Persistence of Antibody Levels and Response to Fifth or Third Meningococcal B Recombinant Vaccine in 4-year Old Healthy Children Who Previously Participated in Study V72P12E1

A Phase 3, Open Label, Multi-Center, Extension Study to Assess Antibody Persistence and Response to a Third or Fifth Dose of Novartis Meningococcal B Recombinant Vaccine in 4-Year-Old Children Who Previously Participated in Study V72P12E1

It is a Phase 3 extension of study V72P12E1 (NCT00944034). The main aim of the second extension study is to explore the bactericidal antibody persistence in 4-year-old children after a fourth dose boost of rMenB+OMV NZ or after a two-dose catch-up schedule of rMenB+OMV NZ administered to toddlers as part of their respective vaccination courses in study V72P12E1.

In addition, this study will characterize the antibody response to a fifth dose boost in all children who received a three-dose primary series of rMenB+OMV NZ at 2, 3, 4 months of age (in parent study V72P12, NCT00721396), and only in a subset of children who received a three-dose primary series of rMenB+OMV NZ at 2, 4, 6 months of age (in parent study V72P12). Antibody response will also be characterized to a third dose boost of rMenB+OMV NZ administered at approximately 4 years of age in all children who received a two catch-up doses of rMenB+OMV NZ as toddlers in study V72P12E1.

Finally, the safety and immunogenicity of two catch-up doses of rMenB+OMV NZ administered 2 months apart to healthy naïve children at 4 years of age will be assessed.

Study Overview

• Status: Completed
• Conditions: Meningococcal Disease; Meningococcal Meningitis
• Intervention / Treatment: Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; Biological: 2 doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine

• Study Type: Interventional
• Enrollment (Actual): 805
• Phase: Phase 3

Contacts and Locations

Study Locations

• Czech Republic
  • Alšova 466
    • Jaromer, Alšova 466, Czech Republic, 55101
      • Ordinace praktického lékaře pro děti a dorost
  • Dr. E.Beneše 191
    • Jaromer, Dr. E.Beneše 191, Czech Republic, 55101
      • Ordinace praktického lékaře pro děti a dorost
  • Havlickova 168
    • Sezemice, Havlickova 168, Czech Republic, 53304
      • Ordinace praktického lékaře pro děti a dorost
  • Hostovského 485
    • Hronov, Hostovského 485, Czech Republic, 54931
      • Ordinace praktického lékaře pro děti a dorost
  • Husovo namesti 36
    • Ceska Skalice, Husovo namesti 36, Czech Republic, 55203
      • Ordinace praktického lékaře pro děti a dorost
  • L.Male 656
    • Pardubice, L.Male 656, Czech Republic, 53012
      • Ordinace praktického lékaře pro děti a dorost
  • Manesova 646
    • Hradec Králové, Manesova 646, Czech Republic, 50002
      • Ordinace praktického lékaře pro děti a dorost
  • Palackeho 517
    • Hronov, Palackeho 517, Czech Republic, 54931
      • Ordinace praktického lékaře pro děti a dorost
  • Pardubicka 752
    • Hradec Králové, Pardubicka 752, Czech Republic, 50004
      • Ordinace praktického lékaře pro děti a dorost
  • Pernstynska 127/I
    • Chlumec nad Cidlinou, Pernstynska 127/I, Czech Republic, 50351
      • Ordinace praktického lékaře pro děti a dorost
  • Purkynova 446
    • Nachod, Purkynova 446, Czech Republic, 54701
      • Nemocnice Náchod
  • Ruských legií 352
    • Jindrichuv Hradec, Ruských legií 352, Czech Republic, 37701
      • Ordinace praktického lékaře pro děti a dorost
  • Sladkovskeho 2617
    • Pardubice, Sladkovskeho 2617, Czech Republic, 53002
      • Ordinace praktického lékaře pro děti a dorost
  • Sídliste Vajgar 724/III
    • Jindrichuv Hradec, Sídliste Vajgar 724/III, Czech Republic, 37701
      • Ordinace praktického lékaře pro děti a dorost
  • Trebesska 1575
    • Hradec Kralove, Trebesska 1575, Czech Republic, 50001
      • Fakulta vojenskeho zdravotnictvi UO
  • U kaplicky 1042
    • Holice, U kaplicky 1042, Czech Republic, 53401
      • Ordinace praktického lékaře pro děti a dorost
  • U nemocnice380/III
    • Jindrichuv Hradec, U nemocnice380/III, Czech Republic, 37701
      • Ordinace praktického lékaře pro děti a dorost
• Italy
  • Florence, Italy, 50139
    • Universita di Firenze -Pediatria
  • Milan, Italy, 20122
    • IRCCS Cà Granda
  • Novara, Italy, 28100
    • Ospedale Maggiore della Carità
  • Padova, Italy, 35128
    • Dip Pediatria AO Padova
• Spain
  • Santiago de Compostela A Coruña, Spain, 15706
    • Hospital Clinico Universitario de Santiago de Compostela
  • Valencia, Spain, 46017
    • Hospital Universitario Dr. Peset
  • Valencia, Spain, 46020/46001
    • Centro Superior de Investigacion en Salud Publica/Clinica Universitaria San Vicente Martir
  • Vigo Pontevedra, Spain, 36204
    • Complexo Hospitalario Xeral Cies
• United Kingdom
  • Bristol, United Kingdom, BS1 3NU
    • North Bristol NHS Trust
  • Exeter, United Kingdom, EX2 5DW
    • Royal Devon and Exeter NHS Foundation Trust
  • London, United Kingdom, SW17 0RE
    • St Georges Hospital
  • Headington
    • Oxford, Headington, United Kingdom, OX3 7LJ
      • Oxford Vaccine Group - Centre for Clinical Vaccinology and Tropical Medicine Churchill Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 4 years to 5 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

A. Inclusion Criteria for naïve subjects, newly enrolled (B48_50):

1. 4 years old (48 to 60 months) healthy male and female subjects will be recruited from the same sites as in study V72P12E1. The age window is defined as the first day the subject turns 4 years old up to the day before the subject turns 5 years old.
2. For whom parent/legal guardian(s) has given written informed consent after the nature of the study has been explained.
3. For whom parent/legal guardian(s) confirmed availability for the visit(s) scheduled in the study.
4. In good health as determined by medical history, physical examination, clinical judgment of the investigator.

B. Inclusion Criteria for follow-on participants (Groups B+R246 12_48, B+R246 18_48, B+R246 24_48, B246 12_48, B246 18_48, B246 24_48, B+R234 12_48, B+R234 18_48, B+R234 24_48, B12 14_48, B18 20_48, B24 26_48):

Inclusion criteria are the same as for Group B48_50, with the addition that they are subjects who completed the vaccination course of V72P12E1 study.

Exclusion Criteria:

A. Exclusion Criteria for naïve subjects, newly enrolled (Group 7):

1. Subjects whose parents/legal guardians are unwilling or unable to give written informed consent to participate in the study.
2. History of any meningococcal B vaccine administration.
3. Previous ascertained or suspected disease caused by N. meningitidis.
4. Household contact with and/or intimate exposure to an individual with laboratory confirmed N. meningitidis.
5. History of allergic reaction to any vaccine component.
6. Significant chronic infection.
7. 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).
8. Known or suspected impairment/alteration of the immune system resulting from (for example) receipt of chronic immunosuppressive therapy or immunostimulants.
9. Participation in another clinical trial within 90 days prior to enrolment or planned for during study.
10. Family members and household members of research staff.
11. Any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives.

B. Exclusion Criteria for follow-on participants ((Groups B+R246 12_48, B+R246 18_48, B+R246 24_48, B246 12_48, B246 18_48, B246 24_48, B+R234 12_48, B+R234 18_48, B+R234 24_48, B12 14_48, B18 20_48, B24 26_48):

Exclusion criteria are the same as for Group B48_50, with the exception of criterion 2 and excluding participation in V72P12E1 for criterion 9.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

13

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: B+R246_12_48; Previously received rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine + routine vaccines at 2, 4 and 6 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 12 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B+R246_18_48; Previously received rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine + routine vaccines at 2, 4 and 6 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 18 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B+R246_24_48; Previously received rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine + routine vaccines at 2, 4 and 6 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 24 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B246_12_48; Previously received 3 doses of rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine at 2, 4 and 6 months of age and routine vaccines at 3, 5 and 7 months of age, followed by a booster dose of rMenB+OMV NZ vaccine at 12 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B246_18_48; Previously received 3 doses of rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine at 2, 4 and 6 months of age and routine vaccines at 3,5 and 7 months of age, followed by a booster dose of rMenB+OMV NZ at 18 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B246_24_48; Previously received 3 doses of rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine at 2, 4 and 6 months of age and routine vaccines at 3, 5 and 7 months of age, followed by a booster dose of rMenB+OMV NZ vaccine at 24 months of age. One third of subjects from this group received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B+R234_12_48; Previously received 3 doses of rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine + routine vaccines at 2, 3 and 4 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 12 months of age. All subjects received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B+R234_18_48; Previously received rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine + routine vaccines at 2, 3 and 4 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 18 months of age. All subjects received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B+R234_24_48; Previously received rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine + routine vaccines at 2, 3 and 4 months of age followed by a booster dose of rMenB+OMV NZ vaccine at 24 months of age. All subjects received a 5th dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B12 14_48; Previously received two catch-up doses of rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine at 12 and14 months of age. All subjects received a 3rd dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B18 20_48; Previously received two catch-up doses of rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine at 18 & 20 months of age. All subjects received a 3rd dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B24 26_48; Previously received two catch-up doses of rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine at 24 & 26 months of age. All subjects received a 3rd dose of rMenB+OMV NZ vaccine in the present study at 4 years of age.	Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, single dose; Other Names: rMenB+OMV NZ
Experimental: B48_50; Newly recruited 4 year old naive subjects who received 2 catch-up doses of rMenB+OMV NZ, ie, Meningococcal (group B) multicomponent recombinant adsorbed vaccine, two months apart, in the present study.	Biological: 2 doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine; 0.5 mL of Meningococcal (group B) multicomponent recombinant adsorbed vaccine, Intramuscular, two doses, two months apart; Other Names: rMenB+OMV NZ

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Subjects With Persisting Serum Bactericidal Titers ≥1:5 and ≥1:8 (at 4 Years of Age), Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules	The antibody persistence at 4 years of age in children who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12,18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the response in naïve children and reported as percentages of subjects with human serum bactericidal assay (hSBA) titers ≥1:5 and ≥1:8. The functional bactericidal antibodies directed against serogroup B meningococci were assessed using the Serum Bactericidal Assay (SBA) using human serum as the source of exogenous complement (hSBA).	Day 1 (24-36 months post booster; baseline for naive)
Persisting Antibody Titers in Children (at 4 Years of Age) Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules	The persisting antibody titers at 4 years of age in children who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the titers in naive children and reported as geometric mean titers (GMTs).	Day 1 (24-36 months post booster; baseline for naive)
Geometric Mean Ratios (GMRs) in Children (at 4 Years of Age) Who Had Previously Received Three Primary Doses and One Booster Dose of rMenB+OMV NZ Vaccine According to Different Schedules	The GMRs of GMTs (48 months/one month post booster vaccination) at 4 years of age in children who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12,18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is reported.	Day 1 (24-36 months post booster dose; baseline for naive)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentages of Subjects With Persisting Serum Bactericidal Titers ≥1:5 and ≥1:8 (at 4 Years of Age), Who Had Previously Received Two Catch up Doses of rMenB+OMV NZ Vaccine According to Different Schedules	The antibody persistence in children at 4 year of age, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) according to different schedules is reported as percentages of subjects with hSBA titers ≥1:5 and hSBA titers ≥1:8.	Day 1 (22-34 months post last MenB vaccine)
Persisting Antibody Titers in Children (at 4 Years of Age) Who Had Previously Received Two Catch up Doses of rMenB+OMV NZ Vaccine According to Different Schedules	The persisting GMTs in children at 4 years of age, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules are reported.	Day 1 (22-36 months post last MenB vaccine; baseline for naive)
GMRs of GMTs in Children (at 4 Years of Age) Who Had Previously Received Two Catch up Doses of rMenB+OMV NZ Vaccine According to Different Schedules	The GMRs of GMTs (48 months/one month post last vaccination) in children at 4 years of age who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules.	Day 1 (22-34 months post last MenB vaccine)
Percentages of Subjects With Serum Bactericidal Titers ≥1:5 and ≥1:8 After a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Had Previously Received 3 Primary Doses and a Booster Dose of the Same Vaccine According to Different Schedules	The Percentages of subjects with hSBA titers ≥1:5 and ≥1:8, one month after a 5th dose of rMenB+OMV NZ vaccine was given children who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of the same vaccine according to different schedules is compared with the hSBA response of children who received first dose of rMenB+OMV NZ at 4 years of age.	Day 31 (1 month post vaccination)
GMTs in Children Following a Fifth Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Had Previously Received 3 Primary Doses and a Booster Dose of the Same Vaccine According to Different Schedules	The GMTs, at one month after a 5th dose of rMenB+OMV NZ vaccine in children who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules, are compared with the GMTs of children who received first dose of rMenB+OMV NZ at 4 years of age.	Day 31 (1 month post vaccination)
Geometric Mean Ratios of GMTs in Subjects Following a Fifth Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age), Who Had Previously Received 3 Primary Doses and a Booster Dose of the Same Vaccine According to Different Schedules	The GMRs of GMTs (one month post booster/48 months persistence), one month after a 5th dose of rMenB+OMV NZ vaccine was given children, who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) and a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the GMR (one month post 1 dose\baseline) of children who received first dose of rMenB+OMV NZ at 4 years of age.	Day 31 (1 month post vaccination)
Percentages of Subjects With Fourfold Increase in hSBA Titers After Receiving a Fifth Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age), Who Had Previously Received 3 Primary Doses and a Booster Dose of the Same Vaccine According to Different Schedules	The fourfold increase in hSBA titers, one month after a 5th dose of rMenB+OMV NZ vaccine was given to children, who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) and a booster dose (at 12,18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules is compared with the response in children who received the first dose of rMenB+OMV NZ vaccine at 4 years of age.	Day 31 (1 month post vaccination)
Percentages of Subjects With hSBA Titers ≥1:5 and ≥1:8 Following a Third Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age), Who Had Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules	The percentages of subjects with hSBA titers ≥1:5 and hSBA titers ≥1:8 at one month after a third dose of rMenB+OMV NZ vaccine was given to children, who had previously received 2 catch up doses (at 12,14 or 18,20 or 24,26 months) of the same vaccine according to different schedules, are reported.	Day 31 (1 month post vaccination)
GMTs Following a Third Dose of rMenB+OMV NZ Vaccine in Children (at 4 Years of Age) Who Had Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules	The GMTs, one month following a third dose of rMenB+OMV NZ vaccine in 4 year old children who had previously received 2 catch up doses (at 12,14 or 18,20 or 24,26 months) of the same vaccine according to different schedules, are reported.	Day 31 (1 month post vaccination)
GMRs of GMTs in Children Following a Third Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age) Who Previously Received 2 Catch up Doses of the Same Vaccine According to Different Schedules.	The GMRs of GMTs following a third dose of rMenB+OMV NZ vaccine (one month post 3rd dose/persistence at 48 months) in children, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of the same vaccine according to different schedules, are reported.	Day 31 (1 month post vaccination)
Percentages of Subjects With a 4-fold Increase in hSBA Titers Following a Third Dose of rMenB+OMV NZ Vaccine Given at 4 Years of Age to Children Who Previously Received 2 Catch up Doses of the Same Vaccine	The percentage of subjects with a four-fold increase in hSBA titers following a third dose of rMenB+OMV NZ vaccine, who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules,are reported. Fourfold increase is defined as- for subjects with a pre-vaccination titer <1:2 to a post-vaccination titer ≥1:8 and for subjects with a pre-vaccination titer ≥1:2 to a post-vaccination titer ≥ 4 fold pre-vaccination titer.	Day 31 (1 month post vaccination)
Percentages of Subjects With hSBA ≥1:5 and ≥1:8 in Response of Two Catch up Doses of rMenB+OMV NZ Vaccine When Administered to Children at 4 Years of Age.	The sufficiency of immune response is reported in terms of percentages of subjects with hSBA ≥1:5 and ≥1:8 in response of two catch up doses of rMenB+OMV NZ vaccine, administered two months apart, in children at 4 years of age. Immune response was considered sufficient if the lower limit of the two-sided 95% CI for the percentage of subjects achieving hSBA ≥ 1:5 at one month after the two-dose series was ≥ 70% for all three indicator (H44/76; 5/99 and NZ 98/254) strains. Immune sufficiency was not applicable for M10713 strain.	Day 91 (1 month post second vaccination)
GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age	The GMTs in children who received two catch up doses of rMenB+OMV NZ vaccine at 48 and 50 months of age are reported.	Day 91 (1 month post second vaccination)
GMRs of GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age	The GMR of GMTs(one month post dose 2/baseline) in children following a two catch up dose of rMenB+OMV NZ at 48 and 50 months of age are reported.	Day 91 (1 month post second vaccination)
Percentages of Subjects With 4-fold Increase in Serum Bactericidal Titers, Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age	The percentages of subjects with 4-fold increase in hSBA titers, one month following a two catch up dose of rMenB+OMV NZ at 4 years of age are reported.	Day 91 (1 month post second vaccination)
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)	The safety and tolerability of the 5th dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 3 primary doses (at 2, 3, 4, or 2, 4, 6 months) followed by a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules in the earlier studies is reported as number of subjects with solicited local and systemic adverse events.	From day 1 to day 7 after vaccination
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)	The safety and tolerability of the 3rd dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules is reported as number of subjects with solicited local and systemic adverse events.	From day 1 to day 7 after vaccination
Number of Subjects Reporting Solicited Local and Systemic Adverse Events After Receiving a 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age	The safety and tolerability of rMenB+OMV NZ vaccine in 4 year old children who received 2 catch up doses of rMenB+OMV NZ vaccine at 48 and 50 months, is reported as number of subjects with solicited local* and systemic adverse events.	From day 1 to day 7 after any vaccination
Number of Subjects Reporting Unsolicited AEs After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)	The safety and tolerability of the 5th dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 3 primary doses (at 2, 3, 4,or 2, 4, 6 months) followed by a booster dose (at 12, 18 or 24 months) of rMenB+OMV NZ vaccine according to different schedules in the earlier studies is reported as number of subjects with unsolicited AEs, Serious Adverse Events (SAE), AEs leading to premature withdrawal.	From day 1 to study termination
Number of Subjects Reporting Unsolicited AEs After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)	The safety and tolerability of the 3rd dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules is reported as number of subjects with Unsolicited AEs, Serious Adverse Events (SAEs), AEs leading to premature withdrawal.	From day 1 to study termination
Number of Subjects Reporting Unsolicited AEs After Any Vaccination.	The safety and tolerability of the 3rd dose rMenB+OMV NZ vaccine in children (at 4 years of age) who had previously received 2 catch up doses (at 12, 14 or 18, 20 or 24, 26 months) of rMenB+OMV NZ vaccine according to different schedules is reported as number of subjects with unsolicited AEs, Serious Adverse Events (SAEs), AEs leading to premature withdrawal.	From day 1 to study termination

Collaborators and Investigators

• Sponsor: Novartis Vaccines

Publications and helpful links

General Publications

• Sadarangani M, Sell T, Iro MA, Snape MD, Voysey M, Finn A, Heath PT, Bona G, Esposito S, Diez-Domingo J, Prymula R, Odueyungbo A, Toneatto D, Pollard AJ; European MenB Vaccine Study Group. Persistence of immunity after vaccination with a capsular group B meningococcal vaccine in 3 different toddler schedules. CMAJ. 2017 Oct 16;189(41):E1276-E1285. doi: 10.1503/cmaj.161288.

Study record dates

Study Major Dates

• Study Start: November 1, 2012
• Primary Completion (Actual): September 1, 2013
• Study Completion (Actual): October 1, 2013

Study Registration Dates

• First Submitted: October 18, 2012
• First Submitted That Met QC Criteria: October 26, 2012
• First Posted (Estimate): October 30, 2012

Study Record Updates

• Last Update Posted (Estimate): January 13, 2015
• Last Update Submitted That Met QC Criteria: December 29, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Keywords: Meningococcal disease, vaccines, children, persistence
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Infections; Central Nervous System Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Meningitis, Bacterial; Central Nervous System Bacterial Infections; Neisseriaceae Infections; Meningitis, Meningococcal; Meningitis; Meningococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V72P12E2; 2011-004931-30 (EudraCT Number)