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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT00937521
First received: June 29, 2009
Last updated: March 17, 2015
Last verified: March 2015
  Purpose
This study is aimed at assessing the safety and immunogenicity of different doses and formulations of a new Novartis Meningococcal B Recombinant Vaccine.

Condition Intervention Phase
Meningococcal Meningitis
Meningococcal Infections
Biological: Meningococcal B vaccine
Biological: Control
Biological: Meningococcal B vaccine with antipyretic
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Percentages of Subjects With Serum Bactericidal Activity (hSBA) ≥ 1:5 at 1 Month After Third Vaccination [ Time Frame: At baseline (pre-vaccination) and 30 days after the third vaccination. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 to day 3 after first vaccination. ] [ Designated as safety issue: Yes ]
    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:
  • Geometric Mean Bactericidal Titers (GMTs), One Month After Third and Booster Vaccination (Men B at 12 Months of Age) [ Time Frame: At baseline (pre-vaccination), 30 days after the third vaccination, at booster Baseline and at booster vaccination (12 months of age) ] [ Designated as safety issue: No ]

    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) [ Time Frame: At Baseline (pre-vaccination), at 30 days after the third vaccination, at booster Baseline, at 30 days ] [ Designated as safety issue: No ]
    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) [ Time Frame: After the third and the booster vaccination. ] [ Designated as safety issue: No ]
    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).

  • Percentage of Subjects With hSBA≥1:5, Persistence of Bactericidal Antibodies at 12 Months of Age (Pre-fourth Dose) [ Time Frame: 12 months (pre-fourth vaccination) ] [ Designated as safety issue: No ]
    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, Persistence of Bactericidal Antibodies at 12 Months of Age (One Month-post Fourth Dose) [ Time Frame: 1 month after fourth vaccination ] [ Designated as safety issue: No ]
    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.

  • Geometric Mean Bactericidal Titers, After Primary and Booster Vaccinations (Men B at 12 Months of Age) [ Time Frame: At 13 months ] [ Designated as safety issue: No ]
    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.

  • Percentage of Subjects With hSBA ≥1:5, First Dose of Meningococcal B Vaccine (One Month After Booster) [ Time Frame: 1 month after booster ] [ Designated as safety issue: No ]
    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).

  • Safety and Reactogenicity of Study Vaccines Within 7 Days After Second and Third Vaccination [ Time Frame: Day 1 through day 7 after second and third vaccination. ] [ Designated as safety issue: No ]
    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 Local Reactions Within 7 Days (Day 1-7) After Each Vaccination [ Time Frame: Day 1 through day 7 after each vaccination. ] [ Designated as safety issue: Yes ]
    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.

  • Number of Subjects With Solicited Systemic Reactions Within 7 Days (Day 1-7) After Each Vaccination [ Time Frame: Day 1 through day 7 after each vaccination. ] [ Designated as safety issue: Yes ]
    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 Unsolicited Adverse Events Within 7 Days (Day 1-7) After Each Vaccination [ Time Frame: Day 1 through day 7 after each vaccination. ] [ Designated as safety issue: Yes ]
    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. [ Time Frame: Overall study period. ] [ Designated as safety issue: No ]
    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 [ Time Frame: Day 1 through day 7 at 13 months age. ] [ Designated as safety issue: Yes ]
    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.


Enrollment: 1507
Study Start Date: July 2009
Study Completion Date: February 2012
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1
Vaccine candidate formulation I
Biological: Meningococcal B vaccine
Vaccine candidate formulation I
2
Vaccine candidate formulation II
Biological: Meningococcal B vaccine
Vaccine candidate formulation II
3
Vaccine candidate formulation III
Biological: Meningococcal B vaccine
Vaccine candidate formulation III
4
Vaccine candidate formulation IV
Biological: Meningococcal B vaccine
Vaccine candidate formulation IV
5
Vaccine candidate formulation V
Biological: Meningococcal B vaccine
Vaccine candidate formulation V
6
Vaccine candidate formulation VI
Biological: Meningococcal B vaccine
Vaccine candidate formulation VI
7
Control
Biological: Control
Control
8
Vaccine candidate formulation I with antipyretic
Biological: Meningococcal B vaccine with antipyretic
Vaccine candidate formulation I with antipyretic

  Eligibility

Ages Eligible for Study:   55 Days to 89 Days   (Child)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00937521

Locations
Argentina
Hospital Privado de Córdoba CMC SA
Naciones Unidas 346, Cordoba, Argentina, X5016KHE
Chile
Universidad de Chile, Av Independencia 1027
Comuna de Independencia, Santiago, Chile
Consultorio Manuel Bustos
Lo Cruzat 486, Quilicura, Santiago, Chile
Czech Republic
Samostatna ordinace praktickeho lekare pro deti a dorost
O. Kubina 17, Boskovice, Czech Republic, 680 01
Samostatna ordinace praktickeho lekare pro deti a dorost
Neklez 3, Brno, Czech Republic, 628 00
Samostatna ordinace praktickeho lekare pro deti a dorost
Pernštýnská 127/l, Chlumec nad Cidlinou, Czech Republic, 503 51
Zdravotní středisko
Vaclavska 4186, Chomutov, Czech Republic, 430 03
Nemocnice Decin, Detske oddělení
U nemocnice 1, Děčín, Czech Republic, 405 01
Fakulta vojenskeho zdravotnictvi UO
Trebešská 1575, Hradec Králové, Czech Republic, 50001
Samostatna ordinace praktickeho lekare pro deti a dorost
Masarykova 389, Humpolec, Czech Republic, 396 01
Samostatna ordinace praktickeho lekare pro deti a dorost
Ruských legii 352, Jindřichův Hradec, Czech Republic, 377 01
Samostatna ordinace praktickeho lekare pro deti a dorost
Hrnčířská 1401, Lipník nad Bečvou, Czech Republic, 751 31
Oblastni nemocnice Nachod, Destske oddělení
Purkyňova 446, Náchod, Czech Republic, 547 01
Samostatna ordinace praktickeho lekare pro deti a dorost
U lékárny 306, Odolena Voda, Czech Republic, 250 70
Prakticky lekar pro deti a dorost
Dvouletky 54, Ostrava, Czech Republic, 700 30
KHS Ostrava, Protiepidemické oddělení
Na Bělidle 7, Ostrava, Czech Republic, 702 00
Nemocnice Pardubice, Destske odděleni
Kyjevská 44, Pardubice, Czech Republic, 532 03
Fakultni nemocnice Bory
E. Beneše 13, Plzeň, Czech Republic, 305 99
Samostatna ordinace praktickeho lekare pro deti a dorost
Chrudimska 2a, Praha 3, Czech Republic, 130 00
Samostatna ordinace praktickeho lekare pro deti a dorost
Kladenská 53, Praha 6, Czech Republic, 160 00
Samostatna ordinace praktickeho lekare pro deti a dorost
Velka Michalska 22, Znojmo, Czech Republic, 669 00
Hungary
Házi Gyermekorvosi szolgálat
Honvéd u.2., Bordány, Hungary, 6795
Medszolg 2000 Bt, 6723, Szeged, Dandár u.4
Ányos u.4., Budapest, Hungary, 1031
Erzsébet Kórház Gyermekosztály
Hodmezovasarhely, dr. Imre József u.2., Hungary
Baby Box Bt,, 6724, Szeged, Kossuth Lajos sgt.109
Szeged, Kossuth Lajos sgt.109, Hungary
Dr. Bán Mariann és Társa Bt.
Kando Kalman u.1, Miskolc, Hungary, 3534
Futurnest Kft
Selyemrét u.1., Miskolc, Hungary, 3527
Ped-Med Kft. , 3434 Mályi, Fő u.12.
Fő u.12., Mályi, Hungary, 3434
S.K. Sipka és Kovács Eü. Bt.
Csongrádi sgt. 63., Szeged, Hungary, 6723
Oszila Kft. 6723, Szeged, Debreceni u.10-14.
Debreceni u.10-14., Szeged, Hungary, 6723
Győriné dr. Bari Eszter egyéni vállalkozó
Csongrad, Szentháromság tér 10, Hungary
Vas Megyei Markusovszky Kórház, Gyermekosztály
Markusovszky u. 1-3, Szombathely, Hungary, 9700
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, 25125
Dipartimento di Pediatria dell'Università degli Studi di Firenze
Viale Pieraccini n. 24, Firenze, Italy, 50139
Università degli Studi di Messina, Pad. NI - A.O.U. Policlinico G.Martino
Via Consolare Valeria, 1, Messina, Italy, 98125
Fondazione IRCCS dell'Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena di Milano
Via Commenda, 9, Milano, Italy, 20122
Pediatria dell'Ospedale Sacco di Milano
Via G.B.Grossi 74, Milano, Italy, 20157
Dipartimento di Pediatria Azienda Ospedaliera di Padova
Via Giustiniani, 3, Padova, Italy, 35128
Sponsors and Collaborators
Novartis Vaccines
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Novartis Vaccines
ClinicalTrials.gov Identifier: NCT00937521     History of Changes
Other Study ID Numbers: V72P16  2009-010106-11 
Study First Received: June 29, 2009
Results First Received: February 13, 2015
Last Updated: March 17, 2015
Health Authority: Italy: AIFA

Keywords provided by Novartis:
Immunogenicity
Meningitis
Antibody
Infants

Additional relevant MeSH terms:
Meningitis
Meningococcal Infections
Meningitis, Meningococcal
Central Nervous System Diseases
Nervous System Diseases
Neisseriaceae Infections
Gram-Negative Bacterial Infections
Bacterial Infections
Meningitis, Bacterial
Central Nervous System Bacterial Infections
Central Nervous System Infections
Vaccines
Antipyretics
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 25, 2016