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

Meningococcal Meningitis Clinical Trial

Official title:

A Phase 2 Partially Observer-Blind Randomized Controlled Multicenter Dose-Ranging and Formulation-Finding Study of a New Novartis Meningococcal B Recombinant Vaccine Evaluating the Safety and Immunogenicity When Given Concomitantly With Routine Vaccines in 2-month-old Infants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00937521
• Other study ID #: V72P16
• Secondary ID: 2009-010106-11
• Status: Completed
• Phase: Phase 2
• First received: June 29, 2009
• Last updated: March 17, 2015
• Start date: July 2009
• Est. completion date: February 2012

Study information

• Verified date: March 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: Italy: AIFA
• Study type: Interventional

Clinical Trial Summary

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1507
• Est. completion date: February 2012
• Est. primary completion date: November 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 55 Days to 89 Days

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Meningitis
• Meningitis, Meningococcal
• Meningococcal Infections
• Meningococcal Meningitis

Intervention

Biological:
• Meningococcal B vaccine
Vaccine candidate formulation I
• Meningococcal B vaccine
Vaccine candidate formulation II
• Meningococcal B vaccine
Vaccine candidate formulation III
• Meningococcal B vaccine
Vaccine candidate formulation IV
• Meningococcal B vaccine
Vaccine candidate formulation V
• Meningococcal B vaccine
Vaccine candidate formulation VI
• Control
Control
• Meningococcal B vaccine with antipyretic
Vaccine candidate formulation I with antipyretic

Locations

Country	Name	City	State
Argentina	Hospital Privado de Córdoba CMC SA	Naciones Unidas 346	Cordoba
Chile	Universidad de Chile, Av Independencia 1027	Comuna de Independencia	Santiago
Chile	Consultorio Manuel Bustos	Lo Cruzat 486, Quilicura	Santiago
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	Chrudimska 2a	Praha 3
Czech Republic	Prakticky lekar pro deti a dorost	Dvouletky 54	Ostrava
Czech Republic	Fakultni nemocnice Bory	E. Beneše 13	Plzen
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	Hrncírská 1401	Lipník nad Becvou
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	Kladenská 53	Praha 6
Czech Republic	Nemocnice Pardubice, Destske oddeleni	Kyjevská 44	Pardubice
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	Masarykova 389	Humpolec
Czech Republic	KHS Ostrava, Protiepidemické oddelení	Na Belidle 7	Ostrava
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	Neklez 3	Brno
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	O. Kubina 17	Boskovice
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	Pernštýnská 127/l	Chlumec nad Cidlinou
Czech Republic	Oblastni nemocnice Nachod, Destske oddelení	Purkynova 446	Náchod
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	Ruských legii 352	Jindrichuv Hradec
Czech Republic	Fakulta vojenskeho zdravotnictvi UO	Trebešská 1575	Hradec Králové
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	U lékárny 306	Odolena Voda
Czech Republic	Nemocnice Decin, Detske oddelení	U nemocnice 1	Decín
Czech Republic	Zdravotní stredisko	Vaclavska 4186	Chomutov
Czech Republic	Samostatna ordinace praktickeho lekare pro deti a dorost	Velka Michalska 22	Znojmo
Hungary	Medszolg 2000 Bt, 6723, Szeged, Dandár u.4	Ányos u.4.	Budapest
Hungary	Gyoriné dr. Bari Eszter egyéni vállalkozó	Csongrad	Szentháromság tér 10
Hungary	S.K. Sipka és Kovács Eü. Bt.	Csongrádi sgt. 63.	Szeged
Hungary	Oszila Kft. 6723, Szeged, Debreceni u.10-14.	Debreceni u.10-14.	Szeged
Hungary	Ped-Med Kft. , 3434 Mályi, Fo u.12.	Fo u.12.	Mályi
Hungary	Erzsébet Kórház Gyermekosztály	Hodmezovasarhely	dr. Imre József u.2.
Hungary	Házi Gyermekorvosi szolgálat	Honvéd u.2.	Bordány
Hungary	Dr. Bán Mariann és Társa Bt.	Kando Kalman u.1	Miskolc
Hungary	Vas Megyei Markusovszky Kórház, Gyermekosztály	Markusovszky u. 1-3	Szombathely
Hungary	Futurnest Kft	Selyemrét u.1.	Miskolc
Hungary	Baby Box Bt,, 6724, Szeged, Kossuth Lajos sgt.109	Szeged	Kossuth Lajos sgt.109
Italy	Dipartimento di Neonatologia e Terapia Intensiva Neonatale, "Ospedale dei Bambini", Presidio Ospedaliero dell'Azienda Ospedaliera Spedali Civili di Brescia	P.le Spedali di Brescia,1	Brescia
Italy	Fondazione IRCCS dell'Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano	Via Commenda, 9	Milano
Italy	Università degli Studi di Messina, Pad. NI - A.O.U. Policlinico G.Martino	Via Consolare Valeria, 1	Messina
Italy	Pediatria dell'Ospedale Sacco di Milano	Via G.B.Grossi 74	Milano
Italy	Dipartimento di Pediatria Azienda Ospedaliera di Padova	Via Giustiniani, 3	Padova
Italy	Dipartimento di Pediatria dell'Università degli Studi di Firenze	Viale Pieraccini n. 24	Firenze

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

Argentina,  Chile,  Czech Republic,  Hungary,  Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentages of Subjects With Serum Bactericidal Activity (hSBA) = 1:5 at 1 Month After 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.	At baseline (pre-vaccination) and 30 days after the third vaccination.	No
Primary	Number of Subjects With Fever = 38.5 °C (Rectal Temperature) Within 3 Days (Day 1-3) 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.	Day 1 to day 3 after first vaccination.	Yes
Secondary	Geometric Mean Bactericidal Titers (GMTs), One Month After Third and Booster Vaccination (Men B at 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: One month after third vaccination.; One month after 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)	No
Secondary	Geometric Mean Bactericidal Titers,One Month After Primary and Booster Vaccination (Men B at 12 Months of Age)	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.	At Baseline (pre-vaccination), at 30 days after the third vaccination, at booster Baseline, at 30 days	No
Secondary	Geometric Mean Ratios, One Month After Primary and Booster Vaccination (Men B at 12 Months of Age)	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).	After the third and the booster vaccination.	No
Secondary	Percentage of Subjects With hSBA=1:5, Persistence of Bactericidal Antibodies at 12 Months of Age (Pre-fourth Dose)	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.	12 months (pre-fourth vaccination)	No
Secondary	Percentage of Subjects With hSBA=1:5, Persistence of Bactericidal Antibodies at 12 Months of Age (One Month-post Fourth Dose)	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.	1 month after fourth vaccination	No
Secondary	Geometric Mean Bactericidal Titers, After Primary and Booster Vaccinations (Men B at 12 Months of Age)	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.	At 13 months	No
Secondary	Percentage of Subjects With hSBA =1:5, First Dose of Meningococcal B Vaccine (One 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).	1 month after booster	No
Secondary	Safety and Reactogenicity of Study Vaccines Within 7 Days 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).	Day 1 through day 7 after second and third vaccination.	No
Secondary	Number of Subjects With Solicited Local Reactions Within 7 Days (Day 1-7) 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.	Day 1 through day 7 after each vaccination.	Yes
Secondary	Number of Subjects With Solicited Systemic Reactions Within 7 Days (Day 1-7) 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.	Day 1 through day 7 after each vaccination.	Yes
Secondary	Number of Subjects With Unsolicited Adverse Events Within 7 Days (Day 1-7) 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.	Day 1 through day 7 after each vaccination.	Yes
Secondary	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.	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.	Overall study period.	No
Secondary	Number of Subjects With Local and Systemic Reactions Within 7 Days (Day 1-7) After Second rMenB+OMV NZ Vaccination in MenC Group	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.	Day 1 through day 7 at 13 months age.	Yes