Safety, Tolerability and Immunogenicity of Meningococcal B Recombinant Vaccine Administered as Booster Dose at 12, 18 or 24 Months of Age in Toddlers (12-24 Months) Primed With a Three-Dose Immunization Series as Infants in Study V72P12

Meningococcal Disease Clinical Trial

Official title:

A Phase 2b, Open Label, Multi-Center, Extension Study to Evaluate the Safety, Tolerability and Immunogenicity of a Booster Dose of Novartis Meningococcal B Recombinant Vaccine Administered at 12, 18 or 24 Months of Age in Subjects Who Previously Received a Three-Dose Primary Series of the Novartis Meningococcal B Recombinant Vaccine as Infants in Study V72P12

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00944034
• Other study ID #: V72P12E1
• Secondary ID: 2009-011676-30
• Status: Completed
• Phase: Phase 2/Phase 3
• First received: July 21, 2009
• Last updated: October 7, 2015
• Start date: July 2009
• Est. completion date: January 2012

Study information

• Verified date: October 2015
• Source: Novartis
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationBelgium: Federal Agency for Medicinal Products and Health ProductsCzech Republic: State Institute for Drug ControlGermany: Federal Institute for Drugs and Medical DevicesItaly: The Italian Medicines AgencySpain: Spanish Agency of MedicinesUnited Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

This extension study V72P12E1 will investigate the safety, tolerability and immunogenicity of a fourth (booster) dose of rMenB+OMV NZ at 12, 18 and 24 months of age in subjects previously primed with rMenB+OMV NZ according to two different three-dose immunization schedules in infancy (2, 4 and 6 or 2, 3 and 4 months of age in the parent study V72P12). The study will also explore the bactericidal antibody persistence at 12, 18 and 24 months of age, following the two different immunization schedules, in order to identify the optimal timing for boosting. Two catch-up rMenB+OMV NZ doses will be given to unprimed, naïve toddlers at 12 (subjects enrolled in the control group of V72P12), 18 and 24 months of age (two new cohort of subjects enrolled). These subjects will generate data for assessing the safety and immunogenicity of a two-dose catch-up regimen at these ages, but will also serve as controls for a descriptive comparison of antibody persistence and booster responses for the other groups.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1588
• Est. completion date: January 2012
• Est. primary completion date: August 2011
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 12 Months to 24 Months

Eligibility

Inclusion Criteria:

Follow-on participants of V72P12:

Healthy toddlers who completed Study V72P12, aged:

• 12 months or older - Groups 1a, 2a, 3a, 4

• 18 months (0/ +29 days window) - Groups 1b, 2b, 3b

• 24 months (0/ +29 days window) - Groups 1c, 2c, 3c

Naive subjects newly enrolled:

• Group 5: healthy 18-month-old toddlers (0/ +29 days window)

• Group 6: healthy 24-month-old toddlers (0/ +29 days window)

Exclusion Criteria:

• History of any meningococcal B vaccine administration (only for groups 5 and 6);

• Previous ascertained or suspected disease caused by N. meningitidis;

• History of severe allergic reaction after previous vaccinations or hypersensitivity to any vaccine component;

• Significant acute or chronic infection within the previous 7 days or axillary temperature major or equal to 38 degrees within the previous day

• Antibiotics within 6 days prior to enrollment;

• Any serious chronic or progressive disease;

• Known or suspected impairment or alteration of the immune system;

• Receipt of blood, blood products and/or plasma derivatives or any parenteral immunoglobulin preparation.

Study Design

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

Related Conditions & MeSH terms

• Meningitis
• Meningitis, Meningococcal
• Meningococcal Disease
• Meningococcal Infections
• Meningococcal Meningitis

Intervention

Biological:
• rMenB+OMV NZ with routine vaccinations
rMenB+OMV NZ with routine vaccinations at 2, 4, and 6 months of age; random allocation in a 1:1:1 ratio to receive a booster dose of rMenB+OMV NZ at 12 months of age
• rMenB+OMV NZ with routine vaccinations
rMenB+OMV NZ with routine vaccinations at 2, 4, and 6 months of age; random allocation in a 1:1:1 ratio to receive a booster dose of rMenB+OMV NZ at 18 months of age
• rMenB+OMV NZ
rMenB+OMV NZ at 2, 4, and 6 months of age and routine vaccinations at 3, 5 and 7 months of age; random allocation in a 1:1:1 ratio to receive a booster dose of rMenB+OMV NZ at 12 months of age
• rMenB+OMV NZ
rMenB+OMV NZ at 2, 4, and 6 months of age and routine vaccinations at 3, 5 and 7 months of age; random allocation in a 1:1:1 ratio to receive a booster dose of rMenB+OMV NZ at 18 months of age
• rMenB+OMV NZ with routine vaccinations
rMenB+OMV NZ with routine vaccinations at 2, 3 and 4 months of age; random allocation in a 1:1:1 ratio to receive 1 booster dose of rMenB+OMV NZ at 12 months of age
• rMenB+OMV NZ with routine vaccinations
rMenB+OMV NZ with routine vaccinations at 2, 3 and 4 months of age; random allocation in a 1:1:1 ratio to receive 1 booster dose of rMenB+OMV NZ at 18 months of age
• two doses of rMenB+OMV NZ
two catch-up doses of rMenB+OMV NZ at 12 and 14 months of age.
• rMenB+OMV NZ with routine vaccinations
rMenB+OMV NZ with routine vaccinations at 2, 4, and 6 months of age; random allocation in a 1:1:1 ratio to receive a booster dose of rMenB+OMV NZ at 24 months of age
• two doses of rMenB+OMV NZ
two catch-up doses of rMenB+OMV NZ at 18 and 20 months of age
• rMenB+OMV NZ
rMenB+OMV NZ at 2, 4, and 6 months of age and routine vaccinations at 3, 5 and 7 months of age; random allocation in a 1:1:1 ratio to receive a booster dose of rMenB+OMV NZ at 24 months of age
• two doses of rMenB+OMV NZ
two catch-up doses of rMenB+OMV NZ at 24 and 26 months of age
• rMenB+OMV NZ with routine vaccinations
rMenB+OMV NZ with routine vaccinations at 2, 3 and 4 months of age; random allocation in a 1:1:1 ratio to receive 1 booster dose of rMenB+OMV NZ at 12 (Group 3a), 18 (Group 3b) or 24 (Group 3c) months of age

Locations

Country	Name	City	State
United Kingdom	South West Medicines for Children Research Network, Child Health Building, Royal Devon and Exeter NHS Foundation Trust	Barrack Road	Exeter
United Kingdom	St. George's University of London	Cranmer Terrace	London
United Kingdom	Oxford Vaccines Group, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Old Road	Headington	Oxford
United Kingdom	University Hospitals Bristol, NHS Foundation Trust, Trust Headquarters	Marlborough Street	Bristol
United Kingdom	Centre for Clinical Vaccinology	Oxford

Sponsors (1)

Lead Sponsor	Collaborator
Novartis Vaccines

Countries where clinical trial is conducted

Belgium,  Czech Republic,  Germany,  Italy,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentages of Subjects With Serum Bactericidal Antibody Titers =1:5 After Receiving a Fourth (Booster) Dose of rMenB+OMV NZ Vaccination in Subjects Who Previously Received 3 Doses of rMenB+OMV NZ and Routine Vaccines at 2, 4 and 6 Months of Age.	Immunogenicity was assessed in terms of percentage of subjects with serum bactericidal antibody (SBA) titers =1:5 (98.3% CI) against N.meningitidis serogroup reference strains H44/76, NZ98/254 and 5/99, one month after the fourth (booster) dose of meningococcal B vaccine at 12 or 18 or24 months of age who were previously vaccinated with 3 doses of rMenB+OMV NZ and routine vaccines at 2, 4 and 6 months of age.	1 month after booster	No
Secondary	Percentages of Subjects With SBA Titers =1:5 After Receiving a Fourth (Booster) Dose of rMenB+OMV NZ Vaccination in Subjects Who Previously Received 3 Doses of rMenB+OMV NZ at 2, 4 and 6 Months of Age and Routine Vaccines at 3, 5 and 7 Months of Age.	Immunogenicity was assessed in terms of Percentages of Subjects With SBA Titers =1:5 (98.3% CI), After Receiving a Fourth (Booster) Dose of rMenB+OMV NZ Vaccination in subjects who previously received 3 doses of rMenB+OMV NZ at 2, 4 and 6 months of age and routine vaccines at 3, 5 and 7 months of age.	1 month after booster	No
Secondary	Percentages of Subjects With Serum Bactericidal Antibody Titers =1:5 After Receiving a Fourth (Booster) Dose of rMenB+OMV NZ Vaccination in Subjects Who Previously Received 3 Doses of rMenB+OMV NZ and Routine Vaccines at 2, 3 and 4 Months of Age.	Immunogenicity was assessed in terms of percentage of subjects with serum bactericidal antibody (SBA) titers =1:5 (98.3% CI) against N.meningitidis serogroup reference strains H44/76, NZ98/254 and 5/99, one month after the fourth (booster) dose of meningococcal B vaccine at 12 or 18 or24 months of age who were previously vaccinated with 3 doses of rMenB+OMV NZ and routine vaccines at 2, 3 and 4 months of age.	1 month after booster	No
Secondary	Geometric Mean Titers (GMTs) in Subjects One Month After Receiving a Fourth (Booster) Dose of rMenB+OMV NZ Vaccination in Subjects at 12 18 or 24 Months of Age Who Previously Received 3 Doses of rMenB+OMV NZ at 2, 3 and 4 or 2, 4 and 6 Months of Age.	The serum antibody titers one month after the fourth (booster) dose of meningococcal B vaccine at 12 or 18 or24 months of age who were previously vaccinated with 3 doses of rMenB+OMV NZ at 2, 3 and 4 or 2, 4 and 6 months of age, are reported as geometric mean titers (GMTs) against N.meningitidis serogroup reference strains H44/76, NZ98/254 and 5/99.	1 month after booster	No
Secondary	GMTs in Subjects One Month After the Fourth (Booster) Dose of Meningococcal B Vaccine at 12 Months of Age Previously Vaccinated With 3 Doses of rMenB+OMV NZ at 2, 3 and 4 or 2, 4 and 6 Months of Age and Single Dose of rMenB+OMV NZ Given at Same Age	Characterization of immunological memory by serum antibody titers (98.3% CI) one month after the fourth (booster) dose of meningococcal B vaccine at 12 months of age who were previously vaccinated with 3 doses of rMenB+OMV NZ at 2, 3 and 4 or 2, 4 and 6 months of age and single dose of rMenB+OMV NZ given at same ages, are reported as geometric mean titers (GMTs) against N.meningitidis serogroup reference strains H44/76, NZ98/254 and 5/99.	1 month after booster	Yes
Secondary	GMTs in Subjects One Month After the Fourth (Booster) Dose of Meningococcal B Vaccine at 18 and 24months of Age, Previously Vaccinated With 3 Doses of rMenB+OMV NZ at 2, 3 and 4 or 2, 4 and 6 Months of Age and Single Dose of rMenB+OMV NZ Given at Same Age	Characterization of immunological memory by serum antibody titers one month after the fourth (booster) dose of meningococcal B vaccine at 18 and 24months of age who were previously vaccinated with 3 doses of rMenB+OMV NZ at 2, 3 and 4 or 2, 4 and 6 months of age and single dose of rMenB+OMV NZ given at same ages, are reported as geometric mean titers (GMTs) against N.meningitidis serogroup reference strains H44/76, NZ98/254 and 5/99.	1 month after booster	Yes
Secondary	Two-dose Catch-up Regimen of rMenB+OMV NZ in Unprimed Toddlers Aged 12, 18 or 24 Months	Immunogenicity evaluation of a two-dose catch-up regimen of rMenB+OMV NZ in unprimed toddlers aged 12, 18 or 24 months as measured by serum antibody titers one month after the second vaccination f meningococcal B vaccine at 18 and 24months of age who were previously vaccinated with 3 doses of rMenB+OMV NZ reported as geometric mean titers (GMTs) against N.meningitidis serogroup reference strains H44/76, NZ98/254 and 5/99.	1 month after second vaccination	Yes
Secondary	Geometric Mean Concentrations Against Vaccine Antigen 287- 953 One Month After Fourth Booster Dose to Previously Primed Toddlers at 12, 18 or 24 Months of Age.	Immunogenicity evaluation against vaccine antigen 287-953 one month after fourth booster dose to previously primed toddlers at 12, 18 or 24 months measured by ELISA.	1 month after booster vaccination	Yes
Secondary	Geometric Mean Concentrations Against Vaccine Antigen 287- 953 One Month After Booster Given After a Two-dose Catch-up Regimen in Toddlers Starting at 12, 18 or 24 Months of Age.	Immunogenicity evaluation against vaccine antigen 287-953 one month after booster given after a two-dose catch-up regimen in toddlers starting at 12, 18 or 24 months of age.one month after fourth booster dose to previously primed toddlers at 12, 18 or 24 months of age measured by ELISA	1 month after booster vaccination	Yes
Secondary	Number of Children Reporting Solicited Local and Systemic Adverse Events After Receiving a Fourth Booster Dose of rMenB+OMV NZ Vaccine at 12, 18 or 24 Months of Age.	The safety and tolerability of the 4th booster dose rMenB+OMV NZ vaccine in children (12, 18 or 24 months age) is reported as number of subjects with solicited local and systemic adverse events.	From day 1 to day 7 after vaccination	Yes
Secondary	Number of Children Reporting Solicited Local and Systemic Adverse Events After Receiving a Two-dose Catch-up Regimen of rMenB+OMV NZ Vaccine at 12, 18 or 24 Months of Age.	The safety and tolerability of the two-dose catch-up regimen of rMenB+OMV NZ vaccine in children (12, 18 or 24 months age) is reported as number of subjects with solicited local and systemic adverse events.	day 1 to day 7 after vaccination	Yes