Safety and Immunogenicity in Dose-Ranging and Formulation-Finding Meningococcal B (MenB) Vaccine Study in 2-month-old Infants

Phase 2

Completed

Conditions: Meningococcal Meningitis
Meningococcal Infections

Interventions: Biological: Meningococcal B vaccine
Biological: Meningococcal B vaccine with antipyretic
Biological: Control

Registration Number: NCT00937521

Lead Sponsor: Novartis Vaccines

Brief Summary: This study is aimed at assessing the safety and immunogenicity of different doses and formulations of a new Novartis Meningococcal B Recombinant Vaccine.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 1507

Inclusion Criteria

Healthy 2-month old infants (55-89 days, inclusive), born after full term pregnancy, gestational age ≥ 37 weeks and a birth weight ≥ 2.5 kg
Available for all the visits scheduled in the study and for whom a parent/legal guardian is willing/able to comply with all protocol requirements

Exclusion Criteria

Any meningococcal B or C vaccine administration
Prior vaccination with any Diphtheria, Tetanus, Pertussis (acellular or whole cell), Polio (either Inactivated or Oral), Haemophilus influenzae type b (Hib), and Pneumococcal antigens;
Any ascertained or suspected disease caused by N. meningitidis
Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis
History of severe allergic reaction after previous vaccinations
Recent significant acute or chronic infection
Oral or parenteral antibiotic treatment in the 7 days prior to the scheduled blood draw;
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)
Any impairment/alteration of the immune system resulting from (for example):
- Receipt of any immunosuppressive therapy at any time since birth
- Receipt of immunostimulants at any time since birth
- Use of systemic corticosteroids or chronic use of inhaled high-potency corticosteroids at any time since birth
Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation
Participation in another clinical trial
Family members and household members of research staff
History of seizure
Any contraindication to paracetamol

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
4	Meningococcal B vaccine	Vaccine candidate formulation IV
8	Meningococcal B vaccine with antipyretic	Vaccine candidate formulation I with antipyretic
2	Meningococcal B vaccine	Vaccine candidate formulation II
3	Meningococcal B vaccine	Vaccine candidate formulation III
7	Control	Control
5	Meningococcal B vaccine	Vaccine candidate formulation V
6	Meningococcal B vaccine	Vaccine candidate formulation VI
1	Meningococcal B vaccine	Vaccine candidate formulation I

Primary Outcome Measures

Name	Time	Method
Percentages of Subjects With Serum Bactericidal Activity (hSBA) ≥ 1:5 at 1 Month After Third Vaccination	At baseline (pre-vaccination) and 30 days after the third vaccination.	To assess the immunogenicity of seven different formulations of 4CMenB (groups I-VI and VIII) given to healthy infants at 2,3 and 4 months of age as measured by percentages of subjects with serum bactericidal activity (SBA) titer≥1:5 against 44/76-SL, 5/99 and NZ98/254 reference strains, at 1 month after the third vaccination.. The analysis was done on the Per Protocol Primary Population at one month after third injection.
Number of Subjects With Fever ≥ 38.5 °C (Rectal Temperature) Within 3 Days (Day 1-3) After First Vaccination	Day 1 to day 3 after first vaccination.	To assess if any of six different formulations of vaccine groups (Group II to Group VI, Group VIII) reduced the incidence of fever \>=38.5C (rectal) occurring within three days (day 1-day3) following first vaccination. The analysis was done on the Safety Population.

Secondary Outcome Measures

Name	Time	Method
Percentage of Subjects With hSBA≥1:5, Persistence of Bactericidal Antibodies at 12 Months of Age (Pre-fourth Dose)	12 months (pre-fourth vaccination)	To assess the persistence of bactericidal antibodies at 12 months of age after primary vaccination - three doses of one of the seven different formulations of rMenB+OMV NZ or rMenB (no OMV) (Group I-VI and VIII) and rMenB+OMV NZ with paracetamol medication.
Percentage of Subjects With hSBA ≥1:5, First Dose of Meningococcal B Vaccine (One Month After Booster)	1 month after booster	To assess the immune response of first dose of meningococcal multi-component recombinant, adsorbed vaccine given at 12 months of age to toddlers who previously received three doses of MenC-CRM197 vaccine as infants (group VII).
Geometric Mean Bactericidal Titers (GMTs), One Month After Third and Booster Vaccination (Men B at 12 Months of Age)	At baseline (pre-vaccination), 30 days after the third vaccination, at booster Baseline and at booster vaccination (12 months of age)	ToTo assess the immune response of seven different formulations of meningococcal multi-component recombinant, adsorbed vaccine (rMenB+OMV NZ or rMenB (no OMV)) in healthy toddlers as measured by SBA geometric mean titers (GMTs) at: 1. One month after third vaccination. 2. One month after booster vaccination (Men B at 12 months of age).
Geometric Mean Bactericidal Titers,One Month After Primary and Booster Vaccination (Men B at 12 Months of Age)	At Baseline (pre-vaccination), at 30 days after the third vaccination, at booster Baseline, at 30 days	To compare the antibody response of meningococcal multi-component recombinant, adsorbed vaccine (formulation I vs. formulation VIII) and of routine infant vaccine given with or without prophylactic administration of paracetamol medication in healthy toddlers.
Geometric Mean Ratios, One Month After Primary and Booster Vaccination (Men B at 12 Months of Age)	After the third and the booster vaccination.	To compare the antibody response between meningococcal multi-component recombinant adsorbed vaccine (formulation I) and routine infant vaccine group along with meningococcal multi-component recombinant adsorbed vaccine with prophylactic administration of paracetamol medication as measured by Geometric Mean Ratios (GMRs).
Geometric Mean Bactericidal Titers, After Primary and Booster Vaccinations (Men B at 12 Months of Age)	At 13 months	To assess the induction of immunological memory of three doses of meningococcal multi-component recombinant, adsorbed vaccine by comparing the serum bactericidal antibodies Geometric Mean Bactericidal Titers (GMTs) response in healthy toddlers administered the fourth dose at 12 months of age to the response in meningococcal B vaccine naive toddlers (Group VII) receiving the first dose of meningococcal multi-component recombinant, adsorbed vaccine at 12 months of age.
Safety and Reactogenicity of Study Vaccines Within 7 Days After Second and Third Vaccination	Day 1 through day 7 after second and third vaccination.	To assess if any of six different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (Group II to VI, Group VIII) reduced the incidence of fever ≥ 38.5ºC (rectal) occurring within 3 days (day 1-3) following second and third vaccination and 7 days (day 1-7) following each vaccination as compared to rMenB+OMV NZ (Group I).
Number of Subjects With Solicited Systemic Reactions Within 7 Days (Day 1-7) After Each Vaccination	Day 1 through day 7 after each vaccination.	To assess the safety and tolerability of each of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (group I to VI, group VIII) in terms of number of subjects reporting solicited systemic reactions within 7 days (day 1-7) after each vaccination.
Number of Subjects With Solicited Local Reactions Within 7 Days (Day 1-7) After Each Vaccination	Day 1 through day 7 after each vaccination.	To assess the safety and tolerability of each of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (group I to VI, group VIII) in terms of number of subjects reporting solicited local reactions within 7 days (day 1-7) after each vaccination.
Percentage of Subjects With hSBA≥1:5, Persistence of Bactericidal Antibodies at 12 Months of Age (One Month-post Fourth Dose)	1 month after fourth vaccination	To assess if any of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (groups I-VI and VIII) induced sufficient immune response when given to healthy toddlers at 12 months of age, as measured by percentage of subjects with SBA titer ≥ 1:5, at 1 month after the fourth vaccination.
Number of Subjects With Unsolicited Adverse Events Within 7 Days (Day 1-7) After Each Vaccination	Day 1 through day 7 after each vaccination.	To assess the safety and tolerability of each of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (group I to VI, group VIII) in terms of number of subjects reporting unsolicited Adverse Events (AEs), serious adverse events (SAEs), medically attended AEs, AEs leading to premature withdrawal (throughout the study period) within 7 days (day 1-7) after each vaccination.
Number of Subjects With Severe Adverse Events and Adverse Events Necessitating a Medical Office or Emergency Room (ER) Visit and/or Resulting in Premature Withdrawal of the Subject From the Study, Throughout the Study Period.	Overall study period.	To assess the safety and tolerability of each of seven different formulations of rMenB+OMV NZ or rMenB (no OMV) vaccine (group I to VI, group VIII) in terms of number of subjects reporting Severe Adverse Events (SAEs) and Adverse Events (AEs) necessitating a medical office or Emergency Room (ER) visit and/or resulting in premature withdrawal of the subject from the study, throughout the study period.
Number of Subjects With Local and Systemic Reactions Within 7 Days (Day 1-7) After Second rMenB+OMV NZ Vaccination in MenC Group	Day 1 through day 7 at 13 months age.	To assess the safety and tolerability of two doses of rMenB+OMV NZ vaccine (Group VII) given at 12 and 13 months of age to toddlers who previously received three doses of Menjugate as infants.

Trial Locations

Locations (29): Vas Megyei Markusovszky Kórház, Gyermekosztály
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Markusovszky u. 1-3, Szombathely, Hungary
Győriné dr. Bari Eszter egyéni vállalkozó
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Csongrad, Szentháromság tér 10, Hungary
KHS Ostrava, Protiepidemické oddělení
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Na Bělidle 7, Ostrava, Czech Republic
Házi Gyermekorvosi szolgálat
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Honvéd u.2., Bordány, Hungary
Erzsébet Kórház Gyermekosztály
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Hodmezovasarhely, dr. Imre József u.2., Hungary
Oszila Kft. 6723, Szeged, Debreceni u.10-14.
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Debreceni u.10-14., Szeged, Hungary
Consultorio Manuel Bustos
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Lo Cruzat 486, Quilicura, Santiago, Chile
Zdravotní středisko
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Vaclavska 4186, Chomutov, Czech Republic
Prakticky lekar pro deti a dorost
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Dvouletky 54, Ostrava, Czech Republic
Nemocnice Pardubice, Destske odděleni
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Kyjevská 44, Pardubice, Czech Republic
Oblastni nemocnice Nachod, Destske oddělení
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Purkyňova 446, Náchod, Czech Republic
Dipartimento di Neonatologia e Terapia Intensiva Neonatale, "Ospedale dei Bambini", Presidio Ospedaliero dell'Azienda Ospedaliera Spedali Civili di Brescia
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P.le Spedali di Brescia,1, Brescia, Italy
Universidad de Chile, Av Independencia 1027
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Comuna de Independencia, Santiago, Chile
Samostatna ordinace praktickeho lekare pro deti a dorost
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Velka Michalska 22, Znojmo, Czech Republic
Fakultni nemocnice Bory
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E. Beneše 13, Plzeň, Czech Republic
Medszolg 2000 Bt, 6723, Szeged, Dandár u.4
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Ányos u.4., Budapest, Hungary
Dr. Bán Mariann és Társa Bt.
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Kando Kalman u.1, Miskolc, Hungary
Hospital Privado de Córdoba CMC SA
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Naciones Unidas 346, Cordoba, Argentina
Nemocnice Decin, Detske oddělení
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U nemocnice 1, Děčín, Czech Republic
Fakulta vojenskeho zdravotnictvi UO
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Trebešská 1575, Hradec Králové, Czech Republic
Baby Box Bt,, 6724, Szeged, Kossuth Lajos sgt.109
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Szeged, Kossuth Lajos sgt.109, Hungary
Futurnest Kft
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Selyemrét u.1., Miskolc, Hungary
Ped-Med Kft. , 3434 Mályi, Fő u.12.
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Fő u.12., Mályi, Hungary
S.K. Sipka és Kovács Eü. Bt.
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Csongrádi sgt. 63., Szeged, Hungary
Dipartimento di Pediatria dell'Università degli Studi di Firenze
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Viale Pieraccini n. 24, Firenze, Italy
Università degli Studi di Messina, Pad. NI - A.O.U. Policlinico G.Martino
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Via Consolare Valeria, 1, Messina, Italy
Fondazione IRCCS dell'Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano
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Via Commenda, 9, Milano, Italy
Pediatria dell'Ospedale Sacco di Milano
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Via G.B.Grossi 74, Milano, Italy
Dipartimento di Pediatria Azienda Ospedaliera di Padova
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Via Giustiniani, 3, Padova, Italy