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

Phase 3

Completed

Conditions: Meningococcal Disease
Meningococcal Meningitis

Interventions: Biological: 1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine
Biological: 2 doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine

Registration Number: NCT01717638

Lead Sponsor: Novartis Vaccines

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 805

Inclusion Criteria

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

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.
For whom parent/legal guardian(s) has given written informed consent after the nature of the study has been explained.
For whom parent/legal guardian(s) confirmed availability for the visit(s) scheduled in the study.
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):

Subjects whose parents/legal guardians are unwilling or unable to give written informed consent to participate in the study.
History of any meningococcal B vaccine administration.
Previous 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 allergic reaction to any vaccine component.
Significant chronic infection.
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).
Known or suspected impairment/alteration of the immune system resulting from (for example) receipt of chronic immunosuppressive therapy or immunostimulants.
Participation in another clinical trial within 90 days prior to enrolment or planned for during study.
Family members and household members of research staff.
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 & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
B246_18_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B246_24_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B246_12_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B+R246_18_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B+R234_12_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B+R234_24_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B48_50	2 doses of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B+R246_12_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B+R246_24_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B+R234_18_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B18 20_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B24 26_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.
B12 14_48	1 dose of Meningococcal (group B) multicomponent recombinant adsorbed vaccine	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.

Primary Outcome Measures

Name	Time	Method
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	Day 1 (24-36 months post booster; baseline for naive)	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).
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	Day 1 (24-36 months post booster dose; baseline for naive)	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.
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	Day 1 (24-36 months post booster; baseline for naive)	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).

Secondary Outcome Measures

Name	Time	Method
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	Day 1 (22-34 months post last MenB vaccine)	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.
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	Day 31 (1 month post vaccination)	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.
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	Day 31 (1 month post vaccination)	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.
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.	Day 31 (1 month post vaccination)	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.
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	Day 31 (1 month post vaccination)	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.
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	Day 31 (1 month post vaccination)	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.
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	Day 1 (22-34 months post last MenB vaccine)	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.
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	Day 31 (1 month post vaccination)	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.
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	Day 31 (1 month post vaccination)	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.
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	From day 1 to day 7 after any vaccination	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.
Number of Subjects Reporting Unsolicited AEs After Receiving a 5th Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)	From day 1 to study termination	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.
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	Day 1 (22-36 months post last MenB vaccine; baseline for naive)	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.
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.	Day 91 (1 month post second vaccination)	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.
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	Day 31 (1 month post vaccination)	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.
GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age	Day 91 (1 month post second vaccination)	The GMTs in children who received two catch up doses of rMenB+OMV NZ vaccine at 48 and 50 months of age are reported.
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	Day 91 (1 month post second vaccination)	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.
GMRs of GMTs Following 2 Catch up Doses of rMenB+OMV NZ Vaccine at 4 Years of Age	Day 91 (1 month post second vaccination)	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.
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)	From day 1 to day 7 after vaccination	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.
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)	From day 1 to day 7 after 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 solicited local and systemic adverse events.
Number of Subjects Reporting Unsolicited AEs After Any Vaccination.	From day 1 to study termination	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.
Number of Subjects Reporting Unsolicited AEs After Receiving a 3rd Dose of rMenB+OMV NZ Vaccine (at 4 Years of Age)	From day 1 to study termination	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.

Trial Locations

Locations (15): Ordinace praktickeho lekare pro deti a dorost
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Jindrichuv Hradec, U nemocnice380/III, Czech Republic
Nemocnice Náchod
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Nachod, Purkynova 446, Czech Republic
Fakulta vojenskeho zdravotnictvi UO
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Hradec Kralove, Trebesska 1575, Czech Republic
IRCCS Cà Granda
🇮🇹
Milan, Italy
Universita di Firenze -Pediatria
🇮🇹
Florence, Italy
Ospedale Maggiore della Carita
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Novara, Italy
Hospital Universitario Dr. Peset
🇪🇸
Valencia, Spain
Dip Pediatria AO Padova
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Padova, Italy
Hospital Clinico Universitario de Santiago de Compostela
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Santiago de Compostela A Coruña, Spain
Centro Superior de Investigacion en Salud Publica/Clinica Universitaria San Vicente Martir
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Valencia, Spain
Oxford Vaccine Group - Centre for Clinical Vaccinology and Tropical Medicine Churchill Hospital
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Oxford, Headington, United Kingdom
North Bristol NHS Trust
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Bristol, United Kingdom
St Georges Hospital
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London, United Kingdom
Royal Devon and Exeter NHS Foundation Trust
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Exeter, United Kingdom
Complexo Hospitalario Xeral Cies
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Vigo Pontevedra, Spain