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

A Phase 3, Open Label, Multi-Center, Extension Study 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 Who Participated in Study V72P13

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

Study Overview

• Status: Completed
• Conditions: Meningococcal Disease
• Intervention / Treatment: Biological: 1a - rMenB+OMV NZ and routine vaccines; Biological: 1b - rMenB+OMV NZ and routine vaccines; Biological: 2a - Routine and rMenB+OMV NZ vaccines; Biological: 2b - rMenB+OMV NZ and routine vaccines; Biological: 3a - rMenB+OMV NZ and routine vaccines; Biological: 3b - 1 dose of rMenB+OMV NZ plus routine infant vaccinations; Biological: 4a- rMenB+OMV NZ and routine vaccines; Biological: 4b - rMenB+OMV NZ and routine vaccines

• Study Type: Interventional
• Enrollment (Actual): 2249
• Phase: Phase 3

Contacts and Locations

Study Locations

• Austria
  • Eisenstadt, Austria, 7000
    • Altenburger
  • Hall in Tirol, Austria, 6060
    • Grässl
  • Kirchdorf, Austria, 4560
    • Häckel
  • Neufeld a.d. Leitha, Austria, 2491
    • Prieler
  • Salzburg, Austria, 5020
    • Maurer
  • Wels, Austria, 4600
    • Angermayr
  • Wien, Austria, 1230
    • Sommer
• Czech Republic
  • Boskovice, Czech Republic, 680 01
    • Site 27
  • Brno, Czech Republic, 628 00
    • Site 19
  • Chomutov, Czech Republic, 430 03
    • Site 22
  • Havlíčkův Brod, Czech Republic, 580 22
    • Site 12
  • Hradec Králové, Czech Republic, 500 01
    • Fakulta vojenskeho zdravotnictví
  • Hranice I-mesto, Czech Republic, 753 01
    • Site 28
  • Humpolec, Czech Republic, 396 01
    • Site 13
  • Kladno 2, Czech Republic, 272 00
    • Site 25
  • Kolín, Czech Republic, 280 02
    • Site 21
  • Liberec, Czech Republic, 460 15
    • Site 10
  • Litomerice, Czech Republic, 412 01
    • Site 24
  • Ostrava, Czech Republic, 702 00
    • Site 17
  • Ostrava-Poruba, Czech Republic, 708 68
    • Site 18
  • Plzeň, Czech Republic, 305 99
    • Site 16
  • Rumburk, Czech Republic, 408 01
    • Site 26
  • Usti nad Labem, Czech Republic, 400 01
    • Site 23
• Finland
  • Espoo, Finland, 02100
    • Site 30
  • Helsinki, Finland, 00100
    • Site 31
  • Helsinki, Finland, 00930
    • Site 32
  • Järvenpää, Finland, 04400
    • Site 34
  • Kokkola, Finland, 67100
    • Site 35
  • Kotka, Finland, 48600
    • Site 45
  • Kuopio, Finland, 70100
    • Site 46
  • Lahti, Finland, 15140
    • Site 47
  • Oulu, Finland, 90220
    • Site 49
  • Pori, Finland, 28100
    • Site 50
  • Seinäjoki, Finland, 60100
    • Site 51
  • Tampere, Finland, 33100
    • Site 52
  • Turku, Finland, 20520
    • Site 53
  • Vantaa, Finland, 01300
    • Site 33
  • Vantaa, Finland, 01600
    • Site 48
• Germany
  • Detmold, Germany, 32756
    • Site 99
  • Espelkamp, Germany, 32339
    • Site 92
  • Freising, Germany, 85354
    • Site 95
  • Fulda, Germany, 36037
    • Site 64
  • Lauffen, Germany, 74348
    • Site 58
  • Marbach a. N., Germany, 71672
    • Site 57
  • München, Germany, 81377
    • Site 97
  • München, Germany, 81475
    • Site 96
  • München, Germany, 80337
    • Site 80
  • München, Germany, 81241
    • Site 83
  • Műnchen, Germany, 81737
    • Site 91
  • Porta Westfalica, Germany, 32457
    • Site 81
  • Schwieberdingen, Germany, 71701
    • Site 65
  • Weilheim, Germany, 82362
    • Site 94
• Italy
  • Genova, Italy, 16132
    • Dipartimento di Scienze della Salute
  • Messina, Italy
    • Universita degli Studi di Messina, Policlinico G. Martino
  • Milano, Italy, 20122
    • Fondazione IRCCS Ospedale Maggiore Policlinico, Mangiagalli e Regina Elena Italia
  • Milano, Italy, 20157
    • Pediatria dell' Ospedale Sacco
  • Novara, Italy, 28100
    • Ospedale Maggiore di Novara
  • Sassari, Italy, 07100
    • Istituto di Igiene e Medicina Preventiva - Università degli Studi di Sassari
  • Taranto, Italy, 74100
    • ASL/TA

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 1 year (CHILD)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy 12-month-old toddlers (0/ +29 days) who completed Study V72P13

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: PREVENTION
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

Number of Arms

8

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: 12B12M (1a); 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.	Biological: 1a - rMenB+OMV NZ and routine vaccines; One dose of rMenB vaccine and routine vaccine at study month 12.
EXPERIMENTAL: 12B13M (1b); 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.	Biological: 1b - rMenB+OMV NZ and routine vaccines; One dose of rMenB vaccine at study month 12 and routine vaccine at study month 13.
EXPERIMENTAL: 12M13B15B (2a); 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.	Biological: 2a - Routine and rMenB+OMV NZ vaccines; One dose of routine vaccine at study month 12 and two doses of rMenB vaccine at study months 13 and 15.
EXPERIMENTAL: 12M12B14B (2b); 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.	Biological: 2b - rMenB+OMV NZ and routine vaccines; Two doses of rMenB vaccine at study months 12 and 14 and one dose of routine vaccine at study month 12.
EXPERIMENTAL: 12B12M (3a); 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.	Biological: 3a - rMenB+OMV NZ and routine vaccines; One dose of rMenB vaccine and one dose of routine vaccine at study month 12.
EXPERIMENTAL: 12B13M (3b); 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.	Biological: 3b - 1 dose of rMenB+OMV NZ plus routine infant vaccinations; One dose of rMenB vaccine at study month 12 and one dose of routine vaccine study month 13.
EXPERIMENTAL: 12B12M_C (4a); 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.	Biological: 4a- rMenB+OMV NZ and routine vaccines; One dose of rMenB vaccine and one dose of routine vaccine at study month 12.
EXPERIMENTAL: 12B13M_C (4b); 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.	Biological: 4b - rMenB+OMV NZ and routine vaccines; One dose of rMenB vaccine and one dose of routine vaccine at study month 12.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Subjects With Serum Bactericidal Antibody Titers ≥1:5 After Receiving the Booster Dose of rMenB+OMV NZ Vaccination	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.	one month after the booster (fourth) dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Subjects With Antibody Response After Receiving the MMRV Vaccination	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.	one month after booster (fourth) dose
The Geometric Mean Titers After Receiving the Booster Dose of rMenB+OMV NZ 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).	one month after booster (fourth) vaccination.
Geometric Mean Titers at 12 Months of Age (Predose 4) After Previously Receiving the Three Doses of rMenB+OMV NZ (Persistence)	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.	one month after third vaccination and pre dose fourth (booster) vaccination
Percentages of Subjects With Serum Bactericidal Antibody Titers ≥1:5 After Previously Receiving the Three Doses of rMenB+OMV NZ Vaccination (Persistence)	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.	One month post vaccination and pe-booster (fourth) dose vaccination
Geometric Mean Titers After Receiving the Booster Dose and Single Dose of rMen+OMV NZ Vaccination (Induction of Immunological Memory)	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.	one month after booster (fourth) dose vaccination and pre-fourth dose vaccination
SBA GMTs After a Two-dose Catch-up Schedule or Two-dose Schedule	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.	One month after the second dose.
Percentages of Subjects With SBA Titers ≥1:5 After a Two-dose Catch-up Schedule or Two-dose Schedule	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.	One month after the second dose.
ELISA Geometric Mean Concentration Against Vaccine Antigen 287-953 One Month After the Fourth (Booster) Dose Given at 12 Months	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).	One month after the fourth (booster) dose.
ELISA Geometric Mean Concentration Against Vaccine Antigen 287-953 After Two-dose Catch-up in Toddlers	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.	One month after the first dose and one month after the second dose.
Percentages of Subjects With Bactericidal Titers ≥ 1:5 (95% CI) Against Strain M10713 One Month After the Fourth (Booster) Dose Given at 12 Months	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).	One month after the fourth (booster) dose.
Number of Subjects Reporting Solicited Local and Systemic Reactions During the 7 Days Following rMenB+OMV NZ Vaccination at 12 Months of Age	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.	From day 1 to day 7 after each rMenB+OMV NZ vaccination.
Number of Subjects Reporting Solicited Local and Systemic Reactions During the 7 Days Following Two-dose Catch-up Schedules of 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 with a two-dose catch-up schedules (groups 12M13B15B and 12M12B14B).	From day 1 to day 7 after each rMenB+MV NZ vaccination.
Number of Subjects Reporting Solicited Local Reactions During the 7 Days Following MMRV Vaccination at 12 Months of Age	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.	From day 1 to day 7 after MMRV vaccination.
Number of Subjects Reporting Solicited Systemic Reactions During 8-28 Days Following MMRV Vaccination at 12 Months of Age	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.	From day 8 to day 28 after MMRV vaccination.

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• Zafack JG, Bureau A, Skowronski DM, De Serres G. Adverse events following immunisation with four-component meningococcal serogroup B vaccine (4CMenB): interaction with co-administration of routine infant vaccines and risk of recurrence in European randomised controlled trials. BMJ Open. 2019 May 19;9(5):e026953. doi: 10.1136/bmjopen-2018-026953.
• Vesikari T, Esposito S, Prymula R, Ypma E, Kohl I, Toneatto D, Dull P, Kimura A; EU Meningococcal B Infant Vaccine Study group. Immunogenicity and safety of an investigational multicomponent, recombinant, meningococcal serogroup B vaccine (4CMenB) administered concomitantly with routine infant and child vaccinations: results of two randomised trials. Lancet. 2013 Mar 9;381(9869):825-35. doi: 10.1016/S0140-6736(12)61961-8. Erratum In: Lancet. 2013 Mar 9;381(9869):804.

Study record dates

Study Major Dates

• Study Start: February 1, 2009
• Primary Completion (ACTUAL): August 1, 2010
• Study Completion (ACTUAL): August 1, 2010

Study Registration Dates

• First Submitted: February 18, 2009
• First Submitted That Met QC Criteria: February 18, 2009
• First Posted (ESTIMATE): February 19, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): March 3, 2015
• Last Update Submitted That Met QC Criteria: March 2, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: prevention; vaccination; toddler; Meningococcal disease
• Additional Relevant MeSH Terms: Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Neisseriaceae Infections; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V72P13E1; 2008-006301-17 (EUDRACT_NUMBER)