Safety, Tolerability and Immunogenicity of Meningococcal B Recombinant Vaccine Administered With or Without Routine Infant Vaccinations to Healthy Infants According to Different Immunization Schedules

Novartis Vaccines1,885 enrolled

Overview

Primary :1.To demonstrate a sufficient immune response of rMenB+OMV NZ, when given concomitantly with routine infant vaccines to healthy infants at 2, 4 and 6 and 2, 3 and 4 months of age, as measured by percentage of subjects with serum bactericidal activity (SBA) titer ≥1:5, at 1 month after the third vaccination Secondary :To demonstrate that immunogenicity of routine infant vaccines, when given concomitantly with rMenB+OMV NZ to healthy infants at 2, 3 and 4 months of age, was non-inferior to that of routine infant vaccines given without rMenB+OMV NZ. 2. To demonstrate that the immunogenicity of rMenB+OMV NZ when given concomitantly with routine infant vaccines was non-inferior to that of rMenB+OMV NZ given without routine infant vaccines at 2, 4 and 6 months of age. 3. To assess prevalence of meningococcal B antibodies over the study period by evaluation of SBA, at baseline and at 1 month after third vaccination, in subjects- received routine infant vaccine without rMenB+OMV NZ.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

1,885

Conditions

Meningococcal Infections

Interventions

Eligibility

Sex: ALLMin age: 55 DaysMax age: 89 DaysHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy 2-month old infants (55-89 days, inclusive), who were born after full term pregnancy with an estimated gestational age ≥ 37 weeks and a birth weight ≥ 2.5 kg; * For whom a parent/legal guardian has given written informed consent after the nature of the study has been explained. Exclusion Criteria: * History of any meningococcal B or C vaccine administration; * prior vaccination with routine infant vaccines (Diphtheria, Tetanus, Pertussis, Polio, Haemophilus influenzae type b (Hib), and Pneumococcal antigens); * 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 to38 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.

Locations (60)

Novartis Investigational Site Nr. 59

Edegem, Antwerpen, Belgium

Novartis Investigational Site Nr. 55

Antwerp, Antwerp, Belgium

Study Investigational Site Nr. 60

Brussels, Brussels Capital, Belgium

Novartis Investigational Site Nr. 57

Brussels, Brussels Capital, Belgium

Novartis Investigational Site Nr. 56

Hasselt, Limburg, Belgium

Outcomes

Primary Outcomes

Percentage of Subjects With Serum Bactericidal Activity ≥1:5 After Receiving Three Doses of rMenB+OMV NZ Vaccine

The percentage of subjects with serum bactericidal activity(hSBA)titer ≥1:5 after receiving three doses of rMenB+OMV NZ vaccine were evaluated to demonstrate sufficient immune response following rMenB+OMV NZ vaccination, when given concomitantly with routine infant vaccines to healthy infants. The serum bactericidal antibodies directed against serogroup B meningococci, are measured by human complement Serum Bactericidal Assay (hSBA). The immune response was considered sufficient for groups B+R246 and B+R234 if the lower limit of the 2-sided 95% confidence interval was ≥ 70% for all three strains.

Time frame: One month after third Men B vaccination

Safety and Tolerability of 3 Doses of rMenB - Concomitantly With Routine Infant Vaccines at 2, 4 and 6 Months of Age - Concomitantly With Routine Vaccines at 2, 3 and 4 Months of Age - Alone at 2, 4 and 6 Months of Age

Safety and Tolerability of 3 Doses of rMenB was assessed in terms of the number of subjects who reported solicited local and systemic adverse events when administered concomitantly with routine infant vaccines at 2,4,6 months of age (B+R246) to when rMenB+OMV NZ and routine vaccines were administered separately (group B246\_R357).

Time frame: 10 months (groups 1 and 2); 8 months (groups 3 and 4)

Secondary Outcomes

Non-inferiority of Immune Response to rMenB+OMV NZ Vaccination When Administered Concomitantly With Routine Infant Vaccines at 2,4,6 Months of Age

The non-inferiority of immune response to rMenB+OMV NZ vaccination when administered concomitantly with routine infant vaccines at 2,4,6 months of age(B+R246) to when rMenB+OMV NZ and routine vaccines were administered separately (group B246\_R357)was assessed in terms of percentage of subjects With hSBA≥ 1:5.

Time frame: One month after 3rd Men B vaccination

Non-inferiority of Immune Response to Diphtheria and Tetanus Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine

Time frame: One month after 3rd vaccination

Geometric Mean Titers Against Neisseria Meningitidis Serogroup B, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines.

The hSBA antibody titers when rMenB+OMV NZ vaccine is administered concomitantly with routine infant vaccines to when rMenB+OMV NZ vaccine and routine vaccines were given separately are reported in terms of vaccine-group-specific geometric mean titers.

Time frame: One month after third Men B vaccination

Geometric Mean Ratio of hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines.

The geometric mean ratio(GMR) of GMTs at 1 month after 3rd rMenB+OMV NZ vaccination to prevaccination GMTs, when rMenB+OMV NZ was administered concomitantly with routine infant vaccines to when rMenB+OMV NZ vaccine and routine vaccines were given separately.

Time frame: one month after third Men B vaccination

Percentage of Subjects With hSBA ≥1:8 After Receiving Three Doses of rMenB+OMV NZ Vaccine.

The percentage of subjects with hSBA titers ≥1:8, following rMenB+OMV NZ vaccination when given concomitantly with routine infant vaccines to when rMenB+OMV NZ and routine vaccines were given separately.

Time frame: One month after third Men B vaccination

Percentage of Subjects With 4-fold Rise in hSBA Titers, When rMenB+OMV NZ Vaccine is Administered Concomitantly With Routine Infant Vaccines.

The percentage of subjects with 4-fold rise in hSBA titers at 1 month after 3rd rMenB+OMV NZ vaccination from baseline, when rMenB+OMV NZ was administered concomitantly with routine infant vaccines to when rMenB+OMV NZ vaccine and routine vaccines were given separately.

Time frame: One month after third Men B vaccination

Non-inferiority of Immune Response to Acellular Pertussis Antigens When Routine Vaccines Are Administered Concomitantly With rMen+OMV NZ Vaccine.

Non-inferiority of immune response to routine vaccine antigens when routine vaccines were administered concomitantly with rMenB+OMV NZ vaccine \[group B+R234\] to when only routine vaccines were given \[Group R234\] were assessed in terms of percentage of subjects achieving seroconversion for pertussis antigens - Filamentous Hemagglutinin (FHA), Pertactin and Pertussis Toxoid (PT) at 1 month after 3rd vaccination versus baseline. Seroconversion was defined as a 4-fold increase for each pertussis antigen or in those initially seropositive, persistence of the pre-vaccination antibody concentration at least at the same antibody concentration as before vaccination, taking into account the decay of maternal antibodies.

Time frame: 1 month after 3rd vaccination