Extension Study of V72P13 to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered as a Booster or as a Two-dose Catch-up to Healthy Toddlers
- Conditions
- Meningococcal Disease
- Interventions
- Biological: 1b - rMenB+OMV NZ and routine vaccinesBiological: 3a - rMenB+OMV NZ and routine vaccinesBiological: 2a - Routine and rMenB+OMV NZ vaccinesBiological: 2b - rMenB+OMV NZ and routine vaccinesBiological: 3b - 1 dose of rMenB+OMV NZ plus routine infant vaccinationsBiological: 4a- rMenB+OMV NZ and routine vaccinesBiological: 1a - rMenB+OMV NZ and routine vaccinesBiological: 4b - rMenB+OMV NZ and routine vaccines
- Registration Number
- NCT00847145
- Lead Sponsor
- Novartis Vaccines
- Brief Summary
The proposed study is an Extension Study of V72P13 to Evaluate the Safety, Tolerability and Immunogenicity of Novartis Meningococcal B Recombinant Vaccine When Administered as a Booster at 12 Months of Age or as a Two-dose Catch-up to Healthy Toddlers
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 2249
- Healthy 12-month-old toddlers (0/ +29 days) who completed Study V72P13
- Previous ascertained or suspected disease caused by N. meningitidis;
- History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component;
- Any serious chronic or progressive disease
- Known or suspected impairment/ alteration of the immune system,
- Receipt of, or intent to immunize with another vaccine, within 30 days prior to enrollment.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 12B13M (1b) 1b - rMenB+OMV NZ and routine vaccines Previously in the parent study subjects had received three doses of rMenB+OMV NZ and routine vaccine at 2, 4 and 6 months of age, respectively. These subjects received a booster (fourth) dose at 12 months and one dose of MMRV vaccine at 13 months of age in the present study. 12B12M (3a) 3a - rMenB+OMV NZ and routine vaccines Previously in the parent study subjects had received three doses of rMenB+OMV NZ at 2, 4 and 6 months of age respectively. These subjects had received one booster (fourth) dose of rMenB+OMV NZ at 12 months of age concomitantly with one dose of MMRV vaccine in the present study. 12M13B15B (2a) 2a - Routine and rMenB+OMV NZ vaccines Previously in the present study subjects had received routine vaccine at 2, 4 and 6 months of age respectively. These subjects received MMRV vaccine at 12 months of age and two catch-up doses of rMenB+OMV NZ vaccine at 13 and 15 months of age in the present study. 12M12B14B (2b) 2b - rMenB+OMV NZ and routine vaccines Previously in the parent study subjects ahd received three doses of routine vaccine at 2, 4 and 6 months of age, respectively. These subjects received two catch-up doses of rMenB+OMV NZ at 12 and 14 months of age and one dose of MMRV vaccine given concomitantly at 12 months of age in the present study. 12B13M (3b) 3b - 1 dose of rMenB+OMV NZ plus routine infant vaccinations Previously in the present study subjects had received three doses of rMenB+OMV NZ at 12 months of age respectively. These subjects one booster (fourth) dose of rMenB+OMV NZ at 12 months of age and one dose of MMRV vaccine at 13 months of age in the present study. 12B12M_C (4a) 4a- rMenB+OMV NZ and routine vaccines Previously in the parent study subjects had received three doses of Meningococcal C vaccine and routine vaccine at 2, 4 and 6 months of age respectively. These subjects had received one single dose of rMenB+OMV NZ at 12 months of age concomitantly with one dose of MMRV vaccine in the present study. 12B12M (1a) 1a - rMenB+OMV NZ and routine vaccines Previously in the parent study subjects had received three doses of rMenB+OMV NZ and routine vaccine at 2, 4 and 6 months of age,respectively. These subjects received a booster (fourth) dose at 12 months of age concomitantly with one dose of MMRV vaccine in the present study. 12B13M_C (4b) 4b - rMenB+OMV NZ and routine vaccines Previously in the parent study subjects had received three doses of Meningococcal C vaccine and routine vaccine at 2, 4 and 6 months of age. These subjects received one single dose o rMenB+OMV NZ at 12 months of age and one dose of MMRV vaccine at 13 months of age in the present study.
- Primary Outcome Measures
Name Time Method Percentages of Subjects With Serum Bactericidal Antibody Titers ≥1:5 After Receiving the Booster Dose of rMenB+OMV NZ Vaccination one month after the booster (fourth) dose Immunogenicity was assessed in terms of the percentage of subjects as measured by serum bactericidal antibody titers ≥1:5 the lower limit of the two-sided 95% confidence interval (CI) was ≥75%, directed against N.meningitidis serogroup B reference strains H44/76-SL , NZ98/254, 5/99, one month after the booster (fourth) dose of meningococcal B vaccine with or without the concomitant Measles, Mumps, Rubella, Varicella (MMRV) vaccine in toddlers who were previously vaccinated with three doses of Meningococcal B vaccine.
- Secondary Outcome Measures
Name Time Method Number of Subjects Reporting Solicited Local and Systemic Reactions During the 7 Days Following Two-dose Catch-up Schedules of rMenB+OMV NZ Vaccination From day 1 to day 7 after each rMenB+MV NZ vaccination. Safety was assessed as the number of subjects who reported solicited local and systemic reactions from day 1 through day 7 after rMenB+OMV NZ vaccination administered with a two-dose catch-up schedules (groups 12M13B15B and 12M12B14B).
Geometric Mean Titers After Receiving the Booster Dose and Single Dose of rMen+OMV NZ Vaccination (Induction of Immunological Memory) one month after booster (fourth) dose vaccination and pre-fourth dose vaccination The immunogenicity was assessed to demonstrate the induction of immunological memory in subjects who were previously received three doses of rMenB+OMV NZ as measured by SBA GMT response in comparison to the fourth dose of rMenB+OMV NZ at 12 months of age ( 12B12M(1a) group) to the response in subjects (12M12B14B 0 who received a single dose of rMenB+OMV NZ vaccine.
SBA GMTs After a Two-dose Catch-up Schedule or Two-dose Schedule One month after the second dose. The immunogenicity of a two-dose catch-up schedule of rMenB+OMV NZ given at 13 and 15 months (12M13B15B) or 12 and 14 months (12M12B14B) to naïve toddlers was assessed by SBA GMTs one month after the second dose.
Percentages of Subjects With Antibody Response After Receiving the MMRV Vaccination one month after booster (fourth) dose Immunogenicity was assessed to demonstrate non-inferiority in terms of percentages of subjects as measured by antibody responses against MMRV vaccine when given concomitantly with the booster (fourth) dose of rMenB+OMV NZ vaccine at 12 months of age when compared to MMRV vaccine when given alone.
The specified cut-off levels for the vaccine antigens : for measles antigen is ≥255mIU/mL, Mumps antigen is ≥10 Enzyme Linked Immunosorbent Assay(ELISA) Antibody(Ab) units, Rubella antigen is ≥10 IU/mL, Varicella antigen is ≥1.25 glycoprotein (gp) ELISA units/ml (seroconversion) and varicella antigen is ≥5 gp ELISA units/ml (seroprotection.ELISA Geometric Mean Concentration Against Vaccine Antigen 287-953 After Two-dose Catch-up in Toddlers One month after the first dose and one month after the second dose. The immune response against vaccine antigen 287-953was measured by ELISA one month after the first dose and one month after the second dose of a two-dose catch-up regimens (12M13B15B and 12M12B14B) in toddlers.
Number of Subjects Reporting Solicited Local and Systemic Reactions During the 7 Days Following rMenB+OMV NZ Vaccination at 12 Months of Age From day 1 to day 7 after each rMenB+OMV NZ vaccination. Safety was assessed as the number of subjects who reported solicited local and systemic reactions from day 1 through day 7 after rMenB+OMV NZ vaccination administered at 12 months. For the safety analysis purpose, Groups 12B12M (1a) and 12B12M (3a) are combined as Group 12B12M and Groups 12B13M (1b) and 12B13M (3b) are combined as Group 12B13M.
Geometric Mean Titers at 12 Months of Age (Predose 4) After Previously Receiving the Three Doses of rMenB+OMV NZ (Persistence) one month after third vaccination and pre dose fourth (booster) vaccination The immunogenicity was assessed as the persistence of bactericidal antibodies at 12 months of age (pre-dose 4) who previously received three doses of rMenB+OMV NZ in the parent study as measured by hSBA GMTs directed against N meningitidis serogroup B reference strains H44/76, NZ98/254 and 5/99.
Percentages of Subjects With Serum Bactericidal Antibody Titers ≥1:5 After Previously Receiving the Three Doses of rMenB+OMV NZ Vaccination (Persistence) One month post vaccination and pe-booster (fourth) dose vaccination Immunogenicity was assessed to evaluate the persistence in terms of percentages of subjects with hSBA titers ≥ 1:5, previously received three doses of rMenB+OMV NZ directed against N meningitidis serogroup B reference strains H44/76, NZ98/254 and 5/99.
Percentages of Subjects With SBA Titers ≥1:5 After a Two-dose Catch-up Schedule or Two-dose Schedule One month after the second dose. The immunogenicity of a two-dose catch-up schedule of rMenB+OMV NZ given at 13 and 15 months (12M13B15B) or 12 and 14 months (12M12B14B) to naïve toddlers was assessed as percentages of subjects with SBA titers ≥1:5 one month after the second dose.
Number of Subjects Reporting Solicited Systemic Reactions During 8-28 Days Following MMRV Vaccination at 12 Months of Age From day 8 to day 28 after MMRV vaccination. Safety was assessed as the number of subjects who reported solicited systemic reactions from day 8 through day 28 after the MMRV vaccination concomitantly with rMenB+OMV NZ at 12 months of age (groups 12B12M, 12M12B14B, 12B12M_C) or after MMRV vaccination alone without rMenB+OMV NZ at 12 months (Group 12M13B15B). For the safety analysis purpose, Groups 12B12M (1a) and 12B12M (3a) are combined as Group 12B12M.
The Geometric Mean Titers After Receiving the Booster Dose of rMenB+OMV NZ Vaccination one month after booster (fourth) vaccination. The human serum bactericidal antibody (hSBA) titer responses, one month after receiving booster dose or rMenB+OMV NZ vaccination, are reported as geometric mean titers (GMTs).
ELISA Geometric Mean Concentration Against Vaccine Antigen 287-953 One Month After the Fourth (Booster) Dose Given at 12 Months One month after the fourth (booster) dose. The immune response against vaccine antigen 287-953 was measured by ELISA, one month after the fourth (booster) dose given at 12 months of age (groups 12B12M (1a), 12B13M (1b).
Percentages of Subjects With Bactericidal Titers ≥ 1:5 (95% CI) Against Strain M10713 One Month After the Fourth (Booster) Dose Given at 12 Months One month after the fourth (booster) dose. The immune response was measured as percentages of subjects with SBA ≥ 1:5 (95% CI) against strain M10713, one month after the fourth (booster) dose given at 12 months of age (groups 12B12M (1a), 12B13M (1b).
Number of Subjects Reporting Solicited Local Reactions During the 7 Days Following MMRV Vaccination at 12 Months of Age From day 1 to day 7 after MMRV vaccination. Safety was assessed as the number of subjects who reported solicited local reactions from day 1 through day 7 after the MMRV vaccination concomitantly with rMenB+OMV NZ at 12 months of age (groups 12B12M, 12M12B14B, 12B12M_C) or after MMRV vaccination alone without rMenB+OMV NZ at 12 months (Group 12M13B15B). For the safety analysis purpose, Groups 12B12M (1a) and 12B12M (3a) are combined as Group 12B12M.
Trial Locations
- Locations (59)
Site 25
🇨🇿Kladno 2, Czech Republic
Site 28
🇨🇿Hranice I-mesto, Czech Republic
Site 45
🇫🇮Kotka, Finland
Site 50
🇫🇮Pori, Finland
Site 99
🇩🇪Detmold, Germany
Site 92
🇩🇪Espelkamp, Germany
Site 64
🇩🇪Fulda, Germany
Site 95
🇩🇪Freising, Germany
Site 58
🇩🇪Lauffen, Germany
Site 80
🇩🇪München, Germany
Site 97
🇩🇪München, Germany
Site 96
🇩🇪München, Germany
Site 91
🇩🇪Műnchen, Germany
Site 83
🇩🇪München, Germany
Site 81
🇩🇪Porta Westfalica, Germany
Site 94
🇩🇪Weilheim, Germany
Dipartimento di Scienze della Salute
🇮🇹Genova, Italy
Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena Italia
🇮🇹Milano, Italy
Universita degli Studi di Messina, Policlinico G. Martino
🇮🇹Messina, Italy
Site 33
🇫🇮Vantaa, Finland
Ospedale Maggiore di Novara
🇮🇹Novara, Italy
Pediatria dell' Ospedale Sacco
🇮🇹Milano, Italy
Istituto di Igiene e Medicina Preventiva - Università degli Studi di Sassari
🇮🇹Sassari, Italy
Site 57
🇩🇪Marbach a. N., Germany
ASL/TA
🇮🇹Taranto, Italy
Maurer
🇦🇹Salzburg, Austria
Angermayr
🇦🇹Wels, Austria
Sommer
🇦🇹Wien, Austria
Häckel
🇦🇹Kirchdorf, Austria
Site 13
🇨🇿Humpolec, Czech Republic
Site 21
🇨🇿Kolín, Czech Republic
Altenburger
🇦🇹Eisenstadt, Austria
Grässl
🇦🇹Hall in Tirol, Austria
Site 35
🇫🇮Kokkola, Finland
Site 46
🇫🇮Kuopio, Finland
Prieler
🇦🇹Neufeld a.d. Leitha, Austria
Site 27
🇨🇿Boskovice, Czech Republic
Site 19
🇨🇿Brno, Czech Republic
Site 22
🇨🇿Chomutov, Czech Republic
Site 12
🇨🇿Havlíčkův Brod, Czech Republic
Fakulta vojenskeho zdravotnictví
🇨🇿Hradec Králové, Czech Republic
Site 10
🇨🇿Liberec, Czech Republic
Site 24
🇨🇿Litomerice, Czech Republic
Site 18
🇨🇿Ostrava-Poruba, Czech Republic
Site 17
🇨🇿Ostrava, Czech Republic
Site 16
🇨🇿Plzeň, Czech Republic
Site 26
🇨🇿Rumburk, Czech Republic
Site 23
🇨🇿Usti nad Labem, Czech Republic
Site 30
🇫🇮Espoo, Finland
Site 31
🇫🇮Helsinki, Finland
Site 32
🇫🇮Helsinki, Finland
Site 34
🇫🇮Järvenpää, Finland
Site 47
🇫🇮Lahti, Finland
Site 49
🇫🇮Oulu, Finland
Site 51
🇫🇮Seinäjoki, Finland
Site 52
🇫🇮Tampere, Finland
Site 53
🇫🇮Turku, Finland
Site 48
🇫🇮Vantaa, Finland
Site 65
🇩🇪Schwieberdingen, Germany