Extension Study Evaluating Antibody Persistence and Safety, Tolerability and Immunogenicity of a Booster Dose of Novartis rMenB±OMV NZ Vaccine in Healthy UK Children Who Previously Received Three Doses of the Same Vaccine

Meningococcal Disease Clinical Trial

Official title:

A Phase 2, Open-Label, Single-Center, Extension Study Evaluating Antibody Persistence Compared to Naïve Children and Safety, Tolerability and Immunogenicity of a Booster Dose of Novartis rMenB±OMV NZ Vaccine in Healthy UK Children Who Previously Received a Three-Dose Series of the Novartis Vaccine as Infants in Study V72P9

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01026974
• Other study ID #: V72P9E1
• Secondary ID: EUDRACT 2009-013
• Status: Completed
• Phase: Phase 2
• First received: December 4, 2009
• Last updated: September 18, 2014
• Start date: February 2010
• Est. completion date: May 2012

Study information

• Verified date: September 2014
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The proposed study V72P9E1 is an Extension Study of V72P9. The objectives of this extension study will be to explore antibody persistence in children at approximately 40 months of age and to evaluate the safety, tolerability and immunogenicity of a booster dose of rMenB±OMV NZ administered to subjects at approximately 40 months of age. Antibody persistence will be subsequently measured at 18-20 months after these booster doses when the subjects are 60 months of age. Two groups of naïve subjects, aged approximately 40 and 60 months, will be recruited in the study to serve as a baseline comparator for assessing antibody persistence at these ages. These subjects will receive a two-dose catch-up regimen with rMenB+OMV NZ. Subjects who are enrolled at 40 months of age are offered DTaP/IPV and MMR vaccinations , if they have not already received these vaccines prior to enrollment.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: May 2012
• Est. primary completion date: September 2010
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 40 Months to 62 Months

Eligibility

Inclusion Criteria:

• Healthy 40 to 44-months-old children, who participated and completed the study V72P9 (follow-on subjects)

• Healthy 40 to 44-months or 60 to 62-months-old children (naïve subjects)

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 and after vaccination with the investigational vaccines (within 14 days for licensed flu vaccines)

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• Meningococcal Disease
• Meningococcal Infections

Intervention

Biological:
• rMenB

• rMenB+OMV NZ

Locations

Country	Name	City	State
United Kingdom	Oxford Vaccine Group, Center for Clinical Vaccinology and Tropical Medicine, Churchill Hospital	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Country where clinical trial is conducted

United Kingdom, 

References & Publications (1)

McQuaid F, Snape MD, John TM, Kelly S, Robinson H, Houlden J, Voysey M, Toneatto D, Kitte C, Dull PM, Pollard AJ. Persistence of bactericidal antibodies to 5 years of age after immunization with serogroup B meningococcal vaccines at 6, 8, 12 and 40 months of age. Pediatr Infect Dis J. 2014 Jul;33(7):760-6. doi: 10.1097/INF.0000000000000327. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Persistence of Serum Bactericidal Antibody Titers in Children (at 40 Months of Age), Twenty-eight Months After Completing Primary Vaccination.	The geometric mean antibody titers (GMTs) against Neisseria meningitidis serogroup B in children (at 40 months of age); twenty-eight months after completion of primary vaccination with either rMenB or rMenB+OMV NZ vaccines, are compared with the GMTs in vaccine-naïve children.	28 months after primary vaccination; Baseline for Naïve	No
Primary	Percentage of Subjects With Persisting Serum Bactericidal Antibodies Titers =4, Twenty-eight Months After Completing Primary Vaccination.	The percentages of subjects with persisting serum bactericidal antibodies (hSBA) titers =4, against N meningitidis serogroup B at 40 months of age; twenty-eight months after completion of primary vaccination with either rMenB or rMenB+OMV NZ as compared to the vaccine-naïve children are reported.; The serum bactericidal antibodies directed against serogroup B meningococci, are measured by human complement Serum Bactericidal Assay (hSBA).	28 months after primary vaccination; Baseline for Naïve	No
Primary	Number of Subjects Reporting Solicited Local and Systemic Adverse Events After a Booster Dose of rMenB or rMenB+OMV NZ Vaccine at Forty Months of Age.	The safety and tolerability of a single booster dose of rMenB or rMenB+OMV NZ vaccine in 40 month old children who had previously received three primary doses of the same vaccine as infants in parent study was assessed in terms of number of subjects with solicited local and systemic reactions following vaccination and compared to tolerability in vaccine-naive children who received 1st catch-up dose of rMenB+OMV NZ at 40 months of age.	Day 1 to Day 7 [after booster vaccination /post dose 1 for naive]	Yes
Secondary	Serum Bactericidal Antibody Titers in Children After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine Given at 40 Months of Age	The serum bactericidal antibody response one month after a booster dose of rMenB or rMenB+OMV NZ vaccine was given to children at 40 months of age is compared with the antibody titers following one catch-up dose rMenB+OMV NZ vaccine given at 40 months to vaccine-naive subjects and reported as GMTs.	1 month post booster /1 month post dose 1 for Naïve	No
Secondary	Percentage of Subjects With Serum Bactericidal Antibody Titers =4 After Receiving a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine at 40 Months of Age	The percentages of subjects with hSBA titers =4 against N meningitidis serogroup B one month after receiving a single booster dose of rMenB or rMenB+OMV NZ vaccine at 40 months of age, is compared with hSBA response following one catch-up dose of rMenB+OMV NZ vaccine given at 40 months in vaccine-naive subjects.	1 month post-booster/ 1 month post-dose 1 for Naïve	No
Secondary	Percentage of Subjects With a 4-fold Increase in Antibody Titers After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine Given at 40 Months of Age	The percentages of subjects with four-fold increase in hSBA titers over baseline against N meningitidis serogroup B, one month after receiving a single booster dose of rMenB or rMenB+OMV NZ vaccine at 40 months of age, and compared with 4-fold increase in hSBA titers following one catch-up dose of rMenB+OMV NZ vaccine given at 40 months to vaccine-naive subjects.; Baseline was defined as either the time that the (first) booster dose was given (i.e. at 40 months of age) or the time of the first vaccination (i.e. at 40 months of age for Naive_4042 group.	1 month post booster / 1 month post dose 1 for Naïve	No
Secondary	Persistence of Serum Bactericidal Antibody Titers in Children (at 60 Months of Age), Twenty Months After Receiving a Booster Dose of rMenB or rMenB+OMV NZ Vaccine	The persisting serum bactericidal antibody titers in children (at 60 months of age), twenty months after receiving a booster dose of either rMenB or rMenB+OMV NZ vaccine (at 40 months of age) is compared with the antibody titers in vaccine -naïve subjects of the same age and reported as GMTs.	20 months post booster/ Baseline for Naïve	No
Secondary	Percentage of Subjects With Persisting Serum Bactericidal Antibody Titers =4, Twenty Months After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine	The percentage of subjects (60 months of age) with persisting hSBA titers =4, twenty months after receiving a booster dose of either rMenB or rMenB+OMV NZ vaccine (at 40 months of age) are compared with hSBA response in vaccine-naïve subjects of the same age.	20 months post booster/ Baseline for Naïve	No
Secondary	Percentage of Subjects With Serum Bactericidal Antibody Titers =4 Following Two Doses of rMenB+OMV NZ Vaccine Given One Month Apart, Either at 40 or 60 Months of Age	The percentage of subjects with hSBA titers =4 after two catch-up doses of rMenB+OMV NZ vaccine when given either at- 40 & 42 months or 60 & 62 months of age is reported.	1 month post -vaccine dose two	No
Secondary	Serum Bactericidal Antibody Titers in Children Following Two Doses of rMenB+OMV NZ Vaccine Given One Month Apart, Either at 40 or 60 Months of Age.	The serum bactericidal antibody response in children after two catch-up doses of rMenB+OMV NZ vaccine when given either at- 40 & 42 months or 60 & 62 months of age are reported as GMTs.	1 month post vaccine dose two	No
Secondary	Percentage of Subjects With a 4-fold Increase in Antibody Titers After Two Catch up Doses of rMenB+OMV NZ Vaccine Given One Month Apart Either at 40 or 60 Months of Age	The percentages of subjects with four-fold increase in hSBA titers over baseline against N meningitidis serogroup B one month after receiving a two catch-up doses of rMenB+OMV NZ vaccine either at 40 & 42 months or 60 & 62 months of age.	1 month post vaccine dose 2	No
Secondary	Persistence of Serum Bactericidal Antibody Titers in Children (at 60 Months), Eighteen Months After Receiving Two Catch-up Doses of rMenB+OMV NZ Vaccine.	The serum bactericidal antibody response in children at 60 months of age who had received two catch-up doses of rMenB+OMV NZ vaccine at- 40 & 42 months age is reported as GMTs.	18 months post vaccine dose 2	No
Secondary	Percentage of Subjects With Serum Bactericidal Antibody Titers =4, Eighteen Months After Receiving Two Catch-up Doses of rMenB+OMV NZ Vaccine.	Persisting hSBA titers =4 in children at 60 months of age, who had received two catch-up doses of rMenB+OMV NZ vaccine at 40 & 42 months age is reported.	18 months post vaccine dose two	No
Secondary	Geometric Mean Antibody Concentrations in Children (at 40 Months of Age), Twenty Eight Months After Completing Primary Vaccination.	The persisting geometric mean antibody concentrations (GMCs) against vaccine antigen 287-953 in children (at 40 months of age), twenty-eight months after completion of primary vaccination with either rMenB or rMen+OMV NZ vaccines, are compared with the GMCs in vaccine-naïve children.; GMCs against vaccine antigen 287-953 were measured using enzyme linked immunosorbent assay (ELISA).	28 months after primary vaccination/ Baseline for Naïve	No
Secondary	Geometric Mean Antibody Concentrations in Children, After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine Given at 40 Months of Age.	The GMCs against vaccine antigen 287-953, in children one month after receiving a single booster dose of either rMenB or rMen+OMV NZ vaccine , is compared with GMCs following one catch-up dose of rMenB+ OMV NZ in children at 40 months.	1 month post booster /1 month post dose 1 for Naïve	No
Secondary	Geometric Mean Antibody Concentrations in Children (at 60 Months of Age), Twenty Months After Receiving a Booster Dose of rMenB or rMenB+OMV NZ Vaccine	The persisting GMCs against vaccine antigen 287-953 in children (at 60 months of age), twenty months after receiving a booster dose of either rMenB or rMenB+OMV NZ vaccine (at 40 months), are compared with GMCs in vaccine-naïve children of same age.	20 months post booster/ Baseline for Naïve	No
Secondary	Geometric Mean Antibody Concentrations in Children After Two Doses of rMenB+OMV NZ Vaccine Given One Month Apart, Either at 40 Months or 60 Months of Age.	The GMCs against vaccine antigen 287-953 in children after two catch-up doses of rMenB+OMV NZ vaccine when given either at 40- & 42- months or 60- & 62- months of age are reported.	1 month post vaccine dose two	No
Secondary	Geometric Mean Antibody Concentrations in Children (at 60 Months), Eighteen Months After Receiving Two Catch-up Doses of rMenB+OMV NZ Vaccine.	Persistence of GMCs against vaccine antigen 287-953 in children (60 months of age), eighteen months after two catch-up doses of rMenB+OMV NZ vaccine given at 40 months of age.	18 months post vaccine dose 2	No
Secondary	Percentage of Subjects With Four Fold Increase in Geometric Mean Antibody Concentrations , After a Single Booster Dose of rMenB or rMenB+OMV NZ Vaccine Given at 40 Months of Age	The percentage of subjects with four fold increase in GMCs over baseline against vaccine antigen 287-953 one month after receiving a single booster dose of either rMenB or rMen+OMV NZ vaccine, is compared with responses following one catch-up dose of rMenB+OMV NZ in children at 40 months.	1 month post booster / 1 month post dose 1	No
Secondary	Percentage of Subjects With 4-fold Increase in Geometric Mean Antibody Concentrations, After Two Catch-up Doses of rMenB+OMV NZ Vaccine Given One Month Apart Either at 40 or 60 Months of Age	The percentages of subjects with four-fold increase in GMCs over baseline against vaccine antigen 287-953, one month after receiving a two catch-up doses of rMenB+OMV NZ vaccine either at 40 & 42 months or 60 & 62 months of age.	1 month post dose 2	No
Secondary	Number of Children Reporting Solicited Local and Systemic Adverse Events After Receiving Two Catch-up Doses of rMenB+OMV NZ Vaccine One Month Apart, Either at 40 or 60 Months of Age	The safety and tolerability of a two doses of rMenB+OMV NZ vaccine in children when given either at 40 & 42 months or 60 & 62 months of age is assessed in terms of number of subjects with solicited local and systemic reactions following vaccination.	Day 1-7 after each vaccination	Yes