies of the complement system, in comparison with healthy individuals as controls, in order to evaluate safety, tolerability and antibody response after the administration of two doses of the Novartis investigational vaccine directed mainly against Meningococcus serogroup B.

A.4.1

Sponsor's protocol code number

V72_62

A.5.4

Other Identifiers

Name:

Not applicable

Number:

Not applicable

A.7

Trial is part of a Paediatric Investigation Plan

Yes

A.8

EMA Decision number of Paediatric Investigation Plan

P/38/2011

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	Clinical Cluster
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.5.4	Telephone number	+39 0577539588
B.5.5	Fax number	+390577539236
B.5.6	E-mail	marco.calabresi@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, Meningococcal group B Vaccine (rDNA, component, adsorbed)
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	Meningococcal group B Vaccine (Bexsero)
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.3.8	INN - Proposed INN	Outer membrane vesicles (OMV) from Neisseria meningitidis group B strain NZ98/254
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 microgram(s)
D.3.10.2	Concentration type	equal
D.3.10.3	Concentration number	25
D.3.8 to D.3.10 IMP Identification Details (Active Substances)
D.3.8	INN - Proposed INN	Recombinant Neisseria meningitidis group B fHbp fusion protein
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 microgram(s)
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	Recombinant Neisseria meningitidis group B NHBA fusion protein
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 microgram(s)
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	Recombinant Neisseria meningitidis group B NadA protein
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	µg microgram(s)
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

Meningococcal Group B disease.

E.1.1.1

Medical condition in easily understood language

Meningitidis.

E.1.1.2

Therapeutic area

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

MedDRA Classification

E.1.2 Medical condition or disease under investigation

E.1.2	Version	18.0
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

Immunogenicity Objective
▫ To evaluate the immunogenicity of two doses of rMenB+OMV NZ in subjects with
increased risk of meningococcal disease because of complement deficiency or
asplenia and in healthy age-matched subjects, at 1 month after the second
vaccination.
Safety Objective
▫ To assess the safety and tolerability of two doses of rMenB+OMV NZ in subjects
with increased risk of meningococcal disease because of complement deficiency or
asplenia and in healthy age-matched subjects.

E.2.2

Secondary objectives of the trial

Not applicable

E.2.3

Trial contains a sub-study

E.3

Principal inclusion criteria

In order to participate in this study, all subjects must meet ALL of the inclusion criteria applicable to the relevant group.
Inclusion criteria applicable to All Groups (A, B and C)
1. Subjects aged 2 to 17 years (inclusive) at enrollment;
2. who have given written informed assent (if appropriate) and whose parent/legal guardian have given written informed consent after the nature of the study has been explained;
3. available for all the visits scheduled in the study;
4. weighing at least 13 Kg at the time of enrollment.
Inclusion criterion applicable to Group A
5. Subjects at risk of meningococcal disease because of primary or secondary complement deficiencies:
a. Primary deficiencies: patients with a congenital condition leading to a reduced concentration of one or more proteins in the complement cascade, including C1 (q,r,s), C2, C3, C4, Factor D, Properdin, C5, C6, C7, C8, C9, Factor H, Factor I (homozygous)
b. Secondary deficiencies: patients with a condition indirectly leading to a reduced concentration of one or more proteins in the complement cascade, including patients who are already in treatment with eculizumab at the time of enrollment and have been diagnosed with paroxysmal nocturnal hemoglobinuria or with atypical hemolytic uremic syndrome
For patients with a secondary complement deficiency the investigator should include in the source documentation evidence of the increased risk of meningococcal disease based on reduced complement protein concentrations or on previous meningococcal infection. This should be documented in the medical records.
Inclusion criterion applicable to Group B
6. Subjects at risk of meningococcal disease because of functional or anatomic asplenia:
a. Congenital anomalies of the spleen, isolated or in association with other splenic anomalies
b. Surgical splenectomy, which may occur after significant splenic trauma or other clinical disorders, such as idiopathic (autoimmune) thrombocytopenic purpura
c. Autosplenectomy (i.e. infarction) which may occur in patients with sickle cell disease or other haemoglobinopathies
For patients with functional asplenia the investigator will collect medical documentation for reduced splenic function diagnosed with an appropriate technique. Patients with anatomic asplenia or sickle-cell disease do not require assessment of the splenic function.
Inclusion criterion applicable to Group C
7. healthy immunocompetent subjects, in good health as determined by medical history, physical examination and clinical judgment of the investigator.

E.4

Principal exclusion criteria

Exclusion criteria applicable to All Groups (A, B and C)
1. History of any previous immunization with a meningococcal B vaccine at the time of
enrollment;
2. History of severe allergic reaction after previous vaccinations, or hypersensitivity to
any component of the vaccine;
3. Known HIV infection;
4. History of any progressive or severe neurologic disorder, or seizure disorder
(exception: one self-limited febrile seizure is acceptable);
5. Contraindication to intramuscular injection or blood drawn;
6. Females who are pregnant, planning a pregnancy or nursing (breastfeeding);
7. Females of childbearing potential who have not used or do not plan to use acceptable
birth control measures, for the 3 months duration of the study. Oral, injected or
implanted hormonal contraceptive, barrier methods (diaphragm or condom with
spermicide), intrauterine device 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 for at least 60 days prior to study entry
8. Child'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;
9. Intent to participate in another clinical study during this study;
10. Family members or household members of site research staff;
11. History or any illness/condition 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.
Exclusion criterion applicable to Groups A and B
12. Previous known or suspected disease caused by N. meningitidis in the last year;
Exclusion criteria applicable to Group C
13. Previous known or suspected disease caused by N. meningitidis;
14. Known or suspected impairment/alteration of the immune system resulting from, for
example, receipt of immunosuppressive/immunostimulant therapy
There may be instances when individuals meet all entry criteria except one that relates to
transient clinical circumstances (e.g., body temperature elevation or recent use of
excluded medication or vaccine). Under these circumstances, a subject may be
considered eligible for study enrollment if the appropriate window for delay has passed,
inclusion/exclusion criteria have been rechecked, and if the subject is confirmed to be
eligible.

E.5 End points

E.5.1

Primary end point(s)

Primary Endpoint(s)
▫ Percentage of subjects with hSBA titers ≥ 5, hSBA titers ≥ 8 and hSBA Geometric Mean Titers (GMTs) against each of the serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain at baseline and one month after the second vaccination. Corresponding to the GMTs, within-subject Geometric Mean Ratios (GMRs), at one month after the second vaccination over baseline.
▫ Percentage of subjects with four-fold increases in hSBA titers against each of the serogroup B indicator strains (H44/76, 5/99, and NZ98/254) and M10713 strain at one month after the second vaccination over baseline.
▫ ELISA geometric mean concentrations (GMCs), to evaluate antibody responses to vaccine antigen 287-953, at baseline and at one month after the second vaccination. Corresponding to the GMCs, within-subject ELISA GMRs, at one month after the second vaccination over baseline.
▫ Percentage of subjects with four-fold increases in ELISA concentrations, to evaluate antibody responses to vaccine antigen 287-953, at one month after the second vaccination over baseline.
Safety Endpoints
▫ The frequencies and percentages of subjects with solicited local and systemic AEs during the 7 days (including the day of vaccination) after Visits 1 and 2.
▫ The frequencies and percentages of subjects with any other (unsolicited) AEs including any SAEs, AEs leading to withdrawal and medically attended AEs during the 7 days (including the day of vaccination) after Visits 1 and 2.
▫ The frequencies and percentages of subjects with SAEs, AEs leading to withdrawal and medically attended AEs throughout the study period.

E.5.1.1

Timepoint(s) of evaluation of this end point

Primary Endpoints:
-at baseline and one month after the second vaccination
Safety Endpoints:
-7 days (including the day of vaccination) after Visits 1 and 2.
-the entire study period.

E.5.2

Secondary end point(s)

Not applicable

E.5.2.1

Timepoint(s) of evaluation of this end point

Not applicable

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

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)

E.7.4

Therapeutic use (Phase IV)

Yes

E.8 Design of the trial

E.8.1

Controlled

Yes

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

Yes

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

Yes

E.8.2.3.1

Comparator description

Healthy subjects arm

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

Italy

Poland

Russian Federation

Spain

United Kingdom

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

The end of study is defined as reported in the study 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:

150

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:

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

Yes

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

F.4.2

For a multinational trial

F.4.2.1

In the EEA

110

F.4.2.2

In the whole clinical trial

150

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

N. Review by the Competent Authority or Ethics Committee in the country concerned

Competent Authority Decision

Authorised

Date of Competent Authority Decision

2014-05-14

Ethics Committee Opinion of the trial application

Favourable

Ethics Committee Opinion: Reason(s) for unfavourable opinion

Date of Ethics Committee Opinion

2014-03-27

P. End of Trial
P.	End of Trial Status	Completed
P.	Date of the global end of the trial	2015-10-22

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