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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

Phase 2
Completed
Conditions
Meningococcal Disease
Meningococcal Meningitis
Interventions
Biological: rMenB+OMV NZ with routine vaccinations
Biological: two doses of rMenB+OMV NZ
Biological: rMenB+OMV NZ
Registration Number
NCT00944034
Lead Sponsor
Novartis Vaccines
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
1588
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

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
B+R246_12rMenB+OMV NZ with routine vaccinationsPreviously received rMenB+OMV NZ 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.
B12 14two doses of rMenB+OMV NZPreviously received two catch-up doses of rMenB+OMV NZ vaccine at 12 and14 months of age.
B24 26two doses of rMenB+OMV NZPreviously received two catch-up doses of rMenB+OMV NZ vaccine at 24 and 26 months of age.
B+R246_18rMenB+OMV NZ with routine vaccinationsPreviously received rMenB+OMV NZ 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.
B246_18rMenB+OMV NZPreviously received 3 doses of rMenB+OMV NZ 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.
B+R234_12rMenB+OMV NZ with routine vaccinationsPreviously received rMenB+OMV NZ vaccine + routine vaccines at 2, 3 and 4 months of age followed by a booster dose of rMenB+OMV NZ at 12 months of age.
B+R234_24rMenB+OMV NZ with routine vaccinationsPreviously received rMenB+OMV NZ 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.
B246_12rMenB+OMV NZPreviously received 3 doses of rMenB+OMV NZ 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.
B18 20two doses of rMenB+OMV NZPreviously received two catch-up doses of rMenB+OMV NZ vaccine at 18 and 20 months of age.
B+R246_24rMenB+OMV NZ with routine vaccinationsPreviously received rMenB+OMV NZ 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.
B246_24rMenB+OMV NZPreviously received 3 doses of rMenB+OMV NZ 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 24 months of age.
B+R234_18rMenB+OMV NZ with routine vaccinationsPreviously received rMenB+OMV NZ 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.
Primary Outcome Measures
NameTimeMethod
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.1 month after booster

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.

Secondary Outcome Measures
NameTimeMethod
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.1 month after booster

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.

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.1 month after booster

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.

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.1 month after booster

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.

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 Age1 month after booster

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.

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 Age1 month after booster

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.

Two-dose Catch-up Regimen of rMenB+OMV NZ in Unprimed Toddlers Aged 12, 18 or 24 Months1 month after second vaccination

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.

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.1 month after booster vaccination

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.

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.1 month after booster vaccination

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

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.From day 1 to day 7 after vaccination

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.

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.day 1 to day 7 after vaccination

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.

Trial Locations

Locations (5)

South West Medicines for Children Research Network, Child Health Building, Royal Devon and Exeter NHS Foundation Trust

🇬🇧

Barrack Road, Exeter, United Kingdom

Oxford Vaccines Group, Centre for Clinical Vaccinology and Tropical Medicine, Churchill Hospital, Old Road

🇬🇧

Headington, Oxford, United Kingdom

Centre for Clinical Vaccinology

🇬🇧

Oxford, United Kingdom

St. George's University of London

🇬🇧

Cranmer Terrace, London, United Kingdom

University Hospitals Bristol, NHS Foundation Trust, Trust Headquarters

🇬🇧

Marlborough Street, Bristol, United Kingdom

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